Comparative analysis of the immune repertoire between peripheral blood and bone marrow fluids in those infected by EBV and immunodeficiency: A retrospective case study.

High-throughput immune repertoire (IR) sequencing provides direct insight into the diversity of B cell receptor (BCR) and T cell receptor (TCR), with great potential to revolutionize the diagnosis, monitoring, and prevention of immune system-related disorders. In this study, multiplex PCR was applied to amplify the complementarity-determining regions of BCR and TCR, followed by comprehensive analysis by high-throughput sequencing. We compare the TCR (BCR) of bone marrow fluid (BMF) and peripheral blood (PB) samples from 17 patients in the Epstein-Barr and immunodeficiency groups, respectively. Our study shows that the diversity of the IR of blood samples is very similar to that of bone marrow samples statistically. However, the distributions of the monoclonal genes are significantly different in these 2 samples of most patients. This suggests that the BMFs can be replaced by the PB samples in diversity detection of IR to monitor the immune status of the body, while the detection of the BMFs is unreplaceable when the monoclonal change occurs. We used high-throughput sequencing to assess the TCR and BCR of the patients and provide a basis for the clinical analysis of PB and bone marrow samples and selection of disease diagnosis and monitoring methods.

Chronic Stress-induced Serotonin Impairs Intestinal Epithelial Cell Mitochondrial Biogenesis via the AMPK-PGC-1α Axis.

Chronic stress is closely associated with gastrointestinal disorders. However, the impact of stress-related neurotransmitters such as serotonin (5-hydroxytryptamine, 5-HT) on the intestines under chronic stress conditions remains poorly understood. This study aims to elucidate the mechanisms by which 5-HT affects mitochondrial biogenesis and intestinal barrier integrity during chronic stress. Employing a chronic restraint stress (CRS) mouse model, we observed elevated intestinal 5-HT levels, altered colonic mucosal structure, and disrupted tight junctions. The increase in 5-HT was associated with up-regulated serotonin synthesis enzymes and downregulated serotonin reuptake transporters, indicating an imbalance in serotonin homeostasis imbalance caused by chronic stress. Furthermore, serotonin exacerbated oxidative stress and impaired tight junction protein expression, highlighting its role in promoting intestinal barrier dysfunction. Experiments with cells in vitro demonstrated that 5-HT impairs mitochondrial biogenesis by inhibiting the AMPK-PGC-1α axis via 5-HT7 receptors and the cAMP-PKA pathway. Pharmacological inhibition of serotonin synthesis or 5-HT7 receptors alleviated the intestinal barrier damage caused by 5-HT and chronic stress, restoring mitochondrial biogenesis. These findings provide compelling evidence that serotonin exacerbates chronic stress-induced intestinal barrier disruption by inhibiting the AMPK-PGC-1α axis, paving the way for novel therapeutic interventions targeting the detrimental effects of serotonin on the intestine, particularly under chronic stress conditions.

Direction Modulation of Intramolecular Electric Field Boosts Hole Transport in Phthalocyanines for Perovskite Solar Cells.

Tuning the strength of intramolecular electric field (IEF) in conjugated molecules has emerged as an effective approach to boost charge transfer. While direction manipulation of IEF would be a potential way that is still unclear. Here, we leverage the control of peripheral substituents of conjugated phthalocyanines to chemically tune the spatial orientation of IEF. By analyzing the spatial swing of side chains using the Kolmogorov-Arnold representation and least squares algorithm, a comprehensive mathematical-physical model has been established. This model enables rapid evaluation of the IEF and maximum hole transport performance induced by spatial swings. The champion phthalocyanine as dopant-free hole transport material in perovskite solar cell realizes a record performance of 23.41%. Greatly device stability is also exhibited. This work affords a new way to enhance hole transport capabilities of conjugated molecules by optimizing their IEF vector for photovoltaic devices.

