JOURNAL/nrgr/04.03/01300535-202501000-00030/figure1/v/2024-05-14T021156Z/r/image-tiff Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery. Our previous in vitro study demonstrated that exosomes/small extracellular vesicles (sEVs) isolated from cerebral endothelial cells (CEC-sEVs) of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a (miR-27a) is an elevated miRNA in ischemic CEC-sEVs. In the present study, we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a (27a-sEVs) further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs. 27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector. Small EVs isolated from CECs transfected with a scramble vector (Scra-sEVs) were used as a control. Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs. An array of behavior assays was used to measure neurological function. Compared with treatment of ischemic stroke with Scra-sEVs, treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side, and significantly improved neurological outcomes. In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth. Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone, while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a, and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone. Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs. Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes. Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.
Rhizosphere microorganisms, as one of the most important components of the soil microbiota and plant holobiont, play a key role in the medicinal plant-soil ecosystem, which are closely related to the growth, adaptability, nutrient absorption, stress tolerance and pathogen resistance of host plants. In recent years, with the wide application of molecular biology and omics technologies, the outcomes of rhizosphere microorganisms on the health, biomass production and secondary metabolite biosynthesis of medicinal plants have received extensive attention. However, whether or to what extent rhizosphere microorganisms can contribute to the construction of the quality evaluation system of Chinese medicinal materials is still elusive. Based on the significant role of rhizosphere microbes in the survival and quality formation of medicinal plants, this paper proposed a new concept of rhizosphere microbial markers (micro-markers), expounded the relevant research methods and ideas of applying the new concept, highlighted the importance of micro-markers in the quality evaluation and control system of traditional Chinese medicines (TCMs), and introduced the potential value in soil environmental assessment, plant pest control and quality assessment of TCMs. It provides reference for developing ecological planting of TCMs and ensuring the production of high quality TCMs by regulating rhizosphere microbial communities.
This study aimed to retrospectively analyze the perioperative and postoperative follow-up data of patients with super obesity who had undergone RYGB, SG, BPD/DS, and SADI-S. A retrospective observational study was conducted to analyze the perioperative and postoperative follow-up data of 60 patients with super obesity who had undergone bariatric surgery. A total of 34 men and 26 women were included in this study. The participants had an average preoperative BMI of 53.81 ± 3.25 kg/m2. The body weight and BMI of all four patient groups decreased significantly at 3, 6, and 12 months postoperatively compared with the preoperative values. Additionally, the TWL (%) and EWL (%) of all four groups increased gradually over the same period. Compared with the preoperative values, the systolic and diastolic blood pressure, glycosylated hemoglobin, uric acid, triglycerides, and total cholesterol decreased to varying degrees in the four groups 1 year postoperatively. RYGB, SG, BPD/DS, and SADI-S are all safe and effective in treating super obese patients and improving their metabolic diseases to a certain extent.
