Targeted Proteomics Profiling for Biomarker Discovery in Glaucoma Using the Olink Proteomics Platform.

Metabolic dysfunction plays a crucial role in the pathogenesis of glaucoma. In this study, we used Olink proteomics profiling to identify potential biomarkers for glaucoma. Aqueous humor samples were obtained from 44 cataract patients and 44 glaucoma patients. We identified 84 differentially expressed metabolic proteins between the glaucoma and the cataract group. Gene Ontology enrichment analysis highlighted the involvement of these proteins in ER-associated degradation pathway, regulation of interleukin-13 production, and DNA damage response pathway. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis further revealed links to pathways, such as tyrosine and pyrimidine metabolism. Among these, ALDH1A1 emerged as a candidate with a significant diagnostic potential for glaucoma. ALDH1A1 also exhibited a prominent role in the protein-protein interaction network. Elevated levels of ALDH1A1 in the aqueous humor of glaucoma patients were confirmed both in clinical samples and in an ischemia/reperfusion model. Functional assays confirmed that elevated ALDH1A1 induced retinal ganglion cell (RGC) apoptosis in vitro and demonstrated its pro-apoptotic role in RGCs in vivo. Collectively, these findings not only underscore the significance of ALDH1A1 in glaucoma but also provide valuable insights into clinical decision-making and therapeutic strategies.

Ultramicroporous crosslinked polyxanthene-poly(biphenyl piperidinium)-based anion exchange membranes for water electrolyzers operating under highly alkaline conditions.

Anion exchange membrane water electrolyzers (AEMWEs) suffer from low efficiencies and durability, due to the unavailability of appropriate anion exchange membranes (AEM). Herein, a rigid ladder-like polyxanthene crosslinker was developed for the preparation of ultramicroporous crosslinked polyxanthene-poly(biphenyl piperidinium)-based AEMs. Due to the synergetic effects of their ultramicroporous structure and microphase-separation morphology, the crosslinked membranes showed high OH- conductivity (up to 163 mS cm-1 at 80 °C). Furthermore, these AEMs also exhibited moderate water uptake, excellent dimensional stability, and remarkable alkaline stability. The single-cell AEMWE based on QPBP-PX-15% and equipped with non-noble catalysts achieved a current density of 3000 mA cm-2 at 2.03 V (compared to PiperION's 2.26 V) in 6 M KOH solution at 80 °C, which outperformed many AEMWEs that used platinum-group-metal catalysts. Thus, the crosslinked AEMs developed in this study showed significant potential for application in AEMWEs fed with concentrated alkaline solutions.

Why rural teachers are in a poor working state: Double marginalization causes a lack of career identity and hope.

Professional development for rural teachers is currently encountering numerous challenges, leading to poor working conditions characterized by a lack of hope. This condition affects not only the quality of rural education but also the physical and mental well-being and work efficiency of rural teachers themselves. To explore why rural teachers experience poor working conditions, 101 of them were surveyed using a questionnaire that covered double marginalization, teacher career identity, and dispositional hope, and the results show the following. 1) Rural teachers' poor work conditions are associated most strongly with double marginalization. 2) Career identity is an important mediating variable of double marginalization and hope for rural teachers. 3) The double marginalization faced by male teachers in rural areas compared to their female counterparts significantly amplifies the lack of hope. 4) Particularly pronounced is the lack of hope resulting from the double marginalization of rural teachers with less than 15 years of experience when compared to those with careers of 26 or more years. Building on these findings, interventions are proposed in three key areas: (i) reducing the double marginalization of rural teachers, (ii) strengthening career identity, and (iii) enhancing hope. These interventions offer feasible pathways tailored to the needs of educational administrators, teacher development departments, rural schools, and rural teachers themselves.

Enhancing the Flotation Separation of Galena and Pyrite in the Presence of Seawater.