Magnetic Field Assisted Enhanced Sensitivity of Nonferromagnetic Materials Boosting the Carrier Transfer: Mechanistic Studies.

The performance of semiconductor sensors is determined by reaction kinetics, conductivity, and electron mobility, which are undoubtedly closely related to the electron motion behavior. Therefore, the effective regulation of electronic states is crucial for improving gas sensing properties. Previous methods of enhancing the gas-sensing performance have induced complex material modifications, and the extent of performance improvement is usually very limited. Further optimization of the gas sensing performance requires continuous efforts to advance new technologies. Toward this issue, a novel magnetic field-induced strategy is adopted to boost the carrier transfer efficiency of nonferromagnetic semiconductors. The gas sensing investigation results manifest that the applied magnetic field can effectively enhance the sensitivity and reduce the baseline resistance. The In2O3 NC-2 (In2O3 nanocubes) with an applied magnetic field have a greatly enhanced response of 161.4 toward 100 ppm formaldehyde, which is 2.5 times higher than that without magnetic field. The enhanced gas sensing properties can be mainly attributed to magnetization of reactive materials, which makes the orientation of electronic magnetic moments consistent, thus greatly contributing to reactivity. This work introduces a practical approach to effectively improve gas sensing performance without further morphology optimization, noble metal catalysis, structural modification, and material cladding. The results of this study provide new insights for designing novel gas sensors to improve the gas sensing performance.

Multidimensional quantitative characterization of periocular morphology: distinguishing esotropia from epicanthus by deep learning network.

Background: Prominent epicanthus could not only diminish the eyes' aesthetics but may be deceptive for its typical appearance of pseudo-esotropia. This study aims to apply a deep learning model to characterize the periocular morphology for preliminary identification. Methods: This prospective study consecutively included 300 subjects visiting the ophthalmology department in a tertiary referral hospital. Children aged 7-18 years with simple epicanthus or concomitant esotropia and healthy volunteers who were age- and gender-matched were eligible for inclusion. Multiple metrics were extracted automatically and manually from facial images to characterize the periocular morphology and binocular symmetry. The dice coefficient (Dice), intraclass correlation coefficient (ICC), and Bland-Altman biases were calculated to evaluate their consistency. The receiver operating characteristic (ROC) curve determined the cut-off values of symmetry indexes (SIs) for distinguishing concomitant esotropia subjects from epicanthus ones. Results: The Dice for eyelid and cornea segmentation were 0.949 and 0.944, respectively. The ICCs of the two measurements ranged from 0.898 to 0.983. Biases ranged from 0.16 to 0.74 mm. The periocular morphology of epicanthus eyes was significantly different from the normal ones, including palpebral fissure width (21.41±1.53 vs. 24.45±1.82 mm; P<0.01), and palpebral fissure height (8.91±1.37 vs. 9.60±1.25 mm; P<0.01). The ROC analysis yielded an area under the curve of 0.971 [95% confidence interval (CI): 0.950-0.991] with SI for distinguishing esotropia subjects. Its optimal cut-off value was 1.296 with 0.920 sensitivity and 0.910 specificity. Conclusions: Our study established a standard deep learning system for characterizing the periocular morphology of epicanthus and esotropia eyes with great accuracy. This objective method could be generalized to other periocular morphological assessments for clinical care.

NOVA2 regulates the properties of liver cancer stem cells and lenvatinib resistance in hepatocellular carcinoma via the Wnt pathway.