Bariatric Surgery , Body Mass Index , Obesity, Morbid , Humans , Male , Female , Adult , Obesity, Morbid/surgery , Obesity, Morbid/complications , Retrospective Studies , Middle Aged , Bariatric Surgery/methods , Treatment Outcome , China , Weight Loss , Follow-Up Studies , East Asian People
Background: Fungal infections are associated with high morbidity and mortality in the intensive care unit (ICU), but their diagnosis is difficult. In this study, machine learning was applied to design and define the predictive model of ICU-acquired fungi (ICU-AF) in the early stage of fungal infections using Random Forest. Objectives: This study aimed to provide evidence for the early warning and management of fungal infections. Methods: We analyzed the data of patients with culture-positive fungi during their admission to seven ICUs of the First Affiliated Hospital of Chongqing Medical University from January 1, 2015, to December 31, 2019. Patients whose first culture was positive for fungi longer than 48 h after ICU admission were included in the ICU-AF cohort. A predictive model of ICU-AF was obtained using the Least Absolute Shrinkage and Selection Operator and machine learning, and the relationship between the features within the model and the disease severity and mortality of patients was analyzed. Finally, the relationships between the ICU-AF model, antifungal therapy and empirical antifungal therapy were analyzed. Results: A total of 1,434 cases were included finally. We used lasso dimensionality reduction for all features and selected six features with importance ≥0.05 in the optimal model, namely, times of arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation. The area under the curve of the model for predicting ICU-AF was 0.981 in the test set, with a sensitivity of 0.960 and specificity of 0.990. The times of arterial catheter (p = 0.011, OR = 1.057, 95% CI = 1.053-1.104) and invasive mechanical ventilation (p = 0.007, OR = 1.056, 95%CI = 1.015-1.098) were independent risk factors for antifungal therapy in ICU-AF. The times of arterial catheter (p = 0.004, OR = 1.098, 95%CI = 0.855-0.970) were an independent risk factor for empirical antifungal therapy. Conclusion: The most important risk factors for ICU-AF are the six time-related features of clinical parameters (arterial catheter, enteral nutrition, corticosteroids, broadspectrum antibiotics, urinary catheter, and invasive mechanical ventilation), which provide early warning for the occurrence of fungal infection. Furthermore, this model can help ICU physicians to assess whether empiric antifungal therapy should be administered to ICU patients who are susceptible to fungal infections.
Apparent diffusion coefficient (ADC) derived from diffusion-weighted magnetic resonance imaging (DWI) may help diagnose endometrial cancer (EC). However, the association between ADC and the recurrence and survival of EC remains unknown. We performed a systematic review and meta-analysis to investigate whether pretreatment ADC on DWI could predict the prognosis of women with EC. PubMed, Embase, and Cochrane's Library were searched for relevant cohort studies comparing the clinical outcomes between women with EC having low versus high ADC on pretreatment DWI. Two authors independently conducted data collection, literature searching, and statistical analysis. Using a heterogeneity-incorporating random-effects model, we analyzed the results. In the meta-analysis, 1358 women with EC were included from eight cohort studies and followed for a median duration of 40 months. Pooled results showed that a low pretreatment ADC on DWI was associated with poor disease-free survival (DFS, hazard ratio [HR]: 3.29, 95% CI: 2.04 to 5.31, p < 0.001; I2 = 41%). Subgroup analysis according to study design, tumor stage, MRI Tesla strength, ADC cutoff, follow-up duration, and study quality score showed consistent results (p for subgroup analysis all > 0.05). The predictive value of low ADC for poor DFS in women with EC decreased in multivariate studies compared to univariate studies (HR: 2.59 versus 32.57, p = 0.002). Further studies showed that a low ADC was also associated with poor overall survival (HR: 3.36, 95% CI: 1.33 to 8.50, p = 0.01, I2 = 0). In conclusion, a low ADC on pretreatment DWI examination may predict disease recurrence and survival in women with EC.
AIM: Ferroptosis is a novel type of programmed cell death that performs a critical function in diabetic nephropathy (DN). Augmenter of liver regeneration (ALR) exists in the inner membrane of mitochondria, and inhibits inflammation, apoptosis, and oxidative stress in acute kidney injury; however, its role in DN remains unexplored. Here, we aimed to identify the role of ALR in ferroptosis induction and macrophage activation in DN. METHODS: The expression of ALR was examined in DN patients, db/db DN mice, and HK-2 cells treated with high glucose (HG). The effects of ALR on ferroptosis and macrophage activation were investigated with ALR conditional knockout, lentivirus transfection, transmission electron microscopy, qRT-PCR and western blotting assay. Mass spectrometry and rescue experiments were conducted to determine the mechanism of ALR. RESULTS: ALR expression was reduced in the kidney tissues of DN patients and mice, serum of DN patients, and HG-HK-2 cells. Moreover, the inhibition of ALR promoted ferroptosis, macrophage activation, and DN progression. Mechanistically, ALR can directly bind to carnitine palmitoyltransferase-1A (CPT1A), the key rate-limiting enzyme of fatty acid oxidation (FAO), and inhibit the expression of CPT1A to regulate lipid metabolism involving FAO and lipid droplet-mitochondrial coupling in DN. CONCLUSION: Taken together, our findings revealed a crucial protective role of ALR in ferroptosis induction and macrophage activation in DN and identified it as an alternative diagnostic marker and therapeutic target for DN.
