Non-volatile 2 × 2 optical switch using multimode interference in an Sb2Se3-loaded waveguide.

We propose a non-volatile 2 × 2 photonic switch based on multimode interference in an Sb2Se3-loaded waveguide. The different modal symmetries of the TE0 and TE1 modes supported in the multimode region change their propagation constants distinctly upon the Sb2Se3 phase transition. Through careful optical design and FDTD optimization of the multimode waveguide dimensions, efficient switching is achieved despite the modest index contrast of Sb2Se3 relative to Ge2Sb2Te5. The fabricated optical switch demonstrates favorable characteristics, including low insertion loss of ∼1 dB, a compact length of ∼27 µm, and small cross talk below -15 dB across a 35 nm bandwidth. Such non-volatile and broadband components will be critical for future high-density programmable photonic-integrated circuits for optical communications and signal processing.

Clinical prognostic value of different NPM1 mutations in acute myeloid leukemia patients.

BACKGROUND: Acute myeloid leukemia (AML) patients with various nucleophosmin 1 (NPM1) mutations are controversial in the prognosis. This study aimed to investigate the prognosis of patients according to types of NPM1 mutations (NPM1mut). METHODS: Bone marrow samples of 528 patients newly diagnosed with AML, were collected for morphology, immunology, cytogenetics, and molecular biology examinations. Gene mutations were detected by next-generation sequencing (NGS) technology. RESULTS: About 25.2% of cases exhibited NPM1mut. 83.5% of cases were type A, while type B and D were respectively account for 2.3% and 3.0%. Furthermore, 15 cases of rare types were identified, of which 2 cases have not been reported. Clinical characteristics were similar between patients with A-type NPM1 mutations (NPM1A - type mut) and non-A-type NPM1 mutations (NPM1non - A-type mut). Event-free survival (EFS) was significantly different between patients with low NPM1non - A-type mut variant allele frequency (VAF) and low NPM1A - type mut VAF (median EFS = 3.9 vs. 8.5 months, P = 0.020). The median overall survival (OS) of the NPM1non - A-type mutFLT3-ITDmut group, the NPM1A - type mutFLT3-ITDmut group, the NPM1non - A-type mutFLT3-ITDwt group, and the NPM1A - type mutFLT3-ITDwt group were 3.9, 10.7, 17.3 and 18.8 months, while the median EFS of the corresponding groups was 1.4, 5.0, 7.6 and 9.2 months (P < 0.0001 and P = 0.004, respectively). CONCLUSIONS: No significant difference was observed in OS and EFS between patients with NPM1A - type mut and NPM1non - A-type mut. However, types of NPM1 mutations and the status of FLT3-ITD mutations may jointly have an impact on the prognosis of AML patients.

Compact nonvolatile polarization switch using an asymmetric Sb2Se3-loaded silicon waveguide.

We propose and simulate a compact (∼29.5 µm-long) nonvolatile polarization switch based on an asymmetric Sb2Se3-clad silicon photonic waveguide. The polarization state is switched between TM0 and TE0 mode by modifying the phase of nonvolatile Sb2Se3 between amorphous and crystalline. When the Sb2Se3 is amorphous, two-mode interference happens in the polarization-rotation section resulting in efficient TE0-TM0 conversion. On the other hand, when the material is in the crystalline state, there is little polarization conversion because the interference between the two hybridized modes is significantly suppressed, and both TE0 and TM0 modes go through the device without any change. The designed polarization switch has a high polarization extinction ratio of > 20 dB and an ultra-low excess loss of < 0.22 dB in the wavelength range of 1520-1585 nm for both TE0 and TM0 modes.

Predictive role of cardiac valvular calcification in all-cause mortality of Chinese initial haemodialysis patients: a follow-up study of 4 years.