The effect of seawater on the flotation of sulfide minerals is a hot research topic at the present. Using seawater instead of fresh water to separate lead-sulfur can save fresh water resources and reduce lime consumption, which has broad prospects in terms of economic and environmental protection. Many studies have shown that divalent calcium and magnesium ions in seawater are hydrolyzed to form hydroxyl complexes under alkaline pH values, which affects the flotation separation of sulfide ore. In this paper, the flotation separation of galena and pyrite in seawater was tested, and the mechanism was analyzed. Compared with that in deionized water, the lead grade of concentrate in seawater flotation increased from 57.40 to 60.20%. Meanwhile, the recovery of galena declined from 68.66 to 61.17%, and the SI value increased from 2.020 to 2.072. With the addition of SHMP, SS, and EDTA, the SI value increased from 2.072 to 2.609, 2.525, and 2.287, respectively. Noteworthily, when EDTA was excessive, the grade of Pb was 69.60%, and the SI value was 3.050. Wettability analysis, zeta potential analysis, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, density functional theory calculation, and E-DLVO calculation verified the microflotation results and revealed the mechanism of action.

Nonlocal meta-lens with Huygens' bound states in the continuum.

Meta-lenses composed of artificial meta-atoms have stimulated substantial interest due to their compact and flexible wavefront shaping capabilities, outperforming bulk optical devices. The operating bandwidth is a critical factor determining the meta-lens' performance across various wavelengths. Meta-lenses that operate in a narrowband manner relying on nonlocal effects can effectively reduce disturbance and crosstalk from non-resonant wavelengths, making them well-suitable for specialized applications such as nonlinear generation and augmented reality/virtual reality display. However, nonlocal meta-lenses require striking a balance between local phase manipulation and nonlocal resonance excitation, which involves trade-offs among factors like quality-factor, efficiency, manipulation dimensions, and footprint. In this work, we experimentally demonstrate the nonlocal meta-lens featuring Huygens' bound states in the continuum (BICs) and its near-infrared imaging application. All-dielectric integrated-resonant unit is particularly optimized to efficiently induce both the quasi-BIC and generalized Kerker effect, while ensuring the rotation-angle robustness for generating geometric phase. The experimental results show that the single-layer nonlocal Huygens' meta-lens possesses a high quality-factor of 104 and achieves a transmission polarization conversion efficiency of 55%, exceeding the theoretical limit of 25%. The wavelength-selective two-dimensional focusing and imaging are demonstrated as well. This work will pave the way for efficient nonlocal wavefront shaping and meta-devices.

[Experimental teaching reform of polymer molar mass determination using gel permeation chromatography coupled with light scattering].

Gel permeation chromatography coupled with light scattering (GPC-LS) is among the most common methods for determining the molar masses of polymers. GPC-LS is widely used in polymer science research and has been adopted for many industrial applications owing to its high sensitivity, accuracy, and precision. The determination of polymer molar masses using GPC-LS is an important experimental component of the "Polymer Physics Experiments" course. However, the present GPC-LS experimental teaching content tends to be overly simplistic and lacking in depth. Herein, the original experimental content is expanded and multiple sets of experiments are redesigned: (1) Using commercial polystyrene as an experimental sample, the molar mass, molar mass distribution, radius of gyration, and other molecular structure parameters are determined using GPC-LS; (2) Using two polyacrylonitriles with similar molecular structure parameters, subtle differences in the molar mass distributions of the samples are explored using differential mass distribution curves; (3) By comparing the chromatograms of a series of polyethylene glycols with different molar masses, the effect of molar mass on chromatographic peaks is investigated; and (4) For three different polymers (polyacrylonitrile, poly(methyl methacrylate), and poly(ß-cyclodextrin)), the polymer chain conformations are analyzed using conformation plots (i.e., radius of gyration vs. molar mass). In addition, the experimental teaching method is modified to convert passive learning into active learning, thereby improving the students' self-directed learning ability. This experimental teaching reform will help students obtain a more comprehensive understanding of GPC-LS principles and applications, stimulate their enthusiasm for learning, and improve the teaching quality of the experimental course.

Metalenses phase characterization by multi-distance phase retrieval.

Metalens, characterized by their unique functions and distinctive physical properties, have gained significant attention for their potential applications. To further optimize the performance of metalens, it is necessary to characterize the phase modulation of the metalens. In this study, we present a multi-distance phase retrieval system based on optical field scanning and discuss its convergence and robustness. Our findings indicate that the system is capable of retrieving the phase distribution of the metalens as long as the measurement noise is low and the total length of the scanned light field is sufficiently long. This system enables the analysis of focal length and aberration by utilizing the computed phase distribution. We extend our investigation to measure the phase distribution of the metalens operating in the near-infrared (NIR) spectrum and identify the impact of defects in the sample on the phase. Additionally, we conduct a comparative analysis of the phase distribution of the metalens in air and ethanol and observe the variations in the phase modulation of the metalens in different working mediums. Our system provides a straightforward method for the phase characterization of metalens, aiding in optimizing the metalens design and functionality.

