Intestinal health of squab pigeons responded to parental dietary protein levels during breeding period.

The objective of this study was to determine the effects of dietary crude protein (CP) levels on intestinal antioxidant status, tight junction proteins expression, and amino acids transporters levels in squabs. A total of 180 pairs of White King parent pigeons approximately 10 mo old were randomly assigned to 5 groups with 6 replications of 6 pairs of parental pigeons each, and were fed with 14, 15, 16, 17, and 18% CP diets for 46 d, respectively. Dietary increasing CP levels increased final body weight (linear and quadratic, P < 0.05), serum urea nitrogen (linear, P<0.05) and triglyceride levels (quadratic, P < 0.05), and reduced kidney relative weight (quadratic, P < 0.05) in squabs. Final body weight of squabs in the 18% CP diet group was higher than that of the 14, 15, and 16% CP diet groups (P < 0.05) but was similar to that of the 17% CP diet group (P > 0.05). Increasing dietary CP levels reduced intestinal malondialdehyde contents (linear and quadratic, P < 0.05) and jejunal total superoxide dismutase (T-SOD) activity (linear, P < 0.05), and enhanced (linear and quadratic, P<0.05) ileal catalase and T-SOD activities in squabs, and these effects were more prominent in the 17% CP diet group. Graded CP levels up-regulated the mRNA expression of intestinal zonula occludens 1 (linear, P < 0.05), solute carrier family 7 members 9 (linear, P < 0.05) and claudin 1 (CLDN1, linear and quadratic, P < 0.05), ileal CLDN3 and solute carrier family 6 members 14 (linear, P < 0.05) but lowered jejunal solute carrier family 6 member 14 (quadratic, P<0.05) mRNA expression in squabs. The effects of dietary CP levels on intestinal tight junction proteins expression were more apparent when its supplemental levels were 18%. These results suggested that increasing parental dietary CP levels ranged from 14 to 18% during breeding period improved growth and intestinal function of squabs, with its recommended level being 17%.

Comparison of HCG Trigger versus Dual Trigger in Improving Pregnancy Outcomes in Patients with Different Ovarian Responses: A Retrospective Study.

Objective: During in vitro fertilization-embryo transfer (IVF-ET) treatment, the reproductive endocrine regulatory mechanisms hold pivotal importance. Specifically, the serum estradiol (E 2) level during ovulation emerges as a critical factor influencing pregnancy outcomes. This retrospective study aimed to comprehensively compare two common clinical regimens based on the grouping of serum E 2 levels and the number of oocytes retrieved on the trigger day. Our objective was to evaluate the pregnancy outcomes in IVF-ET patients across different ovarian response groups, exploring the efficacy of the dual-trigger and single-trigger regimens to provide valuable insights for optimizing clinical strategies in the context of IVF-ET. Methods: A retrospective analysis was conducted on the clinical data of 2778 infertile patients who underwent ART (IVF/ICSI). Subsequently, a detailed statistical analysis was performed on 1032 patients following an antagonist regimen. Participants were categorized into single-trigger and dual-trigger groups based on real-world trigger protocols, considering different ovarian responses. Comprehensive statistical assessments were conducted on baseline characteristics, ovulation induction, and pregnancy outcomes. Results: Baseline characteristics and cycle parameters among the three patient groups (high ovarian response, normal response, and poor response) exhibited no significant differences between the dual-trigger and single-trigger regimen groups. Despite the dual-trigger regimen utilizing a significantly lower HCG dose, no notable discrepancies were observed in laboratory results and pregnancy outcomes (embryo transfer rate, pregnancy rate, and live birth rate) for normal and high responders. Remarkably, E 2 levels were higher in the dual-trigger group compared to the single-trigger group. In high and normal responders, the dual-trigger regimen demonstrated increased oocyte counts and oocyte acquisition rates, coupled with decreased transfer cancellation rates attributed to ovarian hyperstimulation syndrome (OHSS). Intriguingly, patients with a poor ovarian response experienced no graft cancellations due to OHSS prevention in either group. Conclusion: For patients with high and normal ovarian responses, the utilization of a dual-trigger regimen on the trigger day effectively mitigates the risk of OHSS. Our large sample study supports the substitutability of the dual-trigger regimen over the single-trigger regimen without compromising pregnancy outcomes. However, this conclusion is not applicable to patients with poor ovarian responses. The results of this study highlight the necessity of adopting a customized and individualized treatment approach that should be based on the patient's ovarian response. Additionally, recognizing the pivotal role of the endocrine environment in influencing pregnancy outcomes and the occurrence of OHSS, further exploration of the effects of different triggering regimens on endocrine parameters is warranted. Such investigations will contribute to enhancing the reproductive outcomes of IVF-ET technology.

