BRD9 promotes the progression of gallbladder cancer via CST1 upregulation and interaction with FOXP1 through the PI3K/AKT pathway and represents a therapeutic target.

Gallbladder cancer (GBC) is highly aggressive and has poor prognosis, with most patients only diagnosed at an advanced stage. Furthermore, treatment options are limited, and their effect is unsatisfactory. Bromodomain-containing protein (BRD) is an epigenetic regulator that plays a carcinogenic role in several tumors, including squamous cell lung cancer, acute myeloid leukemia, synovial sarcoma, and malignant rhabdomyosarcoma. However, the expression, biological function, and molecular mechanisms of action of BRD9 in GBC are still unknown. Kaplan-Meier analysis, qRT-PCR, and analysis of clinical features were used to assess the clinical significance of BRD9 in GBC. Cell Counting Kit-8 and colony formation assays were performed to determine the effects of BRD9 on cell growth. The functional role of BRD9 in GBC was explored using qRT-PCR, western blotting, siRNA, and CHIP-qPCR. mRNA sequencing was performed to explore the underlying mechanisms of BRD9, and a nude mouse model of GBC was established to explore the anti-tumor effects of the BRD9 inhibitor I-BRD9 in vivo. BRD9 expression was elevated in GBC tissues compared with adjacent non-tumor tissues, and high BRD9 expression was associated with poor prognosis in patients with GBC. BRD9 knockdown by siRNA significantly decreased cell growth. Targeting BRD9 with I-BRD9 inhibited the proliferation of GBC cells without significant toxic effects. Additionally, I-BRD9 treatment suppressed CST1 expression in GBC cell lines, thereby inhibiting the PI3K-AKT pathway. The transcription factor FOXP1 was found to interact with BRD9 to regulate CST1 expression. Collectively, these results suggest that BRD9 may be a promising biomarker and therapeutic target for GBC.

DNA-Peptide Interaction-Modulated Charge Reversal in Biomimetic Nanochannels for Simple and Efficient Detection of Histone Deacetylases.

Protein acetylation, a fundamental post-translational modification, plays a critical role in the regulation of gene expression and cellular processes. Monitoring histone deacetylases (HDACs) is important for understanding epigenetic dynamics and advancing the early diagnosis of malignancies. Here, we leverage the dynamic characteristics of DNA-peptide interactions in biomimetic nanochannels to develop a HDAC detection method. In specific, the catalysis of peptide deacetylation by HDACs triggers alterations in the charge states of the nanochannel surface to accommodate DNA molecules. Then, the interaction between DNA and peptides shifts the nanochannel surface charge from positive to negative, leading to a reversal of the ion current rectification (ICR). By calculation of the ICR ratio, quantitative detection of HDACs can be efficiently achieved using the nanochannel-based method in an enzyme-free and label-free manner. Our experimental results demonstrate that HDACs can be detected by using this method within a concentration range of 0.5-500 nM. The innate simplicity and efficiency of this strategy may render it a valuable tool for advancing both fundamental research and clinical applications in the realm of epigenetics and personalized medicine.

ROS-mediated up-regulation of SAE1 by Helicobacter pylori promotes human gastric tumor genesis and progression.

Helicobacter pylori (H. pylori) is a major risk factor of gastric cancer (GC). The SUMO-activating enzyme SAE1(SUMO-activating enzyme subunit 1), which is indispensable for protein SUMOylation, involves in human tumorigenesis. In this study, we used the TIMER and TCGA database to explore the SAE1 expression in GC and normal tissues and Kaplan-Meier Plotter platform for survival analysis of GC patients. GC tissue microarray and gastric samples from patients who underwent endoscopic treatment were employed to detect the SAE1expression. Our results showed that SAE1 was overexpressed in GC tissues and higher SAE1 expression was associated with worse clinical characteristics of GC patients. Cell and animal models showed that H. pylori infection upregulated SAE1, SUMO1, and SUMO2/3 protein expression. Functional assays suggested that suppression of SAE1 attenuated epithelial-mesenchymal transition (EMT) biomarkers and cell proliferation abilities induced by H. pylori. Cell and animal models of ROS inhibition in H. pylori showed that ROS could mediate the H. pylori-induced upregulation of SAE1, SUMO1, and SUMO2/3 protein. RNA sequencing was performed and suggested that knockdown of SAE1 could exert an impact on IGF-1 expression. General, increased SUMOylation modification is involved in H. pylori-induced GC.