The accuracy and quality of image-based artificial intelligence for muscle-invasive bladder cancer prediction.

PURPOSE: To evaluate the diagnostic performance of image-based artificial intelligence (AI) studies in predicting muscle-invasive bladder cancer (MIBC). (2) To assess the reporting quality and methodological quality of these studies by Checklist for Artificial Intelligence in Medical Imaging (CLAIM), Radiomics Quality Score (RQS), and Prediction model Risk of Bias Assessment Tool (PROBAST). MATERIALS AND METHODS: We searched Medline, Embase, Web of Science, and The Cochrane Library databases up to October 30, 2023. The eligible studies were evaluated using CLAIM, RQS, and PROBAST. Pooled sensitivity, specificity, and the diagnostic performances of these models for MIBC were also calculated. RESULTS: Twenty-one studies containing 4256 patients were included, of which 17 studies were employed for the quantitative statistical analysis. The CLAIM study adherence rate ranged from 52.5% to 75%, with a median of 64.1%. The RQS points of each study ranged from 2.78% to 50% points, with a median of 30.56% points. All models were rated as high overall ROB. The pooled area under the curve was 0.85 (95% confidence interval (CI) 0.81-0.88) for computed tomography, 0.92 (95% CI 0.89-0.94) for MRI, 0.89 (95% CI 0.86-0.92) for radiomics and 0.91 (95% CI 0.88-0.93) for deep learning, respectively. CONCLUSION: Although AI-powered muscle-invasive bladder cancer-predictive models showed promising performance in the meta-analysis, the reporting quality and the methodological quality were generally low, with a high risk of bias. CRITICAL RELEVANCE STATEMENT: Artificial intelligence might improve the management of patients with bladder cancer. Multiple models for muscle-invasive bladder cancer prediction were developed. Quality assessment is needed to promote clinical application. KEY POINTS: Image-based artificial intelligence models could aid in the identification of muscle-invasive bladder cancer. Current studies had low reporting quality, low methodological quality, and a high risk of bias. Future studies could focus on larger sample sizes and more transparent reporting of pathological evaluation, model explanation, and failure and sensitivity analyses.

Analysis of the epidemic characteristics of common respiratory pathogens infection in children in a 3A special hospital.

OBJECTIVE: To analyze the epidemic characteristics of common respiratory tract infection pathogens in children with respiratory tract infection, and provide scientific basis for the prevention and control of respiratory tract infection. METHODS: A retrospective collection of clinical data was conducted on 11,538 children with respiratory tract infections at Luoyang Maternal and Child Health Hospital from December 2022 to November 2023. The types of respiratory tract infections, including upper and lower respiratory tract infections, as well as five respiratory pathogens: influenza A virus (influenza A), influenza B virus (influenza B virus, adenovirus (ADV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP) infections, were analyzed and compared for different genders, ages, temperatures, and air quality in different months; And the changes of five pathogens in children with respiratory tract infections of different disease severity. RESULTS: From December 2022 to November 2023, a total of 11,538 children with respiratory infections were included in the analysis, including 6436 males and 5102 females, with an age of 4.92 ± 2.03 years. The proportion of upper respiratory tract infections is as high as 72.17%, and lower respiratory tract infections account for 27.83%. Among them, 2387 were positive for Flu A antigen, with a positive rate of 20.69%, 51 cases were positive for Flu B antigen, and the positive rate was 0.4%, 1296 cases were positive for adv antigen, with a positive rate of 11.23%, 868 cases were positive for RSV antigen, with a positive rate of 7.52%, 2481 cases were positive for MP IgM antibody or MP antigen, and the positive rate was 21.50%. Flu B in male children The infection rate of ADV and MP was higher than that of female children (p < 0.05); Among children in different age groups, the older the age, the older the Flu A The higher the infection rate of MP (p < 0.05), the higher the positive rate of RSV in children with younger age (p < 0.05). The positive rate of ADV in children aged 3-6 years and > 6 years was higher than that in children aged 0-3 years (p < 0.05); Flu A and MP are popular throughout the year, and the positive rate peaks during the period of temperature rise and air quality decline from February to March, and during the period of temperature drop and air quality index rise from August to November, The positive rate of RSV peaked after the turning point of temperature rise from March to April. The infection rate was higher during the period of sharp decline in air quality from March to May and sharp decline in temperature in November, The positive rate of ADV was higher at the turning point of temperature rise from February to March, and then the infection rate decreased. During the period of sharp temperature drop from August to November, the positive rate increased sharply, and the peak of infection occurred; As the disease worsens, The positive rates of Flu A, Flu B, RSV, MP and combined infection with more than two pathogens were all increased (p < 0.05). CONCLUSION: After the new coronavirus epidemic in 2022, Flu A and MP have the highest infection rate of respiratory pathogens in children, showing a peak growth in general, with epidemic characteristics changing with environmental temperature, air quality and seasons. The main disease type is upper respiratory tract infection, MP and adv infections were mainly in male children, Flu A, MP and ADV infections are more common in older children, RSV infection was more common in younger children; Flu A, Flu B, RSV and MP infection and the co infection of more than two pathogens may more easily lead to the occurrence of severe pneumonia.