A Review of the Impact of Starch on the Quality of Wheat-Based Noodles and Pasta: From the View of Starch Structural and Functional Properties and Interaction with Gluten.

Starch, as a primary component of wheat, plays a crucial role in determining the quality of noodles and pasta. A deep understanding of the impact of starch on the quality of noodles and pasta is fundamentally important for the industrial progression of these products. The starch structure exerts an influence on the quality of noodles and pasta by affecting its functional attributes and the interaction of starch-gluten proteins. The effects of starch structure (amylopectin structure, amylose content, granules size, damaged starch content) on the quality of noodles and pasta is discussed. The relationship between the functional properties of starch, particularly its swelling power and pasting properties, and the texture of noodles and pasta is discussed. It is important to note that the functional properties of starch can be modified during the processing of noodles and pasta, potentially impacting the quality of the end product, However, this aspect is often overlooked. Additionally, the interaction between starch and gluten is addressed in relation to its impact on the quality of noodles and pasta. Finally, the application of exogenous starch in improving the quality of noodles and pasta is highlighted.

Enhancing Stability and Antioxidant Activity of Resveratrol-Loaded Emulsions by Ovalbumin-Dextran Conjugates.

A reliable strategy for improving the stability and shelf life of protein-stabilized systems is by covalently attaching the protein onto a polysaccharide. In this study, ovalbumin (OVA) was modified with dextran (DEX) of different molecular weights by the Maillard reaction, and was used to enhance the stability of emulsions loaded with resveratrol. The surface hydrophobicity, thermal stability, and FT-IR spectroscopy of the OVA-DEX conjugates were evaluated. The results showed that the surface hydrophobicity of OVA decreased, while the thermal stability of OVA was significantly improved after DEX covalent modification. The OVA-DEX1k-stabilized emulsion exhibited high encapsulation efficiency of resveratrol, with the value of 89.0%. In addition, OVA-DEX was considerably more effective in droplet stabilization against different environmental stresses (heat, pH, and ionic strength). After 28 days of storage at 25 °C, the OVA-stabilized emulsion showed faster decomposition of resveratrol, whereas the OVA-DEX-conjugate-stabilized emulsion had approximately 73% retention of resveratrol. Moreover, the antioxidant activity of resveratrol-loaded emulsions stabilized by OVA-DEX was higher during storage under different temperatures. These results proved that the OVA-DEX conjugates had the potential to form stable, food-grade emulsion-based delivery systems against environmental stresses, which strongly supports their potential in the field of food and biomedical applications.

Effects of tumor necrosis factor-alpha inhibitors on lipid profiles in patients with psoriasis: a systematic review and meta-analysis.

Background: There is no consensus on the effect of tumor necrosis factor-alpha (TNF-alpha) inhibitors on lipid profiles in patients with psoriasis. This study aimed to investigate the effects of TNF-alpha inhibitors on lipid profiles (triglycerides, total cholesterol, low-density lipoprotein, or high-density lipoprotein) in patients with psoriasis. Methods: We searched PubMed, Embase, and Cochrane Library databases for articles published before October 17, 2023. Four TNF-alpha inhibitors (infliximab, etanercept, adalimumab, and certolizumab) were included in our study. (PROSPERO ID: CRD42023469703). Results: A total of twenty trials were included. Overall results revealed that TNF-alpha inhibitors elevated high-density lipoprotein levels in patients with psoriasis (WMD = 2.31; 95% CI: 0.96, 3.67; P = 0.001), which was supported by the results of sensitivity analyses excluding the effect of lipid-lowering drugs. Subgroup analyses indicated that high-density lipoprotein levels were significantly increased in the less than or equal to 3 months group (WMD = 2.88; 95% CI: 1.37, 4.4; P < 0.001), the etanercept group (WMD = 3.4; 95% CI = 1.71, 5.09, P < 0.001), and the psoriasis group (WMD = 2.52; 95% CI = 0.57, 4.48, P = 0.011). Triglyceride levels were significantly increased in the 3 to 6-month group (WMD = 4.98; 95% CI = 1.97, 7.99, P = 0.001) and significantly decreased in the 6-month and older group (WMD = -19.84; 95% CI = -23.97, -15.7, P < 0.001). Additionally, Triglyceride levels were significantly increased in the psoriasis group (WMD = 5.22; 95% CI = 2.23, 8.21, P = 0.001). Conclusion: Our results revealed that TNF-alpha inhibitors might temporarily increase high-density lipoprotein levels in patients with psoriasis. However, changes in triglycerides were not consistent among the different durations of treatment, with significant increases after 3 to 6 months of treatment. Future prospective trials with long-term follow-up contribute to confirming and extending our findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023469703.

