Atto-Scale Noise Near-Infrared Organic Photodetectors Enabled by Controlling Interfacial Energetic Offset through Enhanced Anchoring Ability.

The near-infrared (NIR) sensor technology is crucial for various applications such as autonomous driving and biometric tracking. Silicon photodetectors (SiPDs) are widely used in NIR applications; however, their scalability is limited by their crystalline properties. Organic photodetectors (OPDs) have attracted attention for NIR applications owing to their scalability, low-temperature processing, and notably low dark current density (JD), which is similar to that of SiPDs. However, the still high JD (at NIR band) and few measurements of noise equivalent powers (NEPs) pose challenges for accurate performance comparisons. This study addresses these issues by quantitatively characterizing the performance matrix and JD generation mechanism using electron-blocking layers (EBLs) in OPDs. The energy offset at an EBL/photosensitive layer interface determines the thermal activation energy and directly affects JD. A newly synthesized EBL (3PAFBr) substantially enhances the interfacial energy barrier by forming a homogeneous contact owing to the improved anchoring ability of 3PAFBr. As a result, the OPD with 3PAFBr yields a noise current of 852 aA (JD = 12.3 fA cm⁻2 at V → -0.1 V) and several femtowatt-scale NEPs. As far as it is known, this is an ultralow of JD in NIR OPDs. This emphasizes the necessity for quantitative performance characterization.

Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications.

BACKGROUND: Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging. METHODS: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations. RESULTS: scRNA-seq analysis revealed that even a small proportion (22%) of basal-like malignant ductal cells could lead to poor chemotherapy response and patient survival and that epithelial-mesenchymal transition programs were largely subtype-specific. The clonal homogeneity significantly increased with more prevalent and pronounced copy number gains of oncogenes, such as KRAS and ETV1, and losses of tumor suppressor genes, such as SMAD2 and MAP2K4, along PDAC progression and metastasis. Moreover, diverse immune cell populations, including naïve SELLhi regulatory T cells (Tregs) and activated TIGIThi Tregs, contributed to shaping immunosuppressive TMEs of PDAC through cellular interactions with malignant ductal cells in PDAC evolution. Importantly, the proportion of basal-like ductal cells negatively correlated with that of immunoreactive cell populations, such as cytotoxic T cells, but positively correlated with that of immunosuppressive cell populations, such as Tregs. CONCLUSION: We uncover that the proportion of basal-like subtype is a key determinant for chemotherapy response and patient outcome, and that PDAC clonally evolves with subtype-specific dosage changes of cancer-associated genes by forming immunosuppressive microenvironments in its progression and metastasis.

Development of new hormonal male contraception for the couple.

BACKGROUND: Current options for male contraception are limited to condoms, the withdrawal method, or a vasectomy. Studies indicate that men have expressed growing interest in bearing responsibility for family planning. OBJECTIVES: To review prior studies investigating the role of an androgen-only or androgen with progestin regimen for hormonal male contraception and to provide an update of a promising new hormonal agent, a transdermal gel. DISCUSSION: Thus far, there have been six studies conducted in couples evaluating the contraceptive efficacy of an androgen-only or androgen co-administered with a progestin regimen for hormonal male contraception. The only ongoing study is by the National Institute of Child Health and Human Development, in collaboration with the Population Council. They have developed a novel transdermal gel containing testosterone and segesterone acetate (Nestorone), a progestin. An ongoing phase II study enrolling more than 460 couples has shown great potential with respect to the product's efficacy, safety, reversibility, and acceptability. As this agent advances in development, a rapid at-home test for sperm concentration will provide couples with immediate feedback regarding their potential for pregnancy. CONCLUSION: There is promise for the first-of-its-kind hormonal male contraceptive, a transdermal gel, to achieve market approval for distribution in the United States and elsewhere. Its safety, efficacy, reversibility, and user-control are all appealing qualities that make it readily adoptable for clinical practice.

Melatonin alleviates myocardial dysfunction through inhibition of endothelial-to-mesenchymal transition via the NF-κB pathway.

Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.

Evaluating micronized adipose tissue niche and artificial dermis grafts following nonmelanoma skin cancer excision: a pilot study.

