CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation.

AIMS: As our comprehension of the intricate relationship between cellular senescence and tumor biology continues to evolve, the therapeutic potential of cellular senescence is gaining increasing recognition. Here, we identify chromobox 4 (CBX4), a Small Ubiquitin-related Modifier (SUMO) E3 ligase, as an antagonist of cellular senescence and elucidate a novel mechanism by which CBX4 promotes drug resistance and malignant progression of gastric cancer (GC). METHODS: In vitro and in vivo models were conducted to investigate the manifestation and impact of CBX4 on cellular senescence and chemoresistance. High-throughput sequencing, chromatin immunoprecipitation, and co-immunoprecipitation techniques were utilized to identify the upstream regulators and downstream effectors associated with CBX4, revealing its intricate regulatory network. RESULTS: CBX4 diminishes the sensitivity of GC cells to cellular senescence, facilitating chemoresistance and GC development by deactivating the senescence-related Hippo pathway. Mechanistically, low-dose cisplatin transcriptionally downregulates CBX4 through CEBPB. In addition, CBX4 preserves the stability and cytoplasm-nuclear transport of YAP1, the key player of Hippo pathway, by inducing SUMO1 modification at K97 and K280, which competitively inhibits YAP1-S127 phosphorylation. CONCLUSIONS: Our study highlights the anti-senescence role of CBX4 and suggests that CBX4 inhibition in combination with low-dose cisplatin has the potential to overcome chemoresistance and effectively restrict GC progression.

Imprinted gene detection effectively improves the diagnostic accuracy for papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent histological type of thyroid carcinoma. Although an increasing number of diagnostic methods have recently been developed, the diagnosis of a few nodules is still unsatisfactory. Therefore, the present study aimed to develop and validate a comprehensive prediction model to optimize the diagnosis of PTC. METHODS: A total of 152 thyroid nodules that were evaluated by postoperative pathological examination were included in the development and validation cohorts recruited from two centres between August 2019 and February 2022. Patient data, including general information, cytopathology, imprinted gene detection, and ultrasound features, were obtained to establish a prediction model for PTC. Multivariate logistic regression analysis with a bidirectional elimination approach was performed to identify the predictors and develop the model. RESULTS: A comprehensive prediction model with predictors, such as component, microcalcification, imprinted gene detection, and cytopathology, was developed. The area under the curve (AUC), sensitivity, specificity, and accuracy of the developed model were 0.98, 97.0%, 89.5%, and 94.4%, respectively. The prediction model also showed satisfactory performance in both internal and external validations. Moreover, the novel method (imprinted gene detection) was demonstrated to play a role in improving the diagnosis of PTC. CONCLUSION: The present study developed and validated a comprehensive prediction model for PTC, and a visualized nomogram based on the prediction model was provided for clinical application. The prediction model with imprinted gene detection effectively improves the diagnosis of PTCs that are undetermined by the current means.

Solar CO2 Reduction Enabled by Cascade Hole Migration.

Solar-powered photocatalytic conversion of CO2 to hydrocarbon fuels represents an emerging approach to solving the greenhouse effect. However, low charge separation efficiency, deficiency of surface catalytic active sites, and sluggish charge-transfer kinetics, together with the complicated reaction pathway, concurrently hinder the CO2 reduction. Herein, we show the rational construction of transition metal chalcogenides (TMCs) heterostructure CO2 reduction photosystems, wherein the TMC substrate is tightly integrated with amorphous oxygen-containing cobalt sulfide (CoSOH) by a solid non-conjugated polymer, i.e., poly(vinyl alcohol) (PVA), to customize the unidirectional charge-transfer pathway. In this well-defined multilayered nanoarchitecture, the PVA interim layer intercalated between TMCs and CoSOH acts as a hole-relaying mediator and meanwhile boosts CO2 adsorption capacity, while CoSOH functions as a terminal hole-collecting reservoir, stimulating the charge transport kinetics and boosting the charge separation over TMCs. This peculiar interface configuration and charge transport characteristics endow TMC/PVA/CoSOH heterostructures with significantly enhanced visible-light-driven photoactivity and CO2 conversion. Based on the intermediates probed during the photocatalytic CO2 reduction reaction, the photocatalytic mechanism was determined. Our work would inspire sparkling ideas to mediate the charge transfer over semiconductor for solar carbon neutral conversion.

