The application of the "perinephric fat wrapping" technique with oral mucosal graft for the management of ureter repair and reconstruction.

OBJECTIVE: The management of long-segment ureteral stenosis has posed a significant challenge for urologists. Ureteroplasty with oral mucosal graft has emerged as an effective approach for treating long-segment ureteral stenosis and defects. A key step in replacement repair surgery involves suturing the surrounding tissue with an adequate blood supply around the reconstructed ureter. The current study aims to evaluate the potential practical application of the "perinephric fat wrapping" technique in laparoscopic ureteroplasty with oral mucosal graft. METHODS: Between July 2018 and February 2023, 26 patients with ureteral stenosis underwent laparoscopic ureteroplasty with oral mucosal graft at the Second Affiliated Hospital of Anhui Medical University. We used traditional omental wrapping technique (OW group) or perinephric fat wrapping technique (PFW group) to enhance ureter repair. Perioperative and follow-up data for both groups were collected retrospectively and compared. RESULTS: There were 10 patients in OW group, including 4 males and 6 females, with BMI of 23.5±2.8 kg/m2 and stenosis length of 3.6±1.6 cm. There were 16 patients in the PFW group, including 10 males and 6 females, with a BMI of 26.1±3.3 kg/m2 and a median stenosis length of 2.3 cm (range, 1.2~6.0 cm). The operation of both groups was successfully completed, and no serious complications occurred during the operation. The mean operating time (OT) in the OW group was 200.6±41.9 min, the estimated amount of blood loss (EBL) was 25 ml (range, 10~30ml), and the median length of postoperative hospital stay (LHS) was 7.5 days (range 4.0~14.0 days). In the PFW group, the mean operating time (OT) was 211.9±38.3 min, the estimated blood loss (EBL) was 25 ml (range, 5~150ml), and the postoperative hospital stay (LHS) was 6.8±2.0 d. There was no significant difference between the two groups in the above indexes. Postoperative anal exhaust time was 1.0 d (range, 1.0~2.5d) in the PFW group and 1.9±0.5 d in the OW group, with significant difference between the two groups (P=0.009). The mean follow-up time was 36.8±15.9 months, and there was no significant difference between OW group and PFW group in the curative effect of operation. CONCLUSION: Perinephric fat wrapping technique not only avoids the potential effects of using omentum on abdominal organs, it is also as safe and effective as omentum wrapping technique in repairing and reconstructing the ureter using oral mucosal grafts.

Adolescent exposure to tris(1,3-dichloro-2-propyl) phosphate (TCPP) induces reproductive toxicity in zebrafish through hypothalamic-pituitary-gonadal axis disruption.

Tris(1,3-dichloro-2-propyl) phosphate (TCPP), a prevalent organophosphorus flame retardant in aquatic environments, has raised significant concerns regarding its ecological risks. This study aims to explore the impacts of TCPP on the reproductive functions of zebrafish and delineate its gender-related toxic mechanisms. By assessing the effects on zebrafish of 10 mg/L TCPP exposure from 30 to 120 days post-fertilization (dpf), we thoroughly evaluated the reproductive capability and endocrine system alterations. Our findings indicated that TCPP exposure disrupted gender differentiation in zebrafish and markedly impaired their reproductive capacity, resulting in decreased egg laying and offspring development quality. Histological analyses of gonadal tissues showed an abnormal increase in immature oocytes in females and a reduction in mature sperm count and spermatogonial structure integrity in males, collectively leading to compromised embryo quality. Additionally, molecular docking results indicated that TCPP showed a strong affinity for estrogen receptors, and TCPP-treated zebrafish exhibited imbalanced sex hormones and increased estrogen receptor expression. Alterations in genes associated with the hypothalamic-pituitary-gonadal (HPG) axis and activation of the steroidogenesis pathway suggested that TCPP targets the HPG axis to regulate sex hormone homeostasis. Tamoxifen (TAM), as a competitive inhibitor of estrogen, exhibited a biphasic effect, as evidenced by the counteraction of TCPP-induced effects in both male and female zebrafish after TAM addition. Overall, our study underscored the gender-dependent reproductive toxicity of TCPP exposure in zebrafish, characterized by diminished reproductive capacity and hormonal disturbances, likely due to interference in the HPG axis and steroidogenesis pathways. These findings emphasize the critical need to consider gender differences in chemical risk assessments for ecosystems and highlight the importance of understanding the mechanisms underlying the effects of chemical pollutants on the reproductive health of aquatic species.