BACKGROUND: Recently, micronized adipose tissue (MAT) grafts have shown promising results in wound healing, including diabetic ulcers. OBJECTIVE: To assess the possibility of using 3D printed MAT niche grafts in the management of skin and soft tissue defects resulting from non-melanoma skin cancer (NMSC) resections. MATERIALS AND METHODS: A retrospective feasibility study was conducted on patients with skin and soft tissue defects resulting from NMSC resections. Twenty-one patients were treated using either artificial dermis (n = 11) or MAT niche (n = 10) grafting. Healing time and POSAS scores were compared. The Mann-Whitney U test and the Pearson chi-square test were used in statistical analysis to compare between and within groups based on preoperative and postoperative measurements. RESULTS: Wounds in the MAT niche group reepithelialized significantly faster than those in the artificial dermis group (mean [SD] 39.2 [11.4] days vs 63.7 [34.8] days; P = .04). In the 21 scar parameters evaluated, the MAT niche group demonstrated significantly superior outcomes in only 2 parameters based on operator assessment scores: relief (mean [SD] 1.6 [0.7] vs 2.2 [0.6]; P = .047) and scar contracture (mean [SD] 1.3 [0.5] vs 2.5 [1.0]; P = .011). CONCLUSION: This study proves the feasibility of exploring the effects of MAT niche grafting following NMSC excision on healing time and specific parameters of scarring, including scar relief and scar contracture.

Remote optogenetic control of the enteric nervous system and brain-gut axis in freely-behaving mice enabled by a wireless, battery-free optoelectronic device.

Wireless activation of the enteric nervous system (ENS) in freely moving animals with implantable optogenetic devices offers a unique and exciting opportunity to selectively control gastrointestinal (GI) transit in vivo, including the gut-brain axis. Programmed delivery of light to targeted locations in the GI-tract, however, poses many challenges not encountered within the central nervous system (CNS). We report here the development of a fully implantable, battery-free wireless device specifically designed for optogenetic control of the GI-tract, capable of generating sufficient light over large areas to robustly activate the ENS, potently inducing colonic motility ex vivo and increased propulsion in vivo. Use in in vivo studies reveals unique stimulation patterns that increase expulsion of colonic content, likely mediated in part by activation of an extrinsic brain-gut motor pathway, via pelvic nerves. This technology overcomes major limitations of conventional wireless optogenetic hardware designed for the CNS, providing targeted control of specific neurochemical classes of neurons in the ENS and brain-gut axis, for direct modulation of GI-transit and associated behaviours in freely moving animals.

Tofacitinib to prevent anti-drug antibody formation against LMB-100 immunotoxin in patients with advanced mesothelin-expressing cancers.

Background: LMB-100 is a mesothelin (MSLN)-targeting recombinant immunotoxin (iTox) carrying a Pseudomonas exotoxin A payload that has shown promise against solid tumors, however, efficacy is limited by the development of neutralizing anti-drug antibodies (ADAs). Tofacitinib is an oral Janus Kinase (JAK) inhibitor that prevented ADA formation against iTox in preclinical studies. Methods: A phase 1 trial testing LMB-100 and tofacitinib in patients with MSLN-expressing cancers (pancreatic adenocarcinoma, n=13; cholangiocarcinoma, n=1; appendiceal carcinoma, n=1; cystadenocarcinoma, n=1) was performed to assess safety and to determine if tofacitinib impacted ADA formation. Participants were treated for up to 3 cycles with LMB-100 as a 30-minute infusion on days 4, 6, and 8 at two dose levels (100 and 140 µg/kg) while oral tofacitinib was administered for the first 10 days of the cycle (10 mg BID). Peripheral blood was collected for analysis of ADA levels, serum cytokines and circulating immune subsets. Results: The study was closed early due to occurrence of drug-induced pericarditis in 2 patients. Pericarditis with the combination was not reproducible in a transgenic murine model containing human MSLN. Two of 4 patients receiving all 3 cycles of treatment maintained effective LMB-100 levels, an unusual occurrence. Sustained increases in systemic IL-10 and TNF-α were seen, a phenomenon not observed in prior LMB-100 studies. A decrease in activated T cell subsets and an increase in circulating immunosuppressive myeloid populations occurred. No radiologic decreases in tumor volume were observed. Discussion: Further testing of tofacitinib to prevent ADA formation is recommended in applicable non-malignant disease settings. Clinical trial registration: https://www.clinicaltrials.gov/study/NCT04034238.

Assessing the suitability of artificial intelligence-based chatbots as counseling agents for brain tumor patients: A comprehensive survey analysis.

