The impact of road environments on rural periodic market travel satisfaction: a heterogeneity analysis of travel modes.

Introduction: Travel satisfaction as experienced by rural residents is closely related to personal physical and mental health, as well as rural economic conditions. An improved rural road environment can be expected to enhance villagers' satisfaction with regards to visits to markets, but to date this has not been established empirically. Methods: In this study, a questionnaire was designed to obtain local residents' evaluations of road environment characteristics for periodic market travel. And we use an Oprobit regression model and Importance-Performance Map Analysis (IPMA) to explore the heterogeneity of the 14 key elements of the "home-to-market" road environment impact on villagers' satisfaction under different modes of travel. Results: The results of the study reveal that villagers expressed dissatisfaction with the current lack of sidewalks and non-motorized paths, and except for road traffic disturbances and road deterioration, which did not significantly affect mode of travel, other factors proved significant. Significantly, bus services are associated with a significant positive effect on walking, non-motorized and bus travel satisfaction, while distance travel also affects walking, non-motorized and motorized travel satisfaction. It is worth noting that greening and service facilities negatively affect motorized travel satisfaction. In summary, road width, sidewalks, bus service, and road deterioration, are among the elements most in need of urgent improvement for all modes of travel. Discussion: The characteristics of the road environment that influence satisfaction with travel to the periodic market vary by travel mode, and this study is hoped to provide data support and optimization recommendations for the improvement of the rural road environment in China and other countries.

Local thermal adaption mediates the sensitivity of Daphnia magna to nanoplastics under global warming scenarios.

The toxicity of nanoplastics at environmentally relevant concentrations has received widespread attention in the context of global warming. Despite numerous studies on the impact of mean temperature (MT), the effects of daily temperature fluctuations (DTFs) on the ecotoxicity of nanoplastics remains largely unexplored. Moreover, the role of evolutionary adaptation in assessing long-term ecological risks is unclear. Here, we investigated the effects of polystyrene nanoplastics (5 µg L-1) on Daphnia magna under varying MT (20 °C and 24 °C) and DTFs (0 °C, 5 °C, and 10 °C). Capitalizing on a space-for-time substitution approach, we further assessed how local thermal adaptation affect the sensitivity of Daphnia to nanoplastics under global warming. Our results indicated that nanoplastics exposure in general reduced heartbeat rate, thoracic limb activity and feeding rate, and increased CytP450, ETS activity and Hgb concentrations. Higher MT and DTFs enhanced these effects. Notably, clones originating from their respective sites performed better under their native temperature conditions, indicating local thermal adaptation. Warm-adapted low-latitude D. magna showed stronger nanoplastics-induced increases in CytP450, ETS activity and Hgb concentrations under local MT 24 °C, while cold-adapted high-latitude D. magna showed stronger nanoplastics-induced decreases in heartbeat rate, thoracic limb activity and feeding rate under high MT than under low MT.

Development of the fetal brain cortico-cortical structural network during the second-to-third trimester based on diffusion MRI.

During the second-to-third trimester, the neuronal pathways of the fetal brain experience rapid development, resulting in the complex architecture of the inter-wired network at birth. While diffusion MRI-based tractography has been employed to study the prenatal development of structural connectivity network (SCN) in preterm neonatal and post-mortem fetal brains, the in-utero development of SCN in the normal fetal brain remains largely unknown. In this study, we utilized in-utero dMRI data from human fetuses of both sexes between 26 to 38 gestational weeks to investigate the developmental trajectories of the fetal brain SCN, focusing on intra-hemispheric connections. Our analysis revealed significant increases in global efficiency, mean local efficiency, and clustering coefficient, along with significant decrease in shortest path length, while small-worldness persisted during the studied period, revealing balanced network integration and segregation. Widespread short-ranged connectivity strengthened significantly. The nodal strength developed in a posterior-to-anterior and medial-to-lateral order, reflecting a spatiotemporal gradient in cortical network connectivity development. Moreover, we observed distinct lateralization patterns in the fetal brain SCN. Globally, there was a leftward lateralization in network efficiency, clustering coefficient, and small-worldness. The regional lateralization patterns in most language, motor, and visual-related areas were consistent with prior knowledge, except for the Wernicke's area, indicating lateralized brain wiring is an innate property of the human brain starting from the fetal period. Our findings provided a comprehensive view of the development of the fetal brain SCN and its lateralization, as a normative template that may be used to characterize atypical development.Significance Statement We studied the normal development of intra-hemispheric cortico-cortical structural connectivity networks (SCNs) of the fetal brain from 26 to 38 gestational weeks using in-utero diffusion MRI data. Graph-theory-based analysis revealed significant enhancement in network efficiency and clustering, as well as persisted small-worldness with age, revealing balanced integration and segregation in the fetal brain SCN during the studied period, supported by regional developmental patterns. Leftward lateralization in network efficiency, clustering coefficient and small-worldness was observed. Regional lateralization patterns in most language, motor, and visual-related areas were consistent with prior knowledge. We also summarized the challenges of investigating the fetal brain SCN development, and provided suggestions for future studies.