Predicting progression to Alzheimer's disease with human hippocampal progenitors exposed to serum.

Adult hippocampal neurogenesis is important for learning and memory and is altered early in Alzheimer's disease. As hippocampal neurogenesis is modulated by the circulatory systemic environment, evaluating a proxy of how hippocampal neurogenesis is affected by the systemic milieu could serve as an early biomarker for Alzheimer's disease progression. Here, we used an in vitro assay to model the impact of systemic environment on hippocampal neurogenesis. A human hippocampal progenitor cell line was treated with longitudinal serum samples from individuals with mild cognitive impairment, who either progressed to Alzheimer's disease or remained cognitively stable. Mild cognitive impairment to Alzheimer's disease progression was characterized most prominently with decreased proliferation, increased cell death and increased neurogenesis. A subset of 'baseline' cellular readouts together with education level were able to predict Alzheimer's disease progression. The assay could provide a powerful platform for early prognosis, monitoring disease progression and further mechanistic studies.

Potential of PAQosome as a therapeutic target for hepatic fibrosis.

BACKGROUND AND AIM: The condition of hepatic fibrosis is hazardous. Therefore, it is vital that we investigate the mechanism of hepatic fibrosis to provide new targets for treatment. METHODS: Preliminary screening and research was carried out based on our prior results and our speculated role of the particle with quaternary structure arrangement (PAQosome) in hepatic fibrosis. The experiments were conducted using LX-2 or HepG2 cell lines by western blotting, quantitative real-time polymerase chain reaction, luciferase assays, and co-immunoprecipitation and were further validated in the Gene Expression Omnibus (GEO) database. RESULTS: We screened and proved that several subunits of the PAQosome regulate the development of liver fibrosis, including the asparagine synthetase domain-containing 1 upstream open reading frame (ASDURF), prefoldin subunit 4 (PFDN4), prefoldin subunit 5 (PFDN5), unconventional prefoldin RNA polymerase II subunit 5 interactor (URI1), and ubiquitously expressed prefoldin-like chaperone (UXT). ASDURF promotes hepatic fibrosis through the transforming growth factor-ß1 (TGFß1)/Sekelsky mothers against decapentaplegic homologue 3 (Smad3) and NF-κB signaling pathways. ASDURF regulates the expression of asparagine synthetase domain-containing 1 (ASNSD1). PFDN4, PFDN5, URI1, and UXT regulate cell proliferation through the PI3K/AKT pathway, and thus regulate liver fibrosis. A hepatic fibrosis score ≥ F2 was selected as the diagnostic criteria for hepatic fibrosis in the GSE96971 database. The area under the receiver operating characteristic curve of PFDN4, PFDN5, UXT, and ASNSD1 were 0.862 (confidence interval [CI]: 0.6588-1.000), 0.538 (CI: 0.224-0.853), 0.708 (CI: 0.449-0.966), and 0.831 (CI: 0.638-1.000), respectively. CONCLUSIONS: These findings demonstrate that the PAQosome is a brand new target for hepatic fibrosis therapy.

Inhibition mechanism of crude lipopeptide from Bacillus subtilis against Aeromonas veronii growth, biofilm formation, and spoilage of channel catfish flesh.

