Elucidating the modulatory role of dietary hydroxyproline on the integrity and functional performance of the intestinal barrier in early-weaned piglets: A comprehensive analysis of its interplay with the gut microbiota and metabolites.

Piglets receive far less hydroxyproline (Hyp) from a diet after weaning than they obtained from sow's milk prior to weaning, suggesting that Hyp may play a protective role in preserving intestinal mucosal homeostasis. This study aimed to evaluate the effect of Hyp on intestinal barrier function and its associated gut microbiota and metabolites in early-weaned piglets. Eighty weaned piglets were divided into four groups and fed diets containing different Hyp levels (0 %, 0.5 %, 1 %, or 2 %) for 21 days. Samples, including intestinal contents, tissues, and blood, were collected on day 7 for analysis of microbial composition, intestinal barrier function, and metabolites. We demonstrated that dietary supplementation with 2 % Hyp improved the feed conversion ratio and reduced the incidence of diarrhea in early-weaned piglets compared to the control group. Concurrently, Hyp enhanced intestinal barrier function by facilitating tight junction protein (zonula occludens (ZO)-1 and occludin) expression and mucin production in the jejunal, ileal, and colonic mucosas. It also improved mucosal immunity (by increasing the amount of secretory IgA (sIgA) and the ratio of CD4+/CD8+ T lymphocytes and decreasing NF-κB phosphorylation) and increased antioxidant capacity (by raising total antioxidant capacity (T-AOC) and glutathione levels) in the intestinal mucosa. In addition, Hyp supplementation resulted in an increase in the levels of glycine, glutathione, and glycine-conjugated bile acids, while decreasing the concentrations of cortisol and methionine sulfoxide in plasma. Intriguingly, piglets fed diet containing Hyp exhibited a remarkable increase in the abundance of probiotic Enterococcus faecium within their colonic contents. This elevation occurred alongside an attenuation of pro-inflammatory responses and an enhancement in intestinal barrier integrity. Further, these changes were accompanied by a rise in anti-inflammatory metabolites, specifically glycochenodeoxycholic acid and guanosine, along with a suppression of pro-inflammatory lipid peroxidation products, including (12Z)-9,10-dihydroxyoctadec-12-enoic acid (9,10-DHOME) and 13-L-hydroperoxylinoleic acid (13(S)-HPODE). In summary, Hyp holds the capacity to enhance the intestinal barrier function in weaned piglets; this effect is correlated with changes in the gut microbiota and metabolites. Our findings provide novel insights into the role of Hyp in maintaining gut homeostasis, highlighting its potential as a dietary supplement for promoting intestinal health in early-weaned piglets.

A high-fat diet promotes cancer progression by inducing gut microbiota-mediated leucine production and PMN-MDSC differentiation.

A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through the disruption of the intestinal microbiota. However, the role of the HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related gut microbiota were associated with poor prognosis and advanced clinicopathological status in female patients with breast cancer. To investigate the impact of HFD-associated gut microbiota on cancer progression, we established various models, including HFD feeding, fecal microbiota transplantation, antibiotic feeding, and bacterial gavage, in tumor-bearing mice. HFD-related microbiota promotes cancer progression by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, the HFD microbiota released abundant leucine, which activated the mTORC1 signaling pathway in myeloid progenitors for PMN-MDSC differentiation. Clinically, the elevated leucine level in the peripheral blood induced by the HFD microbiota was correlated with abundant tumoral PMN-MDSC infiltration and poor clinical outcomes in female patients with breast cancer. These findings revealed that the "gut-bone marrow-tumor" axis is involved in HFD-mediated cancer progression and opens a broad avenue for anticancer therapeutic strategies by targeting the aberrant metabolism of the gut microbiota.

Organoid intelligence: Integration of organoid technology and artificial intelligence in the new era of in vitro models.

