Artificial intelligence velocimetry reveals in vivo flow rates, pressure gradients, and shear stresses in murine perivascular flows.

Quantifying the flow of cerebrospinal fluid (CSF) is crucial for understanding brain waste clearance and nutrient delivery, as well as edema in pathological conditions such as stroke. However, existing in vivo techniques are limited to sparse velocity measurements in pial perivascular spaces (PVSs) or low-resolution measurements from brain-wide imaging. Additionally, volume flow rate, pressure, and shear stress variation in PVSs are essentially impossible to measure in vivo. Here, we show that artificial intelligence velocimetry (AIV) can integrate sparse velocity measurements with physics-informed neural networks to quantify CSF flow in PVSs. With AIV, we infer three-dimensional (3D), high-resolution velocity, pressure, and shear stress. Validation comes from training with 70% of PTV measurements and demonstrating close agreement with the remaining 30%. A sensitivity analysis on the AIV inputs shows that the uncertainty in AIV inferred quantities due to uncertainties in the PVS boundary locations inherent to in vivo imaging is less than 30%, and the uncertainty from the neural net initialization is less than 1%. In PVSs of N = 4 wild-type mice we find mean flow speed 16.33 ± 11.09 µm/s, volume flow rate 2.22 ± 1.983 × 103 µm3/s, axial pressure gradient ( - 2.75 ± 2.01)×10-4 Pa/µm (-2.07 ± 1.51 mmHg/m), and wall shear stress (3.00 ± 1.45)×10-3 Pa (all mean ± SE). Pressure gradients, flow rates, and resistances agree with prior predictions. AIV infers in vivo PVS flows in remarkable detail, which will improve fluid dynamic models and potentially clarify how CSF flow changes with aging, Alzheimer's disease, and small vessel disease.

A DNA origami device spatially controls CD95 signalling to induce immune tolerance in rheumatoid arthritis.

DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand-receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.

Ubiquitin receptor PSMD4/Rpn10 is a novel therapeutic target in multiple myeloma.

PSMD4/Rpn10 is a subunit of the 19S proteasome unit that is involved with feeding target proteins into the catalytic machinery of the 26S proteasome. Because proteasome inhibition is a common therapeutic strategy in multiple myeloma (MM), we investigated Rpn10 and found that it is highly expressed in MM cells compared with normal plasma cells. Rpn10 levels inversely correlated with overall survival in patients with MM. Inducible knockout or knockdown of Rpn10 decreased MM cell viability both in vitro and in vivo by triggering the accumulation of polyubiquitinated proteins, cell cycle arrest, and apoptosis associated with the activation of caspases and unfolded protein response-related pathways. Proteomic analysis revealed that inhibiting Rpn10 increased autophagy, antigen presentation, and the activation of CD4+ T and natural killer cells. We developed an in vitro AlphaScreen binding assay for high-throughput screening and identified a novel Rpn10 inhibitor, SB699551 (SB). Treating MM cell lines, leukemic cell lines, and primary cells from patients with MM with SB decreased cell viability without affecting the viability of normal peripheral blood mononuclear cells. SB inhibited the proliferation of MM cells even in the presence of the tumor-promoting bone marrow milieu and overcame proteasome inhibitor (PI) resistance without blocking the 20S proteasome catalytic function or the 19S deubiquitinating activity. Rpn10 blockade by SB triggered MM cell death via similar pathways as the genetic strategy. In MM xenograft models, SB was well tolerated, inhibited tumor growth, and prolonged survival. Our data suggest that inhibiting Rpn10 will enhance cytotoxicity and overcome PI resistance in MM, providing the basis for further optimization studies of Rpn10 inhibitors for clinical application.

The Role of N-α-acetyltransferase 10 Protein in DNA Methylation and Genomic Imprinting.

