Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures.

JOURNAL/nrgr/04.03/01300535-202501000-00034/figure1/v/2024-05-14T021156Z/r/image-tiff Certain amino acids changes in the human Na+/K+-ATPase pump, ATPase Na+/K+ transporting subunit alpha 1 (ATP1A1), cause Charcot-Marie-Tooth disease type 2 (CMT2) disease and refractory seizures. To develop in vivo models to study the role of Na+/K+-ATPase in these diseases, we modified the Drosophila gene homolog, Atpα, to mimic the human ATP1A1 gene mutations that cause CMT2. Mutations located within the helical linker region of human ATP1A1 (I592T, A597T, P600T, and D601F) were simultaneously introduced into endogenous DrosophilaAtpα by CRISPR/Cas9-mediated genome editing, generating the AtpαTTTF model. In addition, the same strategy was used to generate the corresponding single point mutations in flies (AtpαI571T, AtpαA576T, AtpαP579T, and AtpαD580F). Moreover, a deletion mutation (Atpαmut) that causes premature termination of translation was generated as a positive control. Of these alleles, we found two that could be maintained as homozygotes (AtpαI571T and AtpαP579T). Three alleles (AtpαA576T, AtpαP579 and AtpαD580F) can form heterozygotes with the Atpαmut allele. We found that the Atpα allele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila. Flies heterozygous for AtpαTTTF mutations have motor performance defects, a reduced lifespan, seizures, and an abnormal neuronal morphology. These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Toward Predicting the Formation of Integral-Asymmetric, Isoporous Diblock Copolymer Membranes.

The self-assembly and nonsolvent-induced phase separation (SNIPS) process of block copolymers and solvents enables the fabrication of integral-asymmetric, isoporous membranes. An isoporous top layer is formed by evaporation-induced self-assembly (EISA) and imparts selectivity for ultrafiltration of functional macromolecules or water purification. This selective layer is supported by a macroporous bottom structure that is formed by nonsolvent-induced phase separation (NIPS) providing mechanical stability. Thereby the permeability/selectivity tradeoff is optimized. The SNIPS fabrication involves various physical phenomena-e.g., evaporation, self-assembly, macrophase separation, vitrification - and multiple structural, thermodynamic, kinetic, and process parameters. Optimizing membrane properties and rationally designing fabrication processes is a challenge which particle simulation can significantly contribute to. Using large-scale particle simulations, it is observed that 1) a small incompatibility between matrix-forming block of the copolymer and nonsolvent, 2) a glassy arrest that occurs at a smaller polymer concentration, or 3) a higher dynamical contrast between polymer and solvent results in a finer, spongy substructure, whereas the opposite parameter choice gives rise to larger macropores with an elongated shape. These observations are confirmed by comparison to experiments on polystyrene (PS)-block-poly(4-vinylpyridine) (P4VP) diblock copolymer membranes, varying the chemical nature of the coagulant or the temperature of coagulation bath.

Integrated respiratory toxicity of municipal wastewater to human bronchial epithelial cells and 3D bronchospheres.

Respiratory symptoms have been reported in wastewater treatment workers and residents living close to sewage treatment plant. However, toxicological research about the respiratory hazards of municipal wastewater is scarce. The present study aims to gain insight into the comprehensive respiratory hazards induced by the contaminant mixtures in municipal wastewater. The integrated respiratory hazards of effluents from four secondary wastewater treatment plants (SWTPs), a tertiary wastewater treatment plant (TTP), and a constructed wetland (CW) were evaluated using normal human bronchial epithelial cells (NHBE) bioassay, and toxicity reduction efficiency of various treatment techniques was analyzed. Effluents caused cytotoxicity, oxidative damage, inflammation response with the increased levels of IL-6 and CXCL8, and impaired barrier integrity with decreased expressions of ZO-1 and occludin in NHBE. Further, the effluents inhibited the development of 3D bronchospheres, increased irregular surface and cell debris, and suppressed the formation of luminal structures. TTP E effluent significantly increased the expression of MUC5AC in bronchospheres. The integrated biomarker response (IBR) of the influent was removed by 40.2% at SWTPs, 18.2% at TTP, and 36.6% at CW, respectively. The IBR of the final effluents from SWTPs, TTP, and CW were 7.2, 7.7, and 7.7, respectively. Significant correlation with toxicity biomarkers was frequently observed for stearyl alcohol, o-cresol, phenanthrene, butylated hydroxytoluene, and dimethyl phthalate. The present study provided human relevant evidence concerning the adverse respiratory effects associated with discharge. The necessity for deep water treatment, performance optimization, and the potential means were suggested for improving water quality and protecting respiratory health.