TCF3 as a multidimensional biomarker: oncogenicity, genomic alterations, and immune landscape in pan-cancer analysis.

Transcription factor 3 (TCF3), a pivotal member of the TCF/LEF family, plays a critical role in tumorigenesis. Nonetheless, its impact on the tumor microenvironment (TME) and cancer phenotypes remains elusive. We perform an exhaustive analysis of TCF3 expression, DNA variation profiles, prognostic implications, and associations with the TME and immunological aspects. This study is based on a large-scale pan-cancer cohort, encompassing over 17,000 cancer patients from multiple independent datasets, validated by in vitro assays. Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses. Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer. Additionally, mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis. Importantly, TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors. Elevated TCF3 expression is correlated with more aggressive cancer subtypes, as validated by immunohistochemistry and diverse cohort data. Furthermore, TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis. In vitro investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition, migration, invasion, and angiogenesis. These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway, which is modulated by IL-17A in human uveal melanoma MUM2B cells. This study elucidates, for the first time, the significant associations of TCF3 with DNA variation profiles, prognostic outcomes, and the TME in multiple cancer contexts. TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies, particularly in uveal melanoma.

Kavain Alleviates Choroidal Neovascularization Via Decreasing the Activity of the HIF-1α/VEGF-A/VEGFR2 Signaling Pathway and Inhibiting Inflammation.

Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (anti-VEGF) drugs, such as aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Methods: Various experiments were conducted to assess the Kavain's toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a laser-induced CNV mice model. To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P<0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P<0.05). These effects were statistically significantly enhanced in the Kavain plus aflibercept groups (P<0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE)/choroid complexes (P<0.05). Mechanistically, Kavain decreased the activity of the hypoxia-inducible factor 1α (HIF-1α)/VEGF-A/ VEGF receptor 2 (VEGFR2) signaling pathway. Conclusion: Our study is the first to demonstrate Kavain's potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

Background: Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. Methods: The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. Results: A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. Conclusions: In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

Meta-analysis of clinical efficacy and safety of transanal endoscopic microsurgery and endoscopic submucosal dissection in the treatment of rectal tumors.

Aim: The aim of the article was to systematically evaluate the clinical efficacy and safety of transanal endoscopic microsurgery (TEM) and endoscopic submucosal dissection (ESD) in the treatment of rectal tumors. Material and methods: Control studies were conducted on cases included in the electronic databases Medline, Embase, Cochrane Library, and CNKI. Patients with colorectal tumors were included in the TEM and ESD groups for treatment, with the main indicators being R0 resection rate, postoperative perforation and bleeding incidence, and tumor recurrence rate. The meta-analysis was carried out using RevMan 5.3 software. Results: A total of 10 studies were included, with 736 patients. The analysis showed that for the recurrence rate in the TEM group compared to ESD, OR = 1.23, 95% CI = 0.56-2.72, p = 0.60; for the R0 resection rate between the TEM group and ESD group, OR = 1.35, 95% CI = 0.82-2.22, p = 0.24; for the incidence of perforation in the TEM and ESD groups, OR = 0.59, 95% CI = 0.25-1.40, p = 0.23. The inter-group comparison of these three items was statistically significant. Compared with the ESD group, the hospitalization time and the incidence of bleeding of the TEM group were both lower, with SD = 0.48, 95% CI = 0.26-0.69, p < 0.001 and OR = 0.35, 95% CI = 0.13-0.92, p = 0.03. The differences were statistically significant. Conclusions: Both TEM and ESD endoscopic treatment techniques can achieve a higher R0 resection rate and lower risk of tumor recurrence in the treatment of colorectal tumors. However, TEM may have higher surgical safety than ESD technology, and can shorten postoperative hospitalization time and lower postoperative bleeding rate.