Genomic imprinting is an allelic gene expression phenomenon primarily controlled by allele-specific DNA methylation at the imprinting control region (ICR), but the underlying mechanism remains largely unclear. N-α-acetyltransferase 10 protein (Naa10p) catalyzes N-α-acetylation of nascent proteins, and mutation of human Naa10p is linked to severe developmental delays. Here we report that Naa10-null mice display partial embryonic lethality, growth retardation, brain disorders, and maternal effect lethality, phenotypes commonly observed in defective genomic imprinting. Genome-wide analyses further revealed global DNA hypomethylation and enriched dysregulation of imprinted genes in Naa10p-knockout embryos and embryonic stem cells. Mechanistically, Naa10p facilitates binding of DNA methyltransferase 1 (Dnmt1) to DNA substrates, including the ICRs of the imprinted allele during S phase. Moreover, the lethal Ogden syndrome-associated mutation of human Naa10p disrupts its binding to the ICR of H19 and Dnmt1 recruitment. Our study thus links Naa10p mutation-associated Ogden syndrome to defective DNA methylation and genomic imprinting.

Race Dialogues and Potential Application in Clinical Environments: A Scoping Review.

BACKGROUND: Race dialogues, conversations about race and racism among individuals holding different racial identities, have been proposed as one component of addressing racism in medicine and improving the experience of racially minoritized patients. Drawing on work from several fields, we aimed to assess the scope of the literature on race dialogues and to describe potential benefits, best practices, and challenges of conducting such dialogues. Ultimately, our goal was to explore the potential role of race dialogues in medical education and clinical practice. METHODS: Our scoping review included articles published prior to June 2, 2022, in the biomedicine, psychology, nursing and allied health, and education literatures. Ultimately, 54 articles were included in analysis, all of which pertained to conversations about race occurring between adults possessing different racial identities. We engaged in an interactive group process to identify key takeaways from each article and synthesize cross-cutting themes. RESULTS: Emergent themes reflected the processes of preparing, leading, and following up race dialogues. Preparing required significant personal introspection, logistical organization, and intentional framing of the conversation. Leading safe and successful race dialogues necessitated trauma-informed practices, addressing microaggressions as they arose, welcoming participation and emotions, and centering the experience of individuals with minoritized identities. Longitudinal experiences and efforts to evaluate the quality of race dialogues were crucial to ensuring meaningful impact. DISCUSSION: Supporting race dialogues within medicine has the potential to promote a more inclusive and justice-oriented workforce, strengthen relationships amongst colleagues, and improve care for patients with racially minoritized identities. Potential levers for supporting race dialogues include high-quality racial justice curricula at every level of medical education and valuation of racial consciousness in admissions and hiring processes. All efforts to support race dialogues must center and uplift those with racially minoritized identities.

Unveiling the Roles of Alloyed Boron in Hexavalent Chromium Removal Using Borohydride-Synthesized Nanoscale Zerovalent Iron: Electron Donor and Antipassivator.

Nanoscale zerovalent iron synthesized using borohydride (B-NZVI) has been widely applied in environmental remediation in recent decades. However, the contribution of boron in enhancing the inherent reactivity of B-NZVI and its effectiveness in removing hexavalent chromium [Cr(VI)] have not been well recognized and quantified. To the best of our knowledge, herein, a core-shell structure of B-NZVI featuring an Fe-B alloy shell beneath the iron oxide shell is demonstrated for the first time. Alloyed boron can reduce H+, contributing to more than 35.6% of H2 generation during acid digestion of B-NZVIs. In addition, alloyed B provides electrons for Fe3+ reduction during Cr(VI) removal, preventing in situ passivation of the reactive particle surface. Meanwhile, the amorphous oxide shell of B-NZVI exhibits an increased defect density, promoting the release of Fe2+ outside the shell to reduce Cr(VI), forming layer-structured precipitates and intense Fe-O bonds. Consequently, the surface-area-normalized capacity and surface reaction rate of B-NZVI are 6.5 and 6.9 times higher than those of crystalline NZVI, respectively. This study reveals the importance of alloyed B in Cr(VI) removal using B-NZVI and presents a comprehensive approach for investigating electron pathways and mechanisms involved in B-NZVIs for contaminant removal.

