Mitochondrial ferritin upregulation by deferiprone reduced neuronal ferroptosis and improved neurological deficits via NDRG1/Yap pathway in a neonatal rat model of germinal matrix hemorrhage.

Ferroptosis contributes to brain injury after germinal matrix hemorrhage (GMH). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, reduces oxidative stress in neurodegenerative diseases. In vitro, Deferiprone has been shown to upregulate FTMT. However, the effects of FTMT upregulation by Deferiprone on neuronal ferroptosis after GMH and its underlying mechanism has not been investigated. In our study, 389 Sprague-Dawley rat pups of postnatal day 7 were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl2 injection. The brain expressions of FTMT, N-myc downstream-regulated gene-1 (NDGR1), Yes-associated protein (YAP), ferroptosis-related molecules including transferrin receptor (TFR) and acyl-CoA synthase long-chain family member 4 (ACSL4) were increased after GMH. FTMT agonist Deferiprone improved neurological deficits and hydrocephalus after GMH. Deferiprone or Adenovirus-FTMT enhanced YAP phosphorylation at the Ser127 site and attenuated ferroptosis, which was reversed by NDRG1 CRISPR Knockout. Iron overload induced neuronal ferroptosis and neurological deficits, which were improved by YAP CRISPR Knockout. Collectively, FTMT upregulation by Deferiprone reduced neuronal ferroptosis and neurological deficits via the NDRG1/YAP signaling pathway after GMH. Deferiprone may serve as a potential non-invasive treatment for GMH patients.

Causal effect of COVID-19 on longitudinal volumetric changes in subcortical structures: A mendelian randomization study.

A few observational neuroimaging investigations have reported subcortical structural changes in the individuals who recovered from the coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the causal relationships between COVID-19 and longitudinal changes of subcortical structures remain unclear. We performed two-sample Mendelian randomization (MR) analyses to estimate putative causal relationships between three COVID-19 phenotypes (susceptibility, hospitalization, and severity) and longitudinal volumetric changes of seven subcortical structures derived from MRI. Our findings demonstrated that genetic liability to SARS-CoV-2 infection had a great long-term impact on the volumetric reduction of subcortical structures, especially caudate. Our investigation may contribute in part to the understanding of the neural mechanisms underlying COVID-19-related neurological and neuropsychiatric sequelae.

A novel fluorescent probe based on dicyanoisophorone derivatives for hypochlorite detection in living cells.

This study presents a long-wavelength fluorescent probe CNC for the detection of ClO- in vitro and in vivo. Upon interaction with ClO-, this probe exhibited a significant increase in fluorescence, with a significant Stokes shift (169 nm), lower detection limit (1.38 µM), high sensitivity and selectivity. Moreover, the probe demonstrated excellent cell permeability and minimal cytotoxicity, allowing for successful imaging of both endogenous and exogenous ClO- in living cells.

Unveiling the Dynamic Pathways of Metal-Organic Framework Crystallization and Nanoparticle Incorporation for Li-S Batteries.

Metal-organic frameworks (MOFs) present diverse building blocks for high-performance materials across industries, yet their crystallization mechanisms remain incompletely understood due to gaps in nucleation and growth knowledge. In this study, MOF structural evolution is probed using in situ liquid phase transmission electron microscopy (TEM) and cryo-TEM, unveiling a blend of classical and nonclassical pathways involving liquid-liquid phase separation, particle attachment-coalescence, and surface layer deposition. Additionally, ultrafast high-temperature sintering (UHS) is employed to dope ultrasmall Cobalt nanoparticles (Co NPs) uniformly within nitrogen-doped hard carbon nanocages confirmed by 3D electron tomography. Lithium-sulfur battery tests demonstrate the nanocage-Co NP structure's exceptional capacity and cycling stability, attributed to Co NP catalytic effects due to its small size, uniform dispersion, and nanocage confinement. The findings propose a holistic framework for MOF crystallization understanding and Co NP tunability through ultrafast sintering, promising advancements in materials science and informing future MOF synthesis strategies and applications.