The internet, particularly social media, has become a popular resource for learning about health and investigating one's own health conditions. The development of AI chatbots has been fueled by the increasing availability of digital health data and advances in natural language processing techniques. While these chatbots are more accessible than before, they sometimes fail to provide accurate information. We used representative chatbots currently available (ChatGPT-3.5, Bing Chat, and Google Bard) to answer questions commonly asked by brain tumor patients. The simulated situations with questions were made and selected by the brain tumor committee. These questions are commonly asked by brain tumor patients. The goal of the study was introduced to each chatbot, the situation was explained, and questions were asked. All responses were collected without modification. The answers were shown to the committee members, and they were asked to judge the responses while blinded to the type of chatbot. There was no significant difference in accuracy and communication ability among the three groups (p=0.253, 0.090, respectively). For empathy, Bing Chat and Google Bard were superior to ChatGPT (p=0.004, 0.002, respectively). The purpose of this study was not to assess or verify the relative superiority of each chatbot. Instead, the aim was to identify the shortcomings and changes needed if AI chatbots are to be used for patient medical purposes. AI-based chatbots are a convenient way for patients and the general public to access medical information. Under such circumstances, medical professionals must ensure that the information provided to chatbot users is accurate and safe.

Total Iodine Quantification and In Vitro Bioavailability Study in Abalone (Haliotis discus hannai) Using Inductively Coupled Plasma Mass Spectrometry.

The aim of this study is to determine the total iodine content in Korean abalone (Haliotis discus hannai) and to investigate the bioavailability of iodine using an in vitro method. This research paper focuses on total iodine quantification in abalone (Haliotis discus hannai) and its components (viscera and muscle) using inductively coupled plasma mass spectrometry (ICP-MS). Additionally, an in vitro bioavailability study explored iodine absorption potential. Abalone pretreatment involved both the European standard method (ES) and microwave-assisted extraction method (MAE). The limits of detection (LOD) were 0.11 ng/g for both ES and MAE, with a limit of quantification (LOQ) of 5.4 ng/g for MAE. Accuracy, assessed using a reference material (fish muscle, ERM-BB422), showed values of 1.5 ± 0.010 mg/kg for ES and 1.6 ± 0.066 mg/kg for MAE, within an acceptable range of 1.4 ± 0.42 mg/kg. Precision, evaluated using the Horwitz ratio (HorRat) with a reference material, was determined to be 0.45 for ES and 0.27 for MAE. Therefore, total iodine contents were estimated as 74 ± 2.2 µg/g for abalone viscera and 17 ± 0.77 µg/g for abalone muscle with ES, and 76 ± 1.0 µg/g for abalone viscera and 17 ± 0.51 µg/g for abalone muscle with MAE. Recovery tests demonstrated an acceptable range of 90-110%. In the in vitro bioavailability assessment, digestion efficiency yielded ranges of 42-50.2% for viscera and 67-115% for muscle. Absorption efficiency variations were determined as 37-43% for viscera and 48-75% for muscle.

Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors.

Central nervous system (CNS) tumors are the leading cause of pediatric cancer death, and these patients have an increased risk for developing secondary neoplasms. Due to the low prevalence of pediatric CNS tumors, major advances in targeted therapies have been lagging compared to other adult tumors. We collect single nuclei RNA-seq data from 84,700 nuclei of 35 pediatric CNS tumors and three non-tumoral pediatric brain tissues and characterize tumor heterogeneity and transcriptomic alterations. We distinguish cell subpopulations associated with specific tumor types including radial glial cells in ependymomas and oligodendrocyte precursor cells in astrocytomas. In tumors, we observe pathways important in neural stem cell-like populations, a cell type previously associated with therapy resistance. Lastly, we identify transcriptomic alterations among pediatric CNS tumor types compared to non-tumor tissues, while accounting for cell type effects on gene expression. Our results suggest potential tumor type and cell type-specific targets for pediatric CNS tumor treatment. Here we address current gaps in understanding single nuclei gene expression profiles of previously under-investigated tumor types and enhance current knowledge of gene expression profiles of single cells of various pediatric CNS tumors.

Associations in cell type-specific hydroxymethylation and transcriptional alterations of pediatric central nervous system tumors.