Aeromonas veronii is associated with food spoilage and some human diseases, such as diarrhea, gastroenteritis, hemorrhagic septicemia or asymptomatic and even death. This research investigated the mechanism of the growth, biofilm formation, virulence, stress resistance, and spoilage potential of Bacillus subtilis lipopeptide against Aeromonas veronii. Lipopeptides suppressed the transmembrane transport of Aeromonas veronii by changing the cell membrane's permeability, the structure of membrane proteins, and Na+/K+-ATPase. Lipopeptide significantly reduced the activities of succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) by 86.03% and 56.12%, respectively, ultimately slowing Aeromonas veronii growth. Lipopeptides also restrained biofilm formation by inhibiting Aeromonas veronii motivation and extracellular polysaccharide secretion. Lipopeptides downregulated gene transcriptional levels related to the virulence and stress tolerance of Aeromonas veronii. Furthermore, lipopeptides treatment resulted in a considerable decrease in the extracellular protease activity of Aeromonas veronii, which restrained the decomposing of channel catfish flesh. This research provides new insights into lipopeptides for controlling Aeromonas veronii and improving food safety.

Graphene Oxide-Mediated Regulation of Volume Exclusion and Wettability in Biomimetic Phosphorylation-Responsive Ionic Gates.

Replicating phosphorylation-responsive ionic gates via artificial fluidic systems is essential for biomolecular detection and cellular communication research. However, current approaches to governing the gates primarily rely on volume exclusion or surface charge modulation. To overcome this limitation and enhance ion transport controllability, we introduce graphene oxide (GO) into nanochannel systems, simultaneously regulating the volume exclusion and wettability. Moreover, inspired by (cAMP)-dependent protein kinase A (PKA)-regulated L-type Ca2+ channels, we employ peptides for phosphorylation which preserves them as nanoadhesives to coat nanochannels with GO. The coating boosts steric hindrance and diminishes wettability, creating a substantial ion conduction barrier, which represents a significant advancement in achieving precise ion transport regulation in abiotic nanochannels. Leveraging the mechanism, we also fabricated a sensitive biosensor for PKA activity detection and inhibition exploration. The combined regulation of volume exclusion and wettability offers an appealing strategy for controlled nanofluidic manipulation with promising biomedical applications in diagnosis and drug discovery.

Dislocations deteriorate postoperative functional outcomes in supination-external rotation ankle fractures.

PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18-65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American orthopedic foot and ankle society score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, preoperative complications with diabetes, smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American orthopedic foot and ankle society score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION: Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.

A PCB image segmentation model based on rotational X-ray computed laminography imaging.

BACKGROUND: The rapid development of industrialization in printed circuit board (PCB) warrants more complexity and integrity, which entails an essential procedure of PCB inspection. X-ray computed laminography (CL) enables inspection of arbitrary regions for large-sized flat objects with high resolution. PCB inspection based on CL imaging is worthy of exploration. OBJECTIVE: This work aims to extract PCB circuit layer information based on CL imaging through image segmentation technique. METHODS: In this work, an effective and applicable segmentation model for PCB CL images is established for the first time. The model comprises two components, with one integrating edge diffusion and l0 smoothing to filter CL images with aliasing artifacts, and the other being the fuzzy energy-based active contour model driven by local pre-fitting energy to segment the filtered images. RESULT: The proposed model is able to suppress aliasing artifacts in the PCB CL images and has good performance on images of different circuit layers. CONCLUSIONS: Results of the simulation experiment reveal that the method is capable of accurate segmentation under ideal scanning condition. Testing of different PCBs and comparison of different segmentation methods authenticate the applicability and superiority of the model.

The spatiotemporal matching pattern of Ezrin/Periaxin involved in myoblast differentiation and fusion and Charcot-Marie-Tooth disease-associated muscle atrophy.