Voluntary exercise sensitizes cancer immunotherapy via the collagen inhibition-orchestrated inflammatory tumor immune microenvironment.

Physical activity reduces cancer-associated mortality through multiple mechanisms, including tumor immune microenvironment (TIME) reprogramming. However, whether and how physiological interventions promote anti-tumor immunity remain elusive. Here, we report that clinically relevant voluntary exercise promotes muscle-derived extracellular vesicle (EV)-associated miR-29a-3p for tumor extracellular matrix (ECM) inhibition in patients and mouse models, thereby permitting immune cell infiltration and immunotherapy. Mechanistically, an unbiased screening identifies EV-associated miR-29a-3p in response to leisure-time physical activity or voluntary exercise. MiR-29a-3p-containing EVs accumulate in tumors and downregulate collagen composition by targeting COL1A1. Gain- and loss-of-function experiments and cytometry by time of flight (CyTOF) demonstrate that myocyte-secreted miR-29a-3p promotes anti-tumor immunity. Combining immunotherapy with voluntary exercise or miR-29a-3p further enhances anti-tumor efficacy. Clinically, miR-29a-3p correlates with reduced ECM, increased T cell infiltration, and response to immunotherapy. Our work reveals the predictive value of miR-29a-3p for immunotherapy, provides mechanistic insights into exercise-induced anti-cancer immunity, and highlights the potential of voluntary exercise in sensitizing immunotherapy.

Tau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies.

The deposition of abnormal tau protein is characteristic of Alzheimer's disease (AD) and a class of neurodegenerative diseases called tauopathies. Physiologically, tau maintains an intrinsically disordered structure and plays diverse roles in neurons. Pathologically, tau undergoes abnormal post-translational modifications and forms oligomers or fibrous aggregates in tauopathies. In this review, we briefly introduce several tauopathies and discuss the mechanisms mediating tau aggregation and propagation. We also describe the toxicity of tau pathology. Finally, we explore the early diagnostic biomarkers and treatments targeting tau. Although some encouraging results have been achieved in animal experiments and preclinical studies, there is still no cure for tauopathies. More in-depth basic and clinical research on the pathogenesis of tauopathies is necessary.

Chitosan-based self-healing hydrogel dressing for wound healing.

Skin has strong self-regenerative capacity, while severe skin defects do not heal without appropriate treatment. Therefore, in order to cover the wound sites and hasten the healing process, wound dressings are required. Hydrogels have emerged as one of the most promising candidates for wound dressings because of their hydrated and porous molecular structure. Chitosan (CS) with biocompatibility, oxygen permeability, hemostatic and antimicrobial properties is beneficial for wound treatment and it can generate self-healing hydrogels through reversible crosslinks, from dynamic covalent bonding, such as Schiff base bonds, boronate esters, and acylhydrazone bonds, to physical interactions like hydrogen bonding, electrostatic interaction, ionic bonding, metal-coordination, host-guest interactions, and hydrophobic interaction. Therefore, various chitosan-based self-healing hydrogel dressings have been prepared in recent years to cope with increasingly complex wound conditions. This review's objective is to provide comprehensive information on the self-healing mechanism of chitosan-based hydrogel wound dressings, discuss their advanced functions including antibacterial, conductive, anti-inflammatory, anti-oxidant, stimulus-responsive, hemostatic/adhesive and controlled release properties, further introduce their applications in the promotion of wound healing in two categories: acute and chronic (infected, burn and diabetic) wounds, and finally discuss the future perspective of chitosan-based self-healing hydrogel dressings for wound healing.

A simplified adversarial architecture for cross-subject silent speech recognition using electromyography.