Preparation and Performance of Leather-Finished Plywood.

In order to achieve batch production, we propose a simple and fast method to prepare leather-finished plywood. In this study, ethylene-vinyl acetate was selected as the intermediate layer to prepare EVA/polyurethane (PU) leather composites. ESEM, tensile property test and compressive property test were used to characterize the microstructure and physical-mechanical properties of the composites. The response surface method (RSM) was also used to explore the relationship between hot pressing temperature, hot pressing pressure and hot pressing time. The significance of the factors and the interactions between the two factors were determined by ANOVA, with the most significant effect being that of the temperature. The theoretical optimal hot pressing process conditions were calculated by the regression equation as a temperature of 124.4 °C, a time of 200 s and a pressure of 1.3 MPa. The surface bond strength of the test specimen measured under this condition was 1.89 MPa, it has good finishing properties and the impregnation peel strength and surface bond strength met the requirements of GB/T 15104-2021.

Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogenesis and prevent obesity.

Obesity is a global issue that warrants the identification of more effective therapeutic targets and a better understanding of the pivotal molecular pathogenesis. Annexin A1 (ANXA1) is known to inhibit phospholipase A2, exhibiting anti-inflammatory activity. However, the specific effects of ANXA1 in obesity and the underlying mechanisms of action remain unclear. Our study reveals that ANXA1 levels are elevated in the adipose tissue of individuals with obesity. Whole-body or adipocyte-specific ANXA1 deletion aggravates obesity and metabolic disorders. ANXA1 levels are higher in stromal vascular fractions (SVFs) than in mature adipocytes. Further investigation into the role of ANXA1 in SVFs reveals that ANXA1 overexpression induces lower numbers of mature adipocytes, while ANXA1-knockout SVFs exhibit the opposite effect. This suggests that ANXA1 plays an important role in adipogenesis. Mechanistically, ANXA1 competes with MYC binding protein 2 (MYCBP2) for interaction with PDZ and LIM domain 7 (PDLIM7). This exposes the MYCBP2-binding site, allowing it to bind more readily to the SMAD family member 4 (SMAD4) and promoting its ubiquitination and degradation. SMAD4 degradation downregulates peroxisome proliferator-activated receptor gamma (PPARγ) transcription and reduces adipogenesis. Treatment with Ac2-26, an active peptide derived from ANXA1, inhibits both adipogenesis and obesity through the mechanism. In conclusion, the molecular mechanism of ANXA1 inhibiting adipogenesis was first uncovered in our study, which is a potential target for obesity prevention and treatment.

Reverse Turnover Pedicled Latissimus Dorsi Muscle Flap for the Repair of Radiation Ulcer in the Back: A Case Report.

Cases of radioactive back ulcers caused by radiation therapy have not been reported. This paper reports a matter of a 55-year-old male patient suffering from chronic back radiation ulcer after coronary stent implantation. Through the repeated and complete expansion of the rear radiation ulcer wound, the back radiation ulcer wound was successfully repaired with the reverse turnover pedicled latissimus dorsi muscle flap, and the clinical effect was satisfactory.

Sesquiterpenoids from Carpesium abrotanoides and their anti-inflammatory activity both in vitro and in vivo.