BACKGROUND: Cardiac valvular calcification (CVC) is prevalent in haemodialysis (HD) patients. Its association with mortality in Chinese incident haemodialysis (IHD) patients remains unknown. METHODS: A total of 224 IHD patients who had just begun HD therapy at Zhongshan Hospital, Fudan University, were enrolled and divided into two groups according to the detection of cardiac valvular calcification (CVC) by echocardiography. The patients were followed for a median of 4 years for all-cause mortality and cardiovascular mortality. RESULTS: During follow-up, 56 (25.0%) patients died, including 29 (51.8%) of cardiovascular disease. The adjusted HR related to all-cause mortality was 2.14 (95% CI, 1.05-4.39) for patients with cardiac valvular calcification. However, CVC was not an independent risk factor for cardiovascular mortality in patients who had just begun HD therapy. CONCLUSION: CVC at baseline is an independent risk factor for all-cause mortality in HD patients and makes an independent contribution to the prediction of all-cause mortality. These findings support the use of echocardiography at the beginning of HD.

Polyphenol and Anthocyanin Composition and Activity of Highland Barley with Different Colors.

In this research, the composition of free phenols, bound phenols, and anthocyanins and their in vitro antioxidant activity and in vitro α-glucosidase inhibiting activity were observed in different barley colors. The outcomes revealed that the contents of total phenols (570.78 mg/100 gDW), total flavonoids (47.08 mg/100 gDW), and anthocyanins (48.07 mg/100 g) were the highest in purple barley. Furthermore, the structure, composition, and concentration of phenolics differed depending on the colors of barley. The types and contents of bound total phenolic acids and flavonoids were greater than those of free total phenolic acids and flavonoids. The main phenolic acids in blue barley were cinnamic acid polyphenols, whereas in black, yellow, and purple barley, benzoic acid polyphenols were the main phenolic acids, and the main types of flavonoids in black and blue barley were chalcones and flavanones, respectively, whereas flavonol was the main type of flavonoid in yellow and purple barley. Moreover, cornflower pigment-3-glucoside was the major anthocyanin in blue, yellow, and purple barley, whereas the main anthocyanin in black barley was delphinidin-3-glucoside. The dark color of barley indicated richness in the anthocyanins. In addition, the free polyphenol fractions had stronger DPPH and ABTS radical scavenging capacity as compared to the bound ones. In vitro α-glucosidase-inhibiting activity was greater in bound polyphenols than in free polyphenols, with differences between different varieties of barley. Purple barley phenolic fractions had the greatest ABTS radical scavenging and iron ion reduction capacities, as well as the highest α-glucosidase-inhibiting activity. The strongest DPPH radical scavenging capacity was found in yellow barley, while the strongest in vitro α-glucosidase-inhibiting activity was found in anthocyanins isolated from black barley. Furthermore, in different colors of barley, there was a strong association between the concentration of specific phenolic compounds and antioxidant and α-glucosidase-inhibiting activities. The outcomes of this study revealed that all colored barley seeds tested were high in phenolic compounds, and had a good antioxidant impact and α-glucosidase-inhibiting activity. As a result, colored barley can serve as an antioxidant and hypoglycemic food. Polyphenols extracted from purple barley and anthocyanins extracted from black barley stand out among them.

Reconfigurable and dual-polarization Bragg grating filter with phase change materials.

Fully reconfigurable optical filters are indispensable building blocks to realize reconfigurable photonic networks/systems. This paper proposes a reconfigurable and dual-polarization optical filter based on a subwavelength grating waveguide operating in the Bragg reflection mechanism and combined with a low-loss phase change material Ge2Sb2Se4Te1. Numerical simulations indicate that, for TE(TM) polarization, the presented Bragg grating filter offers up to 20 nm (17 nm) redshift with amplitude modulation of 6 dB (0.15 dB) at 1550 nm. Using the effective medium theory, we obtained the six-level crystallization performance of the optical filter. The proposed optical filter has potential applications in wavelength-division-multiplexing systems, optical signal processing, and optical communications.

A Predictive Nomogram for Early Mortality in Stage IV Gastric Cancer.