Age-dependent functional development pattern in neonatal brain: An fMRI-based brain entropy study.

The relationship between brain entropy (BEN) and early brain development has been established through animal studies. However, it remains unclear whether the BEN can be used to identify age-dependent functional changes in human neonatal brains and the genetic underpinning of the new neuroimaging marker remains to be elucidated. In this study, we analyzed resting-state fMRI data from the Developing Human Connectome Project, including 280 infants who were scanned at 37.5-43.5 weeks postmenstrual age. The BEN maps were calculated for each subject, and a voxel-wise analysis was conducted using a general linear model to examine the effects of age, sex, and preterm birth on BEN. Additionally, we evaluated the correlation between regional BEN and gene expression levels. Our results demonstrated that the BEN in the sensorimotor-auditory and association cortices, along the 'S-A' axis, was significantly positively correlated with postnatal age (PNA), and negatively correlated with gestational age (GA), respectively. Meanwhile, the BEN in the right rolandic operculum correlated significantly with both GA and PNA. Preterm-born infants exhibited increased BEN values in widespread cortical areas, particularly in the visual-motor cortex, when compared to term-born infants. Moreover, we identified five BEN-related genes (DNAJC12, FIG4, STX12, CETN2, and IRF2BP2), which were involved in protein folding, synaptic vesicle transportation and cell division. These findings suggest that the fMRI-based BEN can serve as an indicator of age-dependent brain functional development in human neonates, which may be influenced by specific genes.

One-step electrodeposition synthesis of NiFePS on carbon cloth as self-supported electrodes for electrochemical overall water splitting.

Electrocatalytic water splitting (EWS) for hydrogen production is considered an ideal strategy for utilizing renewable energy, reducing fossil fuel consumption, and addressing environmental pollution issues. Traditional noble metal electrocatalysts have excellent performance, but their cost is high. Developing efficient, stable, and relatively inexpensive dual functional electrocatalysts is crucial for promoting large-scale EWS hydrogen production processes. Herein, a simple one-step electrodeposition method was used to grow nickel-iron phosphorus-sulfides (NiFePS) on the surface of hydrophilic treated carbon cloth (CC). The resultant NiFePS/CC with a phosphorus to sulfur ratio of 1:4 exhibited the best electrocatalytic performance, requiring only -91 mV and 216 mV overpotentials to generate the current densities of 10 mA·cm-2 in hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. When it was used as a bifunctional electrocatalyst to overall water splitting (OWS), a voltage of 1.536 V can generate a current density of 10 mA·cm-2. The excellent electrocatalytic performance can be ascribed to two factors: 1) the CC with excellent conductivity serves as a growth substrate, reducing the impedance of charge transfer from the electrode to the electrolyte and accelerating the electron transfer rate; 2) The large number of ultra-thin nanosheets formed on the surface of the catalyst increase the electrochemical specific surface area, expose more reaction sites, and thus improve the electrocatalytic reaction performance. This work provides a new approach for designing efficient non-noble metal electrocatalysts for water splitting.