Twenty-nine sesquiterpenoids, including pseudoguaiane-type (1-11), eudesmane-type (12-23), and carabrane-type (24-29), have been identified from the plant Carpesium abrotanoides. Of them, compounds 1-4, 12-15, and 24-27, namely carpabrotins A-L, are twelve previously undescribed ones. Compound 3 possessed a pseudoguaiane backbone with a rearrangement modification at C-11, C-12 and C-13, while compound 4 suffered a carbon bond break between the C-4 and C-5 to form a rare 4,5-seco-pseudoguaiane lactone. Compounds 1-3, 5, 13-16 and 25-27 exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 macrophages with IC50 values less than 40 µM, while compounds 1, 2, 5, 13, 14, 16, and 25-27 showed significant inhibitory activity comparable to that of dexamethasone. The anti-atopic dermatitis (AD) effects of compounds 5 and 16 were tested according to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in KM mice, and the results revealed that the major products 5 and 16 improved the histological features of AD-like skin lesions and mast cell infiltration in mice. This study suggested that sesquiterpenoids in C. abrotanoides should play a key role in its anti-inflammatory use.

Fully forward mode training for optical neural networks.

Optical computing promises to improve the speed and energy efficiency of machine learning applications1-6. However, current approaches to efficiently train these models are limited by in silico emulation on digital computers. Here we develop a method called fully forward mode (FFM) learning, which implements the compute-intensive training process on the physical system. The majority of the machine learning operations are thus efficiently conducted in parallel on site, alleviating numerical modelling constraints. In free-space and integrated photonics, we experimentally demonstrate optical systems with state-of-the-art performances for a given network size. FFM learning shows training the deepest optical neural networks with millions of parameters achieves accuracy equivalent to the ideal model. It supports all-optical focusing through scattering media with a resolution of the diffraction limit; it can also image in parallel the objects hidden outside the direct line of sight at over a kilohertz frame rate and can conduct all-optical processing with light intensity as weak as subphoton per pixel (5.40 × 1018- operations-per-second-per-watt energy efficiency) at room temperature. Furthermore, we prove that FFM learning can automatically search non-Hermitian exceptional points without an analytical model. FFM learning not only facilitates orders-of-magnitude-faster learning processes, but can also advance applied and theoretical fields such as deep neural networks, ultrasensitive perception and topological photonics.

The feasibility and safety of laparoscopic transcystic common bile duct exploration after prior gastrectomy.

The increased incidence of gallstones can be linked to previous gastrectomy (PG). However, the success rate of endoscopic retrograde cholangiopan-creatography after gastrectomy has significantly reduced. In such cases, laparoscopic transcystic common bile duct exploration (LTCBDE) may be an alternative. In this study, LTCBDE was evaluated for its safety and feasibility in patients with PG. We retrospectively evaluated 300 patients who underwent LTCBDE between January 2015 and June 2023. The subjects were divided into 2 groups according to their PG status: PG group and No-PG group. The perioperative data from the 2 groups were compared. The operation time in the PG group was longer than that in the No-PG group (184.69 ±â€…20.28 minutes vs 152.19 ±â€…26.37 minutes, P < .01). There was no significant difference in intraoperative blood loss (61.19 ±â€…41.65 mL vs 50.83 ±â€…30.47 mL, P = .087), postoperative hospital stay (6.36 ±â€…1.94 days vs 5.94 ±â€…1.36 days, P = .125), total complication rate (18.6 % vs 14.1 %, P = .382), stone clearance rate (93.2 % vs 96.3 %, P = .303), stone recurrence rate (3.4 % vs 1.7 %, P = .395), and conversion rate (6.8 % vs 7.0 %, P = .941) between the 2 groups. No deaths occurred in either groups. A history of gastrectomy may not affect the feasibility and safety of LTCBDE, because its perioperative results are comparable to those of patients with a history of No-gastrectomy.

Synchronously in vivo real-time monitoring bacterial load and temperature with evaluating immune response to decipher bacterial infection.