Topology Effect on Order-Disorder Transition of High-χ Block Copolymers.

This work aims to systematically examine the topology effect on the self-assembly of block copolymers. Compositionally, symmetric polystyrene-block-polydimethylsiloxane block copolymers (BCPs) with different chain topologies (diblock, three-arm star-block, and four-arm star-block) and various molecular weights are synthesized. These purposely designed block copolymers are used as a model system to investigate the topology effect on order-to-disorder transition temperature (T ODT) by temperature-resolved small-angle X-ray scattering experiments. An increase of the T ODT is observed when the arm number of BCPs with equivalent arm length (i.e., molecular weight) is increased from one to four. Based on the random-phase approximation (RPA), Flory-Huggins interaction parameter (χ) is determined from the regression of the measured T ODT. The observation by differential scanning calorimetry also demonstrates the shifting of the endothermic peak from the order-to-disorder transition of star-blocks to the higher temperature region, consistent with the scattering experiments and the RPA prediction.

Comparative study of the clinical value of digital subtraction angiography via femoral and radial arterial paths.

OBJECTIVE: To evaluate the clinical efficacy of digital subtraction angiography (DSA) performed via femoral artery and radial artery approaches. METHODS: This retrospective study included 480 patients requiring cerebral vascular angiography at the First People's Hospital of Changde City from March 2020 to February 2022. Patients were divided into the femoral artery group (transfemoral approach, n=400) and the radial artery group (transradial approach, n=80) according to the surgical route. We compared perioperative metrics, success rates of selective angiography and puncture, and complication rates (including pseudoaneurysm, urinary retention, hematoma, vasospasm) between the groups. Multivariate logistic regression was used to analyze factors influencing the failure of angiography by each approach. RESULTS: The radial artery group exhibited shorter durations for puncture, hemostasis, exposure, operation, and postoperative recovery (all P<0.001). The success rate of selective angiography was higher in the radial artery group (93.75%) compared to the femoral artery group (85.25%) (χ2=4.168, P=0.041). No significant difference was found in puncture success rates between the groups (χ2=0.235, P=0.628). The overall complication rate was significantly lower in the radial artery group (2.50%) compared to the femoral artery group (9.25%) (χ2=4.069, P=0.044). Gender and low-density lipoprotein cholesterol levels were significant predictors of angiography failure in both approaches (both P<0.05). CONCLUSION: The transradial approach for DSA is safe and feasible, offering advantages in terms of operational time and complication rates, making it the preferred method in clinical settings.

Room-Temperature Ripening Enabled by Hygroscopic Salts for Hole-conductor-free Printable Perovskite Solar Cells with Efficiency Over 20.