BACKGROUND The study was intended to establish predictive nomogram models for predicting total early mortality (the probability of surviving less than or equal to 3 months) and cancer-specific early mortality in patients with stage IV gastric cancer. This was the first study to establish prognostic survival in patients with stage IV gastric cancer. MATERIAL AND METHODS Patients from the SEER database were identified using inclusion and exclusion criteria. Their clinical characteristics were statistically analyzed. The Kaplan-Meier method and the log-rank test were used to compare the influences of different factors on survival time. Logistic regression models were conducted to explore the correlative factors of early mortality. A nomogram was established based on factors significant in the logistic regression model and an internal validation was performed. RESULTS Of the 11,036 eligible patients included in the study, 4932(44.7%) patients resulted in total early death (42.6% died of the cancer and 2.1% died of other reasons). Larger tumor size, poor differentiation, and liver metastasis were positively related to cancer-specific early mortality. Surgery was negatively related to total early mortality and cancer-specific early mortality, while cardia was only negatively associated with total early death. Predictive nomogram models for total early mortality and cancer-specific early mortality have been validated internally. The areas under the receiver operating characteristics curve were 73.5%, and 68.0%, respectively, and the decision curve analysis also proved the value of the models. CONCLUSIONS The nomogram models proved to be a suitable tool for predicting the early mortality in stage IV gastric cancer.

Value of tumor size as a prognostic factor in metastatic colorectal cancer patients after chemotherapy: a population-based study.

Aim: To evaluate the relationship between tumor size and survival in metastatic colorectal cancer (mCRC) patients who received chemotherapy. Materials & methods: SEER database was accessed for eligible patients. Multivariate Cox regression analysis was performed to compare the effect of tumor size on overall survival (OS) and CRC-specific survival (CCSS). Results: Tumor size ≥5 cm was an independent risk factor for OS and CCSS in mCRC patients treated with chemotherapy. Tumor size <5 cm did not show a survival advantage in patients whose primary tumor site was rectosigmoid junction, while tumor size ≥5 cm was associated with poor OS and CCSS in left-and right-sided colorectal cancer. Conclusion: Tumor size ≥5 cm was associated with poor prognosis after receiving chemotherapy treatment and a risk factor for survival of mCRC.

A Telemedicine-Based Registration System for the Management of Renal Anemia in Patients on Maintenance Hemodialysis: Multicenter Study.

BACKGROUND: Renal anemia is one of the most important complications in patients on maintenance hemodialysis (MHD). Telehealth-based dialysis registration systems have the advantage of real-time monitoring and have gradually been applied to the management of chronic diseases. OBJECTIVE: The objective of our study was to evaluate the impact of a telehealth-based dialysis registration system on patients on MHD in terms of renal anemia control. METHODS: The Red China project aimed to develop a dialysis registration system based on the WeChat mobile platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, and baseline creatinine levels were recorded using this system. In addition, the hemoglobin and hematocrit levels were recorded monthly. The platform then generated a hemoglobin and hematocrit statistics report for each hemodialysis center monthly, including the detection rate, target rate, and distribution of hemoglobin and released it to physicians via the WeChat mobile phone app. The physicians were then able to treat the individual's anemia appropriately by changing the doses of erythropoiesis-stimulating agents or iron use on the basis of this report. We analyzed the demographic and baseline laboratory parameters, detection rate, target rate, and average level and distribution of hemoglobin 28 months after the launch of the project. RESULTS: A total of 8392 patients on MHD from 28 hemodialysis centers in Shanghai were enrolled from June 2015 to October 2017. The detection rate of hemoglobin increased from 54.18% to 73.61% (P<.001), the target rate of hemoglobin increased from 47.55% to 56.07% (P<.001), and the mean level of hemoglobin increased from 10.83 (SD 1. 60) g/dL to 11.07 (SD 1.60) g/dL (P<.001). In addition, the proportion of patients with hemoglobin levels ≥11 g/dL but <13 g/dL increased from 40.40% to 47.48%. CONCLUSIONS: This telehealth-based dialysis registration system can provide timely reporting of the anemia status in patients on MHD, which may improve the awareness of anemia and the attention to and compliance with anemia monitoring.