BACKGROUND: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells. METHOD: A gastrocnemius muscle atrophy model was prepared to mimic CMT4F and its associated muscle atrophy by mechanical clamping of the peroneal nerve. Differentiating C2C12 myoblast cells were treated with adenovirus-mediated overexpression or knockdown of Ezrin. Then, overexpression of L-periaxin and NFATc1/c2 or knockdown of L-periaxin and NFATc3/c4 mediated by adenovirus vectors were used to confirm their role in Ezrin-mediated myoblast differentiation, myotube formation and gastrocnemius muscle repair in a peroneal nerve injury model. RNA-seq, real-time PCR, immunofluorescence staining and Western blot were used in the above observation. RESULTS: For the first time, instantaneous L-periaxin expression was highest on the 6th day, while Ezrin expression peaked on the 4th day during myoblast differentiation/fusion in vitro. In vivo transduction of adenovirus vectors carrying Ezrin, but not Periaxin, into the gastrocnemius muscle in a peroneal nerve injury model increased the numbers of muscle myosin heavy chain (MyHC) I and II type myofibers, reducing muscle atrophy and fibrosis. Local muscle injection of overexpressed Ezrin combined with incubation of knockdown L-periaxin within the injured peroneal nerve or injection of knockdown L-periaxin into peroneal nerve-injured gastrocnemius muscle not only increased the number of muscle fibers but also recovered their size to a relatively normal level in vivo. Overexpression of Ezrin promoted myoblast differentiation/fusion, inducing increased MyHC-I+ and MyHC-II + muscle fiber specialization, and the specific effects could be enhanced by the addition of adenovirus vectors for knockdown of L-periaxin by shRNA. Overexpression of L-periaxin did not alter the inhibitory effects on myoblast differentiation and fusion mediated by knockdown of Ezrin by shRNA in vitro but decreased myotube length and size. Mechanistically, overexpressing Ezrin did not alter protein kinase A gamma catalytic subunit (PKA-γ cat), protein kinase A I alpha regulatory subunit (PKA reg Iα) or PKA reg Iß levels but increased PKA-α cat and PKA reg II α levels, leading to a decreased ratio of PKA reg I/II. The PKA inhibitor H-89 remarkably abolished the effects of overexpressing-Ezrin on increased myoblast differentiation/fusion. In contrast, knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by an increased PKA reg I/II ratio, and the inhibitory effects could be eliminated by the PKA reg activator N6-Bz-cAMP. Meanwhile, overexpressing Ezrin enhanced type I muscle fiber specialization, accompanied by an increase in NFATc2/c3 levels and a decrease in NFATc1 levels. Furthermore, overexpressing NFATc2 or knocking down NFATc3 reversed the inhibitory effects of Ezrin knockdown on myoblast differentiation/fusion. CONCLUSIONS: The spatiotemporal pattern of Ezrin/Periaxin expression was involved in the control of myoblast differentiation/fusion, myotube length and size, and myofiber specialization, which was related to the activated PKA-NFAT-MEF2C signaling pathway, providing a novel L-Periaxin/Ezrin joint strategy for the treatment of muscle atrophy induced by nerve injury, especially in CMT4F.

HMGB1: a potential new target for tendinopathy treatment.

Tendinopathy describes a complex pathology of the tendon characterized by abnormalities in the microstructure, composition, and cellularity of the tendon, leading to pain, limitation of activity and reduced function. Nevertheless, the mechanism of tendinopathy has not been fully elucidated, and the treatment of tendinopathy remains a challenge. High mobility group box 1 (HMGB1), a highly conserved and multifaceted nuclear protein, exerts multiple roles and high functional variability and is involved in many biological and pathological processes. In recent years, several studies have suggested that HMGB1 is associated with tendinopathy and may play a key role in the pathogenesis of tendinopathy. Therefore, this review summarizes the expression and distribution of HMGB1 in tendinopathy, focuses on the roles of HMGB1 and HMGB1-based potential mechanisms involved in tendinopathy, and finally summarizes the findings on HMGB1-based therapeutic approaches in tendinopathy, probably providing new insight into the mechanism and further potential therapeutic targets of tendinopathy.

The regulative effect and repercussion of probiotics and prebiotics on osteoporosis: involvement of brain-gut-bone axis.