Efficacy of a novel affitoxin targeting MOMP against Chlamydia trachomatis in vitro and in vivo.

Targeted therapy is an attractive approach for treating infectious diseases. Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis, one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas Exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C.trachomatis-infected cells, Z461X-CPP induced cell apoptosis in vitro. In animal model, Z461X significantly shortened the duration of C. trachomatis infection and prevented pathological damage in mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C. trachomatis infection.

Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase 3 randomized trial.

BACKGROUND & AIMS: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24. METHODS: In this ongoing, open-label, randomized phase 3 study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/mL from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA. RESULTS: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independent of virologic response. Adverse events (AEs) were mostly mild, with no serious AEs related to BLV. CONCLUSIONS: Virologic and biochemical responses were maintained and/or increased with longer-term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96. IMPACT AND IMPLICATIONS: In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2-mg and 10-mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96. GOV IDENTIFIER: NCT03852719.

Interference of hemoglobin variants with HbA1c measurements: comparison of 6 commonly used HbA1c methods with the IFCC reference method.

BACKGROUND: Glycated hemoglobin, or hemoglobin A1c (HbA1c), serves as a crucial marker for diagnosing diabetes and monitoring its progression. We aimed to assess the interference posed by common Hb variants on popular HbA1c measurement systems. METHODS: A total of 63 variant and nonvariant samples with target values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference method were included. We assessed 6 methods for measuring HbA1c in the presence of HbS, HbC, HbD, HbE, and fetal hemoglobin (HbF): 2 cation-exchange high-performance liquid chromatography (HPLC) methods (Bio-Rad D-100 and HLC-723 G8), a capillary electrophoresis (CE) method (Sebia Capillarys 3 TERA), an immunoassay (Roche c501), an enzyme assay system (Mindray BS-600M), and a boronate affinity method (Primus Premier Hb9210). RESULTS: The HbA1c results for nonvariant samples from the 6 methods were in good agreement with the IFCC reference method results. The Bio-Rad D-100, Capillarys 3, Mindray BS-600M, Premier Hb9210, and Roche c501 showed no interference from HbS, HbC, HbD, and HbE. Clinically significant interference was observed for the HLC-723 G8 standard mode. Elevated HbF levels caused significant negative biases for all 6 methods, which increased with increasing HbF concentration. CONCLUSION: Elevated levels of HbF can severely affect HbA1c measurements by borate affinity, immunoassays, and enzyme assays.

Reconstructing Kaolinite Compounds for Remarkably Enhanced Adsorption of Congo Red.

Organic dyes are widely used in many important areas, but they also bring many issues for water pollution. To address the above issues, a reconstructed kaolinite hybrid compound (γ-AlOOH@A-Kaol) was obtained from raw kaolinite (Kaol) in this work. The product was then characterized by X-ray diffraction (XRD), Fourier-transform infrared (ATR-FTIR), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM), and the absorption properties of γ-AlOOH@A-Kaol for congo red were further studied. The results demonstrated that flower-like γ-AlOOH with nanolamellae were uniformly loaded on the surface of acid-treated Kaol with a porous structure (A-Kaol). In addition, the surface area (36.5 m2/g), pore volume (0.146 cm3/g), and pore size (13.0 nm) of γ-AlOOH@A-Kaol were different from those of A-Kaol (127.4 m2/g, 0.127 cm3/g, and 4.28 nm, respectively) and γ-AlOOH (34.1 m2/g, 0.315 cm3/g, and 21.5 nm, respectively). The unique structure could significantly enhance the sorption capacity for congo red, which could exceed 1000 mg/g. The reasons may be ascribed to the abundant groups of -OH, large specific surface area, and porous structure of γ-AlOOH@A-Kaol. This work provides an efficient route for comprehensive utilization and production of Kaol-based compound materials that could be used in the field of environmental conservation.

Polyacrylamide/sodium alginate/sodium chloride photochromic hydrogel with high conductivity, anti-freezing property and fast response for information storage and electronic skin.