Prognostic Value of the Delivery Dialysis Dose on Twice-Weekly Hemodialysis Patients.

BACKGROUND: Few studies have evaluated the prognostic value of dialysis dose in twice-weekly hemodialysis (HD). A single-pool Kt/V (spKt/V) over 1.70 may benefit patients receiving twice-weekly maintenance HD. METHODS: This is a multicenter randomized controlled trial performed on 163 patients from 17 dialysis centers in Shanghai who were allocated to high- (n = 98) and standard-dose groups (n = 65) and followed through 96 weeks of study period. Therapeutic approaches were given to increase spKt/V to over 1.70 in the high-dose group. Data were collected every 12-24 weeks. The primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACEs) occurrence, and secondary outcomes included residual kidney function (RKF) and health-related quality of life (HR-QOL). RESULTS: The spKt/V in high-dose and standard-dose groups were 1.80 ± 0.23 and 1.55 ± 0.19, respectively, after an 8-week intervention (p < 0.001). At the end of the study, SF-36 physical function and total score in high-dose group were 82 (69-90) and 74 (47-84), respectively, both of which were higher than those in the standard-dose group. Decline in urine volume was observed in both groups with no significant difference (p = 0.431). No difference was found in overall survival between the 2 groups (p = 0.580). The 1-year MACE-free survival for high-dose group was 84.49%, better than 76.72% for standard-dose group (p = 0.029). CONCLUSIONS: Higher spKt/V is also associated with MACE-free survival and better HR-QOL, especially in physical function aspect for twice-weekly dialysis patients. Increasing spKt/V over 1.70 in twice-weekly HD population does not cause loss of RKF.

[In vivo study of the renoprotective effects of EGCG in diabetic db/db mice].

OBJECTIVE: To explore the renoprotective effects of (-)-epigallocatechin-3-gallate (EGCG) and its potential mechanism in type 2 diabetic db/db mice. METHODS: 8-week-old db/db mice (6 h fasting plasma glucose >16.7 mmol/L) were allocated randomly into Control group (non-intervention group, n=8), EGCG A group (50 mg·kg(-1)·d(-1,)n=8), EGCG B group (100 mg·kg(-1)·d(-1,)n=8). Before the study and after the intervention (in the 4(th)and 8(th)week), the body weight, the level of fasting plasma glucose, oral glucose tolerance test (OGTT) were measured and 24 h urine samples were collected. 24 h proteinuria was measured by routine chemical method. The levels of angiotensin Ⅱ(AngⅡ), fasting plasma insulin and urinary 8-OHdG were measured with enzyme-linked immunosorbent assay (ELISA). The protein expression levels of angiotensin Ⅱ type 1 receptor (AT-1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit P22-phox, NADPH oxidase subunit P47-phox, phospho-extracellular regulated protein kinases (p-Erk1/2), phospho-P38 mitogen-activated protein kinase (p-P38MAPK), phospho -phosphatidylinositol 3-hydroxy kinase (p-PI3K) and phospho-protein kinase B (p-AKT) were determined by Western blot. The renal pathological changes were examined by the method of PAS (periodic acid-Schiff stain). RESULTS: After 8 weeks of treatment with EGCG, the level of fasting plasma glucose decreased[(14.4±1.0) mmol/L, (14.2±0.7) mmol/L vs. (17.2±0.8) mmol/L]; the level of fasting plasma insulin increased[(13.2±1.2)mU/L, (13.4±1.3) mU/L vs. (9.9±1.0) mU/L]; the area under the curve (AUC) of OGTT decreased[(49.3±1.8) mmol·L(-1)·h(-1,)(44.8±0.7) mmol·L(-1)·h(-1)vs. (60.0±0.8) mmol·L(-1)·h(-1)]; the level of 24 h proteinuria[(8.8±1.0) mg, (8.6±1.1) mg vs. (11.7±1.3) mg]and urinary 8-OHdG[(90±5) ng/d, (78±5) ng/d vs. (118±10) ng/d]decreased; the level of serum Ang-Ⅱ[(498±23) ng/L, (511±19) ng/L vs. (688±17) ng/L]and renal cortex AngⅡ[(367±5) ng/L, (384±10) ng/L vs. (406±7) ng/L]decreased; the expression levels of AT-1R, P22-phox, P47-phox, p-Erk1/2, p-P38MAPK downregulated obviously and the expression levels of p-PI3K, p-AKT increased significantly (P<0.05), and renal pathology improved as compared with the control group. After 8 weeks of treatment with EGCG, the level of urinary 8-OHdG decreased (P=0.007) and the AUC of OGTT also decreased (P=0.01) in EGCG B group when compared with the EGCG A group. CONCLUSION: EGCG protects the kidney in diabetic db/db mice via anti-oxidative stress pathway, as well as inhibiting Erk1/2-P38MAPK pathway and improving PI3K-AKT signaling transduction pathway.