Organoid Intelligence ushers in a new era by seamlessly integrating cutting-edge organoid technology with the power of artificial intelligence. Organoids, three-dimensional miniature organ-like structures cultivated from stem cells, offer an unparalleled opportunity to simulate complex human organ systems in vitro. Through the convergence of organoid technology and AI, researchers gain the means to accelerate discoveries and insights across various disciplines. Artificial intelligence algorithms enable the comprehensive analysis of intricate organoid behaviors, intricate cellular interactions, and dynamic responses to stimuli. This synergy empowers the development of predictive models, precise disease simulations, and personalized medicine approaches, revolutionizing our understanding of human development, disease mechanisms, and therapeutic interventions. Organoid Intelligence holds the promise of reshaping how we perceive in vitro modeling, propelling us toward a future where these advanced systems play a pivotal role in biomedical research and drug development.

Multifaceted roles of cohesin in regulating transcriptional loops.

Cohesin is required for chromatin loop formation. However, its precise role in regulating gene transcription remains largely unknown. We investigated the relationship between cohesin and RNA Polymerase II (RNAPII) using single-molecule mapping and live-cell imaging methods in human cells. Cohesin-mediated transcriptional loops were highly correlated with those of RNAPII and followed the direction of gene transcription. Depleting RAD21, a subunit of cohesin, resulted in the loss of long-range (>100 kb) loops between distal (super-)enhancers and promoters of cell-type-specific genes. By contrast, the short-range (<50 kb) loops were insensitive to RAD21 depletion and connected genes that are mostly housekeeping. This result explains why only a small fraction of genes are affected by the loss of long-range chromatin interactions due to cohesin depletion. Remarkably, RAD21 depletion appeared to up-regulate genes located in early initiation zones (EIZ) of DNA replication, and the EIZ signals were amplified drastically without RAD21. Our results revealed new mechanistic insights of cohesin's multifaceted roles in establishing transcriptional loops, preserving long-range chromatin interactions for cell-specific genes, and maintaining timely order of DNA replication.

A comparative study on grasping-related muscles in five Accipitriformes species.

Accipitriformes are diverse in their prey preferences and use their grasping feet for hunting. Little is known about the architectural design of muscles related to grasping among species of different sizes, diets, and foraging behaviors. In the present study, we report quantitative data and analysis of the pelvic musculature of the Japanese sparrowhawk (Accipiter gularis), Eurasian sparrowhawk (Accipiter nisus), common buzzard (Buteo buteo), northern goshawk (Accipiter gentilis), and cinereous vulture (Aegypius monachus). As expected, mass and architecture of the considered muscles were very different between the cinereous vulture and the four other species. The cinereous vulture allocates more mass and physiological cross-sectional area (PCSA) to the proximally inserted flexor muscles, which indicates the rudimentary grasping ability of the foot and is a myological reflection of its carrion preference. Furthermore, in the cinereous vulture, muscles were built with the lowest architectural index (AI) compared with the other species, and the intrinsic foot muscles were short-fibered, which is disadvantageous for rapid manipulation and foot dexterity. The other four species, as a whole, featured large flexor hallucis longus (FHL) muscles and better development of distally inserted flexors, reflecting their predatory lifestyle. Some differences were also found between the species that consumed birds and those that consumed mammals. The two avivorous species were superior in AI and fiber length of the intrinsic foot muscles which are suitable for good hunting speed and digit flexibility, the prerequisition for hunting agile prey.

Exposure to the environmental pollutant chlorpyrifos induces hepatic toxicity through activation of the JAK/STAT and MAPK pathways.