The role of CD83 in the pathogenesis of immune thrombocytopenia.

BACKGROUND: CD83 are closely related to the pathogenesis of immune thrombocytopenia (ITP), but the exact mechanism remains unclear. AIM: To explore the relationship between CD83 and CD4+ T cell subsets and clarify the role of CD83 in the pathogenesis of ITP. METHODS: RT-qPCR and Flow cytometry were used to illustrate CD83 expression. The downregulation and overexpression of DC-CD83 were co-cultured with CD4+ T cells to detect cell proliferation, co-cultured supernatant cytokines and Tregs expression. RESULTS: The results indicate that the ITP patients showed higher expression of CD83 than the healthy controls. The proliferation of CD4+ T cells was inhibited by downregulation of DCs-CD83 but promoted by overexpression of DCs-CD83. siRNA-CD83 inhibited proinflammatory IFN-γ and IL-17 secretion while raising TGF-ß, IL-10 concentrations. Overexpression of DCs-CD83 promoted Tregs expression. CONCLUSION: The Th1/Th2 and Th17/Tregs polarization were reversed via interfering DCs with siRNA-CD83. CD83 plays an important role in ITP pathogenesis, suggesting novel treatment for ITP patients.

Single-cell transcriptomic analysis reveals the antiangiogenic role of Mgarp in diabetic retinopathy.

INTRODUCTION: Diabetic retinopathy (DR) is a common vascular complication of diabetes mellitus and a leading cause of vision loss worldwide. Endothelial cell (EC) heterogeneity has been observed in the pathogenesis of DR. Elucidating the underlying mechanisms governing EC heterogeneity may provide novel insights into EC-specific therapies for DR. RESEARCH DESIGN AND METHODS: We used the single-cell data from the Gene Expression Omnibus database to explore EC heterogeneity between diabetic retinas and non-diabetic retinas and identify the potential genes involved in DR. CCK-8 assays, EdU assays, transwell assays, and tube formation assays were conducted to determine the role of the identified gene in angiogenic effects. RESULTS: Our analysis identified three distinct EC subpopulations in retinas and revealed that Mitochondria-localized glutamic acid-rich protein (Mgarp) gene is potentially involved in the pathogenesis of DR. Silencing of Mgarp significantly suppressed the proliferation, migration, and tube formation capacities in retinal endothelial cells. CONCLUSIONS: This study not only offers new insights into transcriptomic heterogeneity and pathological alteration of retinal ECs but also holds the promise to pave the way for antiangiogenic therapy by targeting EC-specific gene.

Development of crosslinked gelatin films through Maillard reaction and reinforced with poly(vinyl alcohol) for active food packaging.

In order to improve the functionality of natural gelatin films for active food packaging applications, a combined strategy of crosslinking via Maillard reaction and blending enhancement incorporated with poly(vinyl alcohol) (PVA) was explored. In this study, when the mass ratio of gelatin to glucose was 10:1, Maillard reaction of crosslinked gelatin films was the highest, UV absorption and browning index reached the maximum. Infrared analysis showed that PVA could form strong interfacial interactions with gelatin matrix. The presence of PVA could significantly improve the toughness, water absorption, transparency, and oxygen barrier properties of crosslinked gelatin films. When the amount of PVA reached 5 %, elongation at break and oxygen barrier properties of crosslinked gelatin films were improved by 76.7 % and 47.9 % compared with pure crosslinked gelatin film. Even when the amount of PVA reached 10 %, UV absorption (at 315 nm) of crosslinked gelatin films still exceeded 98.7 %. The addition of PVA could accelerate the dissolution and swelling of crosslinked gelatin films, promoting the migration and release of active substances (Maillard reaction products (MRPs)). The two antioxidant activities tests (DPPH and ABTS method) achieved the highest radical scavenging rates of 71.6 % and 91.2 %, respectively, with corresponding PVA addition of 5 % and 7.5 %. After continuing to add PVA, antioxidant activities began to significantly decrease, which was directly related to the decrease in the generation of MRPs. Therefore, crosslinked gelatin films reinforced with appropriate amount of PVA can be considerable potential as active films for renewable food packaging applications.