Synthesis of High-Quality Bulk Single-Crystal Black Phosphorus by the Circulating Vapor Growth Approach.

Black phosphorus (BP), a promising two-dimensional (2D) layered semiconductor material, has gained enormous attention due to its impressive properties over the past several years. Although plenty of methods have been developed to synthesize high-quality BP, most of the currently available BP materials still suffer from unsatisfactory crystallization, purity, and stability in air, hindering their practical application. A facile approach to synthesizing ultrahigh-quality single-crystal BP is of significance to shed light on the nature of 2D semiconductor materials and their massive application. In this work, we present the facile and efficient circulating vapor growth approach to growing bulk single-crystal BP. The as-grown BP material features high crystallinity and ultrahigh purity (higher than 99.999 at %), exceeding those of all the previously reported and some commercially available BP crystals. It also maintains excellent stability in air and water after 15 consecutive days of test. Moreover, the as-synthesized BP material features good thermal stability, oxidation resistance, and excellent electrical properties, as well. This study provides a new approach for the fabrication of ultrahigh-quality BP material and thus promotes its application.

Cost-Effectiveness Analysis of Hepatic Arterial Chemotherapy for Advanced Hepatocellular Carcinoma in China: A Comparative Analysis of HAIC-FO and Sorafenib.

BACKGROUND The FOHAIC-1 trial showed hepatic arterial infusion chemotherapy with infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) improved survival, compared with sorafenib, in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to conduct a cost-effectiveness comparison between HAIC-FO and sorafenib from the perspective of the Chinese healthcare system. MATERIAL AND METHODS The economic evaluation was conducted between July 2023 and February 2024, spanning a 10-year investment horizon. A Markov model was developed to perform a cost-effectiveness analysis of HAIC-FO vs sorafenib. Health states incorporated in the model comprised progression-free disease, progressed disease, and death. Transition probabilities were derived from data obtained from the FOHAIC-1 trial. Incremental cost-effectiveness ratio (ICER) was calculated to evaluate cost-effectiveness. Additionally, one-way and probabilistic sensitivity analyses assessed the model's robustness. RESULTS The HAIC-FO group accrued a total cost of $22,781, whereas the sorafenib group totaled $18,795. In terms of effectiveness, the HAIC-FO group achieved 1.06 quality-adjusted life years (QALYs), whereas the sorafenib group attained 0.65 QALYs. Compared with sorafenib, HAIC-FO yielded an additional 0.41 QALYs at a cost of additional $3,985, resulting in an incremental cost of $9,720 per QALY gained. The one-way sensitivity analysis revealed the final ICER remained below the willingness-to-pay (WTP) threshold of $30,492 per QALY, when considering parameter fluctuations. Additionally, probabilistic sensitivity analysis indicated a 99.8% probability that the ICER for HAIC-FO compared with sorafenib would fall below the WTP threshold. CONCLUSIONS Compared with sorafenib, HAIC-FO emerged as a cost-effective first-line treatment option for patients facing advanced HCC in China.

Network pharmacology analysis of the renal protective effects of bracken (Pteridium aquilinum) using experimental data obtained in an avian (quail) hyperuricemia model.