Chlorpyrifos (CHP) is an inexpensive highly effective organophosphate insecticide used worldwide. The unguided and excessive use of CHP by farmers has led to its significant accumulation in crops as well as contamination of water sources, causing health problems for humans and animals. Therefore, this study evaluated the toxicological effects of exposure to the environmental pollutant CHP at low, medium, and high (2.5, 5, and 10 mg·kg-1 BW) levels on rat liver by examining antioxidant levels, inflammation, and apoptosis based on the no observed adverse effect levels (NOAEL) (1 mg·kg-1 BW) and the CHP dose that does not cause any visual symptoms (5 mg·kg-1 BW). Furthermore, the involvement of the JAK/STAT and MAPK pathways in CHP-induced toxic effects was identified. The relationship between the expression levels of key proteins (p-JAK/JAK, p-STAT/STAT, p-JNK/JNK, p-P38/P38, and p-ERK/ERK) in the pathways and changes in the expression of markers associated with inflammation [inflammatory factors (IL-1ß, IL-6, IL-10, TNF-α), chemokines (GCLC and GCLM), and inflammatory signaling pathways (NF-кB, TLR2, TLR4, NLRP3, ASC, MyD88, IFN-γ, and iNOS)] and apoptosis [Bad, Bax, Bcl-2, Caspase3, Caspase9, and the cleavage substrate of Caspase PARP1] were also determined. The results suggest that CHP exposure disrupts liver function and activates the JAK/STAT and MAPK pathways via oxidative stress, exacerbating inflammation and apoptosis. Meanwhile, the JAK/STAT and MAPK pathways are involved in CHP-induced hepatotoxicity. These findings provide a novel direction for effective prevention and amelioration of health problems caused by CHP abuse in agriculture and households.

Expression and influence of KATP in umbilical artery smooth muscle cells of patients with hypertensive disorders of pregnancy.

The objective of this study is to investigate the expression and influence of adenosine triphosphate-sensitive potassium channel (KATP) in human umbilical arterial smooth muscle cells (HUASMCs) of patients with hypertensive disorders of pregnancy (HDP). Western blotting was used to detect the protein expression levels of KATP inwardly rectifying potassium channel (Kir)6.1 and sulphonylurea receptor (SUR)2B subunits in HUASMCs from patients with normal parturients (NP), gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE) and chronic hypertension with superimposed preeclampsia (CHSP), respectively. There was no significant difference in the protein expression of Kir6.1 subunit in NP group, GH group, CH group, PE group and CHSP group (P > 0.05). The protein expression of SUR2B subunit was gradually decreased in NP group, GH group, CH group, PE group and CHSP group, with statistically significant difference among the groups (P < 0.05). The altered expression level of KATP SUR2B subunit may be involved in the pathogenesis of HDP. The severity of HDP may be related to the degree of decrease of SUR2B subunit.

AI-organoid integrated systems for biomedical studies and applications.

In this review, we explore the growing role of artificial intelligence (AI) in advancing the biomedical applications of human pluripotent stem cell (hPSC)-derived organoids. Stem cell-derived organoids, these miniature organ replicas, have become essential tools for disease modeling, drug discovery, and regenerative medicine. However, analyzing the vast and intricate datasets generated from these organoids can be inefficient and error-prone. AI techniques offer a promising solution to efficiently extract insights and make predictions from diverse data types generated from microscopy images, transcriptomics, metabolomics, and proteomics. This review offers a brief overview of organoid characterization and fundamental concepts in AI while focusing on a comprehensive exploration of AI applications in organoid-based disease modeling and drug evaluation. It provides insights into the future possibilities of AI in enhancing the quality control of organoid fabrication, label-free organoid recognition, and three-dimensional image reconstruction of complex organoid structures. This review presents the challenges and potential solutions in AI-organoid integration, focusing on the establishment of reliable AI model decision-making processes and the standardization of organoid research.

Optimizing the Probabilistic Neural Network Model with the Improved Manta Ray Foraging Optimization Algorithm to Identify Pressure Fluctuation Signal Features.

