Sulfated Polysaccharides from Sea Cucumber Cooking Liquid Prevents Obesity by Modulating Gut Microbiome, Transcriptome, and Metabolite Profiles in Mice Fed a High-Fat Diet.

We aimed to explore the anti-obesity mechanism from the microbiome, metabolome, and transcriptome viewpoints, focusing on the sulfated polysaccharides found in the cooking liquid of Apostichopus japonicus (CLSPAJ) to explore the potential mediators of the anti-obesity effects in mice fed a high-fat diet (HFD). The mice treated with CLSPAJ showed a decrease in obesity and blood lipid levels. Gut microbiome dysbiosis caused by the HFD was reversed after CLSPAJ supplementation, along with increased levels of indole-3-ethanol, N-2-succinyl-L-glutamic acid 5-semialdehyde, and urocanic acid. These increases were positively related to the increased Akkermansia, Lactobacillus, Roseburia, and Phascolarctobacterium. Transcriptome analysis showed that B cell receptor signaling and cytochrome P450 xenobiotic metabolism were the main contributors to the improvement in obesity. Metabolome-transcriptome analysis revealed that CLSPAJ reversal of obesity was mainly due to amino acid metabolism. These findings suggest that CLSPAJ could be a valuable prebiotic preparation for preventing obesity-related diseases.

Whole body vibration training promotes proprioceptive pathway for the treatment of stress urinary incontinence in rats.

Background: Stress urinary incontinence (SUI) is the most ubiquitous form of urinary incontinence in women. The therapeutic management of patients with SUI is challenging. The aim of this study is to evaluate the efficacy of whole body vibration training (WBVT) for SUI. Methods: Thirty-five female rats were randomly divided into a sham group (Sham group, n=5), SUI + WBVT group (n=15) and SUI + whole body rest group (SUI + WBR group, n=15). The SUI + WBVT group was trained as follows: frequency 30 Hz, amplitude four mm, one min/repeat, four min rest, repeated 10 times, five days/week. After the intervention, five rats were taken on the 7th, 14th and 21st day to observe the urodynamic changes, levator ani muscle and dorsal root ganglia (DRG) morphology, and to observe the expression of neurotrophic factor-3/tyrosine protein kinase C (NT-3/TrkC) by Western blot. Results: The urodynamic results showed that the difference in bladder leak point pressure/abdominal leak point pressure (BLPP/ALPP) between the Sham group and the SUI + WBR group was statistically significant (P<0.001) on 7th day, indicating successful modeling. The BLPP/ALPP of the SUI + WBVT group and the SUI + WBR group improved on 7th, 14th, and 21st day, and the BLPP/ALPP of SUI + WBVT group was higher than the SUI + WBR group. Compared with the Sham group, pathological changes appeared in the muscle shuttles in the SUI + WBVT group and SUI + WBR group. Western blot showed a gradual up-regulation of NT-3/TrkC. Conclusions: WBVT can be used to treat SUI by affecting the expression of NT-3/TrkC, improving the structural morphology of the proprioceptors, and restoring the urinary control function. This study provides evidence for the clinical practice of WBVT. Future studies could further refine the behavioral and electrophysiological aspects of the assessment.

Icariin Ameliorates D-galactose-induced Cell Injury in Neuron-like PC12 Cells by Inhibiting MPTP Opening.

OBJECTIVE: Icariin (ICA) has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats. Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases. Abnormal opening of the mitochondrial permeability transition pore (mPTP) is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy. This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose (D-gal)-induced cell injury model. METHODS: A cell model of neuronal injury was established in rat pheochromocytoma cells (PC12 cells) treated with 200 mmol/L D-gal for 48 h. In this cell model, PC12 cells were pre-treated with different concentrations of ICA for 24 h. MTT was used to detect cell viability. Senescence associated ß-galactosidase (SA-ß-Gal) staining was used to observe cell senescence. Western blot analysis was performed to detect the expression levels of a senescence-related protein (p21), autophagy markers (LC3B, p62, Atg7, Atg5 and Beclin 1), mitochondrial fission and fusion-related proteins (Drp1, Mfn2 and Opa1), and mitophagy markers (Pink1 and Parkin). The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus. The intracellular ultrastructure was observed by transmission electron microscopy. Immunofluorescence was used to detect mPTP, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS) and ROS levels. ROS and apoptosis levels were detected by flow cytometry. RESULTS: D-gal treatment significantly decreased the viability of PC12 cells, and markedly increased the SA-ß-Gal positive cells as compared to the control group. With the D-gal stimulation, the expression of p21 was significantly up-regulated. Furthermore, D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression. Meanwhile, autophagosomes and autolysosomes were significantly increased, indicating abnormal activation of autophagy levels. In addition, in this D-gal-induced model of cell injury, the mPTP was abnormally open, the ROS generation was continuously increased, the MMP was gradually decreased, and the apoptosis was increased. ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis. It strongly inhibited excessive autophagy by blocking the opening of the mPTP. Cotreatment with ICA and an mPTP inhibitor (cyclosporin A) did not ameliorate mitochondrial dysfunction. However, the protective effects were attenuated by cotreatment with ICA and an mPTP activator (lonidamine). CONCLUSION: ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.