Photochromic hydrogels have promising prospects in areas such as wearable device, information encryption technology, optoelectronic display technology, and electronic skin. However, there are strict requirements for the properties of photochromic hydrogels in practical engineering applications, especially in some extreme application environments. The preparation of photochromic hydrogels with high transparency, high toughness, fast response, colour reversibility, excellent electrical conductivity, and anti-freezing property remains a challenge. In this study, a novel photochromic hydrogel (PAAm/SA/NaCl-Mo7) was prepared by loading ammonium molybdate (Mo7) and sodium chloride (NaCl) into a dual-network hydrogel of polyacrylamide (PAAm) and sodium alginate (SA) using a simple one-pot method. PAAm/SA/NaCl-Mo7 hydrogel has excellent conductivity (175.9 S/cm), water retention capacity and anti-freezing properties, which can work normally at a low temperature of -28.4 °C. In addition, the prepared PAAm/SA/NaCl-Mo7 hydrogel exhibits fast response (<15 s), high transparency (>70 %), good toughness (maximum elongation up to 1500 %), good cyclic compression properties at high compressive strains (60 %), good biocompatibility (78.5 %), stable reversible discolouration and excellent sensing properties, which can be used for photoelectric display, information storage and motion monitoring. This work provides a new inspiration for the development of flexible electronic skin devices.

Engineering Spatially Adjacent Redox Sites with Synergistic Spin Polarization Effect to Boost Photocatalytic CO2 Methanation.

The integration of oxidation and reduction half-reactions to amplify their synergy presents a considerable challenge in CO2 photoconversion. Addressing this challenge requires the construction of spatially adjacent redox sites while suppressing charge recombination at these sites. This study introduces an innovative approach that utilizes spatial synergy to enable synergistic redox reactions within atomic proximity and employs spin polarization to inhibit charge recombination. We incorporate Mn into Co3O4 as a catalyst, in which Mn sites tend to enrich holes as water activation sites, while adjacent Co sites preferentially capture electrons to activate CO2, forming a spatial synergy. The direct H transfer from H2O at Mn sites facilitates the formation of *COOH on adjacent Co sites with remarkably favorable thermodynamic energy. Notably, the incorporation of Mn induces spin polarization in the system, significantly suppressing the recombination of photogenerated charges at redox sites. This effect is further enhanced by applying an external magnetic field. By synergizing spatial synergy and spin polarization, Mn/Co3O4 exhibits a CH4 production rate of 23.4 µmol g-1 h-1 from CO2 photoreduction, showcasing a 28.8 times enhancement over Co3O4. This study first introduces spin polarization to address charge recombination issues at spatially adjacent redox sites, offering novel insights for synergistic redox photocatalytic systems.

Cartilage-Inspired, High-Strength, and Heat-Tolerant Lubricating Hydrogels by Macrophase Separation.

Hydrogels are considered as a potential cartilage replacement material based on their structure being similar to natural cartilage, which are of great significance in repairing cartilage defects. However, it is difficult for the existing hydrogels to combine the high load bearing and low friction properties (37 °C) of cartilage through sample methods. Herein, we report a facile and new fabrication strategy to construct the PNIPAm/EYL hydrogel by using the macrophase separation of supersaturated N-isopropylacrylamide (NIPAm) monomer solution to promote the formation of liposomes from egg yolk lecithin (EYL) and asymmetric template method. The PNIPAm/EYL hydrogels possess a relatively high compressive strength (more than 12 MPa), fracture energy (9820 J/m2), good fatigue resistance, lubricating properties, and excellent biocompatibility. Compared with the PNIPAm hydrogel, the friction coefficient (COF 0.046) of PNIPAm/EYL hydrogel is reduced by 50%. More importantly, the COF (0.056) of PNIPAm/EYL hydrogel above lower critical solution temperature (LCST) does not increase significantly, exhibiting heat-tolerant lubricity. The finite element analysis further proves that PNIPAm/EYL hydrogel can effectively disperse the applied stress and dissipate energy under load conditions. This work not only provides new insights for the design of high-strength lubricating hydrogels but also lays a foundation for the treatment of cartilage injury as a substitute material.

Analytical performance evaluation of the Mindray enzymatic assay for hemoglobin A1c measurement.