Dysregulated RNA editing of EIF2AK2 in polycystic ovary syndrome: clinical relevance and functional implications.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive ages. Our previous study has implicated a possible link between RNA editing and PCOS, yet the actual role of RNA editing, its association with clinical features, and the underlying mechanisms remain unclear. METHODS: Ten RNA-Seq datasets containing 269 samples of multiple tissue types, including granulosa cells, T helper cells, placenta, oocyte, endometrial stromal cells, endometrium, and adipose tissues, were retrieved from public databases. Peripheral blood samples were collected from twelve PCOS and ten controls and subjected to RNA-Seq. Transcriptome-wide RNA-Seq data analysis was conducted to identify differential RNA editing (DRE) between PCOS and controls. The functional significance of DRE was evaluated by luciferase reporter assays and overexpression in human HEK293T cells. Dehydroepiandrosterone and lipopolysaccharide were used to stimulate human KGN granulosa cells to evaluate gene expression. RESULTS: RNA editing dysregulations across multiple tissues were found to be associated with PCOS in public datasets. Peripheral blood transcriptome analysis revealed 798 DRE events associated with PCOS. Through weighted gene co-expression network analysis, our results revealed a set of hub DRE events in PCOS blood. A DRE event in the eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2:chr2:37,100,559) was associated with PCOS clinical features such as luteinizing hormone (LH) and the ratio of LH over follicle-stimulating hormone. Luciferase assays, overexpression, and knockout of RNA editing enzyme adenosine deaminase RNA specific (ADAR) showed that the ADAR-mediated editing cis-regulated EIF2AK2 expression. EIAF2AK2 showed a higher expression after dehydroepiandrosterone and lipopolysaccharide stimulation, triggering changes in the downstrean MAPK pathway. CONCLUSIONS: Our study presented the first evidence of cross-tissue RNA editing dysregulation in PCOS and its clinical associations. The dysregulation of RNA editing mediated by ADAR and the disrupted target EIF2AK2 may contribute to PCOS development via the MPAK pathway, underlining such epigenetic mechanisms in the disease.

Efficacy and safety of acupuncture for postpartum hypogalactia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Postpartum hypogalactia (PH) is prominent during lactation and may negatively impact the mother's or infant's health. Acupuncture is widely used to increase maternal breast milk production. However, the effects of acupuncture on PH remain unclear. Therefore, this review aimed to evaluate the efficacy and safety of acupuncture in individuals with PH. MATERIALS AND METHODS: Articles on potentially eligible randomized controlled trials (RCTs) on acupuncture for PH published from database inception to October 2023 were retrieved from the PubMed, Web of Science, Cochrane Library, EMBASE, EBSCO, Scopus, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, WanFang, and VIP databases. Two reviewers independently screened the records, extracted essential information, and evaluated the methodological quality of the RCTs using the revised Cochrane risk-of-bias (RoB) tool. The primary outcome was a change in serum prolactin (PRL) levels before and after treatment. Secondary outcomes included milk secretion volume (MSV), total effective rate (TER), mammary fullness degree (MFD), and exclusive breastfeeding rate (EBR). Meta-analyses were performed using RevMan v5.4. Finally, the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation tool. RESULTS: This study included 19 RCTs involving 2,400 participants. The included studies were classified as having an unclear to high RoB. Our findings indicated that, overall, acupuncture showed a significant effect in increasing serum PRL levels (standardized mean differences [SMDs] = 1.09, 95% confidence interval [CI]: 0.50, 1.68), MSV (SMD = 1.69, 95% CI: 0.53, 2.86), TER (relative risk [RR] = 1.25, 95% CI: 1.10, 1.42), and EBR (RR = 2.01, 95% CI: 1.07, 3.78) compared to that in the control group; however, no difference in MFD (SMD = 1.17, 95% CI: -0.09, 2.42) was observed. In the subgroup analysis, acupuncture combined with Chinese herbs or conventional treatment was significantly more effective in increasing serum PRL levels, MSV, and TER than did Chinese herbs or conventional treatment alone. Moreover, acupuncture alone resulted in significantly higher serum PRL levels compared to Chinese herbs; however, this benefit was not observed for TER and MFD. The quality of evidence was critically low. CONCLUSION: Acupuncture may effectively increase milk secretion in women with PH. However, owing to the low quality of evidence, further rigorously designed studies are warranted to confirm our findings.

