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OBJECTIVE: The effectiveness of a hospital discharge education program including information on postnatal depression was evaluated to reduce psychological morbidity after childbirth. METHODS: A randomized controlled trial (RCT) was conducted in a regional hospital in Taipei. Two hundred first-time mothers agreed to take part and were randomly allocated to an intervention group (n=100) or control group (n=100). The intervention group received discharge education on postnatal depression provided by postpartum ward nurses. The control group received general postpartum education. The main outcome measure was the Edinburgh Postnatal Depression Scale (EPDS) administered by postal questionnaire at six weeks and three months after delivery. RESULTS: Women who received discharge education intervention on postnatal depression were less likely to have high depression scores when compared to the control group at three months postpartum. CONCLUSION: A discharge educational intervention including postnatal depression information given to women during the postpartum stay benefits psychological well-being. PRACTICE IMPLICATIONS: A postpartum discharge education program including information on postnatal depression should be integrated into postpartum discharge care in general practice. [ABSTRACT FROM AUTHOR]

Three new ent-kaurane diterpenoids, silvaticusins A-C (1-3), along with a new ent-kaurane dimer silvaticusin D (4) were isolated from the aerial parts of Isodon silvaticus. The structures of these new compounds were established mainly by comprehensive analysis of their NMR and MS data. The absolute configuration of compounds 1 and 4 were determined using a single-crystal X-ray diffraction and computational methods, respectively. Compounds 2 and 3 were found to exhibit remarkable cytotoxic effects against five human tumor cell lines (HL-60, A-549, SMMC-7721, MDA-MB-231, and SW-480), with IC 50 values spanning from 1.27 ± 0.08 to 7.52 ± 0.33 μM., (© 2024. The Author(s).)

Non-communicable diseases (NCDs) are defined as a kind of diseases closely related to bad behaviors and lifestyles, e.g., cardiovascular diseases, cancer, and diabetes. Driven by population growth and aging, NCDs have become the biggest disease burden in the world, and it is urgent to prevent and control these chronic diseases. Autophagy is an evolutionarily conserved process that degrade cellular senescent or malfunctioning organelles in lysosomes. Mounting evidence has demonstrated a major role of autophagy in the pathogenesis of cardiovascular diseases, cancer, and other major human diseases, suggesting that autophagy could be a candidate therapeutic target for NCDs. Natural products/phytochemicals are important resources for drugs against a wide variety of diseases. Recently, compounds from natural plants, such as resveratrol, curcumin, and ursolic acid, have been recognized as promising autophagy modulators. In this review, we address recent advances and the current status of the development of natural autophagy modulators in NCDs and provide an update of the latest in vitro and in vivo experiments that pave the way to clinical studies. Specifically, we focus on the relationship between natural autophagy modulators and NCDs, with an intent to identify natural autophagy modulators with therapeutic potential., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Appropriate mixed carbon sources have great potential to enhance denitrification efficiency and reduce operational costs in municipal wastewater treatment plants (WWTPs). However, traditional methods struggle to efficiently select the optimal mixture due to the variety of compositions. Herein, we developed a machine learning-assisted high-throughput method enabling WWTPs to rapidly identify and optimize mixed carbon sources. Taking a local WWTP as an example, a mixed carbon source denitrification data set was established via a high-throughput method and employed to train a machine learning model. The composition of carbon sources and the types of inoculated sludge served as input variables. The XGBoost algorithm was employed to predict the total nitrogen removal rate and microbial growth, thereby aiding in the assessment of the denitrification potential. The predicted carbon sources exhibited an enhanced denitrification potential over single carbon sources in both kinetic experiments and long-term reactor operations. Model feature analysis shows that the cumulative effect and interaction among individual carbon sources in a mixture significantly enhance the overall denitrification potential. Metagenomic analysis reveals that the mixed carbon sources increased the diversity and complexity of denitrifying bacterial ecological networks in WWTPs. This work offers an efficient method for WWTPs to optimize mixed carbon source compositions and provides new insights into the mechanism behind enhanced denitrification under a supply of multiple carbon sources.