Efficacy and safety of neoadjuvant combination immunotherapy in surgically resectable malignant solid tumors: a systematic review and meta-analysis.

OBJECTIVES: Neoadjuvant immunotherapy has emerged as a prominent research focus recently. For potentially operable patients, neoadjuvant therapy serves as a primary method to reduce tumor load and facilitate surgical interventions. METHODS: We retrieved articles from PubMed, Embase, Cochrane Library, American Society of Clinical Oncology, and European Society of Medical Oncology websites from inception to December 2023. Statistical analyses were performed using the R software. Primary outcomes assessed included major pathological response (MPR), pathological complete response (pCR), and treatment-related adverse events (trAEs). RESULTS: 29 studies encompassing 1163 patients were included. The MPR rate of neoadjuvant combination immunotherapy was 38% (95% confidence interval [CI]: 25%-52%), and the pCR rate was 33% (95%CI: 25%-42%). These values were significantly higher than those obtained with single agent immunotherapy (p < 0.001). The pooled incidence of overall trAEs was 83% (95%CI: 73%-92%), and grade (G) 3-4 trAEs was 22% (95%CI: 15%-29%), both significantly higher than those observed with single agent immunotherapy (p < 0.05). CONCLUSION: This study demonstrated the efficacy of neoadjuvant combination immunotherapy. Given that the majority of the included trials were phase II with small sample sizes, further multicenter phase III randomized controlled trials should be conducted to validate the findings of the review.

A multicomponent reaction for modular assembly of indole-fused heterocycles.

Indoles are privileged chemical entities in natural products and drug discovery. Indole-fused heterocycles, particularly seven-membered ones, have received increasing attention due to their distinctive chemical characteristics and wide spectrum of bioactivities. However, the synthetic access to these compounds is highly limited. Herein, we report a unique multicomponent reaction (MCR) for modular assembly of indole-fused seven-membered heterocycles. In this process, indole, formaldehyde and amino hydrochloride could assemble rapidly to yield indole-fused oxadiazepines, and another addition of sodium thiosulphate would furnish indole-fused thiadiazepines. The biological evaluation disclosed the promising anticancer activity of these compounds. Furthermore, this MCR could be applicable in the late-stage and selective modifications of peptides. Therefore, this work provides a powerful strategy for indole functionalization and valuable tool for construction of seven-membered heterocycles.

Performance of a novel eight-color flow cytometry panel for measurable residual disease assessment of chronic lymphocytic leukemia.

