A retrospective analysis of treatment patterns, overall survival, and real-world disease-free survival in early-stage non-small cell lung cancer following complete resection.

BACKGROUND: Real-world data regarding patient characteristics, adjuvant treatment patterns, and long-term survival outcomes are needed to better understand unmet needs among patients with completely resected early-stage non-small cell lung cancer (NSCLC). METHODS: Electronic medical records from the U.S.-based ConcertAI Patient360™ database were analyzed in patients with stage IB-IIIA NSCLC who underwent complete resection prior to March 1, 2016. Patients were followed until death or July 1, 2021. This study evaluated adjuvant chemotherapy use, and overall survival (OS) and real-world disease-free survival (rwDFS) outcomes using the Kaplan-Meier method. The correlation between OS and rwDFS was assessed using the Kendall rank test. Among patients who did not recur 5 years following surgery, landmark analyses of OS and rwDFS were conducted to understand the subsequent survival impact of remaining disease-free for at least 5 years. RESULTS: Data from 441 patients with completely resected stage IB-IIIA NSCLC were included. About 35% of patients received adjuvant chemotherapy post-resection. Median OS and rwDFS from resection were 83.1 months and 42.4 months, respectively. The 5-year OS and rwDFS rates were 65.7% and 42.1%, respectively. OS and rwDFS were positively correlated (Kendall rank correlation coefficient = 0.67; p < 0.0001). Among patients without recurrence within 5 years after resection, the subsequent 5-year OS and rwDFS survival rates were 52.9% and 36.6%, respectively. CONCLUSIONS: Use of adjuvant chemotherapy was low, and the overall 5-year OS rate remained low despite all patients having undergone complete resection. Patients who remained non-recurrent over time had favorable subsequent long-term survival.

Lightweight bobbin yarn detection model for auto-coner with yarn bank.

The automated replacement of empty tubes in the yarn bank is a critical step in the process of automatic winding machines with yarn banks, as the real-time detection of depleted yarn on spools and accurate positioning of empty tubes directly impact the production efficiency of winding machines. Addressing the shortcomings of traditional methods, such as poor adaptability and low sensitivity in optical and visual tube detection, and aiming to reduce the computational and detection time costs introduced by neural networks, this paper proposes a lightweight yarn spool detection model based on YOLOv8. The model utilizes Darknet-53 as the backbone network, and due to the dense spatial distribution of yarn spool targets, it incorporates large selective kernel units to enhance the recognition and positioning of dense targets. To address the issue of excessive focus on local features by convolutional neural networks, a bi-level routing attention mechanism is introduced to capture long-distance dependencies dynamically. Furthermore, to balance accuracy and detection speed, a FasterNeck is constructed as the neck network, replacing the original convolutional blocks with Ghost convolutions and integrating with FasterNet. This design minimizes the sacrifice of detection accuracy while achieving a significant improvement in inference speed. Lastly, the model employs weighted IoU with a dynamic focusing mechanism as the bounding box loss function. Experimental results on a custom yarn spool dataset demonstrate a notable improvement over the baseline model, with a high-confidence mAP of 94.2% and a compact weight size of only 4.9 MB. The detection speed reaches 223FPS, meeting the requirements for industrial deployment and real-time detection.

Regenerative endodontic therapy: From laboratory bench to clinical practice.