To improve the identification accuracy of pressure fluctuation signals in the draft tube of hydraulic turbines, this study proposes an improved manta ray foraging optimization (ITMRFO) algorithm to optimize the identification method of a probabilistic neural network (PNN). Specifically, first, discrete wavelet transform was used to extract features from vibration signals, and then, fuzzy c-means algorithm (FCM) clustering was used to automatically classify the collected information. In order to solve the local optimization problem of the manta ray foraging optimization (MRFO) algorithm, four optimization strategies were proposed. These included optimizing the initial population of the MRFO algorithm based on the elite opposition learning algorithm and using adaptive t distribution to replace its chain factor to optimize individual update strategies and other improvement strategies. The ITMRFO algorithm was compared with three algorithms on 23 test functions to verify its superiority. In order to improve the classification accuracy of the probabilistic neural network (PNN) affected by smoothing factors, an improved manta ray foraging optimization (ITMRFO) algorithm was used to optimize them. An ITMRFO-PNN model was established and compared with the PNN and MRFO-PNN models to evaluate their performance in identifying pressure fluctuation signals in turbine draft tubes. The evaluation indicators include confusion matrix, accuracy, precision, recall rate, F1-score, and accuracy and error rate. The experimental results confirm the correctness and effectiveness of the ITMRFO-PNN model, providing a solid theoretical foundation for identifying pressure fluctuation signals in hydraulic turbine draft tubes.

Deep Learning for Discrimination of Hypertrophic Cardiomyopathy and Hypertensive Heart Disease on MRI Native T1 Maps.

BACKGROUND: Native T1 and radiomics were used for hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) differentiation previously. The current problem is that global native T1 remains modest discrimination performance and radiomics requires feature extraction beforehand. Deep learning (DL) is a promising technique in differential diagnosis. However, its feasibility for discriminating HCM and HHD has not been investigated. PURPOSE: To examine the feasibility of DL in differentiating HCM and HHD based on T1 images and compare its diagnostic performance with other methods. STUDY TYPE: Retrospective. POPULATION: 128 HCM patients (men, 75; age, 50 years ± 16) and 59 HHD patients (men, 40; age, 45 years ± 17). FIELD STRENGTH/SEQUENCE: 3.0T; Balanced steady-state free precession, phase-sensitive inversion recovery (PSIR) and multislice native T1 mapping. ASSESSMENT: Compare HCM and HHD patients baseline data. Myocardial T1 values were extracted from native T1 images. Radiomics was implemented through feature extraction and Extra Trees Classifier. The DL network is ResNet32. Different input including myocardial ring (DL-myo), myocardial ring bounding box (DL-box) and the surrounding tissue without myocardial ring (DL-nomyo) were tested. We evaluate diagnostic performance through AUC of ROC curve. STATISTICAL TESTS: Accuracy, sensitivity, specificity, ROC, and AUC were calculated. Independent t test, Mann-Whitney U-test and Chi-square test were adopted for HCM and HHD comparison. P < 0.05 was considered statistically significant. RESULTS: DL-myo, DL-box, and DL-nomyo models showed an AUC (95% confidential interval) of 0.830 (0.702-0.959), 0.766 (0.617-0.915), 0.795 (0.654-0.936) in the testing set. AUC of native T1 and radiomics were 0.545 (0.352-0.738) and 0.800 (0.655-0.944) in the testing set. DATA CONCLUSION: The DL method based on T1 mapping seems capable of discriminating HCM and HHD. Considering diagnostic performance, the DL network outperformed the native T1 method. Compared with radiomics, DL won an advantage for its high specificity and automated working mode. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.

Who Gains Mental Health Benefits from Work Autonomy? The Roles of Gender and Occupational Class.

In recent years, improving work autonomy as an important priority in the UK labour market has been shown to enhance employee mental health and well-being. However, previous theories and empirical studies have paid little attention to the intersectional inequalities in the mental health benefits of work autonomy, preventing us from gaining a comprehensive understanding of the mental consequences of work autonomy. By integrating literature from occupational psychology, gender and social class, this study develops theoretical hypotheses regarding whether and how the mental health benefits of work autonomy vary alongside the intersectional axes of gender and occupational class and tests these hypotheses using long-term panel data in the UK (2010-2021). Overall, we find that those from higher occupational class and male employees acquire significantly more mental health benefits from high work autonomy compared with those from lower occupational class and female employees. Moreover, further analyses show significant intersectional inequalities of gender and occupational class. While male employees from all occupational classes gain significant mental health benefits from work autonomy, only female employees from higher (but not lower) occupational classes benefit from work autonomy. These findings contribute to the literature in the sociology of work by demonstrating the intersectional inequalities in mental health consequences of work autonomy, especially for women in the lower occupational class, highlighting the need for a more gender- and occupation-sensitive design in future labour market policies.