Solution-processed perovskite films generally possess small grain sizes and high density of grain boundaries, which intensify non-radiative recombination of carriers and limits the power conversion efficiency (PCE) of solar cells. In this study, we report the room-temperature ripening enabled by the synergy of hygroscopic salts and moisture in air for efficient hole-conductor-free printable mesoscopic perovskite solar cells (p-MPSCs). Treating perovskite films with proper hygroscopic salts in damp air induces obvious secondary recrystallization, which coarsens the grains size from hundreds of nanometers to several micrometers. It's proposed that the hygroscopic salt at grain boundaries could absorb moisture and form a complex which could not only serve as mass transfer channel but also assist in the dissolution of perovskite grains. This activates mass transfer between small grains and large grains since they possess different solubilities, and thus ripens the perovskite film. Consequently, p-MPSCs treated with the hygroscopic salt of NH4SCN show an improved power conversion efficiency of 20.13% from 17.94%, and maintain >98% of the initial efficiency under maximum power point tracking at 55±5°C for 350 hours.

Sequential Self-Assembly of Polystyrene-block-Polydimethylsiloxane for 3D Nanopatterning via Solvent Annealing.

This study aims to develop a strategy for the fabrication of multilayer nanopatterns through sequential self-assembly of lamella-forming polystyrene-block-polydimethylsiloxane (PS-b-PDMS) block copolymer (BCP) from solvent annealing. By simply tuning the solvent selectivity, a variety of self-assembled BCP thin-film morphologies, including hexagonal perforated lamellae (HPL), parallel cylinders, and spheres, can be obtained from single-composition PS-b-PDMS. By taking advantage of reactive ion etching (RIE), topographic SiO2 monoliths with well-ordered arrays of hexagonally packed holes, parallel lines, and hexagonally packed dots can be formed. Subsequently, hole-on-dot and line-on-hole hierarchical textures can be created through a layer-by-layer process with RIE treatment as evidenced experimentally and confirmed theoretically. The results demonstrated the feasibility of creating three-dimensional (3D) nanopatterning from the sequential self-assembly of single-composition PS-b-PDMS via solvent annealing, providing an appealing process for nano-MEMS manufacturing based on BCP lithography.

The novel lnc-HZ12 suppresses autophagy degradation of BBC3 by preventing its interactions with HSPA8 to induce trophoblast cell apoptosis.

Abnormal expression of long non-coding RNAs (lncRNAs) is associated with the dysfunctions of human trophoblast cells and the occurrence of miscarriage (abnormal early embryo loss). BBC3/PUMA (BCL2 binding component 3) plays significant roles in regulation of cell apoptosis. However, whether specific lncRNAs might regulate BBC3 in trophoblast cells and further induce apoptosis and miscarriage remains completely unclear. Through screening, we identified a novel lnc-HZ12, which was significantly highly expressed in villous tissues of recurrent miscarriage (RM) patients relative to their healthy control (HC) group. Lnc-HZ12 suppressed chaperone-mediated autophagy (CMA) degradation of BBC3, promoted trophoblast cell apoptosis, and was associated with miscarriage. In mechanism, lnc-HZ12 downregulated the expression levels of chaperone molecules HSPA8 and LAMP2A in trophoblast cells. Meanwhile, lnc-HZ12 (mainly lnc-HZ12-SO2 region in F2 fragment) and HSPA8 competitively bound with the 169RVLYNL174 patch on BBC3, which prevented BBC3 from interactions with HSPA8 and impaired the formation of BBC3-HSPA8-LAMP2A complex for CMA degradation of BBC3. Thus, lnc-HZ12 upregulated the BBC3-CASP9-CASP3 pathway and induced trophoblast cell apoptosis. In villous tissues, lnc-HZ12 was highly expressed, CMA degradation of BBC3 was suppressed, and the apoptosis levels were higher in RM vs HC villous tissues, all of which were associated with miscarriage. Interestingly, knockdown of murine Bbc3 could efficiently suppress placental apoptosis and alleviate miscarriage in a mouse miscarriage model. Taken together, our results indicated that lnc-HZ12 and BBC3 played important roles in trophoblast cell apoptosis and miscarriage and might act as attractive targets for miscarriage treatment.Abbreviation: 7-AAD: 7-aminoactinomycin D; BaP: benzopyrene; BBC3/PUMA: BCL2 binding component 3; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; CMA: chaperone-mediated autophagy; CQ: chloroquine; DMSO: dimethyl sulfoxide; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HC: healthy control; HSPA8: heat shock protein family A (Hsp70) member 8; IP: immunoprecipitation; LAMP2A: lysosomal associated membrane protein 2; LncRNA: long non-coding RNA; mRNA: messenger RNA; MT: mutant-type; NC: negative control; NSO: nonspecific oligonucleotide; PARP1: poly(ADP-ribose) polymerase 1; RIP: RNA immunoprecipitation; RM: recurrent miscarriage; TBP: TATA-box binding protein; WT: wild-type.