Genetic support for the causal association between 91 circulating inflammatory proteins and atopic dermatitis: A two-sample Mendelian randomization trial.

BACKGROUND: Atopic dermatitis (AD) is a refractory disease that occurs in clinical practice. One of the most common inflammatory skin diseases, its occurrence and development are related to inflammation. Nevertheless, the precise nature of the relationship between circulating inflammatory proteins and AD remains uncertain. METHODS: A two-sample MR analysis was performed to determine the causal relationship between the expression of 91 circulating inflammatory proteins and AD by using genome-wide association study (GWAS) summary statistics data from the FinnGen consortia. The robustness of the MR results was assessed by means of sensitivity analysis. RESULTS: The causal relationship between the expression of nine specific circulating inflammatory proteins and AD was corroborated by the inverse variance weighted (IVW) method. The findings indicated that three circulating inflammatory proteins, namely, interleukin-18 receptor 1 [OR (CI) = 1.08 (1.05-1.11); p = 0.000001)], interleukin-8 [OR (CI) = 1.07 (1.00-1.14); p = 0.036244)], and tumor necrosis factor ligand superfamily member 14 [OR (CI) = 1.05 (1.00-1.10); p = 0.036842)], were positively correlated with AD. Additionally, six circulating inflammatory proteins were negatively correlated with AD: the T-cell surface glycoprotein CD5 [OR (CI) = 0.89 (0.84-0.95); p = 0.000191)], macrophage colony-stimulating factor 1 [OR (CI) = 0.93 (0.88-0.99); p = 0.031422)], fractalkine [OR (CI) = 0.91 (0.85-0.97); p = 0.003067)], interleukin-24 [OR (CI) = 0.91 (0.83-0.99); p = 0.031673)], signaling lymphocytic activation molecule [OR(CI) = 0.94 (0.89-1.00); p = 0.039818)], and urokinase-type plasminogen activator [OR(CI) = 0.95 (0.90-1.00); p = 0.037037)]. CONCLUSION: This study confirms the potential causal relationship between circulating inflammatory proteins and AD and provides guidance for the clinical diagnosis and treatment of AD.

Machine Learning Model for Predicting Axillary Lymph Node Metastasis in Clinically Node Positive Breast Cancer Based on Peritumoral Ultrasound Radiomics and SHAP Feature Analysis.

OBJECTIVE: This study seeks to construct a machine learning model that merges clinical characteristics with ultrasound radiomic analysis-encompassing both the intratumoral and peritumoral-to predict the status of axillary lymph nodes in patients with early-stage breast cancer. METHODS: The study employed retrospective methods, collecting clinical information, ultrasound data, and postoperative pathological results from 321 breast cancer patients (including 224 in the training group and 97 in the validation group). Through correlation analysis, univariate analysis, and Lasso regression analysis, independent risk factors related to axillary lymph node metastasis in breast cancer were identified from conventional ultrasound and immunohistochemical indicators, and a clinical feature model was constructed. Additionally, features were extracted from ultrasound images of the intratumoral and its 1-5 mm peritumoral to establish a radiomics feature formula. Furthermore, by combining clinical features and ultrasound radiomics features, six machine learning models (Logistic Regression, Decision Tree, Support Vector Machine, Extreme Gradient Boosting, Random Forest, and K-Nearest Neighbors) were compared for diagnostic efficacy, and constructing a joint prediction model based on the optimal ML algorithm. The use of Shapley Additive Explanations (SHAP) enhanced the visualization and interpretability of the model during the diagnostic process. RESULTS: Among the 321 breast cancer patients, 121 had axillary lymph node metastasis, and 200 did not. The clinical feature model had an AUC of 0.779 and 0.777 in the training and validation groups, respectively. Radiomics model analysis showed that the model including the Intratumor +3 mm peritumor area had the best diagnostic performance, with AUCs of 0.847 and 0.844 in the training and validation groups, respectively. The joint prediction model based on the XGBoost algorithm reached AUCs of 0.917 and 0.905 in the training and validation groups, respectively. SHAP analysis indicated that the Rad Score had the highest weight in the prediction model, playing a significant role in predicting axillary lymph node metastasis in breast cancer. CONCLUSION: The predictive model, which integrates clinical features and radiomic characteristics using the XGBoost algorithm, demonstrates significant diagnostic value for axillary lymph node metastasis in breast cancer. This model can provide significant references for preoperative surgical strategy selection and prognosis evaluation for breast cancer patients, helping to reduce postoperative complications and improve long-term survival rates. Additionally, the utilization of SHAP enhancing the global and local interpretability of the model.