Although intratumoral heterogeneity has been established in pediatric central nervous system tumors, epigenomic alterations at the cell type level have largely remained unresolved. To identify cell type-specific alterations to cytosine modifications in pediatric central nervous system tumors, we utilize a multi-omic approach that integrated bulk DNA cytosine modification data (methylation and hydroxymethylation) with both bulk and single-cell RNA-sequencing data. We demonstrate a large reduction in the scope of significantly differentially modified cytosines in tumors when accounting for tumor cell type composition. In the progenitor-like cell types of tumors, we identify a preponderance differential Cytosine-phosphate-Guanine site hydroxymethylation rather than methylation. Genes with differential hydroxymethylation, like histone deacetylase 4 and insulin-like growth factor 1 receptor, are associated with cell type-specific changes in gene expression in tumors. Our results highlight the importance of epigenomic alterations in the progenitor-like cell types and its role in cell type-specific transcriptional regulation in pediatric central nervous system tumors.

Black Phosphorus-Based Dynamic Self-Healing Hydrogel to Integrate Demineralized Bone Matrix and Noggin-Targeting siRNA for Synergistic Osteogenesis.

Although a demineralized bone matrix (DBM) is often used as an alternative to an autologous bone graft, its clinical application is still hampered by easy dispersion of DBM particles and insufficient osteoinductivity in the defect site. Herein, we designed a self-healing hydrogel for DBM that can rapidly restore its structural integrity after damage based on amino-rich black phosphorus (BP) nanosheets and aldehyde-functionalized hyaluronic acid (AHA). Given the increased expression of bone morphogenetic protein (BMP) antagonists by DBM stimulation, the osteogenic potency of DBM in the hydrogel carrier was further enhanced by abrogating the BMP antagonism. The BP/AHA hydrogel provided dynamic polymer-nanosheet networks that combine injectability, modability, and physical stability with high DBM loading, where the BP nanosheets served as osteogenic cross-linkers to promote biomineralization and deliver siRNA to suppress undesirable expression of BMP antagonist noggin by DBM. As a result, the BP/AHA hydrogel integrated with DBM and noggin-targeting siRNA synergistically promoted osteogenic differentiation of mesenchymal stem cells by enhancing BMP/Smad signaling. This work demonstrates a promising strategy to improve the efficacy of bone regeneration using bone graft.

Bone-Targeted Supramolecular Nanoagonist Assembled by Accurate Ratiometric Herbal-Derived Therapeutics for Osteoporosis Reversal.

Developing novel strategies for defeating osteoporosis has become a world-wide challenge with the aging of the population. In this work, novel supramolecular nanoagonists (NAs), constructed from alkaloids and phenolic acids, emerge as a carrier-free nanotherapy for efficacious osteoporosis treatment. These precision nanoagonists are formed through the self-assembly of berberine (BER) and chlorogenic acid (CGA), utilizing noncovalent electrostatic, π-π, and hydrophobic interactions. This assembly results in a 100% drug loading capacity and stable nanostructure. Furthermore, the resulting weights and proportions of CGA and BER within the NAs are meticulously controlled with strong consistency when the CGA/BER assembly feed ratio is altered from 1:1 to 1:4. As anticipated, our NAs themselves could passively target osteoporotic bone tissues following prolonged blood circulation, modulate Wnt signaling, regulate osteogenic differentiation, and ameliorate bone loss in ovariectomy-induced osteoporotic mice. We hope this work will open a new strategy to design efficient herbal-derived Wnt NAs for dealing with intractable osteoporosis.

Medical Ethics and Artificial Intelligence in Neurosurgery-How Should We Prepare?

BACKGROUND: The development of artificial intelligence (AI) raises ethical concerns about its side effects on the attitudes and behaviors of clinicians and medical practitioners. The authors aim to understand the medical ethics of AI-based chatbots and to suggest coping strategies for an emerging landscape of increased access and potential ambiguity using AI. METHODS: This study examines the medical ethics of AI-based chatbots (Chat generative pretrained transformer [GPT], Bing Chat, and Google's Bard) using multiple-choice questions. ChatGPT and Bard correctly answered all questions (5/5), while Bing Chat correctly answered only 3 of 5 questions. ChatGPT explained answers simply. Bing Chat explained answers with references, and Bard provided additional explanations with details. RESULTS: AI has the potential to revolutionize medical fields by improving diagnosis accuracy, surgical planning, and treatment outcomes. By analyzing large amounts of data, AI can identify patterns and make predictions, aiding neurosurgeons in making informed decisions for increased patient wellbeing. As AI usage increases, the number of cases involving AI-entrusted judgments will rise, leading to the gradual emergence of ethical issues across interdisciplinary fields. The medical field will be no exception. CONCLUSIONS: This study suggests the need for safety measures to regulate medical ethics in the context of advancing AI. A system should be developed to verify and predict pertinent issues.