BACKGROUND: Measurable residual disease (MRD) is an important prognostic indicator of chronic lymphocytic leukemia (CLL). Different flow cytometric panels have been developed for the MRD assessment of CLL in Western countries; however, the application of these panels in China remains largely unexplored. METHODS: Owing to the requirements for high accuracy, reproducibility, and comparability of MRD assessment in China, we investigated the performance of a flow cytometric approach (CD45-ROR1 panel) to assess MRD in patients with CLL. The European Research Initiative on CLL (ERIC) eight-color panel was used as the "gold standard." RESULTS: The sensitivity, specificity, and concordance rate of the CD45-ROR1 panel in the MRD assessment of CLL were 100% (87/87), 88.5% (23/26), and 97.3% (110/113), respectively. Two of the three inconsistent samples were further verified using next-generation sequencing. In addition, the MRD results obtained from the CD45-ROR1 panel were positively associated with the ERIC eight-color panel results for MRD assessment (R = 0.98, p < 0.0001). MRD detection at low levels (≤1.0%) demonstrated a smaller difference between the two methods (bias, -0.11; 95% CI, -0.90 to 0.68) than that at high levels (>1%). In the reproducibility assessment, the bias was smaller at three data points (within 24, 48, and 72 h) in the CD45-ROR1 panel than in the ERIC eight-color panel. Moreover, MRD levels detected using the CD45-ROR1 panel for the same samples from different laboratories showed a strong statistical correlation (R = 0.99, p < 0.0001) with trivial interlaboratory variation (bias, 0.135; 95% CI, -0.439 to 0.709). In addition, the positivity rate of MRD in the bone marrow samples was higher than that in the peripheral blood samples. CONCLUSIONS: Collectively, this study demonstrated that the CD45-ROR1 panel is a reliable method for MRD assessment of CLL with high sensitivity, reproducibility, and reliability.

Adverse events of neoadjuvant combination immunotherapy for resectable cancer patients: a systematic review and meta-analysis.

Background: Neoadjuvant combination immunotherapy is changing the treatment landscape for patients with cancer. Exploring the incidence of immune-related adverse events (irAEs) in relation to this novel approach may provide valuable insights for future clinical investigations. Methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, Cochrane Library, American Society of Clinical Oncology (ASCO), and European Society of Medical Oncology (ESMO) websites were searched for all relevant literature from their inception to November 24, 2023. We then extracted the required data from the included studies and used the R software to analyze the pooled incidence of irAEs. Subgroup analyses examined the pooled incidence of irAEs according to cancer and combination types using a random-effects model. Results: Sixteen studies involving 501 patients were included in the meta-analysis. Considering the heterogeneity of the study design, we analyzed the randomized controlled studies (RCTs) and the single-arm studies separately. In RCTs, the incidence of any-grade irAEs was 95.0% (95% confidence interval [CI] 87.3-99.3) and that of grade ≥3 irAEs was 24.0% (95% CI 13.7-36.0). In single-arm studies, the incidence of any-grade irAEs was 89.4% (95% CI 75.0-98.0) and grade ≥3 irAEs was 20.3% (95% CI 8.7-35.2). In both RCTs and single arms, the most common any- grade irAEs were rash and fatigue, while the most common grade ≥3 irAEs was abnormal liver function and colitis. Due to irAEs, 9.4% of patients in RCTs and 6.9% of patients in single-arm studies did not complete the prescribed neoadjuvant treatment cycle. Conclusion: This study comprehensively summarized the incidence of irAEs in neoadjuvant combination immunotherapy. The occurrence of irAEs varies depending on the cancer and combination types. Our meta-analysis provides clinicians with essential guidance for the management of patients with cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023387969.

Construction of a ratiometric fluorescent probe for visual detection of urea in human urine based on carbon dots prepared from Toona sinensis leaves and 5-carboxyfluorescein.