Dual-Mechanism Tuned Engineered Polyphenols with Cascade Photocatalytic Self-Fenton Reaction for Sustainable Biocidal Coatings.

Traditional disposable personal protective equipment (PPE) only blocks pathogenic bacteria by mechanical filtration, with the risk of recontamination and transmission remaining. Herein, inspired by phenolic-enabled nanotechnology (PEN), we proposed engineered polyphenol coatings by plant-derived aromatic aldehydes and metal involvement, denoted as FQM, to obtain the desired photocatalysis-self-Fenton antibacterial performance. Experiments and theoretical analysis proved the dual mechanism of Fe-induced enhancement: (1) tuning of molecular structure realized improved optical properties; (2) Fe(III)/Fe(II) triggered photocatalytic cascade self-Fenton reaction. Mechanism study reveals FQM killing bacteria by direct-contact ROS attack and gene regulation. Further, the FQM was developed as the ideal antibacterial coating on different fabrics (cloth cotton, polyester, and N95 mask), killing more than 93% of bacteria after 5 cycles of use. Such photocatalysis-self-Fenton coatings based on engineered polyphenols endowed with desirable safety, sustainability, and efficient antibacterial features are promising solutions to meet the challenges of the currently available PPE.

Blap-6, a Novel Antifungal Peptide from the Chinese Medicinal Beetle Blaps rhynchopetera against Cryptococcus neoformans.

Cryptococcus neoformans (C. neoformans) is a pathogenic fungus that can cause life-threatening meningitis, particularly in individuals with compromised immune systems. The current standard treatment involves the combination of amphotericin B and azole drugs, but this regimen often leads to inevitable toxicity in patients. Therefore, there is an urgent need to develop new antifungal drugs with improved safety profiles. We screened antimicrobial peptides from the hemolymph transcriptome of Blaps rhynchopetera (B. rhynchopetera), a folk Chinese medicine. We found an antimicrobial peptide named blap-6 that exhibited potent activity against bacteria and fungi. Blap-6 is composed of 17 amino acids (KRCRFRIYRWGFPRRRF), and it has excellent antifungal activity against C. neoformans, with a minimum inhibitory concentration (MIC) of 0.81 µM. Blap-6 exhibits strong antifungal kinetic characteristics. Mechanistic studies revealed that blap-6 exerts its antifungal activity by penetrating and disrupting the integrity of the fungal cell membrane. In addition to its direct antifungal effect, blap-6 showed strong biofilm inhibition and scavenging activity. Notably, the peptide exhibited low hemolytic and cytotoxicity to human cells and may be a potential candidate antimicrobial drug for fungal infection caused by C. neoformans.

Fragmentation Patterns of Phenolic C-Glycosides in Mass Spectrometry Analysis.