Identification and validation of PCDHGA12 and PRRX1 methylation for detecting lung cancer in bronchial washing sample.

Bronchoscopy is a frequently used initial diagnostic procedure for patients with suspected lung cancer (LC). Cytological examinations of bronchial washing (BW) samples obtained during bronchoscopy often yield inconclusive results regarding LC diagnosis. The present study aimed to identify molecular biomarkers as a non-invasive method for LC diagnosis. Aberrant DNA methylation is used as a useful biomarker for LC. Therefore, microarray-based methylation profiling analyses on 13 patient-matched tumor tissues at stages I-III vs. non-tumor tissues were performed, and a group of highly differentially methylated genes was identified. A subsequent analysis using bisulfite-pyrosequencing with additional tissues and cell lines revealed six methylated genes [ADAM metallopeptidase with thrombospondin type 1 motif 20, forkhead box C2 (mesenchyme forkhead 1), NK2 transcription factor related, locus 5 (Drosophila), oligodendrocyte transcription factor 3, protocadherin γ subfamily A 12 (PCDHGA12) and paired related homeobox 1 (PRRX1)] associated with LC. Next, a highly sensitive and accurate detection method, linear target enrichment-quantitative methylation-specific PCR in a single closed tube, was applied for clinical validation using BW samples from patients with LC (n=68) and individuals with benign diseases (n=33). PCDHGA12 and PRRX1 methylation were identified as the best-performing biomarkers to detect LC. The two-marker combination showed a sensitivity of 82.4% and a specificity of 87.9%, with an area under the curve of 0.891. Notably, the sensitivity for small cell LC was 100%. The two-marker combination had a positive predictive value of 93.3% and a negative predictive value of 70.7%. The sensitivity was higher than that of cytology, which only had a sensitivity of 50%. The methylation status of the two-marker combination showed no association with sex, age or stage, but was associated with tumor location and histology. In conclusion, the present study showed that the regulatory regions of PCDHGA12 and PRRX1 are highly methylated in LC and can be used to detect LC in BW specimens as a diagnostic adjunct to cytology in clinical practice.

Floating electrode-dielectric barrier discharge-based plasma promotes skin regeneration in a full-thickness skin defect mouse model.

Wound healing involves a complex and dynamic interplay among various cell types, cytokines, and growth factors. Macrophages and transforming growth factor-ß1 (TGF-ß1) play an essential role in different phases of wound healing. Cold atmospheric plasma has a wide range of applications in the treatment of chronic wounds. Hence, we aimed to investigate the safety and efficacy of a custom-made plasma device in a full-thickness skin defect mouse model. Here, we investigated the wound tissue on days 6 and 12 using histology, qPCR, and western blotting. During the inflammation phase of wound repair, macrophages play an important role in the onset and resolution of inflammation, showing decreased F4/80 on day 6 of plasma treatment and increased TGF-ß1 levels. The plasma-treated group showed better epidermal epithelialization, dermal fibrosis, collagen maturation, and reduced inflammation than the control group. Our findings revealed that floating electrode-dielectric barrier discharge (FE-DBD)-based atmospheric-pressure plasma promoted significantly faster wound healing in the plasma-treated group than that in the control group with untreated wounds. Hence, plasma treatment accelerated wound healing processes without noticeable side effects and suppressed pro-inflammatory genes, suggesting that FE-DBD-based plasma could be a potential therapeutic option for treating various wounds.

Atypical Gradenigo's syndrome in a pediatric case: A critical review of neuroimaging.

Gradenigo's syndrome, a rare but serious complication of otitis media, encompasses a triad of symptoms including otalgia, facial palsy, and abducens nerve palsy, pointing to the involvement of the petrous apex. This case report presents an 11-year-old boy with an atypical manifestation of Gradenigo's syndrome, characterized by the absence of classic features such as abducens nerve palsy and purulent otorrhea. MRI findings were significant for petrous apicitis extending to Meckel's cave and the cavernous sinus, along with abscess formation and clivus osteomyelitis. The report highlights the critical role of advanced neuroimaging, particularly MRI, in the diagnosis and management of this condition. It underscores the importance of recognizing atypical presentations of Gradenigo's syndrome and the effectiveness of imaging-guided conservative treatment strategies in pediatric otological cases.