Ineffective Learning Behaviors and Their Psychological Mechanisms among Adolescents in Online Learning: A Narrative Review.

During the COVID-19 pandemic, many countries and regions experienced a surge in online learning, but the public complained about and questioned its effectiveness. One of the most important reasons for this was the inadequate metacognitive abilities of adolescents. Studies in learning sciences have identified various inefficient learning behaviors among students in online learning, including help abuse, help avoidance, and wheel spinning; all closely related to metacognition. Despite concerns about ecological validity, researchers in psychology have proposed the agenda-based regulation framework, the COPES model, and MAPS model, which may help explain the inefficient learning behaviors among adolescents in online learning. Future studies should aim to verify these theoretical frameworks within the context of online learning and elucidate the causes of inefficient learning behaviors; the design and optimization of online learning systems should be informed by theories in cognitive psychology.

Txnrd2 Attenuates Early Brain Injury by Inhibition of Oxidative Stress and Endoplasmic Reticulum Stress via Trx2/Prx3 Pathway after Intracerebral Hemorrhage in Rats.

Thioredoxin-reductase 2 (Txnrd2) belongs to the thioredoxin-reductase family of selenoproteins and is a key antioxidant enzyme in mammalian cells to regulate redox homeostasis. Here, we reported that Txnrd2 exerted a major influence in brain damage caused by Intracerebral hemorrhage (ICH) by suppressing endoplasmic reticulum (ER) stress oxidative stress and via Trx2/Prx3 pathway. Furthermore, we demonstrated that pharmacological selenium (Se) rescued the brain damage after ICH by enhancing Txnrd2 expression. Primarily, expression and localization of Txnrd2, Trx2 and Prx3 were determined in collagenase IV-induced ICH model. Txnrd2 was then knocked down using siRNA interference in rats which were found to develop more severe encephaledema and neurological deficits. Mechanistically, we observed that loss of Txnrd2 leads to increased lipid peroxidation levels and ER stress protein expression in neurons and astrocytes. Additionally, it was revealed that Se effectively restored the expression of Txnrd2 in brain and inhibited both the activity of ER stress protein activity and the generation of reactive oxygen species (ROS) by promoting Trx2/Prx3 kilter when administrating sodium selenite in lateral ventricle. This study shed light on the effect of Txnrd2 in regulating oxidative stress and ER stress via Trx2/Prx3 pathway upon ICH and its promising potential as an ICH therapeutic target.

Association of sleep traits with myopia in children and adolescents: A meta-analysis and Mendelian randomization study.

PURPOSE: The association between sleep and myopia in children and adolescents has been reported, yet it remains controversial and inconclusive. This study aimed to investigate the influence of different sleep traits on the risk of myopia using meta-analytical and Mendelian randomization (MR) techniques. METHODS: The literature search was performed in August 31, 2023 based on PubMed, Embase, Web of Science, and Cochrane library. The meta-analysis of observational studies reporting the relationship between sleep and myopia was conducted. MR analyses were carried out to assess the causal impact of genetic pre-disposition for sleep traits on myopia. RESULTS: The results of the meta-analysis indicated a significant association between the risk of myopia and both short sleep duration [odds ratio (OR) = 1.23, 95% confidence interval (CI) = 1.08-1.42, P = 0.003] and long sleep duration (OR = 0.75, 95% CI = 0.66-0.86, P < 0.001). MR analyses revealed no significant causal associations of genetically determined sleep traits with myopia, including chronotype, sleep duration, short sleep duration and long sleep duration (all P > 0.05). CONCLUSIONS: No evidence was found to support a causal relationship between sleep traits and myopia. While sleep may not independently predict the risk of myopia, the potential impact of sleep on the occurrence and development of myopia cannot be disregarded.

