Associations between plant-based dietary patterns and sensory impairments among Chinese older adults: Based on the Chinese Longitudinal Healthy Longevity Survey.

OBJECTIVE: Examining the relationship between the plant-based dietary index and vision impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI) among Chinese aged 65 and older. METHODS: Based on the 2018 data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a cross-sectional study was conducted on 14,859 samples. The assessment of dietary quality utilized the Plant-Based Diet Index (PDI), Healthy Plant-Based Diet Index (hPDI), and Unhealthy Plant-Based Diet Index (uPDI). Logistic regression analysis was used to examine the associations between PDIs and sensory impairments. Additionally, restricted cubic spline analysis was utilized to investigate the non-linear association between PDIs and sensory impairments. RESULTS: Participants in the highest quintile of PDI exhibited reduced prevalence of VI (OR 0.78, 95% CI:0.67-0.90, Ptrend <0.001), HI (OR 0.83, 95% CI:0.70-0.99, Ptrend <0.001) and DSI (OR 0.62, 95%CI:0.51-0.77, Ptrend <0.001) relative to those in the lowest quintile. Moreover, individuals who ranked in the highest quintile for hPDI exhibited a 25% reduced risk of VI disease. Conversely, those in the highest quintile of uPDI were associated with increased prevalence of VI (OR 1.37, 95% CI: 1.17-1.61, Ptrend <0.001), HI (OR 1.36, 95% CI: 1.12-1.65, Ptrend <0.001) and DSI (OR 1.56, 95% CI: 1.25-1.95, Ptrend <0.001). The relationship between PDIs increasing by every 10 units and sensory impairments showed similar patterns. Notably, hPDI demonstrated a non-linear relationship with HI (Pfor nonlinearity = 0.001), while the others exhibited linear associations. CONCLUSION: The increase in PDI and hPDI correlates with a reduced prevalence of one or more sensory impairments. Conversely, an increase in uPDI is associated with an elevated prevalence of multiple sensory impairments. Our study findings emphasize the significance of plant-based food quality, advocating for adherence to a plant-based dietary pattern while reducing the intake of less healthy plant foods and animal-based products.

Unveiling the therapeutic potential of epigallocatechin gallate in liver cancer: insights from network pharmacology and in vitro assays.

Epigallocatechin gallate (EGCG) is a prominent catechin found in green tea polyphenols and has shown promising anti-tumor properties. However, the exact regulatory mechanism of EGCG on liver cancer is not fully revealed. In this study, we conducted integrative analyses using the SwissTargetPrediction and GeneCards repositories, which identified 98 targets. These targets were used to construct a protein-protein interaction network using STRING and visualised with Cytoscape. Central to this network are hub proteins, notably TNF and PIK3CA, suggesting pivotal roles in the therapeutic landscape. Gene Ontology (GO) enrichment analysis unveiled 1,570 biological terms with a notable preponderance within oxidative stress response processes. Complementary pathway enrichment via the Kyoto Encyclopaedia of Genes and Genomes (KEGG) highlighted 134 pathways, with the PI3K-Akt pathway emerging as prominent. In silico molecular docking supported these findings, revealing binding energies of EGCG-target complexes below -7.0 kcal/mol, indicative of robust interactions. Moreover, cellular assays including CCK-8, wound-healing, and Transwell modalities, established EGCG's inhibitory concentration-dependent effects on HepG2 cell proliferation, migration, and invasion. Apoptotic assays affirmed by FACS, evidenced enhanced apoptosis with escalating EGCG concentrations, underpinned by modulations in caspase activity and apoptotic protein levels. Notably, Western blot analysis demonstrated the attenuation of the PI3K/AKT signalling cascade by EGCG, paralleling the inhibitory profile of LY294002. These multifaceted inhibitory effects underscore EGCG's potential as an anti-tumor agent, deploying a strategic blockade of oncogenic pathways and augmenting apoptotic mechanisms, which provide a strong rationale for its application in liver cancer therapeutics.

Continuous Flow Microreactors for the High-efficiency Enzymatic Synthesis of 10-Hydroxystearic Acid from Oleic Acid.