Time trends in the mortality of testicular cancer across the BRICS: an age-period-cohort analysis for the GBD 2019.

Testicular cancer (TCa) is a rare but impactful malignancy that primarily affects young men. Understanding the mortality rate of TCa is crucial for improving prevention and treatment strategies to reduce the risk of death among patients. We obtained TCa mortality data by place (5 countries), age (20-79 years), and year (1990-2019) from the Global Burden of Disease Study 2019. Age-period-cohort model was used to estimate the net drift, local drift, age effects, period and cohort effects. In 2019, the global mortality of TCa increased to 10842 (95% UI 9961, 11902), with an increase of 50.08% compared to 1990.The all-age mortality rate for TCa in 2019 increased from 0.17/100,000 (95% UI 0.13, 0.20) in China to 0.48/100,000 (95% UI 0.38, 0.59) in Russian Federation, whereas the age-standardized mortality rate in 2019 was highest in the South Africa 0.47/100,000 (95% UI 0.42, 0.53) and lowest in the China 0.16/100,000 (95% UI 0.13, 0.19). China's aging population shifts mortality patterns towards the elderly, while in Russian Federation, young individuals are primarily affected by the distribution of deaths. To address divergent TCa mortality advancements in BRICS countries, we propose a contextually adaptive and resource-conscious approach to prioritize TCa prevention. Tailoring strategies to contextual diversity, including policy frameworks, human resources, and financial capacities, will enhance targeted interventions and effectiveness in reducing TCa mortality.

Clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma.

The clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL.

Comparative study on the activation of peroxymonosulfate and peroxydisulfate by Ar plasma-etching CNTs for sulfamethoxazole degradation: Efficiency and mechanisms.

Sulfamethoxazole (SMX), a widely utilized antibiotic, was continually detected in the environment, causing serious risks to aquatic ecology and water security. In this study, carbon nanotubes (CNTs) with abundant defects were developed by argon plasma-etching technology to enhance the activation of persulfate (PS, including peroxymonosulfate (PMS) and peroxydisulfate (PDS)) for SMX degradation while reducing environmental toxicity. Obviously, the increase of ID/IG value from 0.980 to 1.333 indicated that Ar plasma-etching successfully introduced rich defects into CNTs. Of note, Ar-90-CNT, whose Ar plasma-etching time was 90 min with optimum catalytic performance, exhibited a significant discrepancy between PMS activation and PDS activation. Interestingly, though the Ar-90-CNT/PDS system (kobs = 0.0332 min-1) was more efficient in SMX elimination than the Ar-90-CNT/PMS system (kobs = 0.0190 min-1), Ar plasma-etching treatment had no discernible enhancement in the catalytic efficiency of MWCNT for PDS activation. Then the discrepancy on activation mechanism between PMS and PDS was methodically investigated through quenching experiments, electron spin resonance (ESR), chemical probes, electrochemical measurements and theoretical calculations, and the findings unraveled that the created vacancy defects were the ruling active sites for the production of dominated singlet oxygen (1O2) in the Ar-90-CNT/PMS system to degrade SMX, while the electron transfer pathway (ETP), originated from PDS activation by the inherent edge defects, was the central pathway for SMX removal in the Ar-90-CNT/PDS system. Based on the toxicity test of Microcystis aeruginosa, the Ar-90-CNT/PDS system was more effective in alleviating environmental toxicity during SMX degradation. These findings not only provide insights into the discrepancy between PMS activation and PDS activation via carbon-based materials with controlled defects regulated by the plasma-etching strategy, but also efficiently degrade sulfonamide antibiotics and reduce the toxicity of their products.

Recent progress in multifunctional, reconfigurable, integrated liquid metal-based stretchable sensors and standalone systems.