BACKGROUND: Many phenolic C-glycosides possess nutritional benefits and pharmacological efficacies. However, the MS/MS fragmentation pattern of phenolic C-glycosides analysis is understudied. This paper aims to determine the MS/MS fragmentation patterns of phenolic C-glycosides. METHOD: Ten compounds with different sugar moieties, aglycones, and substitutes were analyzed to determine the impact of these structural features on MS/MS fragmentation using UPLC-QTOF-MS analysis. RESULTS: The results showed that water loss followed by RDA reaction and alpha cleavage in the C-C bonded sugar moieties are the major fragmentation pathways. Additionally, the sugar cleavage was not affected by the skeleton and the substitute of the aglycones. These results suggested that the fragmentation patterns of phenolic C-glycosides differ from those in the O-glycosides, where the O-C glycosidic bond is the most cleavage-liable bond in MS/MS analysis. CONCLUSIONS: These MS/MS fragmentation patterns can be used for the identification of C-glycosides from dietary components and herbal medicine as well as developing robust methods using MRM methods to quantify C-glycosides.

Optimized rat models better mimic patients with irinotecan-induced severe diarrhea.

Irinotecan-induced severe diarrhea (IISD) not only limits irinotecan's application but also significantly affects patients' quality of life. However, existing animal models often inadequately represent the dynamics of IISD development, progression, and resolution across multiple chemotherapy cycles, yielding non-reproducible and highly variable response with limited clinical translation. Our studies aim to establish a reproducible and validated IISD model that better mimics the pathophysiology progression observed in patients, enhancing translational potential. We investigated the impact of dosing regimens (including different dose, infusion time, and two cycles of irinotecan administration), sex, age, tumor-bearing conditions, and irinotecan formulation on the IISD incidence and severity in mice and rats. Lastly, we investigated above factors' impact on pharmacokinetics of irinotecan, intestinal injury, and carboxylesterase activities. In summary, we successfully established a standard model establishment procedure for an optimized IISD model with highly reproducible severe diarrhea incidence rate (100%) and a low mortality rate (11%) in F344 rats. Additionally, the rats tolerated at least two cycles of irinotecan chemotherapy treatment. In contrast, the mouse model exhibited suboptimal IISD incidence rates (60%) and an extremely high mortality rate (100%). Notably, dosing regimen, age and tumor-bearing conditions of animals emerged as critical factors in IISD model establishment. In conclusion, our rat IISD model proves superior in mimicking pathophysiology progression and characteristics of IISD in patients, which stands as an effective tool for mechanism and efficacy studies in future chemotherapy-induced gut toxicity research.

[Characteristics of drug resistance and biofilm formation in carbapenem-resistant Acinetobacter baumannii in hospitalized children]. / 住院患儿耐碳青霉烯类鲍曼不动杆菌的耐药及生物膜特征分析.

OBJECTIVES: To study the distribution, drug resistance, and biofilm characteristics of carbapenem-resistant Acinetobacter baumannii (CRAB) isolated from hospitalized children, providing a reference for the prevention and treatment of CRAB infections in hospitalized children. METHODS: Forty-eight CRAB strains isolated from January 2019 to December 2022 were classified into epidemic and sporadic strains using repetitive extragenic palindromic sequence-based polymerase chain reaction. The drug resistance, biofilm phenotypes, and gene carriage of these two types of strains were compared. RESULTS: Both the 22 epidemic strains and the 26 sporadic strains were producers of Class D carbapenemases or extended-spectrum ß-lactamases with downregulated outer membrane porins, harboring the VIM, OXA-23, and OXA-51 genes. The biofilm formation capability of the sporadic strains was stronger than that of the epidemic strains (P<0.05). Genes related to biofilm formation, including Bap, bfs, OmpA, CsuE, and intI1, were detected in both epidemic and sporadic strains, with a higher detection rate of the intI1 gene in epidemic strains (P<0.05). CONCLUSIONS: CRAB strains are colonized in the hospital, with sporadic strains having a stronger ability to form biofilms, suggesting the potential for forming new clonal transmissions in the hospital. Continuous monitoring of the epidemic trends of CRAB and early warning of the distribution of epidemic strains are necessary to reduce the risk of CRAB infections in hospitalized children.