Determining the precise course of bacterial infection requires abundant in vivo real-time data. Synchronous monitoring of the bacterial load, temperature, and immune response can satisfy the shortage of real-time in vivo data. Here, we conducted a study in the joint-infected mouse model to synchronously monitor the bacterial load, temperature, and immune response using the second near-infrared (NIR-II) fluorescence imaging, infrared thermography, and immune response analysis for 2 weeks. Staphylococcus aureus (S. aureus) was proved successfully labeled with glucose-conjugated quantum dots in vitro and in subcutaneous-infected model. The bacterial load indicated by NIR-II fluorescence imaging underwent a sharp drop at 1 day postinfection. At the same time, the temperature gap detected through infrared thermography synchronously brought by infection reached lowest value. Meanwhile, the flow cytometry analysis demonstrated that immune response including macrophage, neutrophil, B lymphocyte, and T lymphocyte increased to the peak at 1 day postinfection. Moreover, both M1 macrophage and M2 macrophage in the blood have an obvious change at ~ 1 day postinfection, and the change was opposite. In summary, this study not only obtained real-time and long-time in vivo data on the bacterial load, temperature gap, and immune response in the mice model of S. aureus infection, but also found that 1 day postinfection was the key time point during immune response against S. aureus infection. Our study will contribute to synchronously and precisely studying the complicated complex dynamic relationship after bacterial infection at the animal level.

Preliminary response to Tislelizumab plus chemotherapy drugs in patient with periampullary carcinoma: a report of one case and a literature review.

Periampullary carcinoma is a malignant gastrointestinal tumor originating from the head of the pancreas, distal bile duct, duodenum, or the ampulla of Vater. Currently, surgery remains the primary treatment option, yet the postoperative recurrence rate remains high. Chemotherapy is the main approach for controlling postoperative recurrence. Histologically, periampullary carcinoma is categorized into two types: intestinal (IN) and pancreaticobiliary (PB) subtype. Each subtype requires different therapeutic approaches, with the PB type primarily treated with gemcitabine and the IN type with 5-FU. Despite these options, patient outcomes are still unsatisfactory. In recent years, the feasibility of immunotherapy in tumor treatment has been increasingly evidenced, although research on its efficacy in periampullary carcinoma treatment is still limited. In this report, we present a case of a periampullary carcinoma patient who experienced recurrence and metastasis after undergoing radical pancreatoduodenectomy and receiving gemcitabine-based chemotherapy post-surgery. Through next-generation sequencing (NGS), we identified high expression levels of programmed cell death-ligand 1 (PD-L1) with a combined positive score (CPS) of 35, high tumor mutation burden (TMB-H), and high microsatellite instability (MSI-H) in this patient. Therefore, we implemented a combination therapy using Tislelizumab and chemotherapy. According to the latest follow-up, the tumors are effectively controlled. Our utilization of immunotherapy combined with chemotherapy holds significant implication for the treatment of periampullary carcinoma.

Nanowatt all-optical 3D perception for mobile robotics.

Three-dimensional (3D) perception is vital to drive mobile robotics' progress toward intelligence. However, state-of-the-art 3D perception solutions require complicated postprocessing or point-by-point scanning, suffering computational burden, latency of tens of milliseconds, and additional power consumption. Here, we propose a parallel all-optical computational chipset 3D perception architecture (Aop3D) with nanowatt power and light speed. The 3D perception is executed during the light propagation over the passive chipset, and the captured light intensity distribution provides a direct reflection of the depth map, eliminating the need for extensive postprocessing. The prototype system of Aop3D is tested in various scenarios and deployed to a mobile robot, demonstrating unprecedented performance in distance detection and obstacle avoidance. Moreover, Aop3D works at a frame rate of 600 hertz and a power consumption of 33.3 nanowatts per meta-pixel experimentally. Our work is promising toward next-generation direct 3D perception techniques with light speed and high energy efficiency.

Induction of insulin resistance in female mice due to prolonged phenanthrene exposure: Unveiling the low-dose effect and potential mechanisms.