Patients with ASPSCR1-TFE3 fusion achieve better response to ICI based combination therapy among TFE3-rearranged renal cell carcinoma.

BACKGROUND: TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates. METHODS: Thirty-eight patients with metastatic TFE3-rRCC were enrolled. Main outcomes included progression-free survival (PFS), overall survival, objective response rate (ORR) and disease control rate. RNA sequencing was performed on 32 tumors. RESULTS: Patients receiving first-line immune checkpoint inhibitor (ICI) based combination therapy achieved longer PFS than those treated without ICI (median PFS: 11.5 vs. 5.1 months, P = 0.098). After stratification of fusion partners, the superior efficacy of first-line ICI based combination therapy was predominantly observed in ASPSCR1-TFE3 rRCC (median PFS: not reached vs. 6.5 months, P = 0.01; ORR: 67.5% vs. 10.0%, P = 0.019), but almost not in non-ASPSCR1-TFE3 rRCC. Transcriptomic data revealed enrichment of ECM and collagen-related signaling in ASPSCR1-TFE3 rRCC, which might interfere with the potential efficacy of anti-angiogenic monotherapy. Whereas angiogenesis and immune activities were exclusively enriched in ASPSCR1-TFE3 rRCC and promised the better clinical outcomes with ICI plus tyrosine kinase inhibitor combination therapy. CONCLUSIONS: The current study represents the largest cohort comparing treatment outcomes and investigating molecular correlates of metastatic TFE3-rRCC based on fusion partner stratification. ICI based combination therapy could serve as an effective first-line treatment option for metastatic ASPSCR1-TFE3 rRCC patients. Regarding with other fusion subtypes, further investigations should be performed to explore the molecular mechanisms to propose pointed therapeutic strategy accordingly.

The prognostic significance of ubiquitination-related genes in multiple myeloma by bioinformatics analysis.

BACKGROUND: Immunoregulatory drugs regulate the ubiquitin-proteasome system, which is the main treatment for multiple myeloma (MM) at present. In this study, bioinformatics analysis was used to construct the risk model and evaluate the prognostic value of ubiquitination-related genes in MM. METHODS AND RESULTS: The data on ubiquitination-related genes and MM samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The consistent cluster analysis and ESTIMATE algorithm were used to create distinct clusters. The MM prognostic risk model was constructed through single-factor and multiple-factor analysis. The ROC curve was plotted to compare the survival difference between high- and low-risk groups. The nomogram was used to validate the predictive capability of the risk model. A total of 87 ubiquitination-related genes were obtained, with 47 genes showing high expression in the MM group. According to the consistent cluster analysis, 4 clusters were determined. The immune infiltration, survival, and prognosis differed significantly among the 4 clusters. The tumor purity was higher in clusters 1 and 3 than in clusters 2 and 4, while the immune score and stromal score were lower in clusters 1 and 3. The proportion of B cells memory, plasma cells, and T cells CD4 naïve was the lowest in cluster 4. The model genes KLHL24, HERC6, USP3, TNIP1, and CISH were highly expressed in the high-risk group. AICAr and BMS.754,807 exhibited higher drug sensitivity in the low-risk group, whereas Bleomycin showed higher drug sensitivity in the high-risk group. The nomogram of the risk model demonstrated good efficacy in predicting the survival of MM patients using TCGA and GEO datasets. CONCLUSIONS: The risk model constructed by ubiquitination-related genes can be effectively used to predict the prognosis of MM patients. KLHL24, HERC6, USP3, TNIP1, and CISH genes in MM warrant further investigation as therapeutic targets and to combat drug resistance.