BACKGROUND: Maintaining the vitality and functionality of dental pulp is paramount for tooth integrity, longevity, and homeostasis. Aiming to treat irreversible pulpitis and necrosis, there has been a paradigm shift from conventional root canal treatment towards regenerative endodontic therapy. AIM OF REVIEW: This extensive and multipart review presents crucial laboratory and practical issues related to pulp-dentin complex regeneration aimed towards advancing clinical translation of regenerative endodontic therapy and enhancing human life quality. KEY SCIENTIFIC CONCEPTS OF REVIEW: In this multipart review paper, we first present a panorama of emerging potential tissue engineering strategies for pulp-dentin complex regeneration from cell transplantation and cell homing perspectives, emphasizing the critical regenerative components of stem cells, biomaterials, and conducive microenvironments. Then, this review provides details about current clinically practiced pulp regenerative/reparative approaches, including direct pulp capping and root revascularization, with a specific focus on the remaining hurdles and bright prospects in developing such therapies. Next, special attention was devoted to discussing the innovative biomimetic perspectives opened in establishing functional tissues by employing exosomes and cell aggregates, which will benefit the clinical translation of dental pulp engineering protocols. Finally, we summarize careful consideration that should be given to basic research and clinical applications of regenerative endodontics. In particular, this review article highlights significant challenges associated with residual infection and inflammation and identifies future insightful directions in creating antibacterial and immunomodulatory microenvironments so that clinicians and researchers can comprehensively understand crucial clinical aspects of regenerative endodontic procedures.

Arginine catabolism is essential to polymyxin dependence in Acinetobacter baumannii.

Polymyxins are often the only effective antibiotics against the "Critical" pathogen Acinetobacter baumannii. Worryingly, highly polymyxin-resistant A. baumannii displaying dependence on polymyxins has emerged in the clinic, leading to diagnosis and treatment failures. Here, we report that arginine metabolism is essential for polymyxin-dependent A. baumannii. Specifically, the arginine degradation pathway was significantly altered in polymyxin-dependent strains compared to wild-type strains, with critical metabolites (e.g., L-arginine and L-glutamate) severely depleted and expression of the astABCDE operon significantly increased. Supplementation of arginine increased bacterial metabolic activity and suppressed polymyxin dependence. Deletion of astA, the first gene in the arginine degradation pathway, decreased phosphatidylglycerol and increased phosphatidylethanolamine levels in the outer membrane, thereby reducing the interaction with polymyxins. This study elucidates the molecular mechanism by which arginine metabolism impacts polymyxin dependence in A. baumannii, underscoring its critical role in improving diagnosis and treatment of life-threatening infections caused by "undetectable" polymyxin-dependent A. baumannii.

Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors.

Background: Front-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing EGFR exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered. Our objectives were to describe baseline characteristics, survival, and subsequent treatment patterns for patients with advanced nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation who received a platinum-based combination regimen after front-line EGFR TKI therapy. Methods: This retrospective study used a nationwide electronic health record-derived deidentified database to select adult patients with advanced nonsquamous NSCLC, evidence of EGFR exon 19 deletion or L858R mutation, and ECOG performance status of 0-2 who initiated platinum-containing chemotherapy, with or without concomitant immunotherapy, from 1-January-2011 to 30-June-2020 following receipt of any EGFR TKI as first-line therapy or, alternatively, a first- or second-generation EGFR TKI (erlotinib, afatinib, gefitinib, dacomitinib) as first-line therapy followed by the third-generation EGFR TKI osimertinib as second-line therapy. Data cut-off was 30-June-2022. The Kaplan-Meier method was used to estimate overall survival (OS) after initiation of pemetrexed-platinum (n=119) or any platinum-based combination regimen (platinum cohort; n=311). Results: The two cohorts included two-thirds women (65%-66%) and 57%-58% nonsmokers; median ages were 66 and 65 years in pemetrexed-platinum and platinum cohorts, respectively. Median OS was 10.3 months (95% CI, 8.1-13.9) from pemetrexed-platinum initiation and 12.4 months (95% CI, 10.2-15.2) from platinum initiation; 12-month survival rates were 48% and 51%, respectively; 260 patients (84%) had died by the end of the study. Conclusion: The suboptimal survival outcomes recorded in this study demonstrate the unmet need to identify more effective subsequent treatment regimens for patients with EGFR-mutated advanced nonsquamous NSCLC after EGFR TKI resistance develops.