Phenanthrene (Phe) is a commonly occurring polycyclic aromatic hydrocarbon (PAH) found in various food sources and drinking water. Previous studies have shown that long-term exposure to Phe in male mice leads to insulin resistance in a dose-dependent manner. However, the effect of Phe on glucose homeostasis in female mice remains unknown. To address this knowledge gap, female Kunming mice were exposed to Phe through their drinking water at concentrations of 0.05, 0.5, and 5 ng/mL. After 270 d of exposure, we surprisingly discovered a low-dose effect of Phe on insulin resistance in female mice, which differed from the effect observed in male mice and showed sexual dimorphism. Specifically, insulin resistance was only observed in the 0.05 ng/mL treatment, and this low-dose effect was also reflected in the concentration of Phe in white adipose tissue (WAT). Differences in metabolic enzyme activities in the liver may potentially explain this effect. The observed sexual dimorphism in Phe exposure could be attributed to variations in estrogen (E2) level and estrogen receptor beta (ERß) expression in WAT. These findings highlight the association between environmental factors and the development of insulin resistance, emphasizing the pathogenic effect of even low doses of Phe. Moreover, sex dependent-effect should be given more attention when studying the toxic effects of environmental pollutants.

Development and validation of a prognostic model for assessing long COVID risk following Omicron wave-a large population-based cohort study.

BACKGROUND: Long coronavirus disease (COVID) after COVID-19 infection is continuously threatening the health of people all over the world. Early prediction of the risk of Long COVID in hospitalized patients will help clinical management of COVID-19, but there is still no reliable and effective prediction model. METHODS: A total of 1905 hospitalized patients with COVID-19 infection were included in this study, and their Long COVID status was followed up 4-8 weeks after discharge. Univariable and multivariable logistic regression analysis were used to determine the risk factors for Long COVID. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%), and factors for constructing the model were screened using Lasso regression in the training cohort. Visualize the Long COVID risk prediction model using nomogram. Evaluate the performance of the model in the training and validation cohort using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). RESULTS: A total of 657 patients (34.5%) reported that they had symptoms of long COVID. The most common symptoms were fatigue or muscle weakness (16.8%), followed by sleep difficulties (11.1%) and cough (9.5%). The risk prediction nomogram of age, diabetes, chronic kidney disease, vaccination status, procalcitonin, leukocytes, lymphocytes, interleukin-6 and D-dimer were included for early identification of high-risk patients with Long COVID. AUCs of the model in the training cohort and validation cohort are 0.762 and 0.713, respectively, demonstrating relatively high discrimination of the model. The calibration curve further substantiated the proximity of the nomogram's predicted outcomes to the ideal curve, the consistency between the predicted outcomes and the actual outcomes, and the potential benefits for all patients as indicated by DCA. This observation was further validated in the validation cohort. CONCLUSIONS: We established a nomogram model to predict the long COVID risk of hospitalized patients with COVID-19, and proved its relatively good predictive performance. This model is helpful for the clinical management of long COVID.

The safety and feasibility of laparoscopic anatomical left hemihepatectomy along the middle hepatic vein from the head side approach.

Background: Laparoscopic left hemihepatectomy (LLH) is commonly used for benign and malignant left liver lesions. We compared the benefits and drawbacks of LLH from the head side approach (LLHH) with those of conventional laparoscopic left hemihepatectomy (CLLH). This study was conducted to investigate the safety and feasibility of LLHH by comparing it with CLLH. Methods: In this study, 94 patients with tumor or hepatolithiasis who underwent LLHH (n = 39) and CLLH (n = 55) between January 2016 and January 2023 were included. The preoperative features, intraoperative details, and postoperative outcomes were compared between the two groups. Results: For hepatolithiasis, patients who underwent LLHH exhibited shorter operative time (p = 0.035) and less blood loss (p = 0.023) than those who underwent CLLH. However, for tumors, patients undergoing LLHH only showed shorter operative time (p = 0.046) than those undergoing CLLH. Moreover, no statistically significant differences in hospital stay, transfusion, hospital expenses, postoperative white blood cell (WBC) count, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were observed between the two groups (p > 0.05) for tumor or hepatolithiasis. For hepatocellular carcinoma (HCC), no differences in both overall survival (p = 0.532) and disease-free survival (p = 0.274) were observed between the two groups. Conclusion: LLHH is a safe and feasible surgical procedure for tumors or hepatolithiasis of the left liver.