Possessing a unique combination of properties that are traditionally contradictory in other natural or synthetical materials, Ga-based liquid metals (LMs) exhibit low mechanical stiffness and flowability like a liquid, with good electrical and thermal conductivity like metal, as well as good biocompatibility and room-temperature phase transformation. These remarkable properties have paved the way for the development of novel reconfigurable or stretchable electronics and devices. Despite these outstanding properties, the easy oxidation, high surface tension, and low rheological viscosity of LMs have presented formidable challenges in high-resolution patterning. To address this challenge, various surface modifications or additives have been employed to tailor the oxidation state, viscosity, and patterning capability of LMs. One effective approach for LM patterning is breaking down LMs into microparticles known as liquid metal particles (LMPs). This facilitates LM patterning using conventional techniques such as stencil, screening, or inkjet printing. Judiciously formulated photo-curable LMP inks or the introduction of an adhesive seed layer combined with a modified lift-off process further provide the micrometer-level LM patterns. Incorporating porous and adhesive substrates in LM-based electronics allows direct interfacing with the skin for robust and long-term monitoring of physiological signals. Combined with self-healing polymers in the form of substrates or composites, LM-based electronics can provide mechanical-robust devices to heal after damage for working in harsh environments. This review provides the latest advances in LM-based composites, fabrication methods, and their novel and unique applications in stretchable or reconfigurable sensors and resulting integrated systems. It is believed that the advancements in LM-based material preparation and high-resolution techniques have opened up opportunities for customized designs of LM-based stretchable sensors, as well as multifunctional, reconfigurable, highly integrated, and even standalone systems.

Direct Laser Processing and Functionalizing PI/PDMS Composites for an On-Demand, Programmable, Recyclable Device Platform.

Skin-interfaced high-sensitive biosensing systems to detect electrophysiological and biochemical signals have shown great potential in personal health monitoring and disease management. However, the integration of 3D porous nanostructures for improved sensitivity and various functional composites for signal transduction/processing/transmission often relies on different materials and complex fabrication processes, leading to weak interfaces prone to failure upon fatigue or mechanical deformations. The integrated system also needs additional adhesive to strongly conform to the human skin, which can also cause irritation, alignment issues, and motion artifacts. This work introduces a skin-attachable, reprogrammable, multifunctional, adhesive device patch fabricated by simple and low-cost laser scribing of an adhesive composite with polyimide powders and amine-based ethoxylated polyethylenimine dispersed in the silicone elastomer. The obtained laser-induced graphene in the adhesive composite can be further selectively functionalized with conductive nanomaterials or enzymes for enhanced electrical conductivity or selective sensing of various sweat biomarkers. The possible combination of the sensors for real-time biofluid analysis and electrophysiological signal monitoring with RF energy harvesting and communication promises a standalone stretchable adhesive device platform based on the same material system and fabrication process.

Multimodal nanoimmunotherapy engages neutrophils to eliminate Staphylococcus aureus infections.

The increasing prevalence of antimicrobial resistance in Staphylococcus aureus necessitates alternative therapeutic approaches. Neutrophils play a crucial role in the fight against S. aureus but suffer from deficiencies in function leading to increased infection. Here we report a nanoparticle-mediated immunotherapy aimed at potentiating neutrophils to eliminate S. aureus. The nanoparticles consist of naftifine, haemoglobin (Hb) and a red blood cell membrane coating. Naftifine disrupts staphyloxanthin biosynthesis, Hb reduces bacterial hydrogen sulfide levels and the red blood cell membrane modifies bacterial lipid composition. Collectively, the nanoparticles can sensitize S. aureus to host oxidant killing. Furthermore, in the infectious microenvironment, Hb triggers lipid peroxidation in S. aureus, promoting neutrophil chemotaxis. Oxygen supplied by Hb can also significantly enhance the bactericidal capability of the recruited neutrophils by restoring neutrophil respiratory burst via hypoxia relief. This multimodal nanoimmunotherapy demonstrates excellent therapeutic efficacy in treating antimicrobial-resistant S. aureus persisters, biofilms and S. aureus-induced infection in mice.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest protein family genetically linked to CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate CMT type C (DI-CMTC) is caused by YARS1 mutations driving a toxic gain-of-function in the encoded tyrosyl-tRNA synthetase (TyrRS), which is mediated by exposure of consensus neomorphic surfaces through conformational changes of the mutant protein. In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not TyrRSWT, into muscles of wild-type mice. Augmenting BDNF in DI-CMTC muscles, through injection of recombinant protein or muscle-specific gene therapy, resulted in complete axonal transport correction. Therefore, this work identifies a non-cell autonomous pathomechanism common to ARS-related neuropathies, and highlights the potential of boosting BDNF levels in muscles as a therapeutic strategy.