Background: The regulation of cancer stem cells (CSCs) is influenced by RNA-binding proteins (RBPs). The present study sought to investigate the role of NOVA2 in the processes of self-renewal, carcinogenesis, and lenvatinib resistance in liver CSCs. Methods: Neuro-oncological ventral antigen 2 (NOVA2) expression in liver CSCs was examined by real-time polymerase chain reaction (PCR). In vitro experiments were used to assess the effects of NOVA2 on liver CSC expansion and lenvatinib resistance. Results: In our study, the expression of the RBP NOVA2 was higher in CSCs. NOVA2 also increased the capacity for self-renewal and carcinogenesis of the liver CSCs via the Wnt pathway. Further, suppressing the Wnt pathway leads to desensitization of the hepatocellular carcinoma (HCC) cells that overexpress NOVA2 to apoptosis caused by lenvatinib. Analyzing patient data confirmed reduced levels of NOVA2 and therefore we speculate that NOVA2 may serve as a potential indicator for response to lenvatinib in patients with HCC. Methyltransferase-like 3 (METTL3) and YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1)-dependent N6-methyladenosine (m6A) methylation were linked to upregulation of NOVA2 in HCC. Furthermore, it was shown that the expression of METTL3 was elevated in cellular models of type 2 diabetes mellitus (T2DM). Conclusions: NOVA2 is involved in the process of liver CSC self-renewal and carcinogenesis. In addition, NOVA2 expression may help identify patients with a higher chance of benefiting from lenvatinib treatment and can be a promising therapeutic target for HCC.

Three new species of Colletotrichum (Glomerellales, Glomerellaceae) associated with walnut (Juglansregia) anthracnose from China.

Colletotrichum species are significant pathogens of various economic plant hosts worldwide. In this study, 45 Colletotrichum isolates were obtained from symptomatic walnut leaves of walnut anthracnose in Shaanxi and Sichuan Provinces. In conjunction with morphological evidence and multi-gene phylogenetic analyses of internal transcribed spacer (ITS), actin (act), chitin synthase 1 (chs1), glyceraldehyde-3-phosphate dehydrogenase (gapdh) and beta-tubulin (tub2) sequences support the introduction of three new species, namely Colletotrichumcordae, C.guangyuanense and C.juglandium. Five species of Colletotrichum were identified to be C.fioriniae of the C.acutatum species complex, C.karsti of the C.boninense species complex, C.gloeosporioides, C.mengyinense and C.siamense of the C.gloeosporioides species complex. The three new species are described and illustrated in this paper and compared with taxa in the Colletotrichumgloeosporioides species complex. The current results improve the understanding of Colletotrichum species causing walnut anthracnose in China.

ADLM Guidance Document on the Measurement and Reporting of Lipids and Lipoproteins.

BACKGROUND: The accurate measurement of blood lipids and lipoproteins is crucial for the clinical management of atherosclerotic disease risk. Despite progress in standardization, there are still significant variations in pre-analytical requirements, methods, nomenclature, and reporting work flows. CONTENT: The guidance document aims to improve standardization of clinical lipid testing work flows. It provides recommendations for the components of the lipid panel, fasting requirements, reporting of results, and specific recommendations for non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], apolipoprotein B (apo B), point-of-care lipid testing, and LDL subfraction testing. SUMMARY: Lipid panels should always report non-HDL-C and LDL-C calculations if possible. Fasting is not routinely required except in specific cases. Modern equations should be utilized for LDL-C calculation. These equations allow for LDL-C reporting at elevated concentrations of triglycerides and obviate the need for direct measured LDL-C in most cases.

Cellulose-based yellow-green emitting carbon dots with large Stokes shift as effective "turn off-on" fluorescence platforms for Cr (VI) and AA dual efficacy detection.