MEMS micro-coils for magnetic neurostimulation.

Micro-coil magnetic stimulation of brain tissue presents new challenges for MEMS micro-coil probe fabrication. The main challenges are threefold; (i) low coil resistance for high power efficiency, (ii) low leak current from the probe into the in vitro experimental set-up, (iii) adaptive MEMS process technology because of the dynamic research area, which requires agile design changes. Taking on these challenges, we present a MEMS fabrication process that has three main features; (i) multilayer resist lift-off process to pattern up to 1800-nm-thick metal films, and special care is taken to obtain high conductivity thin-films by physical vapor deposition, and (ii) all micro-coil Al wires are encapsulated in at least 200 nm of ALD alumina and 6-µm-thick parylene C such the leak resistance is high (>210 GΩ), (iii) combining a multi-step DRIE process and maskless photolithography for adaptive design and device fabrication. The entire process requires four lithography steps. Because we avoided SOI wafers and lithography mask fabrication, the design-to-device time is shortened significantly. The resulting probes are 4-mm-long, 60-µm-thick, and down to 150 µm-wide. Selected MEMS coil devices were validated in vivo using mice and compared to previous work.

MD2 Inhibits Choroidal Neovascularization via Antagonizing TLR4/MD2 Mediated Signaling Pathway.

PURPOSE: To explore the pathological mechanism of Toll-like receptor 4 (TLR4) mediating neovascular age-related macular degeneration (nAMD) and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2). METHODS: In the study, we inhibited MD2 with the chalcone derivative L2H17 and we utilized a laser-induced choroidal neovascularization (CNV) mouse model and Tert-butyl hydroperoxide (TBHP)-challenged rhesus choroid-retinal endothelial (RF/6A) cells to assess the effect of MD2 blockade on CNV. RESULTS: Inhibiting MD2 with L2H17 reduced angiogenesis in CNV mice, and significantly protected against retinal dysfunction. In retina and choroid/retinal pigment epithelium (RPE) tissues, L2H17 reduced phospho-ERK, phospho-P65 but not phospho-P38, phospho-JNK, and reduced the transcriptional levels of IL-6, TNF-α, ICAM-1 but not VCAM-1. L2H17 could protect RF/6A against TBHP-induced inflammation, oxidative stress, and apoptosis, via inhibiting the TLR4/MD2 signaling pathway and the following downstream mitogen-activated protein kinase (MAPK) and nuclear transcription factor-κB (NF-κB) activation. CONCLUSIONS: Inhibiting MD2 with L2H17 significantly reduced CNV, suppressed inflammation, and oxidative stress by antagonizing TLR4/MD2 pathway in an MD2-dependent manner. MD2 may be a potential therapeutic target and L2H17 may offer an alternative treatment strategy for nAMD.

Non-professional Medical Interpreting as a Contextualized Practice: Chinese Volunteer Interpreters' Role-Spaces in Mediating Provider-Patient Conflicts Amid the Pandemic.

Non-professional medical interpreters are frequent participants of bilingual health communication. Yet, scholarly attention paid to this group's roles in less routinized medical encounters is insufficient. Adopting the concept of "role-space," this study explores volunteer medical interpreters' (VMIs) roles in mediating provider-patient conflicts at a designated hospital tasked to admit and treat foreign patients in City Y, China. In-depth interviews with eight VMIs, two doctors, two patients, and one Foreign Affairs officer indicate that VMIs took on the roles of provider proxy, patient advocates, information gatekeepers, and emotional supporters while navigating through challenges at the macro-, meso- and micro-level; Their practices led to four role-spaces that featured high presentation of VMIs' self-driven actions during dyadic communication with patients only and, in most cases, minimal interaction management and participant alignment in provider-patient encounters.