Predicting the wicking rate of nitrocellulose membranes from recipe data: a case study using ANN at a membrane manufacturing in South Korea.

Lateral flow assays have been widely used for detecting coronavirus disease 2019 (COVID-19). A lateral flow assay consists of a Nitrocellulose (NC) membrane, which must have a specific lateral flow rate for the proteins to react. The wicking rate is conventionally used as a method to assess the lateral flow in membranes. We used multiple regression and artificial neural networks (ANN) to predict the wicking rate of NC membranes based on membrane recipe data. The developed ANN predicted the wicking rate with a mean square error of 0.059, whereas the multiple regression had a square error of 0.503. This research also highlighted the significant impact of the water content on the wicking rate through images obtained from scanning electron microscopy. The findings of this research can cut down the research and development costs of novel NC membranes with a specific wicking rate significantly, as the algorithm can predict the wicking rate based on the membrane recipe.

Relationship between sensory attributes and instrumental texture properties in meat analog patty system substituted with sweet potato stem.

BACKGROUND: Understanding the relationship between perceived sensory attributes and measurable instrumental properties is crucial for replicating the distinct textures of meat in plant-based meat analogs. In this study, plant-based patties composed of textured vegetable protein (TVP) and 10%, 20% and 30% TVPs were substituted with fibers from sweet potato stem (SPS), and their instrumental texture and sensory properties were evaluated. RESULTS: Samples with 20% SPS showed hardness, cohesiveness and chewiness, which are the mechanical indicators most similar to those of meat. A descriptive sensory analysis by ten trained participants indicated that the SPS-supplemented meat analog patties exhibited characteristics similar to pork patties in terms of firmness, toughness, cohesiveness and smoothness compared to the TVP-only sample. A strong positive correlation between instrumental hardness and sensory firmness was observed (P < 0.01); however, cohesiveness, springiness and chewiness did not show any correlation between instrumental and sensory analyses. Warner-Bratzler shear force (WBSF) values showed positive correlations with sensory cohesiveness, chewiness, toughness, fibrousness, moistness, firmness and springiness (P < 0.05). CONCLUSION: The results demonstrated the feasibility of physically treated fibers from SPS as a partial substitute for TVP in developing meat analogs. Additionally, this study suggested that instrumental hardness and WBSF measurements can be sound parameters for representing sensory texture characteristics while further developing plant-based meat analogs. © 2024 Society of Chemical Industry.

Impact of Apolipoprotein E4 on the Locus Coeruleus Functional Connectivity in Preclinical Alzheimer's Disease.

Background: Recent interest has surged in the locus coeruleus (LC) for its early involvement in Alzheimer's disease (AD), notably concerning the apolipoprotein ɛ4 allele (APOE4). Objective: This study aimed to discern LC functional connectivity (FC) variations in preclinical AD subjects, dissecting the roles of APOE4 carrier status and amyloid-ß (Aß) deposition. Methods: A cohort of 112 cognitively intact individuals, all Aß-positive, split into 70 APOE4 noncarriers and 42 carriers, underwent functional MRI scans, neuropsychological assessments, and APOE genotyping. The research utilized seed to voxel analysis for illustrating LC rsFC discrepancies between APOE4 statuses and employed a general linear model to examine the interactive influence of APOE4 carrier status and Aß deposition on LC FC values. Results: The investigation revealed no significant differences in sex, age, or SUVR between APOE4 carriers and noncarriers. It found diminished LC FC with the occipital cortex in APOE4 carriers and identified a significant interaction between APOE4 carrier status and temporal lobe SUVR in LC FC with the occipital cortex. This interaction suggested a proportional increase in LC FC for APOE4 carriers. Additional notable interactions were observed affecting LC FC with various brain regions, indicating a proportional decrease in LC FC for APOE4 carriers. Conclusions: These findings confirm that APOE4 carrier status significantly influences LC FC in preclinical AD, showcasing an intricate relationship with regional Aß deposition. This underscores the critical role of genetic and pathological factors in early AD pathophysiology, offering insights into potential biomarkers for early detection and intervention strategies.