Osteoporosis (OP) is a systemic disease characterized by decreased bone mass and degeneration of bone microstructure. In recent years, more and more researches have focused on the close relationship between gut microbiota (GM) and the occurrence and progression of OP, and the regulation of probiotics and prebiotics on bone metabolism has gradually become a research hotspot. Based on the influence of brain-gut-bone axis on bone metabolism, this review expounds the potential mechanisms of probiotics and prebiotics on OP from next perspectives: regulation of intestinal metabolites, regulation of intestinal epithelial barrier function, involvement of neuromodulation, involvement of immune regulation and involvement of endocrine regulation, so as to provide a novel and promising idea for the prevention and treatment of OP in the future.

Risk factors for inadequate bowel preparation before colonoscopy: a retrospective cohort study.

BACKGROUND: Colonoscopy is the standard and most effective screening tool for colonic diseases and the accuracy of colonoscopy depends on the quality of bowel preparation. The aim of this study was to analyze the risk factors for inadequate bowel preparation before colonoscopy. METHODS: In this retrospective study, patients who underwent colonoscopy in 2018 and received 3 L of Polyethylene Glycol Electrolytes powder were included. They were instructed to drink 1.5 L the night before the colonoscopy and 1.5 L 4-6 h before the procedure given in doses of 250 ml every 10 min with 30 ml of simethicone given 4-6 h before the colonoscopy. Patient- and procedure-related parameters were recorded. An adequate bowel preparation was defined as all 3 segments rated 2 or 3 on the Boston Bowel Preparation scale. Risk factors for inadequate bowel preparation were identified using multivariate logistic regression analysis. RESULTS: A total of 6720 patients were included in the present study. The mean age of these patients was 49.7 ± 13.0 years old. Inadequate bowel preparation was found in 233 (12.4%), 139 (6.4%), 131 (7%), 68 (8.6%) patients in spring, summer, autumn and winter respectively. On the multivariate analysis, male gender (OR: 1.295; 95% CI: 1.088-1.542; P = 0.005), inpatient status (OR: 1.377; 95% CI: 1.040-1.822; P = 0.025) and season (spring vs. winter, OR: 1.514; 95% CI: 1.139-2.012; P = 0.004) were the independent risk factors for inadequate bowel preparation. CONCLUSIONS: Male gender, inpatient status and spring season were the independent risk factors for inadequate bowel preparation. For patients with risk factors for inadequate bowel preparation, enhanced bowel preparation and instructions may help to optimize the quality of bowel preparation.

1927nm fractional thulium fiber laser combined with 30% salicylic acid for the treatment of acne and acne scars: A prospective, randomized, and split-face study.

OBJECTIVES: Patients with acne usually develops acne scars subsequently, early intervention of scars is crucial in acne management. 1927nm fractional thulium fiber laser (TFL) is effective in scars improvement and chemical peels with 30% supramolecular salicylic acid (SSA) can be applied for the treatment of acne. The purpose of this study is to evaluate and compare the efficacy and safety of TFL monotherapy versus the concomitant application of TFL and 30% SSA on acne and acne scars. MATERIALS AND METHODS: Thirty-three patients with acne and acne scars were enrolled, and two sides of the face were randomly divided to receive either TFL and SSA chemical peeling or TFL. Four sessions of TFL treatments were applied with 4-week intervals for both sides, SSA combined treatment side received eight SSA chemical peels with 2-week intervals additionally. GAGS, ECCA score, the number of acne lesions, melanin index (MI) and erythema index (EI), transepidermal water loss (TEWL), and side effects were recorded at Weeks 0, 4, 8, 12, and 18. Satisfaction of patients was recorded on both sides at the end of the study. RESULTS: Thirty patients completed the study. Both control group (TFL monotherapy) and SSA group (TFL combined with SSA chemical peeling) significantly improved GAGS and ECCA score. SSA group showed higher efficacy in terms of GAGS and ECCA score, acne lesion count, TEWL, MI, EI, and satisfaction than control group. All the side effects were temporary and tolerable, no adverse effects were observed. CONCLUSIONS: Both TFL and the TFL combined with 30% SSA chemical peeling are safe and effective for the treatment and prevention of acne and acne scars, though the combined group has higher efficacy.