Surface-Clean Au25 Nanoclusters in Modulated Microenvironment Enabled by Metal-Organic Frameworks for Enhanced Catalysis.

Metal nanoclusters (NCs) with atomically precise structures have sparked interest in catalysis. Unfortunately, their high aggregation tendency and the spatial resistance of surface ligands pose significant challenges. Herein, Au25 NCs are encapsulated into isoreticular metal-organic frameworks (MOFs), namely UiO-66-X (X = H, NH2, OH, and NO2), followed by the removal of surface ligands on Au25 NCs. The resulting surface-clean Au25 NCs, protected by the MOF spatial confinement, exhibit much superior activity and stability with respect to pristine Au25 NCs in the oxidative esterification of furfural. Remarkably, experimental and theoretical results jointly demonstrate that diverse functional groups on UiO-66-X modulate the Au25 electronic state, giving rise to the discriminated substrate adsorption energy of Au25@UiO-66-X. As a result, the high electron density and suitable substrate adsorption ability dominate the activity trend: Au25@UiO-66-NH2 > Au25@UiO-66-OH > Au25@UiO-66 > Au25@UiO-66-NO2. This work develops a new strategy for the stabilization of surface-clean metal NCs in pore wall-engineered MOFs for enhanced catalysis.

Integrating nonlinear analysis and machine learning for human induced pluripotent stem cell-based drug cardiotoxicity testing.

Utilizing recent advances in human induced pluripotent stem cell (hiPSC) technology, nonlinear analysis and machine learning we can create novel tools to evaluate drug-induced cardiotoxicity on human cardiomyocytes. With cardiovascular disease remaining the leading cause of death globally it has become imperative to create effective and modern tools to test the efficacy and toxicity of drugs to combat heart disease. The calcium transient signals recorded from hiPSC-derived cardiomyocytes (hiPSC-CMs) are highly complex and dynamic with great degrees of response characteristics to various drug treatments. However, traditional linear methods often fail to capture the subtle variation in these signals generated by hiPSC-CMs. In this work, we integrated nonlinear analysis, dimensionality reduction techniques and machine learning algorithms for better classifying the contractile signals from hiPSC-CMs in response to different drug exposure. By utilizing extracted parameters from a commercially available high-throughput testing platform, we were able to distinguish the groups with drug treatment from baseline controls, determine the drug exposure relative to IC50 values, and classify the drugs by its unique cardiac responses. By incorporating nonlinear parameters computed by phase space reconstruction, we were able to improve our machine learning algorithm's ability to predict cardiotoxic levels and drug classifications. We also visualized the effects of drug treatment and dosages with dimensionality reduction techniques, t-distributed stochastic neighbor embedding (t-SNE). We have shown that integration of nonlinear analysis and artificial intelligence has proven to be a powerful tool for analyzing cardiotoxicity and classifying toxic compounds through their mechanistic action.

Suppressor of Cytokine Signaling 2 Regulates Retinal Pigment Epithelium Metabolism by Enhancing Autophagy.

Retinal pigment epithelium (RPE) serves critical functions in maintaining retinal homeostasis. An important function of RPE is to degrade the photoreceptor outer segment fragments daily to maintain photoreceptor function and longevity throughout life. An impairment of RPE functions such as metabolic regulation leads to the development of age-related macular degeneration (AMD) and inherited retinal degenerative diseases. As substrate recognition subunit of a ubiquitin ligase complex, suppressor of cytokine signaling 2 (SOCS2) specifically binds to the substrates for ubiquitination and negatively regulates growth hormone signaling. Herein, we explore the role of SOCS2 in the metabolic regulation of autophagy in the RPE cells. SOCS2 knockout mice exhibited the irregular morphological deposits between the RPE and Bruch's membrane. Both in vivo and in vitro experiments showed that RPE cells lacking SOCS2 displayed impaired autophagy, which could be recovered by re-expressing SOCS2. SOCS2 recognizes the ubiquitylated proteins and participates in the formation of autolysosome by binding with autophagy receptors and lysosome-associated membrane protein2 (LAMP-2), thereby regulating the phosphorylation of glycogen synthase kinase 3ß (GSK3ß) and mammalian target of rapamycin (mTOR) during the autophagy process. Our results imply that SOCS2 participates in ubiquitin-autophagy-lysosomal pathway and enhances autophagy by regulating GSK3ß and mTOR. This study provides a potential therapeutic target for AMD.