OBJECTIVE: To investigate the nephroprotective potential of orally administered bracken Pteridium aquilinum extract against renal damage in quails, induced by a high-purine diet, to form a foundation for subsequent clinical studies and applications. MATERIALS AND METHODS: A mass spectrometry analysis was conducted on the pteridophyte subjected to steam explosion. Network pharmacological methods were then utilized to pinpoint shared targets and pathways, which suggested that Pteridium aquilinum has a capability to counteract renal injury. A total of 48 specific-pathogen-free (SPF) "Difaku" quails were selected and segregated into six distinct groups. The control group received a standard diet, whereas the other groups were fed a high-purine diet. Beginning on day 14, each group was subjected to designated therapeutic measures. The study continued for 40 days, after which relevant biological markers were assessed. RESULTS: Active compound peaks from the steam-exploded Pteridium aquilinum were isolated. Subsequently, 101 targets and several pathways associated with renoprotective effects were discerned, indicating that the Pteridium aquilinum achieves its nephroprotective function through comprehensive regulatory mechanisms. The high-purine diet successfully induced hyperuricemia in the quails, resulting in renal impairment. Following intervention with varied Pteridium aquilinum dosages, renal protective outcomes were evident, though xanthine oxidase activity remained unaffected. Histological analyses demonstrated a notable decrease in renal lesion dimensions post-intervention. CONCLUSION: The steam-exploded bracken Pteridium aquilinum may provide nephroprotective benefits against hyperuricemia-induced renal damage in quails through comprehensive regulatory processes. This highlights the Pteridium aquilinum's potential as an innovative nephroprotective therapeutic and dietary solution, presenting a promising avenue for hyperuricemia and renal damage treatment and prevention.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

Differential impacts of nonsteroidal anti-inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans.

Aging and age-related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown their promise in mitigating age-related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age-related changes in drug metabolism and tolerance, which could result in age-dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk-1/skn-1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk-1 was knocked out in the pmk-1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age-dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.

Two Novel Diterpenoid Alkaloids from Aconitum Pendulum.

Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19 mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests.

Exploring the challenges of taiwanese nurses in the COVID-19 post-pandemic era.

In the wake of the COVID-19 pandemic, the fluctuating nurse resignation rates highlighted an understudied area in healthcare: post-pandemic challenges in clinical settings. This study, conducted from May to November 2023, employed a qualitative inquiry using focus groups to delve into these challenges. Six focus group sessions, involving 33 nurse participants recruited through snowball sampling from various hospital settings were conducted to explore their clinical experiences during and after the pandemic. Thematic analysis revealed two primary themes: the 'Invisibility of Nurses' within the healthcare system and the 'Moral Duty of Nursing Practice'. These findings illuminate a tension between the overlooked role of nurses and their ethical obligations, underscoring a critical need for policy reassessment. The study advocates for systemic changes, particularly in the undervaluation of the nursing profession and the National Health Insurance system, to address the poor working environment and mitigate long-term nursing shortages. This research deepens understanding of post-pandemic nursing workforce challenges in Taiwan, highlighting the need for policy evolution to enhance recognition and support for the nursing industry. It is suggested to provide tangible compensation to acknowledge nurses' daily care and health education for patients. A healthier working environment can be enhanced by collaborative efforts between healthcare institutions and nurses.

Telemedicine-Enhanced Lung Cancer Screening Using Mobile Computed Tomography Unit with Remote Artificial Intelligence Assistance in Underserved Communities: Initial Results of a Population Cohort Study in Western China.