Ischemic stroke ranks among the leading causes of death and disability in humans and is accompanied by motor and cognitive impairment. However, the precise mechanisms underlying injury after stroke and effective treatment strategies require further investigation. Peroxiredoxin-1 (PRDX1) triggers an extensive inflammatory cascade that plays a pivotal role in the pathology of ischemic stroke, resulting in severe brain damage from activated microglia. In the present study, we used molecular dynamics simulation and nuclear magnetic resonance to detect the interaction between PRDX1 and a specific interfering peptide. We used behavioral, morphological, and molecular experimental methods to demonstrate the effect of PRDX1-peptide on cerebral ischemia-reperfusion (I/R) in mice and to investigate the related mechanism. We found that PRDX1-peptide bound specifically to PRDX1 and improved motor and cognitive functions in I/R mice. In addition, pretreatment with PRDX1-peptide reduced the infarct area and decreased the number of apoptotic cells in the penumbra. Furthermore, PRDX1-peptide inhibited microglial activation and downregulated proinflammatory cytokines including IL-1β, IL-6, and TNF-α through inhibition of the TLR4/NF-κB signaling pathway, thereby attenuating ischemic brain injury. Our findings clarify the precise mechanism underlying PRDX1-induced inflammation after ischemic stroke and suggest that the PRDX1-peptide can significantly alleviate the postischemic inflammatory response by interfering with PRDX1 amino acids 70-90 and thereby inhibiting the TLR4/NF-κB signaling pathway. Our study provides a theoretical basis for a new therapeutic strategy to treat ischemic stroke., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study investigated the use of a modified laparoscopic repair of paraostomy hernia technique, called "D-Type parastomal hernia repair surgery" which combines abdominal wall and extraperitoneal stoma reconstruction, in patients with parastomal hernia (PSH) following colorectal stoma surgery. The aim was to determine whether D-type parastomal hernia repair surgery is a promising surgical approach compared to the traditional laparoscopic repair technique (Sugarbaker method) for patients with PSH., Methods: PSH patients were selected and retrospectively divided into two groups: the study group underwent D-type parastomal hernia repair, while the control group underwent laparoscopic Sugarbaker repair. Clinical data from both groups were analyzed., Result: Compared to control group (n = 68), the study group undergoing D-type stoma lateral hernia repair had significant increase in total operative time (98.82 ± 12.37 min vs 124.61 ± 34.99 min, p < 0.001). The study group also showed better postoperative stoma bowel function scores in sensory ability, frequency of bowel movements, and clothing cleanliness without a stoma bag (p = 0.037, 0.001, 0.002). The treatment cost was significantly higher in the control group (3899.97 ± 260.00$ vs 3215.91 ± 230.03$, p < 0.001). The postoperative recurrence rate in the control group was 26.4%, while in the study group, it was 4.3%, with a significant statistical difference (p = 0.024). In terms of long-term postoperative complications, the study group had an overall lower incidence compared to the control group (p = 0.035). Other parameters showed no significant differences between the two groups., Conclusion: The study suggests that D-type parastomal hernia repair surgery is a safe and feasible procedure. Compared to traditional surgery, it can reduce the recurrence of lateral hernia, improve postoperative stoma bowel function, and save medical resources., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Despite promising overall survival of stage I lung adenocarcinoma (LUAD) patients, 10-25 % of them still went through recurrence after surgery. [1] While it is still disputable whether adjuvant chemotherapy is necessary for stage I patients. [2] IASLC grading system for non-mucinous LUAD shows that minor high-grade patterns are significant indicator of poor prognosis. [3] Other risk factors, such as, pleura invasion, lympho-vascular invasion, STAS, etc. are also related to poor prognosis. [4-6] There still lack evidence whether IASLC grade itself or together with other risk factors can guide the use of adjuvant therapy in stage I patients. In this article, we tried to establish a multi-variable recurrence prediction model for stage I LUAD patients that is able to identify candidates of adjuvant chemotherapy., Methods: We retrospectively collected patients who underwent lung surgery from 2018.8.1 to 2018.12.31 at our institution and diagnosed with lung adenocarcinoma pT1-2aN0M0 (stage I). Clinical data, manifestation on CT scan, pathologic features, driver gene mutations and follow-up information were collected. Cox proportional hazards regression analyses were performed utilizing the non-adjuvant cohort to predict disease free survival (DFS) and a nomogram was constructed and applied to the total cohort. Kaplan-Meier method was used to compare DFS between groups. Statistical analysis was conducted by R version 3.6.3., Findings: A total of 913 stage I LUAD patients were included in this study. Median follow-up time is 48.1 months.4-year and 5-year DFS are 92.9 % and 89.6 % for the total cohort. 65 patient experienced recurrence or death. 4-year DFS are 97.0 %,94.6 % and 76.2 %, and 5-year DFS are 95.5 %, 90.0 % and 74.1 % in IASLC Grade1, 2 and 3, respectively(p < 0.0001). High-risk patients defined by single risk factors, such as, IASLC grade 3, pleura invasion, STAS, less LN resected could not benefit from adjuvant therapy. A LASSO-COX regression model was built and patients are divided into high-risk and low-risk groups. In the high-risk group, patients underwent adjuvant chemotherapy have longer DFS than those who did not (p = 0.024), while in the low-risk group, patients underwent adjuvant chemotherapy have inferior DFS than those who did not (p < 0.001)., Interpretation: IASLC grading is a significant indicator of DFS, however it could not guide adjuvant therapy in our stage I LUAD cohort. Growth patterns and T indicators together with other risk factors could identify high-risk patients that are potential candidate of adjuvant therapy, including some stage IA LUAD patients., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: China faces various public health emergencies, and emergency responders at the Centers for Disease Control and Prevention (CDC emergency responders) are a mainstay in responding to public health emergencies. Career resilience can help CDC emergency responders to effectively respond to and recover from public health emergencies, but there is no specific measurement instrument available. In this study, we aimed to develop and conduct an initial validation of the career resilience instrument for CDC emergency responders in China within the context of public health emergencies from a process perspective., Methods: Based on a survey conducted in Shanghai, interpretive phenomenological analysis (IPA), which is a qualitative research approach to describing and analyzing individual experiences, was used to analyze the interview texts to develop the initial career resilience instrument for CDC emergency responders. The initial career resilience instrument was revised through two rounds of expert consultation. Cronbach's α coefficient and exploratory factor analysis were used to test the reliability and validity of the revised career resilience instrument., Results: The initial career resilience instrument for CDC emergency responders contained three first-level measurement dimensions, 9 second-level measurement dimensions, and 52 measurement items. After expert consultation, the first-level and second-level measurement dimensions were not revised, 13 measurement items were deleted or revised, and six measurement items were added, resulting in 48 measurement items. The revised career resilience instrument was tested for good reliability and validity., Conclusion: Career resilience for CDC emergency responders can be regarded as a set of protective factors and dynamic processes that can be cultivated and intervened in cognitive, affective, and behavioral dimensions to improve their ability to respond to and recover from public health emergencies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Cheng, Fu, Luo, Li, Wang and Jin.)

With the rapid development of Internet technology, more and more college students are facing the threat of mobile phone addiction. However, the relationship and underlying mechanism between mobile phone addiction and academic burnout haven't been explored in depth. This study proves the mediating role of technology conflict and the moderating role of mindfulness in the relation between mobile phone addiction and academic burnout. 752 college students were recruited to complete the questionnaire of mobile phone addiction, technology conflict, mindfulness and academic burnout. Results showed that mobile phone addiction was significantly and positively associated with academic burnout, and this relationship could be mediated by technology conflict. Besides, the direct effect of mobile phone addiction on academic burnout and the indirect effect of technology conflict in this link were moderated by mindfulness. Both these two effects are stronger for college students with lower level of mindfulness. Our findings enrich our understanding of how and when mobile phone addiction was related to academic burnout. Educational professionals and parents should take timely measure to the academic burnout of college students suffering from mobile phone addiction, particularly for those with lower level of mindfulness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yang, Cao, Fu, Wang and Lian.)