BACKGROUND: Hexavalent chromium (Cr (VI)) is highly carcinogenic to humans. Ascorbic acid (AA) deficiency can be hazardous to health. And the dual-effect fluorescence detection of them is an important research topic. Carbon dots (CDs) based on cellulose are excellent candidates for the fluorescence probes due to their low cost and environmental friendliness. But most of them exhibit shortwave emission, small Stokes shift and poor fluorescence performance, all of which limit their use. Therefore, there is an urgent need for cellulose CDs with longer emission wavelengths and larger Stokes shifts in dual-effect fluorescence detection of Cr (VI) and AA. RESULTS: Under optimal conditions (180 °C, 12 h), we prepared cellulose-based nitrogen-doped carbon dots (N-CDs) by a simple one-step hydrothermal process, which display longer emission wavelengths (ex: 370 nm, em: 510 nm), larger Stokes shifts (140 nm) and high fluorescence quantum yield (QY: 19.27 %). The continuous "turn-off" and "turn-off-on" fluorescence detection platforms were constructed based on the internal filtering effect (IFE) between Cr6+ and N-CDs, and Cr6+ reduced to Cr3+ by AA at pH = 6. The platform has been successfully simultaneous detect Cr (VI) and AA with a wide range of 0.01-40 µM and 0.1-100 µM. And the lowest limits of detection (LOD) are 0.0303 µM and 0.072 µM, respectively. In the presence of some other metals, non-metal ions and water-soluble acids in the fruits, this fluorescent platform can demonstrate a high level of interference immunity. SIGNIFICANCE AND NOVELTY: This represents the first yellow-green cellulose-based N-CDs with large Stokes shift for dual-effect detection of Cr (VI) and AA in real water samples and fresh fruits. The fluorescence detection platform has the advantage of low volume detection. Less than 2 mL of sample is required for testing and results are available in <5 min. This method is rare and supply a novel idea for the quantitative monitoring of Cr (VI) and AA.

Polar Metallicity Controlled by Epitaxial Strain Engineering.

The discovery of polar metal opens the door to incorporating electric polarization into electronics with the potential to invigorate next-generation multifunctional electronic devices. Especially, electric polarization can be induced by geometric design in non-polar perovskite oxides. Here, the epitaxial strain exerted on the deposited single-crystalline NdNiO3 thin films is systematically varied in both sign and amplitude by choosing substrates with different lattice mismatch. The pseudocubic NdNiO3(111) film, which is non-polar in its bulk state, is induced to be polar under both compressive and tensile strain. The fine-tuning of epitaxial strain is realized by continuously varying the film thickness using the "thickness-wedge" growth technique, and from the elucidated thickness dependence, the electric polarization and metallicity can be further optimized. Moreover, transitioning from isotropic to anisotropic epitaxial strain gives rise to an ideal polar metal state in the pseudocubic NdNiO3(102) film on an orthorhombic substrate, achieving a remarkably low resistivity of 173 µΩ cm at room temperature. The metal-insulator transition in NdNiO3 is completely suppressed and the polar metal state becomes the ground state at all temperatures. These results demonstrate alluring possibilities of induction and manipulation of both electric polarization and electric transport properties in functional perovskite oxides by epitaxial strain engineering.

Remazolam combined with transversus abdominis plane block in gastrointestinal tumor surgery: Have we achieved better anesthetic effects?

Laparoscopic surgery is the main treatment method for patients with gastrointestinal malignant tumors. Although laparoscopic surgery is minimally invasive, its tool stimulation and pneumoperitoneum pressure often cause strong stress reactions in patients. On the other hand, gastrointestinal surgery can cause stronger pain in patients, compared to other surgeries. Transversus abdominis plane block (TAPB) can effectively inhibit the transmission of nerve impulses caused by surgical stimulation, alleviate patient pain, and thus alleviate stress reactions. Remazolam is an acting, safe, and effective sedative, which has little effect on hemodynamics and is suitable for most patients. TAPB combined with remazolam can reduce the dosage of total anesthetic drugs, reduce adverse reactions, reduce stress reactions, and facilitate the rapid postoperative recovery of patients.

Biotransformation, Bioaccumulation, and Bioelimination of Triphenyl Phosphate and Its Dominant Metabolite Diphenyl Phosphate In Vivo.