OBJECTIVES: This study aimed to compare the intestinal and pancreatobiliary subtypes of ampullary adenocarcinoma in a large patient group due to limited data on survival and risk factors. METHODS: A retrospective analysis of the clinical and pathological findings and the survival of 184 patients with ampullary adenocarcinoma who underwent curative operation between 2007 and 2018 was performed. RESULTS: Pancreatobiliary subtype had a higher prevalence of jaundice before operation than the intestinal subtype (p < 0.05). Pancreatobiliary subtype had a larger tumor size (> 2 mm) (p < 0.01) and poorer differentiation (p < 0.05) than the intestinal subtype. Perineural invasion more frequently occurred in pancreatobiliary subtype than the intestinal subtype (p < 0.01) and pancreatobiliary subtype had a higher prevalence of positive dissected lymph nodes (p < 0.05) with an advanced disease stage (p < 0.01) than the intestinal subtype. Patients of the pancreatobiliary subtype had poorer disease-free and overall survival than patients of the intestinal subtype. No survival benefit of adjuvant chemotherapy was found in either patients of the intestinal subtype or pancreatobiliary subtype. No significant difference was found in any subtypes regarding the recurrent regions. CONCLUSIONS: Pancreatobiliary subtype exhibited a higher recurrence rate and a poorer overall survival rate with more unfavorable pathological characteristics than the intestinal subtype.
OBJETIVOS: Los datos sobre la supervivencia y los factores de riesgo del adenocarcinoma ampular son limitados debido a su rareza. Este estudio buscó comparar el subtipo intestinal y el subtipo pancreático-biliar en pacientes con adenocarcinoma ampular. MÉTODOS: Análisis retrospectivo de hallazgos clínicos y patológicos y la supervivencia de 184 pacientes con adenocarcinoma ampular tratados entre 2007 y 2018. RESULTADOS: El subtipo pancreático-biliar tuvo una mayor prevalencia de ictericia antes de la operación y un tamaño de tumor mayor, y una peor diferenciación, que el subtipo intestinal. La invasión perineural fue más frecuente en el subtipo pancreático-biliar, con una mayor prevalencia de linfonodos disecados positivos y un estadio avanzado de la enfermedad. Los pacientes del subtipo pancreático-biliar tuvieron una supervivencia libre de enfermedad y una supervivencia general peores que los pacientes del subtipo intestinal. No se encontró ningún beneficio de la quimioterapia adyuvante en pacientes del subtipo intestinal o pancreático-biliar. No hubo diferencia significativa en las regiones recurrentes. CONCLUSIÓN: El subtipo pancreático-biliar mostró una tasa de recurrencia y una tasa de supervivencia general peores, con características patológicas más desfavorables que el subtipo intestinal.
Adenocarcinoma , Ampulla of Vater , Common Bile Duct Neoplasms , Humans , Retrospective Studies , Ampulla of Vater/pathology , Male , Female , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adenocarcinoma/mortality , Adenocarcinoma/classification , Common Bile Duct Neoplasms/pathology , Common Bile Duct Neoplasms/surgery , Common Bile Duct Neoplasms/mortality , Common Bile Duct Neoplasms/classification , Middle Aged , Aged , Chemotherapy, Adjuvant , Adult , Neoplasm Invasiveness , Aged, 80 and over , Neoplasm Recurrence, Local , Lymphatic Metastasis , Tumor Burden , Disease-Free Survival
As a complex anisotropic medium, variation in birefringence within biological tissues is closely associated with numerous physiological behaviors and phenomena. In this Letter, we propose a polarization feature fusion method and corresponding polarimetric parameters, which exhibit excellent performance of capturing the birefringence dynamic variation process in complex anisotropic media. By employing the feature fusion method, we combine and transform polarization basis parameters (PBPs) to derive fused polarization feature parameters (FPPs) with explicit expressions. Subsequently, we conduct Monte Carlo (MC) simulation to demonstrate the effectiveness of the proposed FPPs from two variation dimensions of birefringence direction θ and modulus Δn. Leveraging mathematical modeling and linear transformations, we investigate and abstract their response patterns concerning θ and Δn. Finally, the experiments confirm that the FPPs show superior adaptability and interpretability in characterizing the birefringence dynamic process of turbid media. The findings presented in this study provide new, to the best of our knowledge, methodological insights of information extraction for computational polarimetry in biomedical research.