The effect of collectivism-oriented human resource management on employee resilience of hospitality employees.

Introduction: In the face of an increasingly challenging and rapidly evolving business environment, not all the employees exhibit the requisite resilience necessary to recover from adversity. From both the individual and organizational perspectives, enhancing employee resilience emerges as a critical issue not only in the practical and academic fields. In the Chinese culture, this research aims to investigate how and why collectivism-oriented human resource management (C-HRM) fosters employee resilience. Drawing on the group engagement model, we propose a serial mediating effect of perceived overall fairness and three dimensions of social identity between C-HRM and employee resilience. Methods: Using a sample of frontline employees in the hospitality industry, we conducted a field survey among 342 employees (study 1) and a two-wave online survey among 294 hospitality employees (study 2). Results: Findings from empirical analysis indicated that C-HRM significantly increases overall fairness perception of hospitality frontline employees and in turn, their identification and respect, which further fertilize employee resilience. In addition, the indirect effect of C-HRM on employee resilience through perceived overall fairness and pride was not statistically significant. Discussion: These important findings are expected to help employees cope with the workplace pressures caused by ongoing challenges and change, and contribute to sustainable career development.

First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden: A Population-based Real-world Study with Focus on Immunotherapy.

BACKGROUND AND PURPOSE: The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. MATERIALS AND METHODS: Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. RESULTS: A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. INTERPRETATION: The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.

Real-World Neoadjuvant Treatment Patterns and Outcomes in Resected Non-Small-Cell Lung Cancer.

BACKGROUND: Novel neoadjuvant chemoimmunotherapy treatments are being investigated for locally advanced non-small-cell lung cancer (NSCLC), but real-world outcomes for neoadjuvant treatments are poorly understood. This study examined neoadjuvant treatment patterns, real-world event-free survival (rwEFS) and overall survival (OS) in patients with resected, stage II-III NSCLC in the United States (US). METHODS: This retrospective study identified patients in the SEER-Medicare database (2007-2019) with newly diagnosed stage II, IIIA, and IIIB (N2) NSCLC (AJCC 8th edition) treated with neoadjuvant chemo/chemoradiotherapy and resection (index date: neoadjuvant therapy initiation). Neoadjuvant treatment regimens were described. rwEFS (time from index to first recurrence or death, whichever occurred first) and OS (time from index to death) were summarized by Kaplan-Meier analysis for overall population, by disease stage at diagnosis, and by neoadjuvant treatment modality. RESULTS: 221 patients (stage II, N=70; stage III, N=151) met eligibility criteria. The median follow-up from index was 32.7 months. All patients received neoadjuvant chemotherapy (51%) or chemoradiotherapy (49%) prior to surgery; 97% of patients received platinum-based regimens, among which carboplatin+paclitaxel was the most frequent (45%). In all patients, median rwEFS was 17.6 months and 5-year rwEFS was 20.9%; median OS was 48.5 months and 5-year OS was 44.9%. 71% of patients had disease recurrence during follow-up; among them, 28% developed locoregional recurrence as the first recurrence event. CONCLUSIONS: Patients with resected, stage II-III NSCLC who received neoadjuvant chemo/chemoradiotherapy have high rates of disease recurrence and poor survival outcomes, highlighting need for more effective treatments to improve survival rates.

Exosomes as Promising Therapeutic Tools for Regenerative Endodontic Therapy.

Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects. As one of the crucial paracrine effectors, the roles and functions of exosomes in pulp-dentin complex regeneration have gained considerable attention. Due to their advantages of cost-effectiveness, extensive sources, favorable biocompatibility, and high safety, exosomes are considered promising therapeutic tools to promote dental pulp regeneration. Accordingly, in this article, we first focus on the biological properties of exosomes, including their biogenesis, uptake, isolation, and characterization. Then, from the perspectives of cell proliferation, migration, odontogenesis, angiogenesis, and neurogenesis, we aim to reveal the roles and mechanisms of exosomes involved in regenerative endodontics. Lastly, immense efforts are made to illustrate the clinical strategies and influencing factors of exosomes applied in dental pulp regeneration, such as types of parental cells, culture conditions of parent cells, exosome concentrations, and scaffold materials, in an attempt to lay a solid foundation for exploring and facilitating the therapeutic strategy of exosome-based regenerative endodontic procedures.