A Drosophila Model Reveals the Potential Role for mtt in Retinal Disease.

Congenital stationary night blindness (CSNB) is a genetically heterogeneous inherited retinal disorder, caused by over 300 mutations in 17 different genes. While there are numerous fly models available for simulating ocular diseases, most are focused on mimicking retinitis pigmentosa (RP), with animal models specifically addressing CSNB limited to mammals. Here, we present a CSNB fly model associated with the mtt gene, utilizing RNA interference (RNAi) to silence the mtt gene in fly eyes (homologous to the mammalian GRM6 gene) and construct a CSNB model. Through this approach, we observed significant defects in the eye structure and function upon reducing mtt expression in fly eyes. This manifested as disruptions in the compound eye lens structure and reduced sensitivity to light responses. These results suggest a critical role for mtt in the function of fly adult eyes. Interestingly, we found that the mtt gene is not expressed in the photoreceptor neurons of adult flies but is localized to the inner lamina neurons. In summary, these results underscore the crucial involvement of mtt in fly retinal function, providing a framework for understanding the pathogenic mechanisms of CSNB and facilitating research into potential therapeutic interventions.

The endogenous antioxidant ability of royal jelly in Drosophila is independent of Keap1/Nrf2 by activating oxidoreductase activity.

Royal jelly (RJ) is a biologically active substance secreted by the hypopharyngeal and mandibular glands of worker honeybees. It is widely claimed that RJ reduces oxidative stress. However, the antioxidant activity of RJ has mostly been determined by in vitro chemical detection methods or by external administration drugs that cause oxidative stress. Whether RJ can clear the endogenous production of reactive oxygen species (ROS) in cells remains largely unknown. Here, we systematically investigated the antioxidant properties of RJ using several endogenous oxidative stress models of Drosophila. We found that RJ enhanced sleep quality of aging Drosophila, which is decreased due to an increase of oxidative damage with age. RJ supplementation improved survival and suppressed ROS levels in gut cells of flies upon exposure to hydrogen peroxide or to the neurotoxic agent paraquat. Moreover, RJ supplementation moderated levels of ROS in endogenous gut cells and extended lifespan after exposure of flies to heat stress. Sleep deprivation leads to accumulation of ROS in the gut cells, and RJ attenuated the consequences of oxidative stress caused by sleep loss and prolonged lifespan. Mechanistically, RJ prevented cell oxidative damage caused by heat stress or sleep deprivation, with the antioxidant activity in vivo independent of Keap1/Nrf2 signaling. RJ supplementation activated oxidoreductase activity in the guts of flies, suggesting its ability to inhibit endogenous oxidative stress and maintain health, possibly in humans.

Printable Counter Electrode with Metal Nitride as the Conductive Medium for Perovskite Solar Cells.

Perovskite solar cells (PSCs) with a booming high power conversion efficiency (PCE) are on their road toward industrialization. A proper design of the counter electrode (CE) with low cost, high conductivity, chemical stability, and good interface contact with the other functional layer atop the perovskite layer is vital for the overall performance of PSCs. Herein, the application of titanium nitride (TiN) is reported as a conductive medium for the printable CE in hole-conductor-free mesoscopic PSCs. TiN improves the conductivity of the CE and reduces the resistivity from 20 to 10 mΩ∙cm. TiN also improves the wettability of the CE with perovskite and enhances the back interface contact, which promotes charge collection. On the other hand, TiN is chemically stable during processing and undergoes no distinguishable chemical reaction with halide perovskite. Devices with TiN as the conductive media in the CE deliver a champion PCE of 19.01%. This work supplies a considerable choice for the CE design of PSCs toward industrial applications.