Zinc caproate: Ecofriendly synthesis, structural characterization, and antibacterial action.

Disease-causing microorganisms such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are among the primary contributors to morbidity and mortality of diarrhea in humans. Considering the challenges associated with antibiotic use, including antimicrobial resistance, this study aimed to develop a novel zinc-based agent for bacterial inactivation. To this end, zinc caproate (ZnCA) was synthesized using caproic acid (CA) and zinc oxide (ZnO) in anhydrous ethanol via the solvothermal method. Structural characterization techniques, including Fourier-transform infrared spectroscopy, single crystal X-ray diffraction analysis, and nuclear magnetic resonance spectroscopy, revealed the bidentate bridging coordination of zinc atoms with CA. The resulting two-dimensional ZnCA network was found to be composed of a distinct lamellar pattern, without any evident inter-layer interactions. Powder X-ray diffraction analysis, elemental analysis, and melting point analysis confirmed that ZnCA had an average particle size of 1.320 µm, a melting point of 147.2 °C, and a purity exceeding 98 %. Remarkably, ZnCA demonstrated potent antibacterial activity against E. coli and S. aureus, which exceeded the antibacterial efficacy of ZnO. ZnCA exerted its antibacterial effects by inhibiting biofilm formation, disrupting cell membrane integrity, increasing cell membrane permeability, and altering intracellular Ca2+-Mg2+-ATPase activity. These findings highlight the potential of ZnCA as a promising antibiotic substitute for the treatment of diarrhea in humans.

Smart touchless human-machine interaction based on crystalline porous cages.

The rise of touchless technology, driven by the recent pandemic, has transformed human-machine interaction (HMI). Projections indicate a substantial growth in the touchless technology market, nearly tripling from $13.6 billion in 2021 to an estimated $37.6 billion by 2026. In response to the pandemic-driven shift towards touchless technology, here we show an organic cage-based humidity sensor with remarkable humidity responsiveness, forming the basis for advanced touchless platforms in potential future HMI systems. This cage sensor boasts an ultrafast response/recovery time (1 s/3 s) and exceptional stability (over 800 cycles) across relative humidity (RH) changes from 11% to 95%. The crystal structure's 3D pore network and luxuriant water-absorbing functional groups both inside and outside of the cage contribute synergistically to superior humidity sensing. Demonstrating versatility, we showcase this cage in smart touchless control screens and touchless password managers, presenting cost-effective and easily processable applications of molecularly porous materials in touchless HMI.

Subgrouping testicular germ cell tumors based on immunotherapy and chemotherapy associated lncRNAs.

Testicular germ cell tumors (TGCT) are the most common reproductive system malignancies in men aged 15-44 years, accounting for 95 % of all testicular tumors. Our previous studies have been shown that long non-coding RNAs (lncRNAs), such as LINC00313, TTTY14 and RFPL3S, were associated with development of TGCT. Subgrouping TGCT according to differential expressed lncRNAs and immunological characteristics is helpful to comprehensively describe the characteristics of TGCT and implement precise treatment. In this study, the TGCT transcriptome data in The Cancer Genome Atlas Program (TCGA) database was used to perform consensus clustering analysis to construct a prognostic model for TGCT. TGCT was divided into 3 subtypes C1, C2, and C3 based on the differentially expressed lncRNAs. C1 subtype was sensitive to chemotherapy drugs, while the C2 subtype was not sensitive to chemotherapy drugs, and C3 subtype may benefit from immunotherapy. We defined the C1 subtype as epidermal progression subtype, the C2 subtype as mesenchymal progression subtype, and the C3 subtype as T cell activation subtype. Subgrouping based on differentially expressed genes (DEGs) and immunological characteristics is helpful for the precise treatment of TGCT.