Hemoglobin A1c (HbA1c) plays a crucial role in diabetes management. We aimed to evaluate the analytical performance of a new enzymatic method kit for HbA1c measurement. The performance of the enzymatic method, including precision, accuracy, and linearity, was evaluated. Moreover, the interference effect from conventional interferents, Hb derivatives, Hb variants, and common drugs were assessed. In addition, the agreement of HbA1c results was compared between enzymatic methods, cation-exchange high-performance liquid chromatography (HPLC), and immunoassays. The intra-assay, between-assay, and total precision of HbA1c were all lower than 2%. HbA1c showed good linearity within the range of 3.96-20.23%. The enzymatic assay yielded results consistent with the external quality control samples, with a bias of less than ± 6% from the target values. The enzymatic method showed no interference from bilirubin, intralipid, vitamin C, Hb derivatives, common Hb variants, as well as antipyretic analgesics and hypoglycemic drugs. The HbA1c results of the enzymatic assay showed good agreement and accuracy compared to those obtained from the HPLC method and the immunoassay. The enzymatic method kit performed on the BS-600M chemistry analyzer is a reliable and robust method for measuring HbA1c. It is suitable for routine practice in clinical chemistry laboratories.

Regulating the mobility of lattice oxygen on hollow cobalt-manganese sub-nanospheres for enhanced catalytic oxidation of toluene and o-xylene.

Promoting lattice oxygen mobility of Co-based catalysts is crucial to making progress in catalytic oxidation technology. The addition of manganese, a transition metal with similar ionic radius to cobalt and variable valence, was supposed to enhance the mobility of lattice oxygen species of Co-based oxide. A range of hollow CoMnaOx sub-nanosphere catalysts with different Mn/Co ratios was synthesized via a template-sacrificed method, and the effects of different Mn/Co ratios on the structural properties of the catalysts and their catalytic performance for benzene series volatile organic compounds (VOCs) oxidation were investigated. Hollow CoMn2Ox sub-nanosphere exhibited good catalytic activity for oxidation of toluene (T90 = 265 °C) and o-xylene (T90 = 297 °C), as well as excellent recycling ability and water resistance. By adjusting the Mn/Co ratio, metal ions enter into the different tetrahedral or octahedral active sites. Compared with Co3O4, the desorption temperature of surface lattice oxygen on CoMn2Ox decreased by 110 °C. These results demonstrate that the addition of manganese can encourage the electron transfer on CoMnaOx, indicating that the introduction of the appropriate amount of manganese accelerates the activation of gas O2 and mobility of surface lattice oxygen species, thereby expediting the oxidation of benzene series VOCs.

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

A patient with BRAF N581S mutation-positive lung adenocarcinoma demonstrates durable response to combined anlotinib and tislelizumab: A case report and literature review.

BACKGROUND: Targeted therapy with combined dabrafenib and trametinib has been proven to provide clinical benefits in patients with BRAF V600E mutation-positive NSCLC. Nevertheless, the treatment strategy for NSCLC patients with BRAF non-V600E mutations remains limited. CASE PRESENTATION: Here, we present a NSCLC patient with a BRAF N581S mutation, which is a class III BRAF mutation, and this patient had a durable response to targeted therapy with combined anlotinib and tislelizumab. CONCLUSION: We hope to bring more attention to rare non-V600 BRAF mutations by presenting this case of NSCLC.

Efficient photocatalytic degradation of perfluorooctanoic acid by bismuth nanoparticle modified titanium dioxide.