Converting fatty acids into specialty chemicals is sustainable but hindered by the low efficiency and thermal instability of current oleic acid hydratases, along with mass transfer limitations in emulsion reactions. This study introduces an optimized continuous flow micro-reactor (CFMR) that efficiently transforms oleic acid at low (15 g·L-1) and high (50 g·L-1) concentrations, improving reaction efficiency and overcoming key conversion barriers. The first CFMR model showed reaction speeds surpassing traditional batch stirred tank reactors (BSTR). Optimizations were performed on three key components: liquid storage, mixer, and reaction section of the CFMR, with each round's best conditions carried into the next. This achieved a space-time yield of 597 g·L-1·d-1 at a 15 g·L-1 oleic acid load. To further enhance the yield, we optimized the emulsifier system to solve incomplete emulsification and developed a two-component feed microreactor (TCFMR) that addressed substrate and product inhibition at high loads, reaching a 91% conversion of 50 g·L-1 oleic acid in 30 minutes, with a space-time yield of 2312 g·L-1·d-1. These advancements represent significant progress in utilizing fatty acids and advancing sustainable chemical synthesis.

Deciphering deep-sea chemosynthetic symbiosis by single-nucleus RNA-sequencing.

Bathymodioline mussels dominate deep-sea methane seep and hydrothermal vent habitats and obtain nutrients and energy primarily through chemosynthetic endosymbiotic bacteria in the bacteriocytes of their gill. However, the molecular mechanisms that orchestrate mussel host-symbiont interactions remain unclear. Here, we constructed a comprehensive cell atlas of the gill in the mussel Gigantidas platifrons from the South China Sea methane seeps (1100 m depth) using single-nucleus RNA-sequencing (snRNA-seq) and whole-mount in situ hybridisation. We identified 13 types of cells, including three previously unknown ones, and uncovered unknown tissue heterogeneity. Every cell type has a designated function in supporting the gill's structure and function, creating an optimal environment for chemosynthesis, and effectively acquiring nutrients from the endosymbiotic bacteria. Analysis of snRNA-seq of in situ transplanted mussels clearly showed the shifts in cell state in response to environmental oscillations. Our findings provide insight into the principles of host-symbiont interaction and the bivalves' environmental adaption mechanisms.

Deep Learning Based Automatic Left Ventricle Segmentation from the Transgastric Short-Axis View on Transesophageal Echocardiography: A Feasibility Study.

Segmenting the left ventricle from the transgastric short-axis views (TSVs) on transesophageal echocardiography (TEE) is the cornerstone for cardiovascular assessment during perioperative management. Even for seasoned professionals, the procedure remains time-consuming and experience-dependent. The current study aims to evaluate the feasibility of deep learning for automatic segmentation by assessing the validity of different U-Net algorithms. A large dataset containing 1388 TSV acquisitions was retrospectively collected from 451 patients (32% women, average age 53.42 years) who underwent perioperative TEE between July 2015 and October 2023. With image preprocessing and data augmentation, 3336 images were included in the training set, 138 images in the validation set, and 138 images in the test set. Four deep neural networks (U-Net, Attention U-Net, UNet++, and UNeXt) were employed for left ventricle segmentation and compared in terms of the Jaccard similarity coefficient (JSC) and Dice similarity coefficient (DSC) on the test set, as well as the number of network parameters, training time, and inference time. The Attention U-Net and U-Net++ models performed better in terms of JSC (the highest average JSC: 86.02%) and DSC (the highest average DSC: 92.00%), the UNeXt model had the smallest network parameters (1.47 million), and the U-Net model had the least training time (6428.65 s) and inference time for a single image (101.75 ms). The Attention U-Net model outperformed the other three models in challenging cases, including the impaired boundary of left ventricle and the artifact of the papillary muscle. This pioneering exploration demonstrated the feasibility of deep learning for the segmentation of the left ventricle from TSV on TEE, which will facilitate an accelerated and objective alternative of cardiovascular assessment for perioperative management.

Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice.

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex-mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.

Application of a simplified transesophageal echocardiography examination sequence in high-risk cardiac surgery.