MZ1, a BRD4 inhibitor, exerted its anti-cancer effects by suppressing SDC1 in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. METHODS: The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. RESULTS: In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. CONCLUSION: In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

Necrotizing enterocolitis: current understanding of the prevention and management.

Necrotizing enterocolitis (NEC) is one of the diseases in neonates, with a high morbidity and mortality rate, especially in preterm infants. This review aimed to briefly introduce the latest epidemiology, susceptibility factors, and clinical diagnosis and presentation of NEC. We also organized new prevention strategies by risk factors according to different pathogeneses and then discussed new treatment methods based on Bell's staging and complications, and the classification of mild to high severity based on clinical and imaging manifestations. Such a generalization will help clinicians and researchers to gain a deeper understanding of the disease and to conduct more targeted classification, grading prevention, and exploration. We focused on prevention and treatment of the early and suspected stages of NEC, including the discovery of novel biomarkers and drugs to control disease progression. At the same time, we discussed its clinical application, future development, and shortcomings.

Gender differences in brain region activation during verbal fluency task as detected by fNIRS in patients with depression.

BACKGROUND: Gender plays a role in the mechanisms of depression, but fewer studies have focused on gender differences in the abnormal activation of brain regions when patients perform specific cognitive tasks. METHODS: A total of 110 major depressive disorder (MDD) patients and 106 healthy controls were recruited. The relative change in oxygen-haemoglobin (oxy-Hb) concentration during the verbal fluency task were measured by a 52-channel near-infra-red spectroscopy (NIRS) system. Differences in brain region activation between patients and healthy controls and between genders of depression patients were compared. RESULTS: MDD patients demonstrated significantly decreased [oxy-Hb] changes in the right inferior frontal gyrus (p = 0.043) compared to healthy controls. A marked increase in leftward functional language lateralisation in the inferior frontal gyrus was observed in the MDD group in contrast to the HC group (p = 0.039). Furthermore, female patients in the MDD group exhibited significant reductions in [oxy-Hb] changes in the right frontal region (specifically, the superior and middle frontal gyrus; p = 0.037) compared with male patients. CONCLUSIONS: Gender impacts depression-related brain activation during cognitive tasks, potentially influencing depression's pathogenesis.

Reduction of renal interstitial fibrosis by targeting Tie2 in vascular endothelial cells.

BACKGROUND: Tie2, a functional angiopoietin receptor, is expressed in vascular endothelial cells and plays an important role in angiogenesis and vascular stability. This study aimed to evaluate the effects of an agonistic Tie2 signal on renal interstitial fibrosis (RIF) and elucidate the underlying mechanisms. METHODS: We established an in vivo mouse model of folic acid-induced nephropathy (FAN) and an in vitro model of lipopolysaccharide-stimulated endothelial cell injury, then an agonistic Tie2 monoclonal antibody (Tie2 mAb) was used to intervent these processes. The degree of tubulointerstitial lesions and related molecular mechanisms were determined by histological assessment, immunohistochemistry, western blotting, and qPCR. RESULTS: Tie2 mAb attenuated RIF and reduced the level of fibroblast-specific protein 1 (FSP1). Further, it suppressed vascular cell adhesion molecule-1 (VCAM-1) and increased CD31 density in FAN. In the in vitro model, Tie2 mAb was found to decrease the expression of VCAM-1, Bax, and α-smooth muscle actin (α-SMA). CONCLUSIONS: The present findings indicate that the agonistic Tie2 mAb exerted vascular protective effects and ameliorated RIF via inhibition of vascular inflammation, apoptosis, and fibrosis. Therefore, Tie2 may be a potential target for the treatment of this disease. IMPACT: This is the first report to confirm that an agonistic Tie2 monoclonal antibody can reduce renal interstitial fibrosis in folic acid-induced nephropathy in mice. This mechanism possibly involves vascular protective effects brought about by inhibition of vascular inflammation, apoptosis and fibrosis. Our data show that Tie2 signal may be a novel, endothelium-specific target for the treatment of tubulointerstitial fibrosis.