Introduction: Lung cancer is a leading cause of cancer deaths globally. Despite favorable recommendations, low-dose computed tomography (LDCT) lung screening adoption remains low in China. Barriers such as limited infrastructure, costs, distance, and personnel shortages restrict screening access in disadvantaged regions. We initiated a telemedicine-enabled lung cancer screening (LCS) program in a medical consortium to serve people at risk in underserved communities. The objective of this study was to describe the implementation and initial results of the program. Methods: From 2020 to 2021, individuals aged 40-80 years were invited to take LCS by mobile computed tomography (CT) units in three underserved areas in Western China. Numerous CT scans were remotely reported by radiologists aided by artificial intelligence (AI) diagnostic systems. Abnormal cases were tracked through an integrated hospital network for follow-up. A retrospective cohort study documented participant demographics, health history, LDCT results, and outcomes. Descriptive analysis was conducted to report baseline characteristics and first-year follow-up results. Results: Of the 28,728 individuals registered in the program, 19,517 (67.94%) participated in the screening. The study identified 2.68% of participants with high-risk pulmonary nodules and diagnosed 0.55% with lung cancer after a 1-year follow-up. The majority of high-risk participants received timely treatment in hospitals. Conclusions: This study demonstrated mobile CT units with remote AI assistance improved access to LCS in underserved areas, with high participation and early detection rates. Our implementation supports the feasibility of deploying telemedicine-enabled LCS to increase access to a large scale of basic radiology and diagnostic services in resource-limited settings. Clinical Trial Registration Number: ChiCTR1900024623.

Extraction Optimization of Phenolic Compounds from Triadica sebifera Leaves: Identification, Characterization and Antioxidant Activity.

Triadica sebifera (T. sebifera) has attracted much attention because of the high oil content in its seeds, but there are few systematic studies on the phenolic compounds of T. sebifera leaves (TSP). In this study, the extraction process of TSP was optimized by response surface methodology. The phenolic components of these extracts were analyzed by high-performance liquid chromatography (HPLC). Moreover, the effects of hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activity and characterization of T. sebifera leaf extract (TSLE) were evaluated. Under the conditions of ethanol concentration 39.8%, liquid-solid ratio (LSR) 52.1, extraction time 20.2 min and extraction temperature 50.6 °C, the maximum TSP yield was 111.46 mg GAE/g dw. The quantitative analysis and correlation analysis of eight compounds in TSP showed that the type and content of phenolic compounds had significant correlations with antioxidant activity, indicating that tannic acid, isoquercitrin and ellagic acid were the main components of antioxidant activities. In addition, through DPPH and ABTS determination, VD-TSLE and FD-TSLE showed strong scavenging ability, with IC50 values of 138.2 µg/mL and 135.5 µg/mL and 73.5 µg/mL and 74.3 µg/mL, respectively. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) infrared spectroscopy revealed small differences in the extracts of the three drying methods. This study lays a foundation for the effective extraction process and drying methods of phenolic antioxidants from T. sebifera leaves, and is of great significance for the utilization of T. sebifera leaves.

Relevance and mechanism of STAT3/miR-221-3p/Fascin-1 axis in EGFR TKI resistance of triple-negative breast cancer.

The epidermal growth factor receptor 1 (EGFR) plays a crucial role in the progression of various malignant tumors and is considered a potential target for treating triple-negative breast cancer (TNBC). However, the effectiveness of representative tyrosine kinase inhibitors (TKIs) used in EGFR-targeted therapy is limited in TNBC patients. In our study, we observed that the TNBC cell lines MDA-MB-231 and MDA-MB-468 exhibited resistance to Gefitinib. Treatment with Gefitinib caused an upregulation of Fascin-1 (FSCN1) protein expression and a downregulation of miR-221-3p in these cell lines. However, sensitivity to Gefitinib was significantly improved in both cell lines with either inhibition of FSCN1 expression or overexpression of miR-221-3p. Our luciferase reporter assay confirmed that FSCN1 is a target of miR-221-3p. Moreover, Gefitinib treatment resulted in an upregulation of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in MDA-MB-231 cells. Using Stattic, a small-molecule inhibitor of STAT3, we observed a significant enhancement in the inhibitory effect of Gefitinib on the growth, migration, and invasion of MDA-MB-231 cells. Additionally, Stattic treatment upregulated miR-221-3p expression and downregulated FSCN1 mRNA and protein expression. A strong positive correlation was noted between the expression of STAT3 and FSCN1 in breast cancer tissues. Furthermore, patients with high expression levels of both STAT3 and FSCN1 had a worse prognosis. Our findings suggest that elevated FSCN1 expression is linked to primary resistance to EGFR TKIs in TNBC. Moreover, we propose that STAT3 regulates the expression of miR-221-3p/FSCN1 and therefore modulates resistance to EGFR TKI therapy in TNBC. Combining EGFR TKI therapy with inhibition of FSCN1 or STAT3 may offer a promising new therapeutic option for TNBC.