Age- and glaucoma-induced changes to the ocular glymphatic system.

The ocular glymphatic system supports bidirectional fluid transport along the optic nerve, thereby removes metabolic wastes including amyloid-ß. To better understand this biological process, we examined the distributions of intravitreally and intracisternally infused tracers in full-length optic nerves from different age groups of mice. Aging was linked to globally impaired ocular glymphatic fluid transport, similar to what has seen previously in the brain. Aging also reduced the pupillary responsiveness to light stimulation and abolished light-induced facilitation in anterograde ocular glymphatic flow. In contrast to normal aging, in the DBA/2 J model of glaucoma, we found a pathological increase of glymphatic fluid transport to the anterior optic nerve that was associated with dilation of the perivascular spaces. Thus, aging and glaucoma have fundamentally different effects on ocular glymphatic fluid transport. Manipulation of glymphatic fluid transport might therefore present a new target for the treatment of glaucoma.

Nature-Derived Hollow Micron-Tubular Signal Tracers Conquering the Size Limitations for Multimodal Immunochromatographic Detection of Antibiotics.

Developing signal tracers (STAs) with large size, multifunctionality, and high retention bioaffinity is believed to be a potential solution for achieving high-performance immunochromatographic assays (ICAs). However, the size limitations of STAs on strips are always a challenge because of the serious steric hindrance. Here, based on metal-quinone coordination and further metal etching, hollow micron-tubular STAs formed by natural alizarin and Fe3+ ions (named ALIFe) are produced to break through size limitations, provide more active sites, and achieve three-mode ICAs (ALIFe STAs-ICAs). Thanks to the special tubular morphology, ALIFe can successfully pass through the strip and provide an ideal signal intensity within 7 min at low mAb and probe dosages to achieve stable ICA analysis. Importantly, ALIFe shows excellent antibody enrichment and bioaffinity retention capability. With a proof-of-concept for streptomycin, the ALIFe STAs-ICAs showed the limit of detection (LOD) at 0.39 ng mL-1 for colorimetric mode, 0.32 ng mL-1 for catalytic mode, and 0.016 ng mL-1 for photothermal mode with total recoveries ranging from 80.46 to 121.59% in mike and honey samples. We anticipate that our study will help expand the ideas for the design of high-performance STAs with large size and broaden the practical application of ICA.

Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

Photosynthesis of Hydrogen Peroxide Based on g-C3 N4 : The Road of a Cost-Effective Clean Fuel Production.

Emerging artificial photosynthesis promises to offer a competitive means for solar energy conversion and further solves the energy crisis facing the world. Hydrogen peroxide (H2 O2 ), which is considered as a benign oxidant and a prospective liquid fuel, has received worldwide attention in the field of artificial photosynthesis on account of the source materials are just oxygen, water, and sunlight. Graphitic carbon nitride (g-C3 N4 )-based photocatalysts for H2 O2 generation have attracted extensive research interest due to the intrinsic properties of g-C3 N4 . In this review, research processes for H2 O2 generation on the basis of g-C3 N4 , including development, fabrication, merits, and disadvantages, and the state-of-the-art methods to enhance the performance are summarized after a brief introduction and the mechanism analysis of an efficient catalytic system. Also, recent applications of g-C3 N4 -based photocatalysts for H2 O2 production are reviewed, and the significance of active sites and synthetic pathways are highlighted from the view of reducing barriers. Finally, this paper ends with some concluding remarks to reveal the issues and opportunities of g-C3 N4 -based photocatalysts for producing H2 O2 in a high yield.

Exercise is inversely associated with functional dyspepsia among a sample of Chinese male armed police recruits.