Malignant ventricular arrhythmia (VA) after myocardial infarction (MI) is mainly caused by myocardial electrophysiological remodeling. Brahma-related gene 1 (BRG1) is an ATPase catalytic subunit that belongs to a family of chromatin remodeling complexes called Switch/Sucrose Non-Fermentable Chromatin (SWI/SNF). BRG1 has been reported as a molecular chaperone, interacting with various transcription factors or proteins to regulate transcription in cardiac diseases. In this study, we investigated the potential role of BRG1 in ion channel remodeling and VA after ischemic infarction. Myocardial infarction (MI) mice were established by ligating the left anterior descending (LAD) coronary artery, and electrocardiogram (ECG) was monitored. Epicardial conduction of MI mouse heart was characterized in Langendorff-perfused hearts using epicardial optical voltage mapping. Patch-clamping analysis was conducted in single ventricular cardiomyocytes isolated from the mice. We showed that BRG1 expression in the border zone was progressively increased in the first week following MI. Cardiac-specific deletion of BRG1 by tail vein injection of AAV9-BRG1-shRNA significantly ameliorated susceptibility to electrical-induced VA and shortened QTc intervals in MI mice. BRG1 knockdown significantly enhanced conduction velocity (CV) and reversed the prolonged action potential duration in MI mouse heart. Moreover, BRG1 knockdown improved the decreased densities of Na + current (I Na ) and transient outward potassium current (I to ), as well as the expression of Na v 1.5 and K v 4.3 in the border zone of MI mouse hearts and in hypoxia-treated neonatal mouse ventricular cardiomyocytes. We revealed that MI increased the binding among BRG1, T-cell factor 4 (TCF4) and β-catenin, forming a transcription complex, which suppressed the transcription activity of SCN5A and KCND3, thereby influencing the incidence of VA post-MI., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Corticosteroid treatment (CST) failure is associated with poor outcomes for patients with gastrointestinal (GI) graft-versus-host disease (GVHD). CST is intended to target the immune system, but the glucocorticoid receptor (GR) is widely expressed, including within the intestines, where its effects are poorly understood. Here, we report that corticosteroids (CS) directly targeted intestinal epithelium, potentially worsening immune-mediated GI damage. CS administered to mice in vivo and intestinal organoid cultures ex vivo reduced epithelial proliferation. Following irradiation, immediate CST mitigated GI damage but delayed treatment attenuated regeneration and exacerbated damage. In a murine steroid-refractory (SR) GVHD model, CST impaired epithelial regeneration, worsened crypt loss, and reduced intestinal stem cell (ISC) frequencies. CST also exacerbated immune-mediated damage in organoid cultures with SR, GR-deficient T cells or IFN-γ. These findings correlated with CS-dependent changes in apoptosis-related gene expression and STAT3-related epithelial proliferation. Conversely, IL-22 administration enhanced STAT3 activity and overcame CS-mediated attenuation of regeneration, reducing crypt loss and promoting ISC expansion in steroid-treated mice with GVHD. Therefore, CST has the potential to exacerbate GI damage if it fails to control the damage-inducing immune response, but this risk may be countered by strategies augmenting epithelial regeneration, thus providing a rationale for clinical approaches combining such tissue-targeted therapies with immunosuppression.

Ischemic stroke is a devastative nervous system disease associated with high mortality and morbidity rates. Unfortunately, no clinically effective neuroprotective drugs are available now. In ischemic stroke, S100 calcium-binding protein b (S100b) binds to receptor for advanced glycation end products (Rage), leading to the neurological injury. Therefore, disruption of the interaction between S100B and Rage can rescue neuronal cells. Here, we designed a peptide, termed TAT-W61, derived from the V domain of Rage which can recognize S100b. Intriguingly, TAT-W61 can reduce the inflammatory caused by ischemic stroke through the direct binding to S100b. The further investigation demonstrated that TAT-W61 can improve pathological infarct volume and reduce the apoptotic rate. Particularly, TAT-W61 significantly improved the learning ability, memory, and motor dysfunction of the mouse in the ischemic stroke model. Our study provides a mechanistic insight into the abnormal expression of S100b and Rage in ischemic stroke and yields an invaluable candidate for the development of drugs in tackling ischemic stroke. KEY MESSAGES: S100b expression is higher in ischemic stroke, in association with a high expression of many genes, especially of Rage. S100b is directly bound to the V-domain of Rage. Blocking the binding of S100b to Rage improves the injury after ischemic stroke., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Early and accurate diagnosis of ear deformities in newborns is crucial for an effective non-surgical correction treatment, since this commonly seen ear anomalies would affect aesthetics and cause mental problems if untreated. It is not easy even for experienced physicians to diagnose the auricular deformities of newborns and the classification of the sub-types, because of the rich bio-metric features embedded in the ear shape. Machine learning has already been introduced to analyze the auricular shape. However, there is little publicly available datasets of ear images from newborns. We released a dataset that contains quality-controlled photos of 3,852 ears from 1,926 newborns. The dataset also contains medical diagnosis of the ear shape, and the health data of each newborn and its mother. Our aim is to provide a freely accessible dataset, which would facilitate researches related with ear anatomies, such as the AI-aided detection and classification of auricular deformities and medical risk analysis., (© 2024. The Author(s).)

Ecological comprehensive index can quantitatively and visually analyze the temporal and spatial variations of ecological environment quality in a region. Based on the five indices of fractional vegetation coverage, leaf area index, total primary productivity, land surface temperature and wetness obtained by MODIS satellite data in 2001, 2005, 2010, 2015 and 2020, and coupled the comprehensive quality of the eco-environment ( K ), we analyzed the temporal and spatial variations of ecological quality along the Yellow River of Shanxi Province from 2001 to 2020 by using the principal component analysis and spatial autocorrelation method. The results showed that the mean value of K in the study area increased from 0.3354 to 0.4389 during 2001-2020. The ecological quality along the Yellow River of Shanxi Province improved overall, but with obvious temporal and spatial variations. On the large scale, it presented a pattern of "better in the south and worse in the north". There was difference between hills and mountains on the small scale. It showed a trend of continuous improvement in time, but the rate of change was different. The trend of improvement in the south was stronger than that in the north. From 2001 to 2020, the global Moran I values of K were all greater than 0.93, indicating that the ecological quality along the Yellow River of Shanxi Province had a strong spatial correlation. The types of spatial agglomeration were mainly high-high and low-low. The high-high agglomeration areas were mainly distributed in blocks in the south, while the low-low agglomeration areas were mainly concentrated in the north. The ecological quality of areas alone the Yellow River of Shanxi Province had been greatly improved during the research period, but there was still obvious spatial heterogeneity, which need to strengthen ecological protection.