In this work, pH-sensitive blue fluorescent carbon dots (CDs) with high fluorescence quantum yield (17.24%) were synthesized by hydrothermal method using Toona sinensis leaves and ethylenediamine (EDA) as raw materials. The CDs can detect urea with a limit of detection (LOD) of 6.700 mmol L-1. For more sensitive detection of urea, we constructed a ratiometric fluorescent probe (CDs@5-FAM) using CDs and 5-carboxyfluorescein (5-FAM). The CDs@5-FAM probe can rapidly and sensitively detect urea according to the changes of I514/I405, with LOD as low as 0.014 mmol L-1. Furthermore, with the help of a smartphone and RGB analysis software, urea's visual intelligent detection was realized using a CDs@5-FAM probe. The method proposed in this paper is consistent with the standard method, which indicates that the pH-sensitive ratiometric fluorescent probe CDs@5-FAM is accurate and reliable for practical application. It provides a new way for rapid and visual detection of urea.

Base-Promoted Tandem Synthesis of 2-Substituted Indoles and N-Fused Polycyclic Indoles.

Herein is developed a base-promoted approach for the synthesis of C2-substituted indoles and N-fused polycyclic indoles via 5-endo-dig cyclization of 2-alkynyl anilines, followed by a 1,3'-acyl migration or a dearomatizing Michael addition process. A range of N-H free indoles and 8,9-dihydropyrido[1,2-a]indol-6(7H)-one scaffolds were synthesized in good to excellent yields with broad scope.

Integration of RRBS and RNA-seq unravels the regulatory role of DNMT3A in porcine Sertoli cell proliferation.

DNMT3A participates in de novo methylation, yet its impact on the proliferation of testicular Sertoli cells remains unclear. Development-specific methylation has been proven to be associated with cellular development. Therefore, in this study, we simulated DNMT3A expression pattern during testicular development by DNMT3A interference. Then, RRBS and RNA-seq were used to decipher DNMT3A regulatory mechanisms on Sertoli cell proliferation. Immunofluorescence staining revealed the expression of DNMT3A in the Sertoli cells of the prepubertal testis. DNMT3A was demonstrated to inhibit the cell cycle and proliferation of Sertoli cells, while promoting cell apoptosis. After transfected with DNMT3A interference, a total of 560 DEGs and 2,091 DMGs produced by DNMT3A interference were identified between two treated groups, respectively. Integrating the results from RRBS and RNA-seq, the overlapping genes between DMGs and DEGs were found to be enriched in the Gene Ontology (GO) terms related to cellular development and the Apelin signaling pathway. The present study demonstrated the impact of DNMT3A on the proliferation of porcine testicular Sertoli cells, suggesting that DNMT3A primarily acts through the Apelin signaling pathway. These findings provide valuable insights into how DNMT3A influences testicular development and health, offering new perspectives.

Ellagic acid prevents gut damage via ameliorating microbe-associated intestinal lymphocyte imbalance.

Inflammatory bowel disease (IBD) pathogenesis involves a sustained microbial-mediated immune response following intestinal stress. Although administration of antibiotics can be an effective therapy, the misuse of antibiotics may risk unknown drug-resistant bacteria. In this study, piglets pretreated with ellagic acid (EA) and Ampicillin (AMP) for 21 days, and were injected intraperitoneally with paraquat (PQ) on 14 and 18 days. We found piglets lost most of their gut microbes in the AMP group, protected from subsequent intestinal damage caused by gut oxidative stress. Hence, we identified some gut microbes that may play a critical role in mediating cellular responses following cytokine stimulation in PQ-induced stress. EA preprocessing exhibited the same performance as AMP. Pretreatment of EA reduced Streptococcus abundance in the gut. Particularly, EA modulated intestinal lymphocyte distribution, reduced the frequency of CD79a+ cells, and alleviated the upward migration of CD3+ cells to the apex of the intestinal villi in the intestinal epithelium. Additionally, the intestinal immune response had been known associated closely with the abundance of Streptococcus in the gut. Thus, we concluded that EA has the potential to replace antibiotics to prevent microbial-mediated immune responses in the gut, and EA can be applied as a supplement candidate to alleviate the development of inflammation caused by intestinal stress.