BACKGROUND: In cardiac surgical procedures, patients carrying high-risk profiles are prone to encompass complicated cardiopulmonary bypass (CPB) separation. Intraoperative transesophageal echocardiography (TEE), a readily available tool, is utilized to detect cardiac structural and functional pathologies as well as to facilitate clinical management of CPB separation, especially in the episodes of hemodynamic compromise. However, the conventional TEE examination, always performed in a liberal fashion without any restriction of view acquisition, is relatively time-consuming; there appear its flaws in the context of critically severe status. We therefore developed the perioperative rescue transesophageal echocardiography (PReTEE), a simplified three-view TEE protocol consisting of midesophageal four chamber, midesophageal left ventricular long axis, and transgastric short axis. METHODS: This is a single-center and randomized controlled trial which will be implemented in Peking Union Medical College Hospital, Beijing, China. A total of 46 TEE scans are schemed to be performed by 6 operators participating in and randomly assigned to either the PReTEE or the conventional TEE group. This study is purposed to investigate whether the efficiency of discriminating leading causes of difficult CPB wean-off can be significantly improved via an abbreviated sequence of TEE views. The primary outcome of interest is the difference between the groups of PReTEE and the conventional TEE in the successful discrimination of etiologies in specified 120 s. Cox proportional hazards model will be further employed to calculate the outcome difference. DISCUSSION: The estimated results of this trial are oriented at verifying whether a simplified TEE exam sequence can improve the efficiency of etiologies discrimination during CPB separation in cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT05960552. Registered on 6 July 2023.

Soil organic carbon formation efficiency from straw/stover and manure input and its drivers: Estimates from long-term data in global croplands.

New soil organic carbon (SOC) formation in cropland from straw/stover or manure input is a vital source of SOC for climate change mitigation. However, location and variations in the efficiency, specifically the ratio of new SOC formation to organic C input (NCE), remain unquantified globally. In this study, the spatial variability of cropland NCE from straw/stover or manure input and explanatory factors were determined by analyzing 897 pairs of long-term field measurements from 404 globally distributed sites and by mapping grid-level cropland NCEs. The global NCE for paddy and upland averaged 13.8% (8.7%-25.1%, 5th-95th percentile) and 10.9% (6.8%-17.3%), respectively. The initial SOC and the clay content of soil, rather than temperature, were the most important factors regulating NCE. A parabola with an apex at approximately 17 g kg-1 between the initial SOC and NCE was resolved, and a positive correlation between soil clay content and NCE was observed. High-resolution mapping of the global NCE derived from manure/straw and insight into NCE dynamics provide a benchmark for diagnosing cropland soil C dynamics under climate change and identifying priority regions and actions for C management.

Transcriptional dynamics of Fusarium pseudograminearum under high fungicide stress and the important role of FpZRA1 in fungal pathogenicity and DON toxin production.

Fusarium pseudograminearum, the causal agent of Fusarium crown rot, poses a significant threat to cereal crops. Building upon our previous investigation of the transcriptional response of this pathogen to four key fungicides (carbendazim, phenamacril, pyraclostrobin, and tebuconazole), this study delves into the impact of elevated fungicide concentrations using RNA-seq. Global transcriptomic analysis and gene clustering revealed significant enrichment of genes involved in the ABC transporter pathway. Among these transporters, FPSE_06011 (FpZRA1), a conserved gene in eukaryotes, exhibited consistent upregulation at both low and high fungicide concentrations. Targeted deletion of FpZRA1 resulted in reduced sporulation, spore germination, and tolerance to cell wall stress, osmotic stress, and oxidative stress. Furthermore, the FpZRA1 knockout mutants exhibited decreased pathogenicity on wheat coleoptiles and reduced production of the mycotoxin deoxynivalenol (DON), as evidenced by the markedly down-regulated expression of TRI5, TRI6, and TRI10 in the RT-qPCR analysis. In summary, our findings highlight the impact of fungicide concentration on transcriptional reprogramming in F. pseudograminearum and identify FpZRA1 as a critical regulator of fungal development, stress tolerance, and pathogenicity.

Landscape and conservation genetics of western black crested gibbons (Nomascus concolor) in China.

Despite decades of field study, very little is known about the molecular ecology of gibbons, particularly as it relates to their ability to disperse across degraded and fragmentary landscapes. The critically endangered western black crested gibbon (Nomascus concolor) has been reduced to a small, fragmented population with about 1300 individuals. In the largest population genetic study of free-ranging gibbons to date, we sampled 47 of these gibbons from 13 sites in China and generated 15 polymorphic autosomal microsatellite markers. We identify three population clusters of N. concolor in Yunnan centered in 1) the Wuliang and Ailao Mountains, 2) the Yongde Daxueshan Mountains, and 3) an isolated remnant near the border with Vietnam. Within the Wuliang Mountains, we identified four subclusters, three of which are bounded by high-altitude rhododendron forest, and one that is isolated from the main population by ~2 km of degraded forest and pasture. Least-cost path analysis and isolation by resistance modeling demonstrates that the population genetic distances among gibbons in Wuliangshan National Nature Reserve are significantly correlated with geographic paths that avoid use of high-altitude rhododendron forest in favor of evergreen broadleaf forest. Although these gibbons have likely undergone reductions in heterozygosity from recent consanguineous mating, we suggest that their active avoidance of inbreeding on the population level maintains higher than expected levels of genetic diversity. This research provides new insights into how gibbons interact with heterogeneous environments and expands our understanding of their molecular ecology and conservation genetics.