Comparisons of Accelerated Continuous and Intermittent Theta Burst Stimulation for Treatment-Resistant Depression and Suicidal Ideation.

BACKGROUND: Suicidal ideation is a substantial clinical challenge in treatment-resistant depression (TRD). Recent work demonstrated promising antidepressant effects in TRD patients with no or mild suicidal ideation using a specific protocol termed intermittent theta burst stimulation (iTBS). Here, we examined the clinical effects of accelerated schedules of iTBS and continuous TBS (cTBS) in patients with moderate to severe suicidal ideation. METHODS: Patients with TRD and moderate to severe suicidal ideation (n = 44) were randomly assigned to receive accelerated iTBS or cTBS treatment. Treatments were delivered in 10 daily TBS sessions (1800 pulses/session) for 5 consecutive days (total of 90,000 pulses). Neuronavigation was employed to target accelerated iTBS and cTBS to the left and right dorsolateral prefrontal cortex (DLPFC), respectively. Clinical outcomes were evaluated in a 4-week follow-up period. RESULTS: Accelerated cTBS was superior to iTBS in the management of suicidal ideation (pweek 1 = .027) and anxiety symptoms (pweek 1 = .01). Accelerated iTBS and cTBS were comparable in antidepressant effects (p < .001; accelerated cTBS: mean change at weeks 1, 3, 5 = 49.55%, 54.99%, 53.11%; accelerated iTBS: mean change at weeks 1, 3, 5 = 44.52%, 48.04%, 51.74%). No serious adverse events occurred during the trial. One patient withdrew due to hypomania. The most common adverse event was discomfort at the treatment site (22.73% in both groups). CONCLUSIONS: These findings provide the first evidence that accelerated schedules of left DLPFC iTBS and right DLPFC cTBS are comparably effective in managing antidepressant symptoms and indicate that right DLPFC cTBS is potentially superior in reducing suicidal ideation and anxiety symptoms.

Event-free survival as a predictor of overall survival and recurrence burden of patients with non-small cell lung cancer receiving neoadjuvant therapy.

OBJECTIVES: Event-free survival has replaced overall survival as a primary end point in many recent and ongoing clinical trials. This study aims to examine the correlation between real-world event-free survival and overall survival and to assess the clinical and economic burden associated with disease recurrence among patients with resected stage II to III non-small cell lung cancer who received neoadjuvant therapy in the United States. METHODS: This retrospective study used the Surveillance, Epidemiology, and End Results Medicare database (2007-2019) to identify patients with newly diagnosed, resected, stage II to IIIB (N2) non-small cell lung cancer who received neoadjuvant therapy. The correlation between real-world event-free survival and overall survival was assessed using the normal scores rank correlation and landmark analysis. Overall survival, all-cause health care resource use and costs, and non-small cell lung cancer-related health care resource use and costs were compared between patients with and without recurrence. RESULTS: A total of 221 patients met the eligibility criteria (median follow-up time from neoadjuvant treatment initiation: 32.7 months). The mean age was 72.1 years, and 57.0% of patients were male. Real-world, event-free survival and overall survival are positively and significantly correlated (0.68; 95% CI, 0.52-0.79). Patients with recurrence had significantly shorter median overall survival (19.3 vs 116.9 months), 4.59 times increased risk of death (95% CI, 2.56-8.26), and significantly higher all-cause and non-small cell lung cancer-related health care resource use and costs (adjusted mean monthly costs per patient difference: $5758 and $3187, respectively [all P < .001]). CONCLUSIONS: These findings help validate event-free survival as a clinically meaningful end point and strong predictor for overall survival and highlight the need for additional novel therapies that may delay or prevent recurrence in resectable stage II and III non-small cell lung cancer.