Early acne scar intervention with 1064 nm picosecond laser in patients receiving oral isotretinoin: a randomized split-face controlled pilot study.

Early acne scar intervention is important. Oral isotretinoin is widely used in patients with moderate to severe acne. Picosecond laser has shown a promising effect on scar clearance. However, there is a lack of reports on the efficacy and safety of early acne scar management by using 1064-nm picosecond laser in patients receiving low-dose oral isotretinoin. Twenty-four patients with atrophic acne scars of Fitzpatrick skin type III to V were enrolled. All patients were receiving low-dose oral isotretinoin (0.12-0.22 mg/kg/day) during the treatment. The face of the participants was randomly assigned to receive 2 sessions of fractional picosecond 1064 nm Nd: YAG laser (FxPico) treatment and 2 follow-ups, with an interval of 1 month (month 0-3). Clinical efficacy and safety were assessed by photographs, ECCA grading scale, the number of scar lesions melanin and erythema indexes (MI and EI), TEWL, DLQI, and patient satisfaction and the adverse events were recorded on every visit. FxPico significantly decreased the ECCA score and showed higher improvement in the ECCA score. FxPico treated side achieved a significant reduction in all acne scar types, while only boxcar scars and rolling scars showed higher improvement. TEWL but not MI or EI were significantly improved. DLQI and patient satisfaction were higher with the FxPico-treated side than control side. No adverse effects were observed and all the side effects observed were temporary and tolerable. Early intervention by FxPico on patients receiving low-dose oral isotretinoin is a safe and effective modality to improve atrophic acne scars.

Peptide Assembled in a Nano-confined Space as a Molecular Rectifier for the Availability of Ionic Current Modulation.

Bioinspired nanochannels have emerged as a powerful tool for bioengineering and biomedical research due to their robust mechanical and controllable chemical properties. Inspired by inward-rectifier potassium (K+) channels, herein, the charged peptide assembly has been introduced into a nano-confined space for the modulation of ion current rectification (ICR). Peptide-responsive reaction-triggered sequence changes can contribute to polarity conversion of the surface charge; therefore, ICR reversal (ICRR) is generated. Compared with other responsive elements, natural charged peptides show the merit of controllable charge polarity. By electrochemically monitoring the ICRR as an output signal, one can utilize the peptide assembly-mediated ICRR to construct an ionic sensory platform. In addition, a logic gate has been established to demonstrate the availability of an ionic sensory platform for inhibitor screening. As peptide nanoassemblies may also have various structures and functions due to their diverse properties, the ionic modulation system can provide alternatives for the assay of peptide-associated biotargets with biomedical applications.

Artificial intelligence for biomarker discovery in Alzheimer's disease and dementia.

With the increase in large multimodal cohorts and high-throughput technologies, the potential for discovering novel biomarkers is no longer limited by data set size. Artificial intelligence (AI) and machine learning approaches have been developed to detect novel biomarkers and interactions in complex data sets. We discuss exemplar uses and evaluate current applications and limitations of AI to discover novel biomarkers. Remaining challenges include a lack of diversity in the data sets available, the sheer complexity of investigating interactions, the invasiveness and cost of some biomarkers, and poor reporting in some studies. Overcoming these challenges will involve collecting data from underrepresented populations, developing more powerful AI approaches, validating the use of noninvasive biomarkers, and adhering to reporting guidelines. By harnessing rich multimodal data through AI approaches and international collaborative innovation, we are well positioned to identify clinically useful biomarkers that are accurate, generalizable, unbiased, and acceptable in clinical practice. HIGHLIGHTS: Artificial intelligence and machine learning approaches may accelerate dementia biomarker discovery. Remaining challenges include data set suitability due to size and bias in cohort selection. Multimodal data, diverse data sets, improved machine learning approaches, real-world validation, and interdisciplinary collaboration are required.