Neural network (NN) controllers have shown great potential in solving complex control or decision-making tasks. However, most of the NN controllers either rely on the availability of large datasets or require dense interactions with the environment, which hinders their application in real systems. In this paper, we introduce a model-based reinforcement learning (MBRL) algorithm, aimed at realizing ultra-fast tuning of deep NN controller from a small sample set of real-world data. The algorithm uses Gaussian processes (GPs) to model the unknown dynamics of real system and updates controller parameters through stochastic gradient descent. By using particle-based method for long-term predictions, the algorithm can easily incorporate online state estimators and filters into controller learning, which is conductive to learning from systems with partially measurable states and stochastic control delay. We apply the algorithm to calibrate a deep NN controller for the path tracking of a full-size autonomous vehicle (AV). Simulation and field test results show that the deep NN controller can be well calibrated after only one interaction with the environment and can achieve similar tracking performance to optimization-based methods such as nonlinear model prediction control (NMPC) in various test scenarios by combining with a feed-forward pure pursuit (PP) controller.
To identify novel susceptibility genes for hepatocellular carcinoma (HCC), we performed a rare-variant association study in Chinese populations consisting of 2,750 cases and 4,153 controls. We identified four HCC-associated genes, including NRDE2, RANBP17, RTEL1, and STEAP3. Using NRDE2 (index rs199890497 [p.N377I], p = 1.19 × 10-9) as an exemplary candidate, we demonstrated that it promotes homologous recombination (HR) repair and suppresses HCC. Mechanistically, NRDE2 binds to the subunits of casein kinase 2 (CK2) and facilitates the assembly and activity of the CK2 holoenzyme. This NRDE2-mediated enhancement of CK2 activity increases the phosphorylation of MDC1 and then facilitates the HR repair. These functions are eliminated almost completely by the NRDE2-p.N377I variant, which sensitizes the HCC cells to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with chemotherapy. Collectively, our findings highlight the relevance of the rare variants to genetic susceptibility to HCC, which would be helpful for the precise treatment of this malignancy.
Carcinoma, Hepatocellular , Liver Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Recombinational DNA Repair , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Recombinational DNA Repair/drug effects , Casein Kinase II/genetics , Casein Kinase II/metabolism , Male , Mice , Animals , Female , Cell Line, Tumor , Middle Aged , Genetic Predisposition to Disease
Photobiocatalysis-where light is used to expand the reactivity of an enzyme-has recently emerged as a powerful strategy to develop chemistries that are new to nature. These systems have shown potential in asymmetric radical reactions that have long eluded small-molecule catalysts1. So far, unnatural photobiocatalytic reactions are limited to overall reductive and redox-neutral processes2-9. Here we report photobiocatalytic asymmetric sp3-sp3 oxidative cross-coupling between organoboron reagents and amino acids. This reaction requires the cooperative use of engineered pyridoxal biocatalysts, photoredox catalysts and an oxidizing agent. We repurpose a family of pyridoxal-5'-phosphate-dependent enzymes, threonine aldolases10-12, for the α-C-H functionalization of glycine and α-branched amino acid substrates by a radical mechanism, giving rise to a range of α-tri- and tetrasubstituted non-canonical amino acids 13-15 possessing up to two contiguous stereocentres. Directed evolution of pyridoxal radical enzymes allowed primary and secondary radical precursors, including benzyl, allyl and alkylboron reagents, to be coupled in an enantio- and diastereocontrolled fashion. Cooperative photoredox-pyridoxal biocatalysis provides a platform for sp3-sp3 oxidative coupling16, permitting the stereoselective, intermolecular free-radical transformations that are unknown to chemistry or biology.