Perfluorooctanoic acid (PFOA) is potentially toxic and exceptionally stable attributed to its robust CF bond, which is hard to be removed by UV/TiO2 systems. In this research, bismuth nanoparticle (Bi NP) modified titanium oxides (Bi/TiO2) were synthesized by a simple photochemical deposition-calcination method and were applied as photocatalysts for the first time to degrade PFOA. The removal rate of 50 mg/L PFOA reached 99.3 % with 58.6 % defluorination rate after 30 min of irradiation via a mercury lamp. Bi/TiO2 exhibited superior performance in PFOA degradation compared to commercial photocatalysts (TiO2, Ga2O3, Bi2O3 and In2O3). In addition, Bi/TiO2 showed high degradation activity under actual sunlight, achieved 100 % removal rate and 59.3 % defluorination rate within 2 h. Bi NPs increase the light trapping ability of Bi/TiO2 and promote the separation of photogenerated electron-hole pairs via local surface plasmon resonance (LSPR) effect, which results in more photogenerated holes (h+) and hydroxyl radicals (OH). Combined with DFT calculations and intermediate detections, the degradation reaction is initiated from the oxidation of the PFOA carboxyl group via h+, followed by the loss of the CF2 unit step by step with the participation of OH. This work presents a novel approach for the practical implementation of TiO2-based photocatalysts to achieve highly efficient photocatalytic degradation of perfluorocarboxylic acids (PFCAs).

Mitochondria-associated endoplasmic reticulum membranes tethering protein VAPB-PTPIP51 protects against ischemic stroke through inhibiting the activation of autophagy.

AIMS: Mitochondria-associated endoplasmic reticulum membranes (MAMs) serve as a crucial bridge connecting the endoplasmic reticulum (ER) and mitochondria within cells. Vesicle-associated membrane protein-associated protein B (VAPB) and protein tyrosine phosphatase interacting protein 51 (PTPIP51) are responsible for the formation and stability of MAMs, which have been implicated in the pathogenesis of various diseases. However, the role of MAMs in ischemic stroke (IS) remains unclear. We aimed to investigate the role of MAMs tethering protein VAPB-PTPIP51 in experimental cerebral ischemia. METHODS: We simulated cerebral ischemia-reperfusion injury (CIRI) by using a mouse middle cerebral artery occlusion (MCAO) model. RESULTS: We observed a decrease in VAPB-PTPIP51 expression in the brain tissue. Our findings suggested compromised MAMs after MCAO, as a decreased mitochondria-ER contact (MERC) coverage and an increased distance were observed through the transmission electron microscope (TEM). Upon VAPB or PTPIP51 knockdown, the damage to MAMs was exacerbated, accompanied by excessive autophagy activation and increased reactive oxygen species (ROS) production, resulting in an enlarged infarct area and exacerbated neurological deficits. Notably, we observed that this damage was concomitant with the inhibition of the PI3K/AKT/mTOR pathway and was successfully mitigated by the treatment with the PI3K activator. CONCLUSIONS: Our findings suggest that the downregulation of VAPB-PTPIP51 expression after IS mediates structural damage to MAMs. This may exacerbate CIRI by inhibiting the PI3K pathway and activating autophagy, thus providing new therapeutic targets for IS.

A High-Stretching, Rapid-Self-Healing, and Printable Composite Hydrogel Based on Poly(Vinyl Alcohol), Nanocellulose, and Sodium Alginate.

Hydrogels with excellent flexibility, conductivity, and controllable mechanical properties are the current research hotspots in the field of biomaterial sensors. However, it is difficult for hydrogel sensors to regain their original function after being damaged, which limits their practical applications. Herein, a composite hydrogel (named SPBC) of poly(vinyl alcohol) (PVA)/sodium alginate (SA)/cellulose nanofibers (CNFs)/sodium borate tetrahydrate was synthesized, which has good self-healing, electrical conductivity, and excellent mechanical properties. The SPBC0.3 hydrogel demonstrates rapid self-healing (<30 s) and achieves mechanical properties of 33.92 kPa. Additionally, it exhibits high tensile strain performance (4000%). The abundant internal ions and functional groups of SPBC hydrogels provide support for the good electrical conductivity (0.62 S/cm) and electrical response properties. In addition, the SPBC hydrogel can be attached to surfaces such as fingers and wrists to monitor human movements in real time, and its good rheological property supports three-dimensional (3D) printing molding methods. In summary, this study successfully prepared a self-healing, conductive, printable, and mechanically superior SPBC hydrogel. Its suitability for 3D-printing personalized fabrication and outstanding sensor properties makes it a useful reference for hydrogels in wearable devices and human motion monitoring.