Regulation of NAD+/NADH Redox Involves the Protective Effects of Ginsenoside Rb1 against Oxygen-Glucose Deprivation/Reoxygenation-Induced Astrocyte Lesions.

The aim of this study was to investigate NAD+/NADH redox regulation in astrocytes by Ginsenoside Rb1 subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and to reveal the neuroprotective mechanism of ginseng. Neonatal mouse brain was used to culture primary astrocytes. The third generation of the primary astrocytes was used for the experiments. OGD/R was introduced by culturing the cells in a glucose-free media under nitrogen for 6 h followed by a regular culture for 24 h. Ginsenoside Rb1 attenuated OGD/R-induced astrocyte injury in a dose-dependent manner. It improved the mitochondrial function of OGD/R astrocytes indicated by improving mitochondrial distribution, increasing mitochondrial membrane potential, and enhancing mitochondrial DNA copies and ATP production. Ginsenoside Rb1 significantly lifted intracellular NAD+/NADH, NADPH/NADP+, and GSH/GSSG in OGD/R astrocytes. It inhibited the protein expression of both PARP1 and CD38, while attenuating the SIRT1 drop in OGD/R cells. In line with its effects on PARP1, Ginsenoside Rb1 significantly reduced the expression of poly-ADP-ribosylation (PARylation) proteins in OGD/R cells. Ginsenoside Rb1 also significantly increased the expression of NAMPT and NMNAT2, both of which are key players in NAD/NADH synthesis. The results suggest that the regulation of NAD+/NADH redox involves the protective effects of ginsenoside Rb1 against OGD/R-induced astrocyte injury.

Phase Behavior of Binary Blends of Diblock Copolymers: Progress and Opportunities.

The phase behavior of binary blends of diblock copolymers has been examined extensively in the past decades. Experimental and theoretical studies have demonstrated that mixing two different block copolymers provides an efficient and versatile route to regulate their self-assembled morphologies. A good understanding of the principles governing the self-assembly of block copolymer blends has been obtained from the study of A1B1/A2B2 diblock copolymer blends. The second (A2B2) diblocks could act synergistically as fillers and cosurfactants to regulate the domain size and interfacial properties, resulting in the formation of ordered phases not found in the parent (A1B1 or A2B2) diblock copolymer melts. The study of A1B1/A2B2 block copolymer blends further provides a solid foundation for future research on more complex block copolymer blends.

Design and Evaluation of CPR Emergency Equipment for Non-Professionals.

Sudden cardiac death is a sudden and highly fatal condition. Implementing high-quality emergency cardiopulmonary resuscitation (CPR) early on is an effective rescue method for this disease. However, the rescue steps of CPR are complicated and difficult to remember, and the quantitative indicators are difficult to control, which leads to a poor quality of CPR emergency actions outside the hospital setting. Therefore, we have developed CPR emergency equipment with a multisensory feedback function, aiming to guide rescuers in performing CPR through visual, auditory, and tactile interaction. This equipment consists of three components: first aid clothing, an audio-visual integrated terminal, and a vital sign detector. These three components are based on a micro-power WiFi-Mesh network, enabling the long-term wireless transmission of the multisensor data. To evaluate the impact of the multisensory feedback CPR emergency equipment on nonprofessionals, we conducted a controlled experiment involving 32 nonmedical subjects. Each subject was assigned to either the experimental group, which used the equipment, or the control group, which did not. The main evaluation criteria were the chest compression (CC) depth, the CC rate, the precise depth of the CC ratio (5-6 cm), and the precise rate of the CC ratio -(100-120 times/min). The results indicated that the average CC depth in the experimental group was 51.5 ± 1.3 mm, which was significantly better than that of the control group (50.2 ± 2.2 mm, p = 0.012). Moreover, the average CC rate in the experimental group (110.1 ± 6.2 times/min) was significantly higher than that of the control group (100.4 ± 6.6 times/min) (p < 0.001). Compared to the control group (66.37%), the experimental group showed a higher proportion of precise CC depth (82.11%), which is closer to the standard CPR rate of 100%. In addition, the CC ratio of the precise rate was 93.75% in the experimental group, which was significantly better than that of 56.52% in the control group (p = 0.024). Following the experiment, the revised System Availability Scale (SUS) was utilized to evaluate the equipment's usability. The average total SUS score was 78.594, indicating that the equipment's acceptability range was evaluated as 'acceptable', and the overall adjective rating was 'good'. In conclusion, the multisensory feedback CPR emergency equipment significantly enhances the CC performance (CC depth, CC rate, the precise depth of CC ratio, the precise rate of CC ratio) of nonprofessionals during CPR, and the majority of participants perceive the equipment as being easy to use.