Amino Acids , Biocatalysis , Oxidative Coupling , Photochemical Processes , Amino Acids/biosynthesis , Amino Acids/chemistry , Amino Acids/metabolism , Biocatalysis/radiation effects , Directed Molecular Evolution , Free Radicals/chemistry , Free Radicals/metabolism , Glycine/chemistry , Glycine/metabolism , Glycine Hydroxymethyltransferase/metabolism , Glycine Hydroxymethyltransferase/chemistry , Indicators and Reagents , Light , Oxidative Coupling/radiation effects , Pyridoxal Phosphate/metabolism , Stereoisomerism , Amino Acids, Branched-Chain/chemistry , Amino Acids, Branched-Chain/metabolism
The occurrence of microplastics (MPs) in aquatic ecosystems and their ability to absorb hydrophobic pollutants, such as persistent organic pollutants (POPs), is currently a significant concern. MPs, which are the main breakdown product of plastics, have been frequently detected in the environment, posing serious threats to organisms' health. One particular pollutant, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), is a dominant congener of PBDEs and is highly toxic to organisms. However, there is limited knowledge regarding the exposure of marine fishes to PBDEs through MPs and their combined toxic effects. In this study, the embryo toxicity of Hexagrammos otakii was conducted to investigate the combined effects of MPs and BDE-47. The results showed that MPs and BDE-47 co-exposure had detrimental effects on embryonic development, such as reduced hatchability, increased mortality, decreased heart rate, and body malformation. Moreover, the combined toxicity of these substances appeared more pronounced harmful effects compared to exposure to BDE-47 alone. Histopathological examination revealed that co-exposure can cause greater damage to hatching glands and yolk. The enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways included phagosome, metabolism of xenobiotics by cytochrome P450, TCA cycle, and Wnt signaling pathway, which are closely related to embryonic growth. BDE-47 and MPs may activate the Wnt signaling pathway to affect the normal development of embryos. Our results suggest that MPs and BDE-47 exposure may cause growth disorders in the early life stages of H.otakii, leading to abnormal embryonic development. All these results will contribute to the further study of the ecological risk assessment and toxicity of MPs and organic pollutant mixtures in marine fish.
Embryo, Nonmammalian , Halogenated Diphenyl Ethers , Microplastics , Water Pollutants, Chemical , Animals , Halogenated Diphenyl Ethers/toxicity , Water Pollutants, Chemical/toxicity , Microplastics/toxicity , Embryo, Nonmammalian/drug effects , Polystyrenes/toxicity , Embryonic Development/drug effects
The introduction of axial-coordinated heteroatoms in FeâNâC single-atom catalysts enables the significant enhancement of their oxygen reduction reaction (ORR) performance. However, the interaction relationship between the axial-coordinated heteroatoms and their carbon supports is still unclear. In this work, a gas phase surface treatment method is proposed to prepare a series of XâFeâNâC (X = O, P, and S) single-atom catalysts with axial X-coordination on graphitic-N-rich carbon supports. Synchrotron-based X-ray absorption near-edge structure spectra and X-ray photoelectron spectroscopy indicate the formation of an axial charge transfer channel between the graphitic-N-rich carbon supports and single-atom Fe sites by axial O atoms in OâFeâNâC. As a result, the OâFeâNâC exhibits excellent ORR performance with a half-wave potential of 0.905 V versus RHE and a high specific capacity of 884 mAh g-1 for zinc-air battery, which is superior to other XâFeâNâC catalysts without axial charge transfer and the commercial Pt/C catalyst. This work not only demonstrates a general synthesis strategy for the preparation of single-atom catalysts with axial-coordinated heteroatoms, but also presents insights into the interaction between single-atom active sites and doped carbon supports.