Emerging role and mechanism of HACE1 in the pathogenesis of neurodegenerative diseases: A promising target.

HACE1 is a member of the HECT domain-containing E3 ligases with 909 amino acid residues, containing N-terminal ankyrin-repeats (ANK) and C-terminal HECT domain. Previously, it was shown that HACE1 is inactive in human tumors and plays a crucial role in the initiation, progression, and invasion of malignant tumors. Recent studies indicated that HACE1 might be closely involved in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. HACE1 interacts with its substrates, including Ras-related C3 botulinum toxin substrate 1 (Rac1), nuclear factor erythroid 2-related factor 2 (Nrf2), tumor necrosis factor receptor (TNFR), and optineurin (OPTN), through which participates in several pathophysiological processes, such as oxidative stress, autophagy and inflammation. Therefore, in this review, we elaborately describe the essential substrates of HACE1 and illuminate the pathophysiological processes by which HACE1 is involved in neurodegenerative diseases. We provide a new molecular target for neurodegenerative diseases.

Iterative learning control for differential inclusion systems with random fading channels by varying average technique.

The aim of this paper is to study iterative learning control for differential inclusion systems with random fading channels between the plant and the controller. In reality, the phenomenon of fading will inevitably occur in network transmission, which will greatly affect the tracking ability of output trajectory. This study discusses the impact of fading channel on tracking performance at the input and output sides, respectively. First, a set-valued mapping in a differential inclusion system with uncertainty is converted into a single-valued mapping by means of a Steiner-type selector. Then, to offset the effect of the fading channel and improve the tracking ability, a variable local average operator is constructed. The convergence of the learning control algorithm designed by the average operator is proved. The results show that the parameters in the varying local average operator can be adjusted to trade-off between the learning rate and the fading offset rate. Finally, the theoretical results are verified by numerical simulation of the switched reluctance motors.

Ionic Covalent Organic Framework-Based Membranes for Selective and Highly Permeable Molecular Sieving.

Two-dimensional covalent organic frameworks (COFs) with uniform pores and large surface areas are ideal candidates for constructing advanced molecular sieving membranes. However, a fabrication strategy to synthesize a free-standing COF membrane with a high permselectivity has not been fully explored yet. Herein, we prepared a free-standing TpPa-SO3H COF membrane with vertically aligned one-dimensional nanochannels. The introduction of the sulfonic acid groups on the COF membrane provides abundant negative charge sites in its pore wall, which achieve a high water flux and an excellent sieving performance toward water-soluble drugs and dyes with different charges and sizes. Furthermore, the COF membrane exhibited long-term stability, fouling resistance, and recyclability in rejection performance. We envisage that this work provides new insights into the effect of ionic ligands on the design of a broad range of COF membranes for advanced separation applications.

circCD2AP promotes epithelial mesenchymal transition and stemness in bladder cancer by regulating FOXQ1/USP21 axis.

Bladder cancer (BC) is a prevalent and deadly disease. circCD2AP was suggested to be highly expressed in BC. However, the exact mechanism needs further investigation. In this study, circCD2AP was observed to be upregulated in BC and linked to poor prognosis in individuals. Functionally, circCD2AP or USP21 knockdown inhibited BC cell EMT and stemness both in vitro and in vivo. Mechanistically, circCD2AP interacted with ELAVL1 to enhance the stability of USP21 mRNA, which, in turn, inhibited the ubiquitination degradation of FOXQ1. Through rescue assay, USP21 or FOXQ1 knockdown was found to abolish the promoting effects of circCD2AP or USP21 overexpression on BC cell EMT and stemness. Overall, this study has unveiled the role of circCD2AP/ELAVL1/USP21/FOXQ1 axis in BC EMT and stemness regulation, offering insights into the mechanisms underlying BC progression, with potential implications for therapeutic strategies.

Knockdown of Notch Suppresses Epithelial-mesenchymal Transition and Induces Angiogenesis in Oral Submucous Fibrosis by Regulating TGF-ß1.