Background: The feasibility and effectiveness of selecting an intracorporeal or extracorporeal technique in left hemicolectomy remain poorly understood. This meta-analysis aimed to evaluate the difference between the two approaches regarding intraoperative and postoperative outcomes., Methods: A thorough exploration of online databases (PubMed, Embase, Cochrane, and Web of Science) was executed to identify randomized controlled trials, cohort studies, and case control studies. The outcomes contained four aspects: intraoperative outcomes, postoperative complications, postoperative patient conditions, and postoperative outcomes. All of these data were analyzed using RevMan 5.4. Seven retrospective control trials (intracorporeal, 396 patients; extracorporeal, 426 patients) were evaluated., Results: Compared to the extracorporeal group, the intracorporeal group demonstrated superiority in incision length (P = 0.005), overall complications (P = 0.01), time to first flatus (P < 0.001), time to first stool (P = 0.005), time to first diet (P < 0.001) and hospital stay duration (P = 0.001)., Conclusions: The intracorporeal technique is associated with superiority over the extracorporeal technique in reducing postoperative complications, promoting postoperative recovery of gastrointestinal function, and reducing hospital stay duration., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A11 dopaminergic neurons regulate somatosensory transduction by projecting from the diencephalon to the spinal cord, but the function of this descending projection in itch remained elusive. Here, we report that dopaminergic projection neurons from the A11 nucleus to the spinal dorsal horn (dopaminergic A11-SDH ) are activated by pruritogens. Inhibition of these neurons alleviates itch-induced scratching behaviors. Furthermore, chemogenetic inhibition of spinal dopamine receptor D1-expressing (DRD1 + ) neurons decreases acute or chronic itch-induced scratching. Mechanistically, spinal DRD1 + neurons are excitatory and mostly co-localize with gastrin-releasing peptide (GRP), an endogenous neuropeptide for itch. In addition, DRD1 + neurons form synapses with GRP receptor-expressing (GRPR + ) neurons and activate these neurons via AMPA receptor (AMPAR). Finally, spontaneous itch and enhanced acute itch induced by activating spinal DRD1 + neurons are relieved by antagonists against AMPAR and GRPR. Thus, the descending dopaminergic pathway facilitates spinal itch transmission via activating DRD1 + neurons and releasing glutamate and GRP, which directly augments GRPR signaling. Interruption of this descending pathway may be used to treat chronic itch., (© 2023 The Authors.)

Bone conduction devices (BCDs) are widely used in the treatment of conductive hearing loss (CHL), but their applications on unilateral CHL (UCHL) patients remain controversial. To evaluate the effects of BCDs in UCHL, a systematic search was undertaken until May 2023 following the PRISMA guidelines. Among the 391 references, 21 studies met the inclusion criteria and were ultimately selected for review. Data on hearing thresholds, speech recognition, sound localization, and subjective questionnaire outcomes were collected and summarized. Moderate hearing threshold improvements were found in UCHL patients aided with BCDs. Their speech recognition abilities improved significantly. However, sound localization results showed wide individual variations. According to subjective questionnaires, BCDs had an overall positive influence on the daily life of UCHL patients, although several unfavorable experiences were reported by some of them. We concluded that the positive audiological benefits and subjective questionnaire results have made BCDs a credible intervention for UCHL patients. Before final implantations, UCHL patients should first go through a period of time when they were fitted with non-implantable BCDs as a trial.

Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury., (© 2023. Springer Nature Limited.)

The limited information on microbial interactions and metabolic patterns in denitrification systems, especially those fed with different carbon sources, has hindered the establishment of ecological linkages between microscale connections and macroscopic reactor performance. In this work, denitrification performance, metabolic patterns, and ecological structure were investigated in parallel well-controlled bioreactors with four representative carbon sources, i.e., methanol, glycerol, acetate, and glucose. After long-term acclimation, significant differences were observed among the four bioreactors in terms of denitrification rates, organic utilization, and heterotrophic bacterial yields. Different carbon sources induced the succession of denitrifying microbiota toward different ecological structures and exhibited distinct metabolic patterns. Methanol-fed reactors showed distinctive microbial carbon utilization pathways and a more intricate microbial interaction network, leading to significant variations in organic utilization and metabolite production compared to other carbon sources. Three keystone taxa belonging to the Verrucomicrobiota phylum, SJA-15 order and the Kineosphaera genus appeared as network hubs in the methanol, glycerol, and acetate-fed systems, playing essential roles in their ecological functions. Several highly connected species were also identified within the glucose-fed system. The close relationship between microbial metabolites, ecological structures, and system performances suggests that this complex network relationship may greatly contribute to the efficient operation of bioreactors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: PFI-3 is a small-molecule inhibitor that targets the bromodomains (BRDs) of Brahma-related gene 1 (BRG1). This monomeric compound, which has high selectivity and potent cellular effects, has recently been developed. Although PFI-3 has been reported as a potential therapeutic agent targeting thrombomodulin, its role in the regulation of vascular function remains unknown. Therefore, we aimed to investigate the impact of PFI-3 on arterial vessel tone., Methods: A microvascular tension measurement device (DMT) was utilized to identify alterations in vascular tension within the mesenteric artery. To detect variations in cytosolic [Ca 2+ ] i , a Fluo-3/AM fluorescent probe and fluorescence microscope were employed. Additionally, whole-cell patch clamp techniques were utilized to evaluate the activity of L-type voltage-dependent calcium channels (VDCCs) in cultured arterial smooth muscle cells (A10 cells)., Results: PFI-3 exerted a dose-dependent relaxation effect on rat mesenteric arteries with both intact and denuded endothelium after phenylephrine (PE)- and high-K + -induced constriction. PFI-3-induced vasorelaxation was not affected by the presence of L-NAME/ODQ or K + channel blockers (Gli/TEA). PFI-3 abolished Ca 2+ -induced contraction on endothelium-denuded mesenteric arteries preincubated by PE in Ca 2+ -free solution. Incubation with TG had no impact on PFI-3-induced vasorelaxation pre-contracted by PE. PFI-3 reduced Ca 2+ -induced contraction on endothelium-denuded mesenteric arteries pre-incubated by KCl (60 mM) in Ca 2+ -free solution. PFI-3 declined extracellular calcium influx in A10 cells detected by Fluo-3/AM fluorescent probe and fluorescence microscope. Furthermore, we observed that PFI-3 decreased the current densities of L-type VDCC by whole-cell patch clamp techniques., Conclusions: PFI-3 blunted PE and high K + -induced vasoconstriction independent of endothelium on rat mesenteric artery. The vasodilatory effect of PFI-3 may be attributed to its inhibition of VDCCs and receptor-operated calcium channels (ROCCs) on vascular smooth muscle cells (VSMCs)., Competing Interests: The authors declare there are no competing interests., (©2023 Li et al.)