A single-dose, randomized, open-label, four-period, crossover equivalence trial comparing the clinical similarity of the proposed biosimilar rupatadine fumarate to reference Wystamm® in healthy Chinese subjects.

Purpose: The aim of this study was to evaluate the bioequivalence of two formulations of rupatadine (10-mg tablets) under fasting and fed conditions in healthy Chinese subjects. Methods: A total of 72 subjects were randomly assigned to the fasting cohort (n = 36) and fed cohort (n = 36). Each cohort includes four single-dose observation periods and 7-day washout intervals. Blood samples were collected at several timepoints for up to 72 h post-dose. The plasma concentration of rupatadine and the major active metabolites (desloratadine and 3-hydroxydesloratadine) were analyzed by a validated HPLC-MS/MS method. The non-compartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation of the reference formulation, a reference-scaled average bioequivalence or average bioequivalence method was used to evaluate the bioequivalence of the two formulations. Results: For the fasting status, the reference-scaled average bioequivalence method was used to evaluate the bioequivalence of the maximum observed rupatadine concentration (Cmax; subject standard deviation > 0.294), while the average bioequivalence method was used to evaluate the bioequivalence of the area under the rupatadine concentration-time curve from time 0 to the last detectable concentration (AUC0-t) and from time 0 to infinity (AUC0-∞). The geometric mean ratio (GMR) of the test/reference for Cmax was 95.91%, and the upper bound of the 95% confidence interval was 95.91%. For AUC0-t and AUC0-∞ comparisons, the GMR and 90% confidence interval (CI) were 98.76% (93.88%-103.90%) and 98.71% (93.93%-103.75%), respectively. For the fed status, the subject standard deviation values of Cmax, AUC0-t, and AUC0-∞ were all <0.294; therefore, the average bioequivalence method was used. The GMR and 90% CI for Cmax, AUC0-t, and AUC0-∞ were 101.19% (91.64%-111.74%), 98.80% (94.47%-103.33%), and 98.63% (94.42%-103.03%), respectively. The two-sided 90% CI of the GMR for primary pharmacokinetic endpoints of desloratadine and 3-hydroxydesloratadine was also within 80%-125% for each cohort. These results met the bioequivalence criteria for highly variable drugs. All adverse events (AEs) were mild and transient. Conclusion: The test drug rupatadine fumarate showed a similar safety profile to the reference drug Wystamm® (J. Uriach y Compañía, S.A., Spain), and its pharmacokinetic bioequivalence was confirmed in healthy Chinese subjects based on fasting and postprandial status. Clinical trial registration: http://www.chinadrugtrials.org.cn/index.html, identifier CTR20213217.

Repeated trans-spinal magnetic stimulation promotes microglial phagocytosis of myelin debris after spinal cord injury through LRP-1.

Spinal cord injury (SCI) is a serious trauma of the central nervous system. The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). Recent studies have begun to reveal critical roles for professional phagocytes in the central nervous system, microglia, and their receptors in the control of myelin debris in neurodegenerative disease. Repeated trans-spinal magnetic stimulation (rTSMS) has been demonstrated as a noninvasive SCI treatment that enhances tissue repair and functional recovery. In this study, we investigated the role and molecular mechanism of rTSMS on microglial phagocytosis of myelin debris in a rat SCI model. In our studies, we found that rTSMS significantly promoted the motor function recovery of SCI rats associated with the inhibition the neuroinflammation and glia scar formation. Immunofluorescence results further showed that the rTSMS promotes the clearance of myelin debris by microglia in vivo and in vitro. Additionally, receptor-associated protein (RAP), a Low-density lipoprotein receptor-related protein-1 (LRP-1) inhibitor, could cancel the accelerated microglial phagocytosis of myelin debris after rTSMS in vitro experiments. Simultaneously, Elisa's results and western blotting respectively showed that rTSMS significantly decreased the levels of soluble LRP-1(sLRP-1) and the LRP-1 splicing enzyme of ADAM17. In conclusion, rTSMS could promote the clearance of myelin debris by microglia through LRP-1 to improve the functional recovery of SCI rats.