Boosting BDNF in muscle rescues impaired axonal transport in a mouse model of DI-CMTC peripheral neuropathy.

Charcot-Marie-Tooth disease (CMT) is a genetic peripheral neuropathy caused by mutations in many functionally diverse genes. The aminoacyl-tRNA synthetase (ARS) enzymes, which transfer amino acids to partner tRNAs for protein synthesis, represent the largest protein family genetically linked to CMT aetiology, suggesting pathomechanistic commonalities. Dominant intermediate CMT type C (DI-CMTC) is caused by YARS1 mutations driving a toxic gain-of-function in the encoded tyrosyl-tRNA synthetase (TyrRS), which is mediated by exposure of consensus neomorphic surfaces through conformational changes of the mutant protein. In this study, we first showed that human DI-CMTC-causing TyrRSE196K mis-interacts with the extracellular domain of the BDNF receptor TrkB, an aberrant association we have previously characterised for several mutant glycyl-tRNA synthetases linked to CMT type 2D (CMT2D). We then performed temporal neuromuscular assessments of YarsE196K mice modelling DI-CMT. We determined that YarsE196K homozygotes display a selective, age-dependent impairment in in vivo axonal transport of neurotrophin-containing signalling endosomes, phenocopying CMT2D mice. This impairment is replicated by injection of recombinant TyrRSE196K, but not TyrRSWT, into muscles of wild-type mice. Augmenting BDNF in DI-CMTC muscles, through injection of recombinant protein or muscle-specific gene therapy, resulted in complete axonal transport correction. Therefore, this work identifies a non-cell autonomous pathomechanism common to ARS-related neuropathies, and highlights the potential of boosting BDNF levels in muscles as a therapeutic strategy.

Genomic Insights into Combating Anthracnose with an Endophytic Bacillus amyloliquefaciens Strain.

Anthracnose, caused by Colletotrichum spp., is a common disease of Camellia oleifera. In this study, a Bacillus amyloliquefaciens strain, GZY63, was isolated from fruit of the anthracnose-resistant cultivar of Ca. oleifera "Ganzhouyou7." Plate confrontation assays and field experiments demonstrated the strong inhibitory effect of GZY63 on anthracnose, and this strain exhibited broad-spectrum resistance to nine pathogenic Colletotrichum spp. This strain shows potential as a fungicide alternative, but genetic information on this strain is critical for its optimal use. Combining Illumina and Nanopore sequencing, we assembled a high-quality circular genome of GZY63 that contained no plasmids. The GZY63 complete genome was approximately 3.93 Mb and had an average guanine-cytosine content of 46.5%. The genome comprised 4,024 predicted coding sequences and 12 types of gene clusters involved in secondary metabolite production. This genome information provides insights into the mechanism underlying the antagonistic impact of the GZY63 strain on anthracnose and its symbiotic relationship with Ca. oleifera.

Measuring the quality of transitional care based on elderly patients' experiences with the partners at care transitions measure: a cross-sectional survey.

BACKGROUND: The quality of transitional care is closely related to the health outcomes of patients, and understanding the status of transitional care for patients is crucial to improving the health outcomes of patients. Therefore, this study aims to investigate the quality of transitional care in elderly patients with chronic diseases and analyze its influencing factors, to provide a basis for improving transitional care services. METHODS: This is a cross-sectional study. We used the Chinese version of the Partners at Care Transitions Measure (PACT-M) to survey patients with chronic diseases aged 60 years and older who were about to be discharged from five tertiary hospitals in Henan and Shanxi provinces. We used the mean ± standard deviation to describe the quality of transitional care, t-test or one-way ANOVA, and regression analysis to explore the factors affecting the quality of transitional care for patients. RESULTS: 182 elderly patients with chronic diseases aged ≥ 60 years completed the PACT-M survey. The scores of PACT-M1 and PACT-M2 were (30.69 ± 7.87) and (25.59 ± 7.14) points, respectively. The results of the t-test or one-way ANOVA showed that the patient's marital status, ethnicity, religion, educational level, preretirement occupation, residence, household income per month, and living situation had an impact on the quality of transitional care for elderly patients with chronic diseases (P < 0.05). The results of regression analyses showed that patients' preretirement occupation, social support, and health status were the main influences on the quality of transitional care for elderly patients with chronic diseases (P < 0.05), and they explained 63.1% of the total variance. CONCLUSIONS: The quality of transitional care for older patients with chronic illnesses during the transition from hospital to home needs further improvement. Factors affecting the quality of transitional care included patients' pre-retirement occupation, social support, and health status. We can improve the hospital-community-family tertiary linkage service to provide coordinated and continuous transitional care for patients based on their occupation, health status, and social support to enhance the quality of transitional care and the patient's health.