Mixotrophic denitrification processes have a great potential in nitrogen removal in biological wastewater treatment processes. However, so far, few studies have focused on the mixotrophic denitrification system using Fe(II) as an exclusively assisted electron donors and the underlying mechanisms in such a process remain unclear. Furthermore, the mechanisms by which microorganisms cover carbon, nitrogen, phosphorus and iron in an iron-assisted mixotrophic system remain unrevealed. In this work, we explore the feasibility of using Fe(II) as an assisted electron donor for enhancing simultaneous nitrogen and phosphorus removal via long-term reactor operation and batch tests. The results show that Fe(II) could provide electrons for efficient nitrate reduction and that biological reactions played a predominant role in these systems. In these systems Thermomonas , a strain of nitrate-reduction Fe(II)-oxidation bacterium, was enriched and accounted for a maximum abundance of 60.2%. These findings indicate a great potential of the Fe(II)-assisted mixotrophic denitrification system for practical use as an efficient simultaneous nitrogen and phosphorus removal process., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (©2023TheAuthors.PublishedbyElsevierLtd.)

Objective: This study aimed to evaluate the effects on the dislocation and misalignment of the cuffed end of a double-lumen endobronchial tube (DLT) when a patient moves from a horizontal to a lateral position without fixation., Methods: A total of 148 patients who had undergone video-assisted thoracoscope surgery were enrolled and randomly divided into two groups: a group in which the periportal end of the DLT was fixed with tape (group I; n  = 74) and a group in which the periportal end of the DLT remained unfixed (group II; n  = 74). Both groups were given an intravenous induction for double-lumen endobronchial intubation and then moved from a horizontal position to a lateral position, after which the alignment of the bronchial cuffed end of the DLT was assessed using a fiberoptic bronchoscope., Results: After lateral position, the dislocation rate of group I and group II was 44.6% and 20.2%, and the misalignment rate was 27.0% and 8.1%, respectively, the incidence of dislocation and misalignment was significantly lower in group II than in group I after the change to a lateral position ( p  < 0.05). After lateral position, the total rate of airway injury was 25.7% in group I and 5.4% in group II, the incidence of airway injury was significantly lower in group II than in group I ( p  < 0.05), as was the incidence of sore throat, hoarseness, and cough on postoperative day 1 ( p  < 0.05). The average outward dislocation of the periportal end of the DLT in group II was 1.5 cm., Conclusion: A DLT without periportal fixation is less likely to be displaced and poorly aligned when the patient moves from a horizontal to a lateral position, which could facilitate intra-operative management and reduce the incidence of postoperative complications.

Competing Interests: Conflicts of interest: There are no conflicts of interest.

Background: Neuroinflammation plays a pivotal role in the pathogenesis of Central Nervous System (CNS) diseases. The phenolic glucoside gastrodin (GAS), has been known to treat CNS disorders by exerting anti-inflammatory activities. Our aim was to investigate the potential neuroprotective mechanisms of GAS on lipopolysaccharide (LPS)-induced mice. Methods: Male C57BL/6J mice were treated by LPS, before which GAS was adminisrated. The behavior tests such as forced swim test, tail suspension test, and elevated plus maze were performed to evaluate depressive-anxiety-like behaviors. A high-throughput sequencing (HTS) analysis was performed to screen out distinctive miRNAs which were validated using quantitative real-time PCR. Then, miRNA agomir or NC was injected stereotaxically into hippocampus of mice to explore the role of miRNA on GAS in response to LPS. Furthermore, Immunofluorescence and the hematoxylin and eosin (H&E) staining were employed to observe the cellular morphology. The protein levels of pro-inflammatory factors were evaluated by western blot. Finally, the target mRNA of miRNA was predicted using bioinformatics analysis. GO and KEGG enrichment analyses were conducted to clarify the potential function of target protein, which were visualized by bubble charts. Results: The behavioral data showed that mice in the LPS group had obvious depressive-anxiety-like behaviors, and 100 mg/kg GAS could improve these behavioral changes and alleviate the levels of pro-inflammatory cytokines in the hippocampus when mice were exposed to LPS for 6 h. Meanwhile, LPS-induced microglia and astrocyte activation in the CA1, CA2, CA3, and DG regions of the hippocampus were also reversed by GAS. Furthermore, miR-107-3p were screened out and verified for GAS in response to LPS. Importantly, miR-107-3p overexpression negatively abrogated the neuroprotective effects of GAS. Moreover, KPNA1 might be the target molecular of miR-107-3p. KPNA1 might regulate 12 neuroinflammation-related genes, which were mainly involved in cytokine-mediated signaling pathway. Conclusion: These results suggested that GAS might alleviate the LPS-induced neuroinflammation and depressive-anxiety-like behaviors in mice by downregulating miR-107-3p and upregulating the downstream target KPNA1. The indicates miR-107-3p may provide a new strategy for the treatment of CNS diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Song, Li, Wang, Zhou, Liu, Zhang, Feng, Chen, Liu, Liang, Ma, Wen and Fu.)