Objective. The decline in the performance of electromyography (EMG)-based silent speech recognition is widely attributed to disparities in speech patterns, articulation habits, and individual physiology among speakers. Feature alignment by learning a discriminative network that resolves domain offsets across speakers is an effective method to address this problem. The prevailing adversarial network with a branching discriminator specializing in domain discrimination renders insufficiently direct contribution to categorical predictions of the classifier.Approach. To this end, we propose a simplified discrepancy-based adversarial network with a streamlined end-to-end structure for EMG-based cross-subject silent speech recognition. Highly aligned features across subjects are obtained by introducing a Nuclear-norm Wasserstein discrepancy metric on the back end of the classification network, which could be utilized for both classification and domain discrimination. Given the low-level and implicitly noisy nature of myoelectric signals, we devise a cascaded adaptive rectification network as the front-end feature extraction network, adaptively reshaping the intermediate feature map with automatically learnable channel-wise thresholds. The resulting features effectively filter out domain-specific information between subjects while retaining domain-invariant features critical for cross-subject recognition.Main results. A series of sentence-level classification experiments with 100 Chinese sentences demonstrate the efficacy of our method, achieving an average accuracy of 89.46% tested on 40 new subjects by training with data from 60 subjects. Especially, our method achieves a remarkable 10.07% improvement compared to the state-of-the-art model when tested on 10 new subjects with 20 subjects employed for training, surpassing its result even with three times training subjects.Significance. Our study demonstrates an improved classification performance of the proposed adversarial architecture using cross-subject myoelectric signals, providing a promising prospect for EMG-based speech interactive application.

Polysaccharide fraction from Triplostegia glandulifera Wall and its renoprotective effect in streptozotocin-induced diabetic mice by attenuating oxidative stress.

Triplostegia glandulifera Wall (T. glandulifera) is an ethnomedicine commonly used by ethnic minorities in Yunnan, China, to treat kidney disease. However, there are few reports on the renoprotective effects of this substance, and the active ingredients remain unclear. In this study, we extracted the polysaccharide fractions TGB and TGC using the water extraction-alcohol precipitation method and determined their molecular weight (Mw) and monosaccharide composition. The study investigated the protective effects of TGB and TGC fractions against diabetic nephropathy (DN) using an in vitro high glucose-induced HRMCs model and an in vivo STZ-induced diabetic mouse model. HPLC analysis revealed that TGB contained D-galacturonic acid, D-glucose, D-galactose, and D-arabinose, and had a lower Mw than TGC. In vitro, TGB showed concentration-dependent antioxidant activity and effectively reduced abnormal proliferation and while attenuating oxidative stress in HRMCs. In mice with diabetes, TGB corrected the dysregulation of glucose-lipid metabolism and alleviated oxidative stress in the kidneys. Additionally, it improved renal function and reduced renal tissue damage. The study suggests that the low Mw polysaccharides (TGB) have better activity against DN through the antioxidative stress mechanism.

Assembly and evolutionary analysis of the complete mitochondrial genome of Trichosanthes kirilowii, a traditional Chinese medicinal plant.

Trichosanthes kirilowii (T. kirilowii) is a valuable plant used for both medicinal and edible purposes. It belongs to the Cucurbitaceae family. However, its phylogenetic position and relatives have been difficult to accurately determine due to the lack of mitochondrial genomic information. This limitation has been an obstacle to the potential applications of T. kirilowii in various fields. To address this issue, Illumina and Nanopore HiFi sequencing were used to assemble the mitogenome of T. kirilowii into two circular molecules with sizes of 245,700 bp and 107,049 bp, forming a unique multi-branched structure. The mitogenome contains 61 genes, including 38 protein-coding genes (PCGs), 20 tRNAs, and three rRNAs. Within the 38 PCGs of the T. kirilowii mitochondrial genome, 518 potential RNA editing sites were identified. The study also revealed the presence of 15 homologous fragments that span both the chloroplast and mitochondrial genomes. The phylogenetic analysis strongly supports that T. kirilowii belongs to the Cucurbitaceae family and is closely related to Luffa. Collinearity analysis of five Cucurbitaceae mitogenomes shows a high degree of structural variability. Interestingly, four genes, namely atp1, ccmFC, ccmFN, and matR, played significant roles in the evolution of T. kirilowii through selection pressure analysis. The comparative analysis of the T. kirilowii mitogenome not only sheds light on its functional and structural features but also provides essential information for genetic studies of the genus of Cucurbitaceae.