HMGA1 promotes the progression of esophageal squamous cell carcinoma by elevating TKT-mediated upregulation of pentose phosphate pathway.

Esophageal squamous cell carcinoma (ESCC) possesses a poor prognosis and treatment outcome. Dysregulated metabolism contributes to unrestricted growth of multiple cancers. However, abnormal metabolism, such as highly activated pentose phosphate pathway (PPP) in the progression of ESCC remains largely unknown. Herein, we report that high-mobility group AT-hook 1 (HMGA1), a structural transcriptional factor involved in chromatin remodeling, promoted the development of ESCC by upregulating the PPP. We found that HMGA1 was highly expressed in ESCC. Elevated HMGA1 promoted the malignant phenotype of ESCC cells. Conditional knockout of HMGA1 markedly reduced 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumorigenesis in mice. Through the metabolomic analysis and the validation assay, we found that HMGA1 upregulated the non-oxidative PPP. With the transcriptome sequencing, we identified that HMGA1 upregulated the expression of transketolase (TKT), which catalyzes the reversible reaction in non-oxidative PPP to exchange metabolites with glycolytic pathway. HMGA1 knockdown suppressed the PPP by downregulating TKT, resulting in the reduction of nucleotides in ESCC cells. Overexpression of HMGA1 upregulated PPP and promoted the survival of ESCC cells by activating TKT. We further characterized that HMGA1 promoted the transcription of TKT by interacting with and enhancing the binding of transcription factor SP1 to the promoter of TKT. Therapeutics targeting TKT with an inhibitor, oxythiamine, reduced HMGA1-induced ESCC cell proliferation and tumor growth. Together, in this study, we identified a new role of HMGA1 in ESCCs by upregulating TKT-mediated activation of PPP. Our results provided a new insight into the role of HMGA1/TKT/PPP in ESCC tumorigenesis and targeted therapy.

Intelligent diagnostic model for pterygium by combining attention mechanism and MobileNetV2.

AIM: To evaluate the application of an intelligent diagnostic model for pterygium. METHODS: For intelligent diagnosis of pterygium, the attention mechanisms-SENet, ECANet, CBAM, and Self-Attention-were fused with the lightweight MobileNetV2 model structure to construct a tri-classification model. The study used 1220 images of three types of anterior ocular segments of the pterygium provided by the Eye Hospital of Nanjing Medical University. Conventional classification models-VGG16, ResNet50, MobileNetV2, and EfficientNetB7-were trained on the same dataset for comparison. To evaluate model performance in terms of accuracy, Kappa value, test time, sensitivity, specificity, the area under curve (AUC), and visual heat map, 470 test images of the anterior segment of the pterygium were used. RESULTS: The accuracy of the MobileNetV2+Self-Attention model with 281 MB in model size was 92.77%, and the Kappa value of the model was 88.92%. The testing time using the model was 9ms/image in the server and 138ms/image in the local computer. The sensitivity, specificity, and AUC for the diagnosis of pterygium using normal anterior segment images were 99.47%, 100%, and 100%, respectively; using anterior segment images in the observation period were 88.30%, 95.32%, and 96.70%, respectively; and using the anterior segment images in the surgery period were 88.18%, 94.44%, and 97.30%, respectively. CONCLUSION: The developed model is lightweight and can be used not only for detection but also for assessing the severity of pterygium.

Primary cilia mediate skeletogenic BMP and Hedgehog signaling in heterotopic ossification.

Heterotopic ossification (HO), defined as the formation of extraskeletal bone in muscle and soft tissues, is a diverse pathological process caused by either genetic mutations or inciting trauma. Fibrodysplasia ossificans progressiva (FOP) is a genetic form of HO caused by mutations in the bone morphogenetic protein (BMP) type I receptor gene activin A receptor type 1 (ACVR1). These mutations make ACVR1 hypersensitive to BMP and responsive to activin A. Hedgehog (Hh) signaling also contributes to HO development. However, the exact pathophysiology of how skeletogenic cells contribute to endochondral ossification in FOP remains unknown. Here, we showed that the wild-type or FOP-mutant ACVR1 localized in the cilia of stem cells from human exfoliated deciduous teeth with key FOP signaling components, including activin A receptor type 2A/2B, SMAD family member 1/5, and FK506-binding protein 12kD. Cilia suppression by deletion of intraflagellar transport 88 or ADP ribosylation factor like GTPase 3 effectively inhibited pathological BMP and Hh signaling, subdued aberrant chondro-osteogenic differentiation in primary mouse or human FOP cells, and diminished in vivo extraskeletal ossification in Acvr1Q207D, Sox2-Cre; Acvr1R206H/+ FOP mice and in burn tenotomy-treated wild-type mice. Our results provide a rationale for early and localized suppression of cilia in affected tissues after injury as a therapeutic strategy against either genetic or acquired HO.

IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10.

Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)-IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV-IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10-null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV-IL-27. Our study revealed a major role for IL-10 in AAV-IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy.

Two Calcium Sensor-Activated Kinases Function in Root Hair Growth.

Plant pollen tubes and root hairs typical polarized tip growth. It is well established that calcium ions (Ca2+) play essential roles in maintaining cell polarity and guiding cell growth orientation. Ca2+ signals are encoded by Ca2+ channels and transporters and are decoded by a variety of Ca2+-binding proteins often called Ca2+ sensors, in which calcineurin B-like protein (CBL) proteins function by interacting with and activating a group of kinases, activate CBL-interacting protein kinases (CIPKs). Some CBL-CIPK complexes, such as CBL2/3-CIPK12/19, act as crucial regulators of pollen tube growth. Whether these calcium decoding components regulate the growth of root hairs, another type of plant cell featuring Ca2+-regulated polarized growth, remains unknown. In this study, we identified CIPK13 and CIPK18 as genes specifically expressed in Arabidopsis (Arabidopsis thaliana) root hairs. The cipk13 cipk18 double mutants showed reduced root hair length and lower growth rates. The calcium oscillations at the root hair tip were attenuated in the cipk13 cipk18 mutants as compared to the wild-type plants. Through yeast two-hybrid screens, CBL2 and CBL3 were identified as interacting with CIPK13 and CIPK18. cbl2 cbl3 displayed a shortened root hair phenotype similar to cipk13 cipk18. This genetic analysis, together with biochemical assays showing activation of CIPK13/18 by CBL2/3, supported the conclusion that CBL2/3 and CIPK13/18 may work as Ca2+-decoding modules in controlling root hair growth. Thus, the findings that CIPK12/19 and CIPK13/18 function in pollen tube and root hair growth, respectively, illustrate a molecular mechanism in which the same CBLs recruit distinct CIPKs in regulating polarized tip growth in different types of plant cells.

CHIP-mediated ubiquitin degradation of BCAT1 regulates glioma cell proliferation and temozolomide sensitivity.

Glioma, a malignant and infiltrative neoplasm of the central nervous system, poses a significant threat due to its high mortality rates. Branched-chain amino acid transaminase 1 (BCAT1), a key enzyme in branched-chain amino acid (BCAA) catabolism, exhibits elevated expression in gliomas and correlates strongly with poor prognosis. Nonetheless, the regulatory mechanisms underlying this increased BCAT1 expression remains incompletely understood. In this study, we reveal that ubiquitination at Lys360 facilitates BCAT1 degradation, with low ubiquitination levels contributing to high BCAT1 expression in glioma cells. The Carboxyl terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase, interacts with BCAT1 via its coiled-coil (CC) domain, promoting its K48-linkage ubiquitin degradation through proteasomal pathway. Moreover, CHIP-mediated BCAT1 degradation induces metabolic reprogramming, and impedes glioma cell proliferation and tumor growth both in vitro and in vivo. Furthermore, a positive correlation is observed between low CHIP expression, elevated BCAT1 levels, and unfavorable prognosis among glioma patients. Additionally, we show that the CHIP/BCAT1 axis enhances glioma sensitivity to temozolomide by reducing glutathione (GSH) synthesis and increasing oxidative stress. These findings underscore the critical role of CHIP/BCAT1 axis in glioma cell proliferation and temozolomide sensitivity, highlighting its potential as a diagnostic marker and therapeutic target in glioma treatment.