Multiomics profiling of human plasma and cerebrospinal fluid reveals ATN-derived networks and highlights causal links in Alzheimer's disease.

INTRODUCTION: This study employed an integrative system and causal inference approach to explore molecular signatures in blood and CSF, the amyloid/tau/neurodegeneration [AT(N)] framework, mild cognitive impairment (MCI) conversion to Alzheimer's disease (AD), and genetic risk for AD. METHODS: Using the European Medical Information Framework (EMIF)-AD cohort, we measured 696 proteins in cerebrospinal fluid (n = 371), 4001 proteins in plasma (n = 972), 611 metabolites in plasma (n = 696), and genotyped whole-blood (7,778,465 autosomal single nucleotide epolymorphisms, n = 936). We investigated associations: molecular modules to AT(N), module hubs with AD Polygenic Risk scores and APOE4 genotypes, molecular hubs to MCI conversion and probed for causality with AD using Mendelian randomization (MR). RESULTS: AT(N) framework associated with protein and lipid hubs. In plasma, Proprotein Convertase Subtilisin/Kexin Type 7 showed evidence for causal associations with AD. AD was causally associated with Reticulocalbin 2 and sphingomyelins, an association driven by the APOE isoform. DISCUSSION: This study reveals multi-omics networks associated with AT(N) and causal AD molecular candidates.

Gas-Pressurized Torrefaction of Lignocellulosic Solid Wastes: Deoxygenation and Aromatization Mechanisms of Cellulose.

A novel gas-pressurized (GP) torrefaction method at 250 °C has recently been developed that realizes the deep decomposition of cellulose in lignocellulosic solid wastes (LSW) to as high as 90% through deoxygenation and aromatization reactions. However, the deoxygenation and aromatization mechanisms are currently unclear. In this work, these mechanisms were studied through a developed molecular structure calculation method and the GP torrefaction of pure cellulose. The results demonstrate that GP torrefaction at 250 °C causes 47 wt.% of mass loss and 72 wt.% of O removal for cellulose, while traditional torrefaction at atmospheric pressure has almost no impact on cellulose decomposition. The GP-torrefied cellulose is determined to be composed of an aromatic furans nucleus with branch aliphatic C through conventional characterization. A molecular structure calculation method and its principles were developed for further investigation of molecular-level mechanisms. It was found 2-ring furans aromatic compound intermediate is formed by intra- and inter-molecular dehydroxylation reactions of amorphous cellulose, and the removal of O-containing function groups is mainly through the production of H2O. The three-ring furans aromatic compound intermediate and GP-torrefied cellulose are further formed through the polymerization reaction, which enhances the removal of ketones and aldehydes function groups in intermediate torrefied cellulose and form gaseous CO and O-containing organic molecules. A deoxygenation and aromatization mechanism model was developed based on the above investigation. This work provides theoretical guidance for the optimization of the gas-pressurized torrefaction method and a study method for the determination of molecular-level structure and the mechanism investigation of the thermal conversion processes of LSW.

Enhancing activity of food protein-derived peptides: An overview of pretreatment, preparation, and modification methods.

Food protein-derived peptides have garnered considerable attention due to their potential bioactivities and functional properties. However, the limited activity poses a challenge in effective utilization aspects. To overcome this hurdle, various methods have been explored to enhance the activity of these peptides. This comprehensive review offers an extensive overview of pretreatment, preparation methods, and modification strategies employed to augment the activity of food protein-derived peptides. Additionally, it encompasses a discussion on the current status and future prospects of bioactive peptide applications. The review also addresses the standardization of mass production processes and safety considerations for bioactive peptides while examining the future challenges and opportunities associated with these compounds. This comprehensive review serves as a valuable guide for researchers in the food industry, offering insights and recommendations to optimize the production process of bioactive peptides.