Oral submucous fibrosis (OSF) is a chronic disorder with a high malignant transformation rate. Epithelial-mesenchymal transition (EMT) and angiogenesis are key events in OSF. The Notch signaling plays an essential role in the pathogenesis of various fibrotic diseases, including OSF. Our study aimed to explore the effects of Notch on the EMT and angiogenesis processes during the development of OSF. The expression of Notch in OSF tissues versus normal buccal mucosa samples was compared. Arecoline was used to induce myofibroblast transdifferentiation of buccal mucosal fibroblasts (BMFs). Short hairpin RNA technique was used to knockdown Notch in BMFs. Pirfenidone and SRI-011381 were used to inhibit and activate the TGF-ß1 signaling pathway in BMFs, respectively. The expression of Notch was markedly upregulated in OSF tissues and fibrotic BMFs. Knockdown of Notch significantly decreased the viability and promoted apoptosis in BMFs subjected to arecoline stimulation. Downregulation of Notch also significantly suppressed the EMT process, as shown by the reduction of N-cadherin and vimentin with concomitant upregulation of E-cadherin. In addition, knockdown of Notch upregulated VEGF and enhanced the angiogenic activity of fBMFs. Moreover, inhibition of TGF-ß1 suppressed viability and EMT, promoted apoptosis, and induced angiogenesis of fBMFs, while activation of TGF-ß1 significantly diminished the effects of Notch knockdown on fBMFs. Knockdown of Notch suppressed EMT and induced angiogenesis in OSF by regulating TGF-ß1, suggesting that the Notch-TGF-ß1 pathway may serve as a therapeutic intervention target for OSF.

Quantized iterative learning control for impulsive differential inclusion systems with data dropouts.

This paper studies the quantized iterative learning control with encoding-decoding mechanism of a class of impulsive differential inclusion systems with random data dropouts. First, the set-valued mappings in the differential inclusion systems are transformed into single-valued mappings by using the Steiner-type selector. Then, a learning algorithm based on the intermittent update principle is designed to address the data asynchronism problem caused by two-sided data dropouts. If the data are successfully transmitted at the actuator and measurement sides, then the control input is effectively updated. Furthermore, a suitable scaling sequence is introduced to ensure the system output to achieve zero-error tracking performance for a desired trajectory. An upper bound of the quantization level is determined such that the quantization error is always bounded. The results show that the quantization method reduces the burden of network communication at the cost of increasing the amount of computation, and the learning algorithm does not require the data dropouts to satisfy a certain probability distribution. Finally, the effectiveness of the learning algorithm is verified by numerical simulations of the switched reluctance motor system.

Role of microencapsulated Lactobacillus plantarum in alleviating intestinal inflammatory damage through promoting epithelial proliferation and differentiation in layer chicks.

The alleviating effects of Lactobacillus plantarum in microencapsulation (LPM) on lipopolysaccharide (LPS)-induced intestinal inflammatory injury were investigated in layer chicks. A total of 252 healthy Hy-Line Brown layer chicks were randomly divided into six groups. Birds were injected with saline or LPS except for the control, and the diets of birds subjected to LPS were supplemented with nothing, L. plantarum, LPM, and wall material of LPM, respectively. The viable counts of LPM reached 109 CFU/g, and the supplemental levels of L. plantarum, LPM, and WM were 0.02 g (109 CFU), 1.0 g, and 0.98 g, per kilogram feed, respectively. LPS administration caused intestinal damage in layer chicks, evidenced by increased proinflammatory factors accompanied by poor intestinal development and morphology (p < 0.05). LPM/LPS significantly increased body weight, small intestine weight and length, villus height, villus height/crypt depth, and mRNA relative expression of tight junction protein genes (p < 0.05) and performed better than free L. plantarum. These findings could be attributed to the significant increase in viable counts of L. plantarum in the small intestine (p < 0.05), as well as the enhanced levels of Actinobacteriota, Lactobacillaceae, and Lactobacillus in intestinal microbiota (p < 0.05). Such results could further significantly increase goblet and PCNA+ cell percentage (p < 0.05); the mRNA relative expressions of epithelial cell, fast-cycling stem cell, quiescent stem cell, endocrine cell, and Paneth cell; and goblet and proliferative cell marker genes, including E-cadherin, Lgr-5, Bmi-1, ChA, Lysozome, Mucin-2, and PCNA (p < 0.05). Furthermore, the mRNA relative expressions of key genes involved in epithelial cell proliferation, namely, c-Myc, Cyclin-1, Wnt-3, Lrp-5, and Olfm-4, exhibited significant upregulation compared with the LPS treatment, as well as the differentiating genes Notch-1 and Hes-1 (p < 0.05). To sum up, microencapsulated L. plantarum supplementation could alleviate intestinal injury in layer chicks induced by LPS by promoting the proliferation and differentiation of intestinal epithelial cells, which could be attributed to the increase in viable count of L. plantarum in the gut and optimization in intestinal microbial flora.