Aryl phosphorus flame retardants (aryl-PFRs), such as triphenyl phosphate (TPHP) and diphenyl phosphate (DPHP), are widely used worldwide. Understanding the fates of aryl-PFRs in vivo is crucial to assessing their toxicity and the risks they pose. Seven TPHP metabolites, including Phase I hydrolysis and hydroxylation and Phase II glucuronidation products, were identified in C57BL/6J male mice following subacute dietary exposure to aryl-PFRs (70 µg/kg body weight (bw)/day) for 7 days. TPHP was almost completely metabolized by mice (∼97%), with DPHP the major metabolite formed (34%-58%). In addition, mice were exposed to aryl-PFRs (7 µg/kg bw/day) for 12 weeks. Both TPHP and DPHP occurred at higher concentrations in the digestive tract (intestine and stomach), liver and heart. The total concentration of DPHP in all organs was 3.55-fold greater than that of TPHP. Recovery analysis showed that the rate of TPHP elimination from mouse organs reached 38%, while only 3%-5% of DPHP was removed, suggesting that the rates of degradation and elimination of DPHP were slower than TPHP and its bioaccumulation potential was higher. These results highlight the critical role of DPHP in the biotransformation, bioaccumulation, and bioelimination of TPHP, providing valuable insights into the fate of aryl-PFRs in vivo.

Metabolomics Reveals Glycerophospholipids, Peptides, and Flavonoids Contributing to Breast Meat Flavor and Benefit Properties of Beijing-You Chicken.

Unique metabolites contribute to the performance of meat flavor and potential function. In this study, UHPLC-Q Exactive HF-X-based metabolomics and multivariate analysis were applied to explore the characteristic metabolites in the breast meat of Beijing-You chicken (BYC) aged 150, 300, and 450 days (D150, D300, and D450). Based on the criteria of variable importance in the projection (VIP) > 1 and p < 0.05, a total of 154 and 97 differential metabolites (DMs) were screened out compared with D450 (D450 vs. D150, D450 vs. D300), respectively. In general, the relative content of carnosine, L-L-homoglutathione, demethyloleuropein, neohesperidin dihydrochalcone, 7-chloro-2-(3,4-dimethoxyphenyl)-3,5-dihydroxy-6,8-dimethoxy-4H-chromen-4-one, glycerophospholipids, exhibited the highest abundance at D450, while balenine, anserine, L-beta-aspartyl-L-leucine, glutathione, oxidized glutathione, stearoylcarnitine, ganoderic acid alpha, oleuroside, Lysoglycerophospholipid species (LGP) presented a downward trend with age. These 210 DMs were involved in 10 significantly enriched pathways related to the synthesis and metabolism of amino acids, peptides, and glycerophospholipid, such as glutathione metabolism, histidine metabolism, glycerophospholipid metabolism, arginine biosynthesis, tyrosine metabolism, and lysine degradation. In conclusion, this work could not only facilitate a better understanding of the differences of chicken flavor and benefit properties with age, but also provide potential valuable bioactive compounds for further research.

Hesperetin alleviates aflatoxin B1 induced liver toxicity in mice: Modulating lipid peroxidation and ferritin autophagy.