Intelligence Sparse Sensor Network for Automatic Early Evaluation of General Movements in Infants.

General movements (GMs) have been widely used for the early clinical evaluation of infant brain development, allowing immediate evaluation of potential development disorders and timely rehabilitation. The infants' general movements can be captured digitally, but the lack of quantitative assessment and well-trained clinical pediatricians presents an obstacle for many years to achieve wider deployment, especially in low-resource settings. There is a high potential to explore wearable sensors for movement analysis due to outstanding privacy, low cost, and easy-to-use features. This work presents a sparse sensor network with soft wireless IMU devices (SWDs) for automatic early evaluation of general movements in infants. The sparse network consisting of only five sensor nodes (SWDs) with robust mechanical properties and excellent biocompatibility continuously and stably captures full-body motion data. The proof-of-the-concept clinical testing with 23 infants showcases outstanding performance in recognizing neonatal activities, confirming the reliability of the system. Taken together with a tiny machine learning algorithm, the system can automatically identify risky infants based on the GMs, with an accuracy of up to 100% (99.9%). The wearable sparse sensor network with an artificial intelligence-based algorithm facilitates intelligent evaluation of infant brain development and early diagnosis of development disorders.

Correction: MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer.

Correction for 'MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer' by Jie Liu et al., Biomater. Sci., 2022, 10, 4596-4611, https://doi.org/10.1039/D2BM00543C.

PARP-1 inhibitor alleviates cerebral ischemia/reperfusion injury by reducing PARylation of HK-1 and LDH in mice.

Poly (ADP-ribose) polymerase-1 (PARP-1) activity significantly increases during cerebral ischemia/reperfusion. PARP-1 is an NAD+-consumption enzyme. PARP-1 hyperactivity causes intracellular NAD+ deficiency and bioenergetic collapse, contributing to neuronal death. Besides, the powerful trigger of PARP-1 causes the catalyzation of poly (ADP-ribosyl)ation (PARylation), a posttranslational modification of proteins. Here, we found that PARP-1 was activated in the ischemic brain tissue during middle-cerebral-artery occlusion and reperfusion (MCAO/R) for 24 h, and PAR accumulated in the neurons in mice. Using immunoprecipitation, Western blotting, liquid chromatography-mass spectrometry, and 3D-modeling analysis, we revealed that the activation of PARP-1 caused PARylation of hexokinase-1 and lactate dehydrogenase-B, which, therefore, caused the inhibition of these enzyme activities and the resulting cell energy metabolism collapse. PARP-1 inhibition significantly reversed the activity of hexokinase and lactate dehydrogenase, decreased infarct volume, and improved neuronal deficiency. PARP-1 inhibitor combined with pyruvate further alleviated MCAO/R-induced ischemic brain injury in mice. As such, we conclude that PARP-1 inhibitor alleviates neuronal death partly by inhibiting the PARylation of metabolic-related enzymes and reversing metabolism reprogramming during cerebral ischemia/reperfusion injury in mice. PARP-1 inhibitor combined with pyruvate might be a promising therapeutic approach against brain ischemia/reperfusion injury.

Stretchable, Flexible, Breathable, Self-Adhesive Epidermal Hand sEMG Sensor System.

Hand function rehabilitation training typically requires monitoring the activation status of muscles directly related to hand function. However, due to factors such as the small surface area for hand-back electrode placement and significant skin deformation, the continuous real-time monitoring of high-quality surface electromyographic (sEMG) signals on the hand-back skin still poses significant challenges. We report a stretchable, flexible, breathable, and self-adhesive epidermal sEMG sensor system. The optimized serpentine structure exhibits a sufficient stretchability and filling ratio, enabling the high-quality monitoring of signals. The carving design minimizes the distribution of connecting wires, providing more space for electrode reservation. The low-cost fabrication design, combined with the cauterization design, facilitates large-scale production. Integrated with customized wireless data acquisition hardware, it demonstrates the real-time multi-channel sEMG monitoring capability for muscle activation during hand function rehabilitation actions. The sensor provides a new tool for monitoring hand function rehabilitation treatments, assessing rehabilitation outcomes, and researching areas such as prosthetic control.

A Multifunctional Bimetallic Nanoplatform for Synergic Local Hyperthermia and Chemotherapy Targeting HER2-Positive Breast Cancer.

Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.