The application of CGF combined with GBR in alveolar bone increment for patients with anxiety disorder: A rare case report and literature review.

RATIONALE: Selective serotonin reuptake inhibitors (SSRIs), one of the commonly used anti-anxiety drugs, may have impacts on bone metabolism and potentially lead to drug-induced osteoporosis. The traditional approach of oral implantation in individuals with both anxiety disorder and drug-induced osteoporosis poses a significant challenge. To address this issue, concentrated growth factor (CGF) has been utilized in patients undergoing concurrent alveolar ridge augmentation during oral implantation, resulting in favorable clinical outcomes. Consequently, combining CGF with guided bone regeneration (GBR) in alveolar bone increment may represent a promising new surgical approach for such patients. In this report, we present a case study of a 25-year-old male with anxiety disorder and drug-induced osteoporosis, in who CGF combined with GBR was employed in alveolar bone increment. PATIENT CONCERNS: This article reports the case of a 25-year-old male who underwent cone beam computed tomography (CBCT) due to the absence of his right lower second molar for a period of six months. The CBCT scan revealed significant bone defects, which were attributed to the tooth loss and prolonged use of anti-anxiety drugs. Consequently, the patient sought medical assistance from our department. DIAGNOSES: Based on the patient's self-report, he was diagnosed with an anxiety disorder. Additionally, the CBCT scan confirmed the loss of the right mandibular second molar and revealed the presence of dental irregularity and an alveolar bone defect. INTERVENTIONS: During the patient's course of treatment with anti-anxiety medication, a combination of CGF and GBR was employed for the simultaneous implantation of the missing right mandibular second molar, along with bone augmentation. OUTCOMES: The patient had a follow-up visit two weeks after the surgical procedure, and the wound in the operation area had healed satisfactorily. Six months later, CBCT images revealed excellent osseointegration. The buccal and lingual width of the alveolar bone measured 6.95mm, which was an increase of 1.35mm compared to the pre-implantation stage. LESSONS: This article presents a case study in which CGF combined with GBR were utilized to address alveolar bone augmentation during the implantation phase in patients taking anti-anxiety medication. The results demonstrated that CGF combined with GBR, as a cutting-edge platelet concentrate technique, could effectively stimulate bone tissue proliferation in individuals who have been on long-term anti-anxiety medication, specifically in oral implant areas. This approach can help prevent poor osseointegration, promote higher osseointegration rates, and facilitate wound healing.

Could the New pN Staging Classification Better Predict the Prognosis of Penile Cancer? A Population-Based Analysis.

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) has made new revisions to the N staging of penile cancer (PeCa). This study aimed to evaluate the prognostic value of the new N staging classification. METHODS: This cohort was included from the Surveillance, Epidemiology, and End Results (SEER) database (1988-2016). Overall survival (OS) and cancer-specific survival (CSS) were evaluated using Kaplan-Meier survival curve. The Cox proportional hazards model was employed to calculate hazard ratio (HR) and 95% confidence intervals (CI). RESULTS: Among the included 583 patients, 270 patients had only one positive inguinal lymph node (ILNP), 115 had two ILNPs, and 198 had 3 or more ILNPs. Kaplan-Meier analysis indicated that The OS and CSS of patients with ILNP = 2 were not statistically different from those with ILNP = 1 (p = 0.394; p = 0.760), but had OS and CSS benefit over those with ILNP ≥3 (p = 0.017; p = 0.020). Cox proportional hazards regression analysis indicated that patients with ILNP = 2 and ILNP = 1 have similar OS and CSS (HR = 0.80, p = 0.153; HR = 0.74, p = 0.148), but patients with ILNP ≥3 had worse OS and CSS than patients with ILNP = 2 (HR = 1.56, p = 0.007; HR = 1.86, p = 0.003). CONCLUSIONS: PeCa patients with only one or two lymph node metastases had similar survival outcomes. AJCC 8th edition pN staging has a better discriminative ability to predict the prognosis and can accurately stratify mortality risk in PeCa.