Enhancing Pseudomonas cell growth for the production of medium-chain-length polyhydroxyalkanoates from Antarctic krill shell waste.

Antarctic krill shell waste (AKSW), a byproduct of Antarctic krill processing, has substantial quantity but low utilization. Utilizing microbial-based cell factories, with Pseudomonas putida as a promising candidate, offers an ecofriendly and sustainable approach to producing valuable bioproducts from renewable sources. However, the high fluoride content in AKSW impedes the cell growth of P. putida. This study aims to investigate the transcriptional response of P. putida to fluoride stress from AKSW and subsequently conduct genetic modification of the strain based on insights gained from transcriptomic analysis. Notably, the engineered strain KT+16840+03100 exhibited a remarkable 33.7-fold increase in cell growth, capable of fermenting AKSW for medium-chain-length-polyhydroxyalkanoates (mcl-PHA) biosynthesis, achieving a 40.3-fold increase in mcl-PHA yield compared to the control strain. This research advances our understanding of how P. putida responds to fluoride stress from AKSW and provides engineered strains that serve as excellent platforms for producing mcl-PHA through AKSW.

Dynamic Microcirculation Characteristics of Plantar Skin Under Metatarsal Head of Human Foot in Response to Life-Like Pressure Stimulus.

OBJECTIVE: Diabetic foot ulcer (DFU) is a severe complication with high mortality. High plantar pressure and poor microcirculation are considered main causes of DFU. The specific aims were to provide a novel technique for real-time measurement of plantar skin blood flow (SBF) under walking-like pressure stimulus and delineate the first plantar metatarsal head dynamic microcirculation characteristics because of life-like loading conditions in healthy individuals. METHODS: Twenty young healthy participants (14 male and 6 female) were recruited. The baseline (i.e., unloaded) SBF of soft tissue under the first metatarsal head were measured using laser Doppler flowmetry (LDF). A custom-made machine was utilized to replicate daily walking pressure exertion for 5 min. The exerted plantar force was adjusted from 10 N (127.3 kPa) to 40 N (509.3 kPa) at an increase of 5 N (63.7 kPa). Real-time SBF was acquired using the LDF. After each pressure exertion, postload SBF was measured for comparative purposes. Statistical analysis was performed using the R software. RESULTS: All levels of immediate-load and postload SBF increased significantly compared with baseline values. As the exerted load increased, the postload and immediate-load SBF tended to increase until the exerted load reached 35 N (445.6 kPa). However, in immediate-load data, the increasing trend tended to level off as the exerted pressure increased from 15 N (191.0 kPa) to 25 N (318.3 kPa). For postload and immediate-load SBF, they both peaked at 35 N (445.6 kPa). However, when the exerted force exceeds 35 N (445.6 kPa), both the immediate-load and postload SBF values started to decrease. CONCLUSIONS: Our study offered a novel real-time plantar soft tissue microcirculation measurement technique under dynamic conditions. For the first metatarsal head of healthy people, 20 N (254.6 kPa)-plantar pressure has a fair microcirculation stimulus compared with higher pressure. There might be a pressure threshold at 35 N (445.6 kPa) for the first metatarsal head, and soft tissue microcirculation may decrease when local pressure exceeds it.

Home Anxiety Assessment and Influencing Factors among Adolescent Athletes in Yantai City.