The autonomic nerve system (ANS) innervates organs and tissues throughout the body and maintains functional balance among various systems. Further investigations have shown that excessive activation of ANS not only causes disruption of homeostasis, but also may promote tumor formation. In addition, the dynamic interaction between nerve and tumor cells in the tumor microenvironment also regulate tumor progression. On the one hand, nerves are passively invaded by tumor cells, that is, perineural invasion (PNI). On the other hand, compared with normal tissues, tumor tissues are subject to more abundant innervation, and nerves can influence tumor progression through regulating tumor proliferation, metastasis and drug resistance. A large number of studies have shown that nerve-tumor crosstalk, including PNI and innervation, is closely related to the prognosis of patients, and contributes to the formation of cancer pain, which significantly deteriorates the quality of life for patients. These findings suggest that nerve-tumor crosstalk represents a potential target for anti-tumor therapies and the management of cancer pain in the future. In this review, we systematically describe the mechanism by which nerve-tumor crosstalk regulates tumorigenesis and progression.
Liver metastasis stands as the primary contributor to mortality among patients diagnosed with colorectal cancer (CRC). Neutrophil extracellular traps (NETs) emerge as pivotal players in the progression and metastasis of cancer, showcasing promise as prognostic biomarkers. Our objective is to formulate a predictive model grounded in genes associated with neutrophil extracellular traps and identify novel therapeutic targets for combating CRLM. We sourced gene expression profiles from the Gene Expression Omnibus (GEO) database. Neutrophil extracellular trap-related gene set was obtained from relevant literature and cross-referenced with the GEO datasets. Differentially expressed genes (DEGs) were identified through screening via the least absolute shrinkage and selection operator regression and random forest modeling, leading to the establishment of a nomogram and subtype analysis. Subsequently, a thorough analysis of the characteristic gene CYP4F3 was undertaken, and our findings were corroborated through immunohistochemical staining. We identified seven DEGs (ATG7, CTSG, CYP4F3, F3, IL1B, PDE4B, and TNF) and established nomograms for the occurrence and prognosis of CRLM. CYP4F3 is highly expressed in CRC and colorectal liver metastasis (CRLM), exhibiting a negative correlation with CRLM prognosis. It may serve as a potential therapeutic target for CRLM. A novel prognostic signature related to NETs has been developed, with CYP4F3 identified as a risk factor and potential target for CRLM.
Biomarkers, Tumor , Colorectal Neoplasms , Cytochrome P450 Family 4 , Extracellular Traps , Liver Neoplasms , Humans , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Liver Neoplasms/secondary , Liver Neoplasms/genetics , Cytochrome P450 Family 4/genetics , Cytochrome P450 Family 4/metabolism , Prognosis , Extracellular Traps/metabolism , Biomarkers, Tumor/genetics , Nomograms , Gene Expression Profiling , Male , Female , Gene Expression Regulation, Neoplastic , Neutrophils/metabolism
Background: Diet/nutrition is critically important in the pathogenesis, progression, and treatment outcomes of various mental disorders. Current research predominantly focuses on the role of diet in the development and treatment of depression, with less attention given to the relationship between diet and Bipolar Disorder (BD). Method: We employed Mendelian Randomization (MR) to investigate the relationship between 28 dietary habits and BD. An analysis was conducted using publicly available genome-wide association study data from the UK Biobank dataset. Various dietary habits were analyzed as exposures with BD as the outcome, mainly using the Inverse Variance Weighted (IVW) method. Results: Intake of non-oily fish and sponge pudding both have a positive association with BD. Oily fish, dried fruit, apples, salt, and cooked vegetables intake also appeared potentially risky for BD, although the possibility of false positives cannot be ruled out. Sensitivity analysis further confirmed the robustness of these findings. Conclusion: Our research provides evidence of a relationship between various dietary habits and BD. It underscores the need for careful dietary management and balance to reduce the risk of BD, suggesting caution with dietary preferences for fish and sponge pudding. Furthermore, more detailed studies are needed to further understand the potential impacts of high-sugar and high-protein diets on BD development.