Countercurrent chromatography separation of vitamin E isomers in a co-current mode.

Vitamin E represents a group of lipophilic phenolic compounds, including α-tocopherol, ß-tocopherol, γ-tocopherol, and δ-tocopherol, and α-tocotrienol, ß-tocotrienol, γ-tocotrienol, and δ-tocotrienol isomers. Different forms of vitamin E have been proven to exhibit varying biological activities. However, due to their structural similarities, the separation of vitamin E isomers is a challenging task. Therefore, it is crucial to establish an efficient method for isolating individual isomers. In this study, co-current countercurrent chromatography was employed to isolate vitamin E isomers from commercial capsules using a n-heptane-methanol-water (10:9.5:0.5, v/v) solvent system. The partition coefficients of the main constituents in the capsules ranged from 0.94 to 6.23, requiring over 450 min for a complete separation. To improve separation efficiency, a co-current elution mode was implemented and the flow rates of the two liquid phases as well as sample amount were examined. The results suggested that increasing the flow rate of the stationary phase and sample size could result in more effective separation, shorter separation time, and higher yield. It proved that co-current countercurrent chromatography was an effective method for the separation of vitamin E isomers.

DNA methyltransferase 3A induces the occurrence of oral submucous fibrosis by promoting the methylation of the von Hippel-Lindau.

BACKGROUND: Oral submucous fibrosis (OSF) is associated with malignant disorders. DNA methyltransferase 3A (DNMT3A) is a DNA methylesterase reported to be upregulated in multiple organs and shown to inhibit fibrosis. However, the detailed effect of DNMT3A on OSF remains unclear. METHODS: To mimic OSF in vitro, oral fibroblasts were exposed to arecoline and molecular biological experiments were performed to detect the function of DNMT3A in OSF. RESULTS: We found that von Hippel-Lindau (VHL) was downregulated and highly methylated in OSF. Arecoline remarkably increased the viability, invasiveness, and migration of oral fibroblasts, but upregulation of VHL partially reversed these effects. DNMT3A induces DNA hypermethylation in the VHL promoter, and VHL markedly inhibits the level of tenascin-C (TNC) by inducing the ubiquitination of TNC. TNC reversed the inhibitory effect of VHL upregulation on the differentiation of oral fibroblasts into myofibroblasts. CONCLUSION: DNMT3A induces OSF by promoting methylation of the VHL promoter. Hence, our study provides novel insights into the discovery of novel strategies that can be employed against OSF.

Multi-dimensional preparation of Thymus quinquecostatus Celak. by normal-phase flash chromatography coupled to counter-current chromatography.

In this study, a multi-dimensional chromatography system was developed by integrating normal-phase flash chromatography and counter-current chromatography to isolate flavonoids, phenylpropanoids, and thymol from the aerial parts of Thymus quinquecostatus Celak. In the online multi-dimensional switching system, a normal-phase flash chromatograph packed with 1.2 g of dry homogeneous silica gel mixture (containing 600 mg of methanol extract) was connected to counter-current chromatography via a six-port valve. Two two-dimensional separations were performed using n-heptane-ethyl acetate-methanol-water (6:4:6:4, v/v) and ethyl acetate-water solvent systems sequentially to separate the constituents of Thymus quinquecostatus Celak. The upper phase of the former solvent system was utilized as both elution solvent for flash chromatography and the stationary phase for counter-current chromatography, while the lower phase of the latter solvent system containing 10 mM trifluoroacetic acid was employed as elution solvent for flash chromatography and one mobile phase in pH gradient counter-current chromatography. Thymol (7) and xanthomicrol (8), two hydrophobic ingredients, were purified in the initial two-dimensional separation. The subsequent two-dimensional separation yielded six hydrophilic compounds, namely dihydrokaempferol-7-O-D-glucopyranoside (1), lithospermic acid (2), luteolin-7-O-glucuronide (3), rosmarinic acid (4), messerschmidin (5) and apigenin-7-O-D-glucuronide (6). This study represents the first documented use of online multi-dimensional normal-phase flash chromatography coupled to counter-current chromatography for separating constituents from Thymus quinquecostatus Celak.