OBJECTIVE: To understand the prevalence of home-related anxiety among adolescent athletes during the novel coronavirus pandemic and to ascertain the factors influencing this anxiety. METHODS: We employed cluster sampling to select 1150 adolescent athletes (aged 8-18 years) from six sports training schools in Yantai City, Shandong Province. Mental health status was assessed and recorded. Chi-square tests and multivariable logistic regression were used to analyze the factors contributing to athletes' anxiety. RESULTS: The survey revealed a COVID-19 infection rate of 38.23% (437 individuals) with an anxiety score of 40.98 ± 8.20 and an anxiety detection rate of 11.29% (129 individuals) during the COVID-19 epidemic. Female athletes exhibited a higher anxiety rate of 14.40% compared to 8.40% in male athletes. Multivariate analysis identified female gender as a risk factor for anxiety (OR = 1.64), while participation in aquatics emerged as a protective factor (OR = 0.24, 95% CI: 1.08-2.48). Professional training duration exceeding three years increased anxiety risk (OR = 3.05, 95% CI: 1.67-5.58), as did not seeking help during difficulties (OR = 2.59, 95% CI: 1.33-5.01). Interestingly, parental care was linked to increased anxiety risk (OR = 2.44, 95% CI 1.34-4.44), while care from friends was protective (OR = 0.60, 95% CI: 0.36-1.01), which was possibly due to the pressure associated with parental expectations. CONCLUSIONS: Adolescent athletes, particularly females and those with extended training durations, exhibit a heightened susceptibility to anxiety. This study also highlights that athletes who proactively seek assistance during challenging situations tend to experience lower anxiety levels. Additionally, a lack of COVID-19 infection and the involvement of concerned parents contribute to reduced anxiety among these young athletes.

Survival after live donor versus deceased donor liver transplantation: propensity score-matched study.

BACKGROUND: For individuals with advanced liver disease, equipoise in outcomes between live donor liver transplant (LDLT) and deceased donor liver transplant (DDLT) is uncertain. METHODS: A retrospective cohort study was performed using data extracted from the Scientific Registry of Transplant Recipients. Adults who underwent first-time DDLT or LTDL in the United States between 2002 and 2020 were paired using propensity-score matching with 1:10 ratio without replacement. Patient and graft survival were compared using the model for end-stage liver disease (MELD) score for stratification. RESULTS: After propensity-score matching, 31 522 DDLT and 3854 LDLT recipients were included. For recipients with MELD scores ≤15, LDLT was associated with superior patient survival (HR = 0.92; 95% c.i. 0.76 to 0.96; P = 0.013). No significant differences in patient survival were observed for MELD scores between 16 and 30. Conversely, for patients with MELD scores >30, LDLT was associated with higher mortality (HR 2.57; 95% c.i. 1.35 to 4.62; P = 0.003). Graft survival was comparable between the two groups for MELD ≤15 and for MELD between 21 and 30. However, for MELD between 16 and 20 (HR = 1.15; 95% c.i. 1.00 to 1.33; P = 0.04) and MELD > 30 (HR = 2.85; 95% c.i. 1.65 to 4.91; P = 0.001), graft survival was considerably shorter after LDLT. Regardless of MELD scores, re-transplantation rate within the first year was significantly higher after LDLT. CONCLUSIONS: In this large propensity score-matched study using national data, comparable patient survival was found between LDLT and DDLT in recipients with MELD scores between 16 and 30. Conversely, for patients with MELD > 30, LDLT was associated with worse outcomes. These findings underscore the importance of transplant selection for patients with high MELD scores.

Free-space coupled, large-active-area superconducting microstrip single-photon detector for photon-counting time-of-flight imaging.

Numerous applications at the photon-starved regime require a free-space coupling single-photon detector with a large active area, low dark count rate (DCR), and superior time resolutions. Here, we developed a superconducting microstrip single-photon detector (SMSPD), with a large active area of 260 µm in diameter, a DCR of ∼5k c p s, and a low time jitter of ∼171p s, operated at a near-infrared of 1550 nm and a temperature of ∼2.0K. As a demonstration, we applied the detector to a single-pixel galvanometer scanning system and successfully reconstructed the object information in depth and intensity using a time-correlated photon counting technology.

Applications of Functional Near-Infrared Spectroscopy (fNIRS) Neuroimaging During Rehabilitation Following Stroke: A Review.