A Visual Analysis of the Research Dynamics in Resistance to EGFR Inhibitors for NSCLC.

Purpose: Activating mutations in epidermal growth factor receptor (EGFR) have been identified as key predictive biomarkers for the customized treatment with EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), aiding in improving patient response rates and survival. However, resistance challenges the efficacy of these treatments, with limited understanding of post-resistance therapeutic strategies. A deep understanding of the biology and resistance mechanisms of EGFR-mutant NSCLC is crucial for developing new treatment approaches. This study, through bibliometric analysis, summarizes the trends in research on resistance to EGFR-TKIs. Methods: Research papers on NSCLC with EGFR inhibitor resistance were collected from the Web of Science Core Collection (WoSCC). The analysis utilized bibliometric tools like CiteSpace, VOSviewer, and other platforms for comprehensive analysis and visualization of the outcomes. Results: The WoSCC database contains a total of 5866 documents on resistance to EGFR-TKIs treatment, including 4727 articles (93.48%) and 1139 reviews (6.52%), spanning 81 countries and regions, 4792 institutions, with the involvement of 23,594 authors. Since 2016, there has been a significant increase in publications in this field. China has the highest publication output, while the United States has the highest citation count for papers. Harvard University leads in terms of the number of publications. Among the top ten journals with the highest output, Clinical Cancer Research has the highest impact factor at 11.5, with 90% of the journals classified in Q1 or Q2. Rafael Rosell is one of the most influential authors in this field, ranking second in publication volume and fourth in citation count. Research on EGFR-TKIs resistance mainly focuses on genetic testing, resistance mechanisms, and post-resistance treatment strategies. Conclusion: This study provides researchers with a reliable basis and guidance for finding authoritative references, understanding research trends, and exploring potential directions.

Neural Circuitry Polarization in the Spinal Dorsal Horn (SDH): A Novel Form of Dysregulated Circuitry Plasticity during Pain Pathogenesis.

Pathological pain emerges from nociceptive system dysfunction, resulting in heightened pain circuit activity. Various forms of circuitry plasticity, such as central sensitization, synaptic plasticity, homeostatic plasticity, and excitation/inhibition balance, contribute to the malfunction of neural circuits during pain pathogenesis. Recently, a new form of plasticity in the spinal dorsal horn (SDH), named neural circuit polarization (NCP), was discovered in pain models induced by HIV-1 gp120 and chronic morphine administration. NCP manifests as an increase in excitatory postsynaptic currents (EPSCs) in excitatory neurons and a decrease in EPSCs in inhibitory neurons, presumably facilitating hyperactivation of pain circuits. The expression of NCP is associated with astrogliosis. Ablation of reactive astrocytes or suppression of astrogliosis blocks NCP and, concomitantly, the development of gp120- or morphine-induced pain. In this review, we aim to compare and integrate NCP with other forms of plasticity in pain circuits to improve the understanding of the pathogenic contribution of NCP and its cooperation with other forms of circuitry plasticity during the development of pathological pain.

[Research progress in the mechanism of intestinal environmental disturbance on the occurrence and development of sepsis-associated liver injury].

Sepsis-associated liver injury (SALI) is a common complication of sepsis, which is characterized by systemic immune disorders induced by sepsis leading to liver damage. Currently, there are no effective treatments for SALI, which is related to its complex pathophysiological mechanisms. In recent years, the disorder of intestinal environment after sepsis has been considered as an important factor for SALI, but the specific molecular mechanism of the above process is still unclear. This article will review the pathological role and molecular mechanisms between intestinal environmental disturbance and SALI, aiming to analyze the potential research direction of SALI and identify potential therapeutic targets for its treatment.