Iris lactea Pall. var. chinensis (Fisch.) Koidz ( Iris lactea ) is an herbaceous perennial widely distributed in China, India, and South Korea. Iris lactea has been extensively used in traditional Chinese medicine. The present study isolated a new oligostilbene (compound 1), together with three known oligostilbenes (compounds 2, 3 and 4) from the seeds of Iris lactea. The structures of these compounds were elucidated by HRESIMS, NMR, and chemical analyses. The network-based pharmacologic analysis platform was used to predict the target proteins related to inflammation of isolated compounds. Furthermore, the isolated compounds were tested for their anti-inflammatory effects in LPS-stimulated RAW 264.7 cells. In this network, 138 candidate targets of compounds related to its therapeutic effect on inflammation were identified. In addition, compounds 1, 2, 3 and 4 significantly decreased NO content and the IL-6 levels as well as the expression of COX-2 in LPS-stimulated RAW 264.7 cells., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Extracorporeal membrane oxygenation (ECMO) is a superior life support technology, commonly employed in critical patients with severe respiratory or hemodynamic failure to provide effective respiratory and circulatory support, which is especially recommended for the treatment of critical neonates. However, the vascular management of neonates with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is still under controversy. Reconstruction or ligation for the right common carotid artery (RCCA) after ECMO is inconclusive. This review summarized the existed studies on hemodynamics and neurological function after vascular ligation or reconstruction hoping to provide better strategies for vessel management in newborns after ECMO. After reconstruction, the right cerebral blood flow can increase immediately, and the normal blood supply can be restored rapidly. But the reconstructed vessel may be occluded and stenotic in long-term follow-ups. Ligation may cause lateralization damage, but there could be no significant effect owing to the establishment of collateral circulation. The completion of the circle of Willis, the congenital anomalies of cerebral or cervical vasculature, the duration of ECMO, and the vascular condition at the site of arterial catheterization should be assessed carefully before making the decision. It is also necessary to follow up on the reconstructed vessel sustainability, and the association between cerebral hemodynamics and neurological function requires further large-scale multi-center studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Mao, Ju, Fu, Zhang and Yue.)

Phospholipid peroxidation of polyunsaturated fatty acids at the bis-allylic position drives ferroptosis. Here we identify a novel role for phospholipid peroxidation in the inhibition of autophagy. Using in vitro and in vivo models, we report that phospholipid peroxidation induced by glutathione peroxidase-4 inhibition and arachidonate 15-lipoxygenase overexpression leads to overload of peroxidized phospholipids and culminate in inhibition of autophagy. Functional and lipidomics analysis further demonstrated that inhibition of autophagy was associated with an increase of peroxidized phosphatidylethanolamine (PE) conjugated LC3. We further demonstrate that autophagy inhibition occurred due to preferential cleavage of peroxidized LC3-PE by ATG4B to yield delipidated LC3. Mouse models of phospholipid peroxidation and autophagy additionally supported a role for peroxidized PE in autophagy inhibition. Our results agree with the recognized role of endoplasmic reticulum as the primary source for autophagosomal membranes. In summary, our studies demonstrated that phospholipid peroxidation inhibited autophagy via stimulating the ATG4B-mediated delipidation of peroxidized LC3-PE., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Temporoparietal fascia is important for auricular reconstruction or repair after auricular reconstruction. Thus, the course of the superficial temporal artery (STA) is of vital importance to prevent destruction of the artery. The purpose of this study was to evaluate the course of the superficial temporal artery in patients with congenital microtia and its relationship with remnants., Methods: This was a prospective study. Patients with microtia who underwent auricular reconstruction in our hospital from January 2021 to July 2021 underwent ultrasound examination of the STA. Under the guidance of ultrasound, the superficial temporal artery and its branches were located and marked on the body surface before the operation, ranging from the zygomatic arch plane to the temporal parietal artery. In addition, the hemodynamics of the STAs were recorded., Results: A total of 108 patients with microtia were collected, including 106 patients with unilateral microtia and 2 patients with bilateral microtia. There were 82 cases of lobule type, 21 cases of small concha type, and 7 cases of large concha type. The superficial temporal artery in 103 ears was divided into two branches: the parietal branch and the frontal branch, but there was only one branch in 7 ears. The parietal branch was absent in 5 cases, and the frontal branch was absent in 2 cases. In most of the ears, the bifurcation was located above the zygomatic arch plane. Only in 2 ears was the bifurcation located below the zygomatic arch, and the most common bifurcation position was the eyebrow arch level (43.7%). Regarding the shortest distances between the STA and the remnant, they were less than 0.5 cm in 47 ears, more than 1 cm in 30 ears, and 0.5 cm to 1 cm in 33 ears., Conclusion: The course of STA varied greatly and there were occasional single branches. The distances between the STA and remnant were often near 0.5 cm by ultrasonography. Therefore, when removing the remnant and separating the pocket, care should be taken to avoid arterial injury., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Cellular senescence is associated with tumorigenesis, and the subtype and prognostic signatures of senescence-related genes (SRGs) in the tumor microenvironment (TME) and gut microbiota have not been fully determined. Analysis of 91 SRGs obtained from the GSEA and MSigDB, and mRNA sequencing of genes in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases enabled the identification of two distinct molecular types of colorectal cancer (CRC). Patient samples were clustered into two subtypes, with Kaplan-Meier survival analyses showing significant differences in patient survival between the two subtypes. Cluster C2 was associated with patient clinicopathological features, high immune score, high abundance of immune infiltrating cells and somewhat high abundance of bacteria. A risk model based on eight SRGs showed that a low risk score was characterized by inhibition of immune activity and was indicative of better prognosis in patients with CRC. In combination with clinical characteristics, risk score was found to be an independent prognostic predictor of survival in patients with CRC. In conclusion, the present study showed that senescence-related subtypes and a signature consisting of eight SRGs were associated with CRC patient prognosis, as well as with immune cell infiltration and gut microbiota. These findings may enable better prediction of CRC patient prognosis and facilitate individualized treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dai, Fu, Zhong, Cen, Ye, Chen, Pan and Ye.)

Background: Venous thromboembolism (VTE) is a major cause of unexpected and perioperative in-hospital deaths. It is characterized by high morbidity, high mortality, high misdiagnosis rate, and high missed diagnosis rates. VTE is a common postoperative complication in cancer patients. VTE is preventable, and early identification of risk factors leading to VTE and appropriate early preventive actions can reduce its occurrence and mortality. Presently, there is no uniform standard for the prevention and control of VTE in clinical practice, and hospitals in China lack mature and effective protocols for the assessment, prevention, and treatment of VTE., Aim: To explore whether an early warning program could influence the occurrence of deep vein thrombosis (DVT) postoperatively., Methods: This is a comparative retrospective cohort study, which enrolled patients who underwent laparotomic or laparoscopic gastrointestinal tumor resection for gastrointestinal cancer between January 2016 and December 2019. Patients were divided into a control group and an early warning group depending on whether or not the early warning program was implemented. A venous thromboembolism prevention and control team was established. The outcomes included the occurrence of DVT, the correct rate of VTE assessment, the coagulation indicators, and the mastery of VTE knowledge by the nurses., Results: A total of 264 patients were included in this study, with 128 patients in the control group and 136 patients in the early warning group. The occurrence rate of DVT in the early warning group was 6.6% (9/136), compared with 14.1% (18/128) in the control group ( P < 0.05). The correct rates of VTE risk assessment by the nurses and standard implementation rate of VTE preventive measures were 86.8% vs 65.6% and 80.2% vs 57.8% in early warning and control groups, respectively (all P < 0.001). The independent factors associated with postoperative DVT occurrence were age (OR = 1.083, 95%CI: 1.070-3.265, P = 0.032), Hyperlipidemia (OR = 1.127, 95%CI: 1.139-2.564, P = 0.042), preoperative high VTE risk (OR = 2.131, 95%CI: 1.085-5.178, P = 0.001), time of operation (OR = 2.268, 95%CI: 2.005-5.546, P = 0.026) and not adoption of early warning prevention (OR = 3.747, 95%CI: 1.523-6.956, P = 0.017)., Conclusion: The early warning strategy was independently associated with the decreasing occurrence of VTE, and it might be suitable for protection from VTE in patients undergoing gastrointestinal cancer surgery., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ginsenoside Rh2 is one of the major bioactive ginsenosides in Panax ginseng . Although Rh2 is known to enhance immune cells activity for treatment of cancer, its anti-inflammatory and neuroprotective effects have yet to be determined. In this study, we investigated the effects of Rh2 on spared nerve injury (SNI)-induced neuropathic pain and elucidated the potential mechanisms. We found that various doses of Rh2 intrathecal injection dose-dependently attenuated SNI-induced mechanical allodynia and thermal hyperalgesia. Rh2 also inhibited microglia and astrocyte activation in the spinal cord of a murine SNI model. Rh2 treatment inhibited SNI-induced increase of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1 and IL-6. Expression of miRNA-21, an endogenous ligand of Toll like receptor (TLR)8 was also decreased. Rh2 treatment blocked the mitogen-activated protein kinase (MAPK) signaling pathway by inhibiting of phosphorylated extracellular signal-regulated kinase expression. Finally, intrathecal injection of TLR8 agonist VTX-2337 reversed the analgesic effect of Rh2. These results indicated that Rh2 relieved SNI-induced neuropathic pain via inhibiting the miRNA-21-TLR8-MAPK signaling pathway, thus providing a potential application of Rh2 in pain therapy.

The present study investigated the main components of fenugreek(Trigonella foenum-graecum L.) leaf flavonoids(FLFs) and their antioxidant activity. FLFs were prepared and enriched by solvent extraction, and the flavonoids were characterized by high-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS). The protective effect of FLFs against H&#95;2O&#95;2-induced stress damage to L02 hepatocytes was also investigated. Firstly, the cell viability was measured by MTT assay. The oxidative stress injury model was induced by H&#95;2O&#95;2 in L02 cells. The release of lactate dehydrogenase(LDH), the content of reduced glutathione(GSH) and malondialdehyde(MDA), and the activities of superoxide dismutase(SOD) and catalase(CAT) were measured by assay kits. Hoechst fluorescence staining was performed to observe the cell apoptosis. The expression levels of c-Jun N-terminal kinase(JNK), extracellular signal-regulated kinase 1/2(ERK1/2), nuclear factor erythroid-2 related factor 2(Nrf2), heme oxygenase 1(HO-1), and their phosphorylated proteins were detected by Western blot. Based on the MS fragment ion information and data in databases, FLFs contained eight flavonoids with quercetin and kaempferol as the main aglycons. The cell viabi-lity assay revealed that as compared with the conditions in the H&#95;2O&#95;2 treatment group, 3.125-25 μg·mL~(-1) FLFs could increase the viability of L02 cells, reduce LDH release and MDA content in a dose-dependent manner, potentiate the activities of SOD, CAT, and GSH, decrease the phosphorylation of JNK and ERK1/2 proteins, and up-regulate the expression of Nrf2 and HO-1. The results of fluorescence staining showed that the nucleus of the H&#95;2O&#95;2 treatment group showed concentrated and dense strong blue fluorescence, while the blue fluorescence intensity of the FLFs group decreased significantly. FLFs showed a protective effect against H&#95;2O&#95;2-induced oxidative damage in L02 cells, and the underlying mechanism is associated with the enhancement of cell capability in clearing oxygen free radicals and the inhibition of apoptosis by the activation of the MAPKs/Nrf2/HO-1 signaling pathway. The antioxidant effect of fenugreek leaf is related to its rich flavonoids.

Objective: To investigate whether the contralateral normal external auditory canal (EAC) skin graft can maintain the ear canal health after EAC reconstruction in unilateral congenital aural atresia (CAA) cases. Methods: A Zelen design randomized controlled study was used to collect unilateral CAA patients for EAC reconstruction prospectively (clinical trial registration number: ChiCTR2000032103). The patients were randomly divided into the control group and the trial group. The trial group used the contralateral normal EAC skin graft group (transplant part of the contralateral normal EAC skin to repair the atresia side for unilateral CAA patients), the control group all used scalp blade thick skin. We observed the EAC health and hearing results of the two groups after EAC reconstruction. Results: A total of 13 cases were enrolled from July 2020 to August 2021. There were eight patients in the trial group, including six males and two females, with an average age of 22.3 years (14-36 years). There were two patients with CAA on the left and six patients on the right. The average follow-up time was 8.8 months (4-14 months). There were five patients in the control group, all cases were male with an average age of 16.2 years (12-20 years). There were four patients with CAA on the left and one patient on the right. The average follow-up time was 7.0 months (2-14 months). In the trial group, eight cases of reconstructed EAC epithelium were healthy, one patient had cicatricial stenosis of EAC opening and lateralization of the tympanic membrane. The other patient had cicatricial stenosis of reconstructed EAC, this case also had scar hyperplasia of the contralateral EAC opening but recovered after soft packing and triamcinolone acetonide injection treatment. The healthy side EAC of the rest trial group had no scarring stenosis or local bone hyperplasia during long-term follow-up. In the control group, one patient was lost to follow-up and the other four patients had dry ears of reconstructed EAC, but easily to form crusts and needed to be cleaned repeatedly, one patient had lateralization of the tympanic membrane, the EAC epithelium was not healthy for long-term follow-up. The incidence of complications related to EAC reconstruction was lower than previous studies ( χ²= 5.55, P =0.018), and the average postoperative Air-Bone Gap increased (18.8±10.0)dB. Conclusion: By optimizing the EAC reconstruction technology, the health of the reconstructed EAC is improved compared with the previous study. After active intervention and treatment, there should be no scarring stenosis or local bone hyperplasia on the contralateral side EAC.