This prospective birth cohort study evaluated the association of exposure to PM2.5 (diameter ≤2.5 µm), PM1-2.5 (1-2.5 µm), and PM1 (≤1 µm) with maternal thyroid autoimmunity and function during early pregnancy. A total of 15,664 pregnant women were included at 6 to 13+6 gestation weeks in China from 2018 to 2020. Single-pollutant models using generalized linear models (GLMs) showed that each 10 µg/m3 increase in PM2.5 and PM1-2.5 was related with 6% (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01, 1.12) and 15% (OR = 1.15, 95% CI: 1.08, 1.22) increases in the risk of thyroid autoimmunity, respectively. The odds of thyroid autoimmunity significantly increased with each interquartile range increase in PM2.5 and PM1-2.5 exposure (P for trend <0.001). PM1 exposure was not significantly associated with thyroid autoimmunity. GLM with natural cubic splines demonstrated that increases in PM2.5 and PM1-2.5 exposure were associated with lower maternal FT4 levels, while a negative association between PM1 and FT4 levels was found when exposure exceeded 32.13 µg/m3. Only PM2.5 exposure was positively associated with thyrotropin (TSH) levels. Our findings suggest that high PM exposure is associated with maternal thyroid disruption during the early pregnancy.
Autoimmunity , Particulate Matter , Thyroid Gland , Humans , Female , Pregnancy , Adult , China , Prospective Studies , Air Pollutants , Maternal Exposure
Biofilms are communities formed by bacteria adhering to surfaces, widely present in porous medium, and their growth can lead to clogging. Our experiment finds that under certain flow conditions, biofilms detach in pores and form a dynamically changing flow path. We define detachment that occurs far from the boundary of the flow path (with a distance greater than 200 µm) as internal detachment and detachment that occurs at the boundary of the flow path as external detachment. To understand the mechanism of biofilm detachment, we study the detachment behaviors of the Bacillus subtilis biofilm in a porous medium in a microfluidic device, where Bacillus subtilis strain is triple fluorescent labeled, which can represent three main phenotypes during the biofilm formation: motile cells, matrix-producing cells, and spores. We find that slow small-scale internal detachment occurs in regions with very few motile cells and matrix-producing cells, and bacterial movement in these areas is disordered. The increase in the number of matrix-producing cells induces clogging, and after clogging, the rapid detachment of the bulk internal biofilm occurs due to the increased pressure difference at the inlet and outlet. When both internal and external detachments occur simultaneously, the number of matrix-producing cells in the internal detachment area is 2.5 times that in the external detachment area. The results indicate that biofilm detachment occurs in areas with fewer matrix-producing cells, as matrix-producing cells can help resist detachment by secreting extracellular polymeric substances (EPSs).
In this paper, using the data of private sector enterprises listed in China from 2009 to 2014, we study the relationships between corporate social responsibility, political connections, and barrier industry diversification among Chinese public-listed private-sector enterprises. The empirical test results reveal that establishing political connections can contribute to diversification of these firms, while engaging in corporate social responsibility helps to promote their barrier industry diversification. More engagement in corporate social responsibility makes it easier for them to establish political connections and strengthen the association between political connections and barrier industry diversification. This study provides new empirical evidence for not only understanding the relationship between political connections of these firms and access to economic resources but also a new perspective regarding their conduct related to corporate social responsibility (CSR).
We report a novel organic photoredox catalysis to achieve unprecedented γ-(hetero)aryl/alkenyl-δ-silyl aliphatic amines via silyl-mediated distal (hetero)aryl/alkenyl migration of aromatic/alkenyl amines bearing unactivated alkenes with hydrosilanes. This protocol features mild and metal-free reaction conditions, high atom economy, excellent selectivity, and functional group compatibility. Mechanistic studies suggest that silylation and (hetero)aryl/alkenylation involve photoredox hydrogen atom transfer catalysis and subsequent 1,4-migration of a remote (hetero)aryl/alkenyl group from nitrogen to carbon.