Toward Earth system modeling with resolved clouds and ocean submesoscales on heterogeneous many-core HPCs.

With the aid of the newly developed 'Sunway' heterogeneous-architecture supercomputer, which has world-leading HPC (high-performance computer) capability, a series of high-resolution coupled Earth system models (SW-HRESMs) with up to 5 km of atmosphere and 3 km of ocean have been developed. These models can meet the needs of multiscale interaction studies with different computational costs. Here we describe the progress of SW-HRESMs development, with an overview of the major advancements made by the international Earth science community in HR-ESMs. We also show the preliminary results of SW-HRESMs with regard to capturing major weather-climate extremes in the atmosphere and ocean, stressing the importance of permitted clouds and ocean submesoscale eddies in modeling tropical cyclones and eddy-mean flow interactions, and paving the way for further model development to resolve finer scales with even higher resolution and more realistic physics. Finally, in addition to increasing model resolution, the development procedure for a non-hydrostatic cloud and ocean submesoscale resolved ESM is discussed, laying out the major scientific directions of such a huge modeling advancement.

Pectin from plantain peels: Green recovery for transformation into reinforced packaging films.

Plantain peels as agro-waste are generated in the millions of tons per year with no profitable management strategies. On the other hand, the excessive use of plastic packaging threatens the environment and human health. This research aimed to address both problems via a green approach. High-quality pectin was recovered from plantain peels via an enzyme-assisted and ethanol-recycling process. The yield and galacturonic acid (GalA) content of the recovered low methoxy pectin was 12.43% and 25.0%, respectively, when cellulase was added at 50 U per 5 g peel powder, with a significantly higher recovery rate and purity than the pectin products extracted with no cellulase (P ≤ 0.05). The recovered pectin was further integrated and reinforced with beeswax solid-lipid nanoparticles (BSLNs) to fabricate films as a potential alternative packaging material to single-use plastics. The reinforced pectin films showed improved light barrier, water resistance, mechanical, conformational, and morphological properties. This study presents a sustainable strategy to transform plantain peels into pectin products and pectin-based packaging films with broad applications.

Knockdown of NADPH oxidase 4 reduces mitochondrial oxidative stress and neuronal pyroptosis following intracerebral hemorrhage.

Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species, which causes abnormal mitochondrial function and secondary reactive oxygen species generation. This creates a vicious cycle leading to reactive oxygen species accumulation, resulting in progression of the pathological process. Therefore, breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage. Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NADPH oxidase 4, NOX4) led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage. The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress, mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage. We found that NOX4 knockdown by adeno-associated virus (AAV-NOX4) in rats enhanced neuronal tolerance to oxidative stress, enabling them to better resist the oxidative stress caused by intracerebral hemorrhage. Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria, relieved mitochondrial damage, prevented secondary reactive oxygen species accumulation, reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats. Finally, we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4. The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis, which is similar to the effect of AAV-NOX4. This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production, and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage.