SPMLD: A skin pathological image dataset for non-melanoma with detailed lesion area annotation.

Skin tumors are the most common tumors in humans and the clinical characteristics of three common non-melanoma tumors (IDN, SK, BCC) are similar, resulting in a high misdiagnosis rate. The accurate differential diagnosis of these tumors needs to be judged based on pathological images. However, a shortage of experienced dermatological pathologists leads to bias in the diagnostic accuracy of these skin tumors in China. In this paper, we establish a skin pathological image dataset, SPMLD, for three non-melanoma to achieve automatic and accurate intelligent identification for them. Meanwhile, we propose a lesion-area-based enhanced classification network with the KLS module and an attention module. Specifically, we first collect thousands of H&E-stained tissue sections from patients with clinically and pathologically confirmed IDN, SK, and BCC from a single-center hospital. Then, we scan them to construct a pathological image dataset of these three skin tumors. Furthermore, we mark the complete lesion area of the entire pathology image to better learn the pathologist's diagnosis process. In addition, we applied the proposed network for lesion classification prediction on the SPMLD dataset. Finally, we conduct a series of experiments to demonstrate that this annotation and our network can effectively improve the classification results of various networks. The source dataset and code are available at https://github.com/efss24/SPMLD.git.

Altered Brain Glymphatic Function at Diffusion-Tensor MRI in Pre-cirrhotic Metabolic Dysfunction-Associated Fatty Liver Disease.

RATIONALE AND OBJECTIVES: To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. MATERIALS AND METHODS: A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. RESULTS: MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = -0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = -0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (-23.853 [-45.417, -2.289], P = 0.030) in MAFLD with MetS group. CONCLUSION: MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS.

The preparation of edible water-soluble films comprising κ-carrageenan/carboxymethyl starch/gum ghatti and their application in instant coffee powder packaging.

This study successfully prepared an edible packaging film that rapidly dissolves in water by utilizing a combination of κ-carrageenan, carboxymethyl starch, and gum ghatti. We investigated the influence of these three materials on the microstructure and physical properties of the film, as well as the impact of the film's dissolution on the stability of beverages. SEM, FTIR, and XRD analyses revealed that the κ-carrageenan, carboxymethyl starch, and gum ghatti primarily interacted through hydrogen bonding, resulting in a more uniform and dense film structure. Surface hydrophilicity and swelling tests indicated an increased presence of hydrophilic groups in the composite film. The inclusion of carboxymethyl starch and gum ghatti significantly improves the film's physical properties, resulting in a notable reduction in water solubility time, an increase in elongation at break from 19.5 % to 26.0 %, a rise in the contact angle from 49.1° to 67.0°, and a decrease in water vapor permeability from 7.5 × 10-10 to 6.2 × 10-10 g/m·s·Pa. Furthermore, coffee packaging bags made from this composite film dissolved entirely in hot water in just 40 s. Dissolving these bags significantly improved the stability of instant coffee, reducing centrifugal sedimentation from 3.8 % to 1.7 %. This study highlights the substantial potential of the κ-carrageenan/carboxymethyl starch/gum ghatti composite film as a packaging material for solid beverages.

Is conventional functional liver remnant volume higher than 40% still sufficient to prevent post-hepatectomy liver failure in jaundiced patients with hilar cholangiocarcinoma? A single-center experience in China.

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.

Superlong Metal-organic Framework Nanowire Fabricated via Steam-assisted Conversion.

1D nanomaterials have attracted great attention due to their outstanding anisotropic and linear structures. A facile method is developed to fabricate 1D copper metal-organic framework nanowires (Cu-MOF-NW) through steam-assisted conversion from Cu-MOF precursors. During the steam-assisted conversion, Cu-MOF precursor gradually dissolves in methanol steam, and then recrystallized into Cu-MOF-NW, which shows high aspect ratio of about 600 and identical crystal structure of MOF-74. As-prepared Cu-MOF-NW with multiscale porous structure can effectively remove cationic dyes even in dye mixture. Moreover, Cu-MOF-NW, as an ideal template, is calcined to form Cu nanoparticle-doped carbon nanofiber with maintaining its 1D morphology, which shows excellent electrocatalytic activity for the non-enzymatic sensing of glucose.

The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction.

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.

Structural basis for transcription activation through cooperative recruitment of MntR.

The manganese transport regulator (MntR) from B. subtilis is a dual regulatory protein that responds to heightened Mn 2+ availability in the cell by both repressing the expression of uptake transporters and activating the expression of efflux proteins. Recent work indicates that, in its role as an activator, MntR binds several sites upstream of the genes encoding Mn 2+ exporters, leading to a cooperative response to manganese. Here, we use cryo-EM to explore the molecular basis of gene activation by MntR and report a structure of four MntR dimers bound to four 18-base pair sites across an 84-base pair regulatory region of the mneP promoter. Our structures, along with solution studies including mass photometry and in vivo transcription assays, reveal that MntR dimers employ polar and non-polar contacts to bind cooperatively to an array of low-affinity DNA-binding sites. These results reveal the molecular basis for cooperativity in the activation of manganese efflux.

Environmental exposure patterns to 94 current-use pesticides in women of reproductive age who are preparing for pregnancy.

Current-use pesticides (CUPs), including insecticides, fungicides, and herbicides, are extensively employed in agriculture to manage pests, diseases, and weeds. Nonetheless, their widespread application raises significant concerns regarding potential impacts on human health, particularly with reproductive health. This study focuses on exploring the landscape of CUP exposure among pre-pregnancy women. Based on a cohort study comprising 354 pre-pregnancy women of reproductive age in Beijing, China, we measured the concentrations of 94 CUPs in serum and conducted an in-depth analysis of exposure profiles, health risks, and contributing factors. The results revealed that the serum of pre-pregnancy women was contaminated with CUPs, of which the median concentrations ranged from 0.114 (fenamiphos-sulfone) to 61.2 ng/L (mefenacet). Among the 94 CUPs, 54 exhibited detection rates higher than 50 %, including 26 insecticides, 14 fungicides, and 14 herbicides. The exposure concentration profile highlighted that the insecticides contributed 56 % to the total CUP concentration percentages, with organophosphate insecticides being the primary contributors within this category (63.0 %). The average daily intake (ADI) of CUPs ranged from 2.23 to 16,432.28 ng/kg, while diflubenzuron had the highest ADI. Health risk assessments showed that exposure to a combination of total insecticides or herbicides poses a moderate risk for 15.8 % and 30.2 % of women, with mefenacet being the most significant, which showed moderate hazard in 29.4 % of participants. The overlap analysis showed that methiocarb-sulfone, diflubenzuron, and mefenacet were the dominant pesticides. In addition, maternal age, annual income level, smoking, and vitamin B12 supplementation were associated with serum CUP concentrations. Our study contributes a novel and comprehensive exposure profile of CUPs in pre-pregnancy women in northern China, providing valuable insights for evaluating the potential consequences of pre-pregnancy exposure on reproductive health. SYNOPSIS: We provided a comprehensive exposure landscape, health effects, and influential factors of 94 current-use pesticides among pre-pregnancy women in China.

Impaired autophagy-mediated macrophage polarization contributes to age-related hyposalivation.

Age-related dysfunction of salivary glands (SGs) leading to xerostomia or dry mouth is typically associated with increased dental caries and difficulties in mastication, deglutition or speech. Inflammaging-induced hyposalivation plays a significant role in aged SGs; however, the mechanisms by which ageing shapes the inflammatory microenvironment of SGs remain unclear. Here, we show that reduced salivary secretion flow rate in aged human and mice SGs is associated with impaired autophagy and increased M1 polarization of macrophages. Our study reveals the crucial roles of SIRT6 in regulating macrophage autophagy and polarization through the PI3K/AKT/mTOR pathway, as demonstrated by generating two conditional knock out mice. Furthermore, triptolide (TP) effectively rejuvenates macrophage autophagy and polarization via targeting this pathway. We also design a local delivery of TP-loaded apoptotic extracellular vesicles (ApoEVs) to improve age-related SGs dysfunction therapeutically. Collectively, our findings uncover a previously unknown link between SIRT6-regulated autophagy and macrophage polarization in age-mediated hyposalivation, while our locally therapeutic strategy exhibits potential preventive effects for age-related hyposalivation.

Renal denervation alleviates vascular remodeling in spontaneously hypertensive rats by regulating perivascular adipose tissue.

Vascular remodeling is the main pathological process that causes the damage of the target organ of hypertension. Perivascular adipose tissue (PVAT) surrounds blood vessels and plays a key role in the pathogenesis of various cardiovascular diseases. This study aimed to investigate the effects of renal denervation (RDN) on hypertensive vascular remodeling and to elucidate the role of PVAT in this process. Male spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat were selected. Aortic vascular remodeling was evaluated using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Morphological changes in the PVAT were observed through H&E and Oil Red O staining. Dihydroethidium was used to measure oxidative stress levels in PVAT, while western blot analysis was used to determine the expression levels of proteins associated with vascular remodeling. The results showed that the aortic medial thickness, media thickness/lumen diameter, collagen volume fraction, and reactive oxygen species (ROS) level in PVAT were significantly higher in the SHR group than in the WKY group. The indexes mentioned above were lower in the SHR-RDN group than in the SHR group. H&E staining revealed that fat droplets in PVAT in the SHR-RDN group became smaller and browning occurred. Moreover, the protein expression of uncoupling protein-1 (UCP-1) and neuregulin 4 (Nrg4) was significantly increased in the SHR-RDN group. In addition, the expression of adiponectin increased and the expression of leptin decreased in the SHR-RDN group compared to the SHR group. In conclusion, RDN can relieve hypertensive vascular remodeling, which may be associated with PVAT.

Identification of disulfidptosis- and ferroptosis-related transcripts in periodontitis by bioinformatics analysis and experimental validation.

Background: Disulfidptosis and ferroptosis are forms of programmed cell death that may be associated with the pathogenesis of periodontitis. Our study developed periodontitis-associated biomarkers combining disulfidptosis and ferroptosis, which provides a new perspective on the pathogenesis of periodontitis. Methods: Firstly, we obtained the periodontitis dataset from public databases and found disulfidptosis- and ferroptosis-related differentially expressed transcripts based on the disulfidptosis and ferroptosis transcript sets. After that, transcripts that are tissue biomarkers for periodontitis were found using three machine learning methods. We also generated transcript subclusters from two periodontitis microarray datasets: GSE16134 and GSE23586. Furthermore, three transcripts with the best classification efficiency were further screened. Their expression and classification efficacy were validated using qRT-PCR. Finally, periodontal clinical indicators of 32 clinical patients were collected, and the correlation between three transcripts above and periodontal clinical indicators was analyzed. Results: We identified six transcripts that are tissue biomarkers for periodontitis, the top three transcripts with the best classification, and delineated two expression patterns in periodontitis. Conclusions: Our study found that disulfidptosis and ferroptosis were associated with immune responses and may involve periodontitis genesis.

Effect of ultrafine grinding on the structure and physical properties of pregelatinized rice starch.

This study used a combination method of ultrafine grinding and pregelatinization to modify rice starch (RS) to delay its retrogradation and provide a rationale for prolonging rice product shelf life. The structure and physicochemical properties of the pregelatinized ultrafine grinding rice starch (PURS) were compared with those of RS, ultrafine grinding rice starch (URS), and pregelatinized rice starch (PRS). The microstructure, molecular weight, branched starch length distribution, short-range order, crystal structure, and physical properties of RS, URS, PRS, and PURS were analyzed, respectively. Results showed that RS, URS, PRS, and PURS granules exhibited similar spherical or polygonal shapes, and the content of amylose and short-branched starch in PURS increased compared with RS, URS, and PRS. Furthermore, the cross-polarization of PRS and PURS disappeared. Long-chain amylopectin and average molecular weight of PURS decreased significantly after ultrafine grinding. Our study suggested reduced breakdown value and setback value and improved gel stability, and PURS was beneficial for delaying retrogradation compared to RS, URS, and PRS. The ultrafine grinding method improved the water swelling capacity (WSC), solubility, pasting properties, and gelation properties of PRS. The hardness of PURS was reduced by ultrafine grinding. These suggest that the combination of ultrafine grinding and pregelatinization could improve the properties of RS. Pearson's correlation analysis showed that the structure of PURS significantly influenced the physicochemical properties. The present study was helpful in better understanding the importance of ultrafine grinding in improving the anti-retrogradation of PURS and provided new insights into extending the shelf life of rice products by ultrafine grinding and pregelatinization.

Using machine learning to identify environmental factors that collectively determine microbial community structure of activated sludge.

Activated sludge (AS) microbial communities are influenced by various environmental variables. However, a comprehensive analysis of how these variables jointly and nonlinearly shape the AS microbial community remains challenging. In this study, we employed advanced machine learning techniques to elucidate the collective effects of environmental variables on the structure and function of AS microbial communities. Applying Dirichlet multinomial mixtures analysis to 311 global AS samples, we identified four distinct microbial community types (AS-types), each characterized by unique microbial compositions and metabolic profiles. We used 14 classical linear and nonlinear machine learning methods to select a baseline model. The extremely randomized trees demonstrated optimal performance in learning the relationship between environmental factors and AS types (with an accuracy of 71.43%). Feature selection identified critical environmental factors and their importance rankings, including latitude (Lat), longitude (Long), precipitation during sampling (Precip), solids retention time (SRT), effluent total nitrogen (Effluent TN), average temperature during sampling month (Avg Temp), mixed liquor temperature (Mixed Temp), influent biochemical oxygen demand (Influent BOD), and annual precipitation (Annual Precip). Significantly, Lat, Long, Precip, Avg Temp, and Annual Precip, influenced metabolic variations among AS types. These findings emphasize the pivotal role of environmental variables in shaping microbial community structures and enhancing metabolic pathways within activated sludge. Our study encourages the application of machine learning techniques to design artificial activated sludge microbial communities for specific environmental purposes.

[Benefit-risk assessment of three oral Chinese patent medicines for activating blood and eliminating mass in treating primary liver cancer based on network Meta-analysis and multi-criteria decision analysis].

Network Meta-analysis and multi-criteria decision analysis(MCDA) model were performed to evaluate the benefit-risk of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in the adjuvant treatment of primary liver cancer(PLC). The randomized controlled trial(RCT) of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules in treating PLC were retrieved from CNKI, Wanfang, VIP, Web of Science, PubMed, and Cochrane Library. R 4.2 was employed to conduct a network Meta-analysis, on the basis of which the effect values of the three medicines were obtained by indirect comparison. MCDA was performed to establish the value tree based on the benefit-risk indexes. Hiview 3.2 was used to calculate the benefit values, risk values, and benefit-risk values of the three medicines in treating PLC, and a sensitivity analysis was carried out to evaluate the robustness of the results. Oracle Crystal Ball 11.1 was employed to optimize the evaluation results by Monte Carlo simulation. A total of 39 RCTs were included. The results showed that Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules combined with transcatheter arterial chemoembolization(TACE) had the benefit values of 45, 51 and 45, the risk values of 59, 47, and 41, and the benefit-risk values of 52, 49, and 43, respectively. The benefit-risk differences and [95%CI] of Compound Cantharis Capsules vs Huisheng Oral Solution, Compound Cantharis Capsules vs Jinlong Capsules, and Huisheng Oral Solution vs Jinlong Capsules were 3.00[-13.09, 21.82], 9.00[-4.39, 24.62], and 6.00[-8.84, 20.28], respectively. Based on the results of MCDA, Huisheng Oral Solution, Jinlong Capsules, and Compound Cantharis Capsules combined with TACE had the greatest benefit, the greatest risk, and the best overall benefit, respectively. Considering the efficacy and safety, the priority of the three oral Chinese patent medicines combined with TACE for treating PLC followed the trend of Compound Cantharis Capsules, Huisheng Oral Solution, and Jinlong Capsules.

Epigenetic factors direct synergistic and antagonistic regulation of transposable elements in Arabidopsis.

Arabidopsis (Arabidopsis thaliana) HISTONE DEACETYLASE 6 (HDA6) and HISTONE DEMETHYLASES LSD-LIKE 1 (LDL1) and LDL2 synergistically regulate the expression of long non-coding RNAs associated with H3Ac and H3K4me2. The underlying mechanisms of such highly coordinated interactions among genetic and epigenetic factors contributing to this collaborative regulation remain largely unclear. We analyzed all transposable elements (TEs) across the Arabidopsis genome and the individual and combined roles of HDA6 and LDL1/LDL2 by dissecting multi-layered epigenomes and their association with transcription. Instead of an individual synergistic effect, we observed dual synergistic and antagonistic effects, which are positively associated with H3Ac and H3K4me2 while maintaining a negative but moderate association with DNA methylation. Specifically, two modes of synergistic regulation were discovered in TEs: 74% are primarily regulated by HDA6, with less dependence on LDL1/LDL2, and the remaining 26% are co-regulated by both. Between the two modes, we showed that HDA6 has a strong effect on TE silencing, whereas LDL1/LDL2 plays a weaker yet crucial role in co-regulation with HDA6. Our results led to a model of epigenomic regulation - the differential de-repression between the two modes of synergistic regulation of TEs was determined by H3Ac and H3K4me2 levels, where TEs are in accessible chromatins free of DNA methylation, and this open chromatin environment precedes transcriptional changes and epigenome patterning. Our results discovered unbalanced effects of genetic factors in synergistic regulation through delicately coordinated multi-layered epigenomes and chromatin accessibility.

Research progress in the relationship between gut microbiota metabolite trimethylamine N-oxide and ischemic stroke. / è‚ é“èŒç¾¤ä»£è°¢äº§ç‰©æ°§åŒ–ä¸‰ç”²èƒºä¸Žç¼ºè¡€æ€§è„‘å’ä¸­å ³ç³»çš„ç ”ç©¶è¿›å±•.

Ischemic stroke (IS) is a severe cerebrovascular disease that seriously endangers human health. Gut microbiota plays a key role as an intermediate mediator in bidirectional regulation between the brain and the intestine. In recent years, trimethylamine N-oxide (TMAO) as a gut microbiota metabolite has received widespread attention in cardiovascular diseases. Elevated levels of TMAO may increase the risk of IS by affecting IS risk factors such as atherosclerosis, atrial fibrillation, hypertension, and type 2 diabetes. TMAO exacerbates neurological damage in IS patients, increases the risk of IS recurrence, and is an independent predictor of post-stroke cognitive impairment (PSCI) in patients. Current research suggests that the mechanisms of TMAO action include endothelial dysfunction, promoting of foam cell formation, influence on cholesterol metabolism, and enhancement of platelet reactivity. Lowering plasma TMAO levels through the rational use of traditional Chinese medicine, dietary management, vitamins, and probiotics can prevent and treat IS.

pH-Responsive, Wide Color Gamut Dynamic Color Display Enabled by PDMAEMA Brush-Based Fabry-Perot Resonant Cavity.

Dynamic color-changing materials have attracted broad interest due to their widespread applications in visual sensing, dynamic color display, anticounterfeiting, and image encryption/decryption. In this work, we demonstrate a novel pH-responsive dynamic color-changing material based on a metal-insulator-metal (MIM) Fabry-Perot (FP) cavity with a pH-responsive poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) brush layer as the responsive insulating layer. The pH-responsive PDMAEMA brush undergoes protonation at a low pH value (pH < 6), which induces different swelling degrees in response to pH and thus refractive index and thickness change of the insulator layer of the MIM FP cavity. This leads to significant optical property changes in transmission and a distinguishable color change spanning the whole visible region by adjusting the pH value of the external environment. Due to the reversible conformational change of the PDMAEMA and the formation of covalent bonds between the PDMAEMA molecular chain and the Ag substrate, the MIM FP cavity exhibits stable performance and good reproducibility. This pH-responsive MIM FP cavity establishes a new way to modulate transmission color in the full visible region and exhibits a broad prospect of applications in dynamic color display, real-time environment monitoring, and information encryption and decryption.

Genomic profiling of a multi-lineage and multi-passage patient-derived xenograft biobank reflects heterogeneity of ovarian cancer.

Ovarian cancer (OC) manifests as a complex disease characterized by inter- and intra-patient heterogeneity. Despite enhanced biological and genetic insights, OC remains a recalcitrant malignancy with minimal survival improvement. Based on multi-site sampling and a multi-lineage patient-derived xenograft (PDX) establishment strategy, we present herein the establishment of a comprehensive PDX biobank from histologically and molecularly heterogeneous OC patients. Comprehensive profiling of matched PDX and patient samples demonstrates that PDXs closely recapitulate parental tumors. By leveraging multi-lineage models, we reveal that the previously reported genomic disparities of PDX could be mainly attributed to intra-patient spatial heterogeneity instead of substantial model-independent genomic evolution. Moreover, DNA damage response pathway inhibitor (DDRi) screening uncovers heterogeneous responses across models. Prolonged iterative drug exposure recapitulates acquired drug resistance in initially sensitive models. Meanwhile, interrogation of induced drug-resistant (IDR) models reveals that suppressed interferon (IFN) response and activated Wnt/ß-catenin signaling contribute to acquired DDRi drug resistance.

Sex-dependent nonlinear Granger connectivity patterns of brain aging in healthy population.

BACKGROUND: Brain aging is a complex process that involves functional alterations in multiple subnetworks and brain regions. However, most previous studies investigating aging-related functional connectivity (FC) changes using resting-state functional magnetic resonance images (rs-fMRIs) have primarily focused on the linear correlation between brain subnetworks, ignoring the nonlinear casual properties of fMRI signals. METHODS: We introduced the neural Granger causality technique to investigate the sex-dependent nonlinear Granger connectivity (NGC) during aging on a publicly available dataset of 227 healthy participants acquired cross-sectionally in Leipzig, Germany. RESULTS: Our findings indicate that brain aging may cause widespread declines in NGC at both regional and subnetwork scales. These findings exhibit high reproducibility across different network sparsities, demonstrating the efficacy of static and dynamic analysis strategies. Females exhibit greater heterogeneity and reduced stability in NGC compared to males during aging, especially the NGC between the visual network and other subnetworks. Besides, NGC strengths can well reflect the individual cognitive function, which may therefore work as a sensitive metric in cognition-related experiments for individual-scale or group-scale mechanism understanding. CONCLUSION: These findings indicate that NGC analysis is a potent tool for identifying sex-dependent brain aging patterns. Our results offer valuable perspectives that could substantially enhance the understanding of sex differences in neurological diseases in the future, especially in degenerative disorders.

Redox Concomitant Formation Method for Fabrication of Cu(I)-MOF/Polymer Composites with Antifouling Properties.

Marine biofouling, which is one of the technical challenges hindering the growth of the marine economy, has been controlled using cuprous oxide (Cu2O) nanoparticles due to the exceptional antifouling properties of Cu(I) ions. However, Cu2O nanoparticles have encountered bottlenecks due to explosive releases of Cu+ ions, high toxicity at elevated doses, and long-term instability. Here, we present a novel method called Redox Concomitant Formation (RCF) for fabricating a hierarchical Cu(I) metal-organic framework polypyrrole (Cu(I)-MOF/PPy) composite. This method enables in-situ phase transition via successive redox reactions that change the chemical valence state and coordination mode of Cu(II)-MOF, resulting in a new structure of Cu(I)-MOF while creating a PPy layer surrounded by the hierarchical structure. Owing to the steady release of Cu+ ions from the Cu(I) sites and photothermal properties of PPy, Cu(I)-MOF/PPy exhibits superior and broad-spectrum resistance to marine bacteria, algae, and surface-adhered biofilms in complex biological environments, as well as long-term stability, resulting in 100% eradication efficiency under solar-driven heating. Mechanistic insights into successive structural redox reactions and formation using the RCF method are provided in detail, enabling the fabrication of novel MOFs with the desired composition and structure for a wide range of potential applications.