In situ Chromatin Interaction Analysis Using Paired-End Tag Sequencing.

Chromatin Interaction Analysis Using Paired-End Tag Sequencing (ChIA-PET) is an established method to map protein-mediated chromatin interactions. A limitation, however, is that it requires a hundred million cells per experiment, which hampers its broad application in biomedical research, particularly in studies in which it is impractical to obtain a large number of cells from rare samples. To reduce the required input cell number while retaining high data quality, we developed an in situ ChIA-PET protocol, which requires as few as 1 million cells. Here, we describe detailed step-by-step procedures for performing in situ ChIA-PET from cultured cells, including both an experimental protocol for sample preparation and data generation and a computational protocol for data processing and visualization using the ChIA-PIPE pipeline. As the protocol significantly simplifies the experimental procedure, reduces ligation noise, and decreases the required input of cells compared to previous versions of ChIA-PET protocols, it can be applied to generate high-resolution chromatin contact maps mediated by various protein factors for a wide range of human and mouse primary cells. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Sample preparation and data generation Support Protocol: Bridge linker preparation Basic Protocol 2: Data processing and visualization.

Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis.

The gut bacterium Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-associated fatty liver disease (MAFLD). However, its underlying mechanism involved in its well-known metabolic actions needs further evaluation. The present study explored the therapeutic effect and mechanism of A. muciniphila in intervening MAFLD by using a high-fat and high-cholesterol (HFC) diet induced obese mice model. Mice treated with A. muciniphila efficiently reversed MAFLD in the liver, such as hepatic steatosis, inflammatory, and liver injury. These therapeutic effects persisted after long-term drug withdrawal and were slightly weakened in the antibiotics-treated obese mice. A. muciniphila treatment efficiently increased mitochondrial oxidation and bile acid metabolism in the gut-liver axis, ameliorated oxidative stress-induced cell apoptosis in gut, leading to the reshaping of the gut microbiota composition. These metabolic improvements occurred with increased L-aspartate levels in the liver that transported from the gut. The administration of L-aspartate in vitro or in mice displayed the similar beneficial metabolic effects mentioned above and efficiently ameliorated MAFLD. Together, these data indicate that the anti-MAFLD activity of A. muciniphila correlated with lipid oxidation and improved gut-liver interactions through regulating the metabolism of L-aspartate. A. muciniphila could be a potential agent for clinical intervention in MAFLD.

Associations between oil development and sexually transmitted infections: Public health nurse perspectives.

BACKGROUND: Oil development (OD) has been associated with increased sexually transmitted infection (STI) rates, with limited focus on the North Dakota (ND) oil boom. Public health (PH) nurse experiences can provide context related to health challenges during OD-related population booms. OBJECTIVE: To compare reported STI rates in ND oil-producing (OP) and non-oil-producing (NOP) counties before, during, and after the oil boom and describe PH nurse experiences during this time. DESIGN: We conducted secondary data analysis of oil production data and reported rates for chlamydia and gonorrhea, and conducted interviews with ND PH nurses. SAMPLE: PH nurses within ND counties geographically located in or near OD in the state. MEASUREMENTS: ND county-level OD data trends were compared to similarly timed reported rates of chlamydia and gonorrhea in OP and NOP counties. PH nurse interviews were conducted addressing their STI-related experiences working in PH during the oil boom. RESULTS: Significant findings include a correlation between OD and gonorrhea rates. PH nurses described a limited PH infrastructure to meet the health needs of a transient, increasing population. CONCLUSIONS: Expanding the role of PH nurses in ND to implement STI screening and treatment would improve access to STI testing allowing for comprehensive reporting of STIs.