One of the ways Aflatoxin B1 damages the liver is through ferroptosis. Ferroptosis is characterized by the build-up of lipid peroxides and reactive oxygen species (ROS) due to an excess of iron. Dietary supplements have emerged as a promising strategy for treating ferroptosis in the liver. The flavonoid component hesperetin, which is mostly present in citrus fruits, has a number of pharmacological actions, such as those against liver fibrosis, cancer, and hyperglycemia. However, hesperetin's effects and mechanisms against hepatic ferroptosis are still unknown. In this study, 24 male C57BL/6 J mice were randomly assigned to CON, AFB1 (0.45 mg/kg/day), and AFB1+ hesperetin treatment groups (40 mg/kg/day). The results showed that hesperetin improved the structural damage of the mouse liver, down-regulated inflammatory factors (Cxcl1, Cxcl2, CD80, and F4/80), and alleviated liver fibrosis induced by aflatoxin B1. Hesperetin reduced hepatic lipid peroxidation induced by iron accumulation by up-regulating the levels of antioxidant enzymes (GPX4, GSH-Px, CAT, and T-AOC). It is worth noting that hesperetin not only improved lipid peroxidation but also maintained the dynamic balance of iron ions by reducing ferritin autophagy. Mechanistically, hesperetin's ability to regulate ferritin autophagy mostly depends on the PI3K/AKT/mTOR/ULK1 pathway. In AFB1-induced HepG2 cells, the addition of PI3K inhibitor (LY294002) and AKT inhibitor (Miransertib) confirmed that hesperetin regulated the PI3K/AKT/mTOR/ULK1 pathway to inhibit ferritin autophagy and reduced the degradation of ferritin in lysosomes. In summary, our results suggest that hesperetin not only regulates the antioxidant system but also inhibits AFB1-induced ferritin hyperautophagy, thereby reducing the accumulation of iron ions to mitigate lipid peroxidation. This work provides a fresh perspective on the mechanism behind hesperetin and AFB1-induced liver damage in mice.

Effect of rapid rehabilitation nursing on improving clinical outcomes in postoperative patients with colorectal cancer.

BACKGROUND: Surgical resection is the cornerstone treatment for colorectal cancer. Rapid rehabilitation care predicated on evidence-based medical theory aims to improve postoperative nursing care, subsequently reducing the physical and mental traumatic stress response and helping patients who undergo surgery recover rapidly. AIM: To assess the effect of rapid rehabilitation care on clinical outcomes, including overall postoperative complications, anastomotic leaks, wound infections, and intestinal obstruction in patients with colorectal cancer. METHODS: We searched the PubMed, Web of Science, Embase, Elsevier Science Direct, and Springer Link databases from January 1, 2010, to January 1, 2024, to screen eligible studies on rapid rehabilitation care among patients who underwent colorectal cancer surgery. Patients were screened based on the inclusion and exclusion criteria. RevMan 5.4 software was used for statistical analysis of the data. RESULTS: Twelve studies were enrolled, which included 2420 patients. The results showed that rapid rehabilitation care decreased the incidence of overall postoperative complications (OR: 0.44, 95%CI: 0.26-0.74, P = 0.002), anastomotic leaks (OR: 0.68, 95%CI: 0.41-1.12, P = 0.13), wound infections (OR: 0.45, 95%CI: 0.29-0.72, P = 0.0007), and intestinal obstruction (OR: 0.54, 95%CI: 0.34-0.86, P = 0.01) compared to conventional care. Further trials and studies are needed to confirm these results. CONCLUSION: Rapid rehabilitation care decreased the occurrence of postoperative complications, anastomotic leaks, wound infections, and intestinal obstruction compared to conventional care in patients who underwent colorectal surgery. Therefore, promoting the application of rapid rehabilitation care in clinical practice cannot be overemphasized.

Lactating striped hamsters (Cricetulus barabensis) do not decrease the thermogenic capacity to cope with extreme cold temperature.

For small non-hibernating mammals, a high thermogenic capacity is important to increase activity levels in the cold. It has been previously reported that lactating females decrease their thermogenic activity of brown adipose tissue (BAT), whereas their capacity to cope with extreme cold remains uncertain. In this study we examined food intake, body temperature and locomotor behavior, resting metabolic rate, non-shivering thermogenesis, and cytochrome c oxidase activity, and the rate of state 4 respiration of liver, skeletal muscle, and BAT in striped hamsters (Cricetulus barabensis) at peak lactation and non- breeding hamsters (controls). The lactating hamsters and non- breeding controls were acutely exposed to -15°C, and several markers indicative of thermogenic capacity were examined. In comparison to non-breeding females, lactating hamsters significantly increased food intake and body temperature, but decreased locomotor behavior, and the BAT mass, indicative of decreased BAT thermogenesis at peak lactation. Unexpectedly, lactating hamsters showed similar body temperature, resting metabolic rate, non-shivering thermogenesis with non-breeding females after acute exposure to -15°C. Furthermore, cytochrome c oxidase activity of liver, skeletal muscle and BAT, and serum thyroid hormone concentration, and BAT uncoupling protein 1 expression, in lactating hamsters were similar with that in non-breeding hamsters after acute extreme cold exposure. This suggests that lactating females have the same thermogenic capacity to survive cold temperatures compared to non-breeding animals. This is particularly important for females in the field to cope with cold environments during the period of reproduction. Our findings indicate that the females during lactation, one of the highest energy requirement periods, do not impair their thermogenic capacity in response to acute cold exposure.