BACKGROUND: There is no study evaluating the association between exercise and functional dyspepsia (FD) based on the Rome IV criteria. We aimed to investigate the prevalence of FD and evaluate the association between exercise and FD based on Rome IV criteria among a sample of Chinese armed police recruits. METHODS: An on-site questionnaire survey on FD among a sample of Chinese armed police recruits was conducted based on the Rome IV criteria in 2021. Potential confounders included age, body mass index (BMI), race, marriage, education, smoking, and drinking variables were adjusted. RESULTS: A total of 2594 recruits were enrolled, including 46 FD participants and 2548 non-FD participants. In the model adjusted for all demographic variables among participants excluding irritable bowel syndrome (IBS) and functional constipation (FC), compared with no exercise participants, 1 h < each exercise time ≤ 2 h (OR = 0.15, 95% CI: 0.03-0.77, P = 0.0230) was inversely associated with FD and compared with no exercise participants, mild exercise (OR = 0.09, 95% CI: 0.01-0.71, P = 0.0220) was significantly inversely associated with FD. CONCLUSIONS: The incidence rate of FD in this sample Chinese armed police recruits was 1.77%, and 1 h < each exercise time ≤ 2 h and mild intensity exercise were independently inversely associated with FD. However, the causal relationship needs to be verified by further randomized controlled trials.

Cerebrospinal fluid is a significant fluid source for anoxic cerebral oedema.

Cerebral oedema develops after anoxic brain injury. In two models of asphyxial and asystolic cardiac arrest without resuscitation, we found that oedema develops shortly after anoxia secondary to terminal depolarizations and the abnormal entry of CSF. Oedema severity correlated with the availability of CSF with the age-dependent increase in CSF volume worsening the severity of oedema. Oedema was identified primarily in brain regions bordering CSF compartments in mice and humans. The degree of ex vivo tissue swelling was predicted by an osmotic model suggesting that anoxic brain tissue possesses a high intrinsic osmotic potential. This osmotic process was temperature-dependent, proposing an additional mechanism for the beneficial effect of therapeutic hypothermia. These observations show that CSF is a primary source of oedema fluid in anoxic brain. This novel insight offers a mechanistic basis for the future development of alternative strategies to prevent cerebral oedema formation after cardiac arrest.

Activation of LXRα attenuates 2-Ethylhexyl diphenyl phosphate (EHDPP) induced placental dysfunction.

2-Ethylhexyl diphenyl phosphate (EHDPP) is one of the typical organophosphate flame retardants (OPFRs) and has been widely detected in environmental media. Exposure to EHDPP during pregnancy affects placental development and fetal growth. Liver X receptor α (LXRα) is essential to placental development. However, finite information is available regarding the function of LXRα in placenta damages caused by EHDPP. In present study we investigated to figure out whether LXRα is playing roles in EHDPP-induced placenta toxicity. While EHDPP restrained cell viability, migration, and angiogenesis dose-dependently in HTR-8/SVneo and JEG-3 cells, overexpression or activation by agonist T0901317 of LXRα alleviated the above phenomenon, knockdown or inhibition by antagonist GSK2033 had the opposite effects in vitro. Further study indicated EHDPP decreased LXRα expression and transcriptional activity leading to mRNA, protein expression levels downregulation of viability, migration, angiogenesis-related genes Forkhead box M1 (Foxm1), endothelial nitric oxide synthase (eNos), matrix metalloproteinase-2 (Mmp-2), matrix metalloproteinase-9 (Mmp-9), vascular endothelial growth factor-A (Vegf-a) and upregulation of inflammatory genes interleukin-6 (Il-6), interleukin-1ß (Il-1ß) and tumor necrosis factor-α (Tnf-α) in vitro and in vivo. Moreover, EHDPP caused decreased placental volume and fetal weight in mice, treatment with LXRα agonist T0901317 restored these adverse effects. Taken together, our study unveiled EHDPP-induced placenta toxicity and the protective role of LXRα in combating EHDPP-induced placental dysfunction. Activating LXRα could serve as a therapeutic strategy to reverse EHDPP-induced placental toxicity.