Incomplete recovery from acute kidney injury induced by folic acid is a major risk factor for progression to chronic kidney disease. Mitochondrial dysfunction has been considered a crucial contributor to maladaptive repair in acute kidney injury. Treatment with FG-4592, an inhibitor of hypoxia inducible factor prolyl-hydroxylase, is emerging as a new approach to attenuate renal damage; however, the underlying mechanism has not been fully elucidated. The current research demonstrated the protective effect of FG-4592 against renal dysfunction and histopathological damage on the 7th day after FA administration. FG-4592 accelerated tubular repair by promoting tubular cell regeneration, as indicated by increased proliferation of cell nuclear antigen-positive tubular cells, and facilitated structural integrity, as reflected by up-regulation of the epithelial inter-cellular tight junction molecule occludin-1 and the adherens junction molecule E-cadherin. Furthermore, FG-4592 ameliorated tubular functional recovery by restoring the function-related proteins aquaporin1, aquaporin2, and sodium chloride cotransporter. Specifically, FG-4592 pretreatment inhibited hypoxia inducible factor-1α activation on the 7th day after folic acid injection, which ameliorated ultrastructural abnormalities, promoted ATP production, and attenuated excessive reactive oxygen species production both in renal tissue and mitochondria. This was mainly mediated by balancing of mitochondrial dynamics, as indicated by down-regulation of mitochondrial fission 1 and dynamin-related protein 1 as well as up-regulation of mitofusin 1 and optic atrophy 1. Moreover, FG-4592 pretreatment attenuated renal tubular epithelial cell death, kidney inflammation, and subsequent interstitial fibrosis. In vitro, TNF-α-induced HK-2 cells injury could be ameliorated by FG-4592 pretreatment. In summary, our findings support the protective effect of FG-4592 against folic acid-induced mitochondrial dysfunction; therefore, FG-4592 treatment can be used as a useful strategy to facilitate tubular repair and mitigate acute kidney injury progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Jiang, Zou, Zhang, Fu and Zhai.)

Competing Interests: Conflicts of interest: Authors have no financial or other conflicts of interest related to this submission.

Folic acid (FA)-induced acute kidney injury (AKI) is characterized by the disturbance of redox homeostasis, resulting in massive tubular necrosis and inflammation. Α-lipoic acid (LA), as an antioxidant, has been reported to play an important role in renal protection, but the underlying mechanism remains poorly explored. The aim of this study is to investigate the protective effect of LA on FA-induced renal damage. Our findings showed that LA could ameliorate renal dysfunction and histopathologic damage induced by FA overdose injection. Moreover, FA injection induced severe inflammation, indicated by increased release of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and IL-1β, as well as infiltration of macrophage, which can be alleviated by LA supplementation. In addition, LA not only reduced the cellular iron overload by upregulating the expressions of Ferritin and ferroportin (FPN), but also mitigated reactive oxygen species (ROS) accumulation and lipid peroxidation by increasing the levels of antioxidant glutathione (GSH) and glutathione peroxidase-4 (GPX4). More importantly, we found that LA supplementation could reduce the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive tubular cells caused by FA, indicating that the tubular cell death mediated by ferroptosis may be inhibited. Further study demonstrated that LA supplementation could reverse the decreased expression of cystine/glutamate antiporter xCT (SLC7A11), which mediated GSH synthesis. What is more, mechanistic study indicated that p53 activation was involved in the inhibitory effect of SLC7A11 induced by FA administration, which could be suppressed by LA supplementation. Taken together, our findings indicated that LA played the protective effect on FA-induced renal damage mainly by inhibiting ferroptosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Zou, Fu, Xing, Wang, Wan and Zhai.)

Objective: Inflammation plays a crucial role in tumorigenesis and progression. Our purpose was to investigate the prognostic value of neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI) and systemic immune-inflammation index (SII), and develop a nomogram to predict the cancer-specific survival (CSS) and disease-free survival (DFS) of stage I lung adenocarcinoma patients., Methods: 1431 patients undergoing surgical resection with pathologically confirmed stage I lung adenocarcinoma were reviewed. The optimal cut-off values for NLR, SII, and SIRI were defined by the receiver operating characteristic (ROC) curve. Cox proportional hazards regression analyses were performed to recognize factors significantly correlated with CSS and DFS to construct the nomogram. The value of adjuvant chemotherapy on model-defined high-risk and low-risk patients was further explored., Results: The cohort had a median follow-up time of 63 months. Multivariate analysis revealed that higher NLR (≥2.606), higher SIRI (≥0.705), higher SII (≥580.671), later T stage, histological pattern with solid or micropapillary components and radiologic features with solid nodules were significantly associated with worse CSS and DFS. The concordance index (C-index) of the nomogram established by all these factors was higher than that of the TNM staging system both in CSS (validation set 0.778 vs 0.652) and DFS (validation set 0.758 vs 0.695). Furthermore, the value of the established nomogram on risk stratification in stage I lung adenocarcinoma patients was validated., Conclusions: Higher NLR, SII and SIRI pretreatment were associated with worse survival outcomes. A practical nomogram based on these three inflammatory biomarkers may help clinicians to precisely stratify stage I lung adenocarcinoma patients into high- and low-risk and implement individualized treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer LC declared a shared affiliation, with no collaboration, with the authors to the handling editor at the time of review., (Copyright © 2021 Shen, Qian, Ding, Luo, Zhao, Xia, Fu, Feng, Zhang, Yu, Cai and Fu.)