Site-Selective Synthesis of Bilayer Graphene on Cu Substrates Using Titanium as a Carbon Diffusion Barrier.

Chemical vapor deposition (CVD) is a widely used method for graphene synthesis, but it struggles to produce large-area uniform bilayer graphene (BLG). This study introduces a novel approach to meet the demands of large-scale integrated circuit applications, challenging the conventional reliance on uniform BLG over extensive areas. We developed a unique method involving the direct growth of bilayer graphene arrays (BLGA) on Cu foil substrates using patterned titanium (Ti) as a diffusion barrier. The use of the Ti layer can effectively control carbon atom diffusion through the Cu foil without altering the growth conditions or compromising the graphene quality, thereby showcasing its versatility. The approach allows for targeted BLG growth and achieved a yield of 100% for a 10 × 10 BLG units array. Then a 10 × 10 BLG memristor array was fabricated, and a yield of 96% was achieved. The performances of these devices show good uniformity, evidenced by the set voltages concentrated around 4 V, and a high resistance state (HRS) to low resistance state (LRS) ratio predominantly around 107, reflecting the spatial uniformity of the prepared BLGA. This study provides insight into the BLG growth mechanism and opens new possibilities for BLG-based electronics.

Unique myoglobin adaptation to endothermy and flight since the origin of birds.

Myoglobin (Mb) mediates oxygen diffusion and storage in muscle tissue and thus is important for the energy utilization and activity of animals. Birds generally have a high body temperature, and most species also possess the capability of powered flight. Both of these require high levels of aerobic metabolism. Within endothermic mammals, bats also independently evolved flight. Although the functional evolution of myoglobins in deep-diving amniote vertebrates has been well-studied, the functional evolution of myoglobin since the origins of both birds and bats is unclear. Here, with Mb-coding sequences from >200 extant amniote species, we reconstructed ancestral sequences to estimate the functional properties of myoglobin through amniote evolution. A dramatic change in net surface charge on myoglobin occurred during the origin of Aves, which might have been driven by positively selected amino acid substitutions that occurred on the lineage leading to all birds. However, in bats, no change in net surface charge occurred and instead, the Mb genes show evidence of strong purifying selection. The increased net surface charge on bird myoglobins implies an adaptation to flight-related endothermic and higher body temperatures, possibly by reducing harmful protein aggregations. Different from the findings of net surface charge, myoglobins of extant birds show lower stability compared with other amniotes, which probably accelerates the rate of oxygen utilization in muscles. In bats and other mammals, higher stability of Mb may be an alternative pathway for adaptation to endothermy, indicating divergent evolution of myoglobin in birds and bats.

ESMSec: Prediction of Secreted Proteins in Human Body Fluids Using Protein Language Models and Attention.

The secreted proteins of human body fluid have the potential to be used as biomarkers for diseases. These biomarkers can be used for early diagnosis and risk prediction of diseases, so the study of secreted proteins of human body fluid has great application value. In recent years, the deep-learning-based transformer language model has transferred from the field of natural language processing (NLP) to the field of proteomics, leading to the development of protein language models (PLMs) for protein sequence representation. Here, we propose a deep learning framework called ESM Predict Secreted Proteins (ESMSec) to predict three types of proteins secreted in human body fluid. The ESMSec is based on the ESM2 model and attention architecture. Specifically, the protein sequence data are firstly put into the ESM2 model to extract the feature information from the last hidden layer, and all the input proteins are encoded into a fixed 1000 × 480 matrix. Secondly, multi-head attention with a fully connected neural network is employed as the classifier to perform binary classification according to whether they are secreted into each body fluid. Our experiment utilized three human body fluids that are important and ubiquitous markers. Experimental results show that ESMSec achieved average accuracy of 0.8486, 0.8358, and 0.8325 on the testing datasets for plasma, cerebrospinal fluid (CSF), and seminal fluid, which on average outperform the state-of-the-art (SOTA) methods. The outstanding performance results of ESMSec demonstrate that the ESM can improve the prediction performance of the model and has great potential to screen the secretion information of human body fluid proteins.

An antifouling supramolecular polymer ophthalmic ointment alleviates symblepharon in rat alkali burn eyes.

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.