Stroke is a cerebrovascular disease that impairs blood supply to localized brain tissue regions due to various causes. This leads to ischemic and hypoxic lesions, necrosis of the brain tissue, and a variety of functional disorders. Abnormal cortical activation and functional connectivity occur in the brain after a stroke, but the activation patterns and functional reorganization are not well understood. Rehabilitation interventions can enhance functional recovery in stroke patients. However, clinicians require objective measures to support their practice, as outcome measures for functional recovery are based on scale scores. Furthermore, the most effective rehabilitation measures for treating patients are yet to be investigated. Functional near-infrared spectroscopy (fNIRS) is a non-invasive neuroimaging method that detects changes in cerebral hemodynamics during task performance. It is widely used in neurological research and clinical practice due to its safety, portability, high motion tolerance, and low cost. This paper briefly introduces the imaging principle and the advantages and disadvantages of fNIRS to summarize the application of fNIRS in post-stroke rehabilitation.

Research Progress on Helmet Liner Materials and Structural Applications.

As an important part of head protection equipment, research on the material and structural application of helmet liners has always been one of the hotspots in the field of helmets. This paper first discusses common helmet liner materials, including traditional polystyrene, polyethylene, polypropylene, etc., as well as newly emerging anisotropic materials, polymer nanocomposites, etc. Secondly, the design concept of the helmet liner structure is discussed, including the use of a multi-layer structure, the addition of geometric irregular bubbles to enhance the energy absorption effect, and the introduction of new manufacturing processes, such as additive manufacturing technology, to realize the preparation of complex structures. Then, the application of biomimetic structures to helmet liner design is analyzed, such as the design of helmet liner structures with more energy absorption properties based on biological tissue structures. On this basis, we propose extending the concept of bionic structural design to the fusion of plant stalks and animal skeletal structures, and combining additive manufacturing technology to significantly reduce energy loss during elastic yield energy absorption, thus developing a reusable helmet that provides a research direction for future helmet liner materials and structural applications.

Outcome comparison of meniscal allograft transplantation (MAT) and meniscal scaffold implantation (MSI): a systematic review.

BACKGROUND: Although numerous studies have reported successful clinical outcomes of meniscal allograft transplantation (MAT) or meniscal scaffold implantation (MSI), the difference between the outcome of MAT and MSI remains unclear. PURPOSE: To compare the overall outcomes and survival rates of MAT and MSI, aiming to provide comprehensive evidence for determining the optimal treatment strategy for meniscal defects. METHODS: A systematic review was performed via a comprehensive search of PubMed, Embase, and the Cochrane Library. Studies of MAT or MSI were included according to the inclusion and exclusion criteria. The Lysholm score was chosen as the primary outcome measure, while secondary outcomes encompassed patient-reported outcome measures (PROMs), return to sports (RTS) rates, survival rates, and complication rates. The outcomes were stratified into two groups: MAT group and MSI group, followed by statistical comparison ( P <0.05). The quality of the included studies was assessed by the Cochrane Risk of Bias 2 (RoB2) assessment tool for randomized controlled trials (RCTs) and the Coleman Methodology Score (CMS) for non-randomized controlled trials. RESULTS: A total of 3932 patients (2859 MAT, 1073 MSI) in 83 studies (51 MAT, 32 MSI) had the overall significant improvement in all clinical scores. The group MSI had a higher Lysholm score of both preoperative ( P =0.002) and postoperative ( P <0.001) than group MAT; however, the mean improvements were similar between the two groups ( P =0.105). Additionally, MSI had higher improvements of IKDC ( P <0.001), KOOS symptom ( P =0.010), KOOS pain ( P =0.036), and KOOS ADL ( P =0.004) than MAT. Interestingly, MAT had higher preoperative ( P =0.018) and less postoperative VAS pain ( P =0.006), which was more improved in MAT ( P <0.001). Compared with MAT, MSI had a higher 10-year survival rate ( P =0.034), a similar mid-term survival rate MAT ( P =0.964), and a lower complication rate ( P <0.001). CONCLUSION: Both MAT and MSI could have good clinical outcomes after surgery with a similar improvement in Lysholm score. MSI had a higher 10-year survival rate and fewer complications than MAT. LEVEL OF EVIDENCE: Level IV, systematic review.