Hsa_circ_0004776 regulates the retina neovascularization in progression of diabetic retinopathy via hsa-miR-382-5p/BDNF axis.

The aim of this work was to identify the regulatory function of hsa_circ_0004776 in the progression of diabetic retinopathy (DR). The direct interactions between hsa_circ_0004776 and hsa-miR-382-5p and between hsa-miR-382-5p and BDNF, were confirmed via dual-luciferase reporter assays. Quantitative Real-Time PCR analysis indicated that hsa_circ_0004776 was highly expressed in aqueous humour samples of DR patients and human retinal microvascular epithelial cells (hRECs) under a high-glucose environment, whereas hsa-miR-382-5p showed the opposite trend. Overexpressed hsa_circ_0004776 significantly enhanced DNA synthesis, proliferation, migration, and tube formation in hRECs in hyperglycaemia, while hsa-miR-382-5p mimics reversed these changes. Additionally, in a streptozotocin-induced Sprague-Dawley rat model of DR, vitreous microinjection of rno-miR-382-5p agomir reversed the pathologic features in the progression of DR, including retinal vascular leakage, capillary decellularization, loss of pericytes, fibrosis, and gliosis. Our results indicated that under hyperglycaemic conditions, hsa_circ_0004776 influences the progression of DR via hsa-miR-382-5p and thus represents a potential therapeutic target.

Based on proteomics probing into the deterioration mechanism of pork batter gel caused by different cooking temperatures.

The purpose of this experiment was to explore the influence of different cooking temperatures on the deterioration characteristics of pork batter gel by using proteomics, gel electrophoresis, size and chemical bond of aggregates. The results showed that the protein molecules of the pork batter gel was degraded during heating cooking and the protein aggregates were composed of many degraded protein fragments; compared with the control group 75 °C (0 min), the significant degradation of cytoskeleton showed at 110 °C (30 min) and 121 °C (30 min) and the significant degradation of myosin complexonly appeared at 121 °C (30 min). As the heating temperature points increased, compared with the control group 75 °C (0 min), the different temperatures could promote the separation of metal ions with proteins especially at 110 °C (30 min) and 121 °C (30 min), which could ultimately influence quality of pork batter gel by the size of particle. As the increase of heating temperature points, the recombination of aggregates composed of different proteins was not conducive to the retention of capillary water, which reduced the texture of pork batter gel. This research provided theoretical support for improving the process property of the meat products.

Would Combination Be Better: Swimming Exercise and Intermittent Fasting Improve High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Obese Rats via the miR-122-5p/SREBP-1c/CPT1A Pathway.

Background: Swimming and intermittent fasting can both improve obesity-induced NAFLD, but which of the two is more effective and whether the combination of the two has a superimposed effect is inconclusive. Methods: The model of NAFLD in obese rats was established by a high-fat diet and performed swimming, intermittent fasting, and a combination of both interventions for 8 weeks. Serum lipids and enzyme activity were measured by an automatic biochemical analyzer. Liver morphostructural analysis was observed by transmission electron microscopy, and morphology was observed by HE staining. RT‒PCR was used to detect the mRNA level. Results: Morphology and microstructure of the liver of model rats were impaired, with the upregulation of miR-122-5p, SREBP-1c, FASN and ACC1. Eight weeks of swimming exercise, intermittent fasting and the combination of both attenuate these effects, manifested by the downregulation of miR-122-5p and upregulation of CPT1A mRNA levels. There was no significant stacking effect of the combination of the swimming and intermittent fasting interventions. Conclusion: NAFLD leads to pathology in model rats. Eight weeks of swimming exercise, intermittent fasting and the combination of both can inhibit miR-122-5p and improve hepatic lipid metabolism, while no significant additive effects of combining the interventions were found.