Large-scale photonic chiplet Taichi empowers 160-TOPS/W artificial general intelligence.

The pursuit of artificial general intelligence (AGI) continuously demands higher computing performance. Despite the superior processing speed and efficiency of integrated photonic circuits, their capacity and scalability are restricted by unavoidable errors, such that only simple tasks and shallow models are realized. To support modern AGIs, we designed Taichi-large-scale photonic chiplets based on an integrated diffractive-interference hybrid design and a general distributed computing architecture that has millions-of-neurons capability with 160-tera-operations per second per watt (TOPS/W) energy efficiency. Taichi experimentally achieved on-chip 1000-category-level classification (testing at 91.89% accuracy in the 1623-category Omniglot dataset) and high-fidelity artificial intelligence-generated content with up to two orders of magnitude of improvement in efficiency. Taichi paves the way for large-scale photonic computing and advanced tasks, further exploiting the flexibility and potential of photonics for modern AGI.

Toxic effects of triclosan on hepatic and intestinal lipid accumulation in zebrafish via regulation of m6A-RNA methylation.

Triclosan (TCS), recognized as an endocrine disruptor, has raised significant concerns due to its widespread use and potential health risks. To explore the impact of TCS on lipid metabolism, both larval and adult zebrafish were subjected to acute and chronic exposure to TCS. Through analyzes of biochemical and physiological markers, as well as Oil Red O (ORO) and hematoxylin and eosin (H&E) staining, our investigation revealed that TCS exposure induced hepatic and intestinal lipid accumulation in larval and adult zebrafish, leading to structural damage and inflammatory responses in these tissues. The strong affinity of TCS with PPARγ and subsequent pathway activation indicate that PPARγ pathway plays a crucial role in TCS-induced lipid buildup. Furthermore, we observed a decrease in m6A-RNA methylation levels in the TCS-treated group, which attributed to the increased activity of the demethylase FTO and concurrent suppression of the methyltransferase METTL3 gene expression by TCS. The alteration in methylation dynamics is identified as a potential underlying mechanism behind TCS-induced lipid accumulation. To address this concern, we explored the impact of folic acid-a methyl donor for m6A-RNA methylation-on lipid accumulation in zebrafish. Remarkably, folic acid administration partially alleviated lipid accumulation by restoring m6A-RNA methylation. This restoration, in turn, contributed to a reduction in inflammatory damage observed in both the liver and intestines. Additionally, folic acid partially mitigates the up-regulation of PPARγ and related genes induced by TCS. These findings carry substantial implications for understanding the adverse effects of environmental pollutants such as TCS. They also emphasize the promising potential of folic acid as a therapeutic intervention to alleviate disturbances in lipid metabolism induced by environmental pollutants.

Periodic magnetic modulation enhanced electrochemical analysis for highly sensitive determination of genomic DNA methylation.

DNA methylation aberrations have a strong correlation with cancer in early detection, diagnosis, and prognosis, which make them possible candidate biomarkers. Electrochemical biosensors offer rapid protocols for detecting DNA methylation status with minimal pretreatment of samples. However, the inevitable presence of background current in the time domain, including electrochemical noise and variations, limits the detection performance of these biosensors, especially for low concentration analytes. Here, we propose an ultrasensitive frequency-domain electrochemical analysis strategy to effectively separate the weak signals from background current. To achieve this, we employed periodic magnetic field modulation of magnetic beads (MBs) on and off the electrode surface to generate a periodic electrochemical signal for subsequent frequency-domain analysis. By capturing labeled MBs with as low as 0.5 pg of DNA, we successfully demonstrated a highly sensitive electrochemical method for determination of genome-wide DNA methylation levels. We also validated the effectiveness of this methodology using DNA samples extracted from three types of hepatocellular carcinoma (HCC) cell lines. The results revealed varying genomic methylation levels among different HCC cell lines, indicating the potential application of this approach for early-stage cancer detection in terms of DNA methylation status.