Physiologically Based Pharmacokinetic Modeling of Vancomycin in Critically Ill Neonates: Assessing the Impact of Pathophysiological Changes.

Dosing vancomycin for critically ill neonates is challenging owing to substantial alterations in pharmacokinetics (PKs) caused by variability in physiology, disease, and clinical interventions. Therefore, an adequate PK model is needed to characterize these pathophysiological changes. The intent of this study was to develop a physiologically based pharmacokinetic (PBPK) model that reflects vancomycin PK and pathophysiological changes in neonates under intensive care. PK-sim software was used for PBPK modeling. An adult model (model 0) was established and verified using PK profiles from previous studies. A neonatal model (model 1) was then extrapolated from model 0 by scaling age-dependent parameters. Another neonatal model (model 2) was developed based not only on scaled age-dependent parameters but also on quantitative information on pathophysiological changes obtained via a comprehensive literature search. The predictive performances of models 1 and 2 were evaluated using a retrospectively collected dataset from neonates under intensive care (chictr.org.cn, ChiCTR1900027919), comprising 65 neonates and 92 vancomycin serum concentrations. Integrating literature-based parameter changes related to hypoalbuminemia, small-for-gestational-age, and co-medication, model 2 offered more optimized precision than model 1, as shown by a decrease in the overall mean absolute percentage error (50.6% for model 1; 37.8% for model 2). In conclusion, incorporating literature-based pathophysiological changes effectively improved PBPK modeling for critically ill neonates. Furthermore, this model allows for dosing optimization before serum concentration measurements can be obtained in clinical practice.

Polystyrene nano-plastics impede skeletal muscle development and induce lipid accumulation via the PPARγ/LXRß pathway in vivo and in vitro in mice.

Nano-plastics (NPs) have emerged as a significant environmental pollutant, widely existing in water environment, and pose a serious threat to health and safety with the intake of animals. Skeletal muscle, a vital organ for complex life activities and functional demands, has received limited attention regarding the effects of NPs. In this study, the effects of polystyrene NPs (PS-NPs) on skeletal muscle development were studied by oral administration of different sizes (1 mg/kg) of PS-NPs in mice. The findings revealed that PS-NPs resulted in skeletal muscle damage and significantly hindered muscle differentiation, exhibiting an inverse correlation with PS-NPs particle size. Morphological analysis demonstrated PS-NPs caused partial disruption of muscle fibers, increased spacing between fibers, and lipid accumulation. RT-qPCR and western blots analyses indicated that PS-NPs exposure downregulated the expression of myogenic differentiation-related factors (Myod, Myog and Myh2), activated PPARγ/LXRß pathway, and upregulated the expressions of lipid differentiation-related factors (SREBP1C, SCD-1, FAS, ACC1, CD36/FAT, ADIPOQ, C/EBPα and UCP-1). In vitro experiments, C2C12 cells were used to confirm cellular penetration of PS-NPs (0, 100, 200, 400 µg/mL) through cell membranes along with activation of PPARγ expression. Furthermore, to verify LXRß as a key signaling molecule, silencing RNA transfection experiments were conducted, resulting in no increase in the expressions of PPARγ, LXRß, SREBP1C, FAS, CD36/FAT, ADIPOQ, C/EBPα and UCP-1 even after exposure to PS-NPs. However, the expressions of SCD-1and ACC1 remained unaffected. The present study evidenced that exposure to PS-NPs induced lipid accumulation via the PPARγ/LXRß pathway thereby influencing skeletal muscle development.

A New Approach Refined Probabilistic Health Risk Assessment of Shaoguan Smelter Based on Microenvironment - Guangdong Province, China, 2021.

Introduction: This study introduces a novel method for developing an advanced exposure conceptual model tailored for health risk assessment, focusing on microenvironments. Methods: The research was conducted at a major smelter in China to assess the health risks associated with trace metals (TMs) pollutants in the facility and the surrounding soil. Results: Deterministic risk assessment indicated that cobalt, cadmium, antimony, manganese, arsenic, plumbum, and mercury (Co, Cd, Sb, Mn, As, Pb, and Hg) necessitated further evaluation through probabilistic risk assessment to assess potential health risks to residents. The 95% quantile concentrations of other TMs were found to be within acceptable health risk limits. For the probabilistic risk assessment, exposure parameters such as body weight, respiration rate, and exposure duration were collected using a questionnaire. This targeted assessment of the residential microenvironment revealed it as the site of the highest carcinogenic (CR) and non-carcinogenic risks (NCR), with values ranging from 2.84×10-5 to 6.7×10-5 and 1.59 to 5.57, respectively. Conclusion: The primary contaminants posing the greatest health risks in residential and industrial areas have been identified as As, Pb, and Mn. The probabilistic health risk model, which focuses on microenvironmental factors, yields more precise results and offers a valuable tool for managing soil health risks.

Investigating the causal relationship between gut microbiota and gastroenteropancreatic neuroendocrine neoplasms: a bidirectional Mendelian randomization study.

Background: The interaction between the intestinal flora and gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) remains poorly understood, despite the known effect of the gut microbiota on gastrointestinal adenocarcinomas. Hence, the present research aimed to determine the potential causal correlation between the intestinal flora and GEP-NENs by conducting a bidirectional Mendelian randomization (MR) analysis. Methods: Two-sample MR analysis was conducted using the summary statistics of the gut microbiota from the MiBioGen consortium and those of GEP-NENs from the FinnGen research project. The inverse-variance weighted approach was utilized as the primary analytical method. To enhance the robustness of our findings, multiple sensitivity tests were performed, including Cochran's Q test for evaluating heterogeneity, the MR-Egger intercept test to detect horizontal pleiotropy, and the MR-PRESSO test to identify outliers and assess pleiotropy bias. Additionally, a leave-one-out analysis was performed to validate the consistency of our findings. The MR-Steiger test was also utilized to determine the causal direction in the correlation between the gut microbiota and GEP-NENs. Finally, a reverse MR analysis was performed to assess reverse causality between the intestinal flora and GEP-NENs. Results: We identified 42 taxa of the gut microbiota that were potentially causally associated with GEP-NENs; of these taxa, 7, 8, 11, and 16 taxa were causally associated with pancreatic NENs, colorectal NENs, small intestinal NENs, and gastric NENs, respectively. After adjusting for false discovery rate (FDR) correction, we found significant causal links of Euryarchaeota with small intestinal NENs and Family XIII UCG-001 with gastric NENs. The sensitivity analyses confirmed the stability of these correlations. In the reverse MR analysis, colorectal NENs and small intestinal NENs were found to be associated with variations in 8 and 6 different taxa of the gut microbiota, respectively. After adjusting for FDR correction, no significant causal links were detected between GEP-NENs and the intestinal flora. Conclusion: The present study reveals a potential causal association between certain taxa of the intestinal flora and GEP-NENs, thus providing new perspectives regarding the role of the intestinal flora in the development of these tumors. These insights could provide innovative approaches to screen and prevent these diseases.