Active polypeptide MDANP protect against necrotizing enterocolitis (NEC) by regulating the PERK-eIF2ɑ-QRICH1 axis.

The effect of MDANP effects on ER stress signalling not well known or elucidated. Endoplasmic reticulum (ER) stress plays a critical role in necrotizing enterocolitis (NEC) pathogenesis through the PERK-eIF2ɑ-QRICH1 axis. The present study aimed to explore the protective effects of MDANP in NEC development. Firstly, a function screening was designed to identify the candidate peptides in human milk, and then the identified peptides were validated in NEC patients. In vivo, NEC was induced in mice pups and divided into four groups: (1) control group, (2) NEC group, (3) MDANP + NEC group, and (4) NS + NEC group. In vitro, lentivirus-mediated QRICH1 silencing, was used to transfect NCM460 cell lines, then stimulated with LPS. After LPS stimulation, cells were treated with chemically synthesized MDANP, and the essential proteins in the QRICH1 signalling pathway in cells were tested and compared. After the small-scale screening, a peptide (SKSKKFRRPDIQYPDATDED) named MDANP was determined as the principal peptide. Its protective effect against NEC through inhibiting the expression of ERS key proteins and impeding the intestinal cells' apoptosis was observed in the animal models. Furthermore, the inhibitive effect of MDANP on apoptosis of intestinal epithelial cells through modulating the PERK-eIF2ɑ-QRICH1 ERS pathway was also confirmed in vitro. Taken together, our data suggest that MDANP effectively ameliorates apoptosis in NEC through attenuating PERK-eIF2ɑ-QRICH1.

Mechanical Properties of Low-Molecular-Weight Peptide Hydrogels Improved by Thiol-Ene Click Chemistry.

Low-molecular-weight peptide hydrogels can be formed by self-assembly through weak interactions, but the application of the hydrogel is influenced by its weak mechanical properties. Therefore, it is important to construct low-molecular-weight peptide hydrogels with excellent mechanical properties. In this work, we designed the pentapeptide molecule Fmoc-FFCKK-OH (abbreviated as FFCKK) with a sulfhydryl group, and another low-molecular-weight cross-linker N,N'-methylenebis(acrylamide) (MBA) was introduced to construct a hydrogel with excellent mechanical properties. The secondary structure change process of FFCKK and the assembly mechanism of hydrogel were analyzed using theoretical calculations and experimental characterizations. The occurrence of thiol-ene click chemistry provides covalent interaction in the hydrogel, and the synergistic effect ofcovalent interaction and hydrogen bonding improves the mechanical properties of the hydrogel by nearly 10-fold. The hydrogel was observed to be able to withstand a stress of 368 Pa and to break in a layer-by-layer manner by compression testing. The micromechanics of the hydrogels were characterized, and the excellent mechanical properties of the hydrogels were confirmed. The synergistic approach provides a new idea for the preparation of low-molecular-weight peptide hydrogels and facilitates the expansion of their potential applications in biomedical fields.

Fast and robust calibration method of liquid-crystal spatial light modulator based on polarization multiplexing.

We propose a fast and robust method for calibrating Spatial Light Modulators (SLMs) based on polarization phase-shifting interferometry. Our method effectively calibrates the SLM by addressing both the static aberration and nonlinear phase response, utilizing specially designed gray images loaded sequentially onto the SLM. Notably, we introduce a novel kinoform that effectively eliminates the influence of tilt phase shift between two shots of the polarization camera. This results in a highly accurate phase aberration map and phase modulation curve with exceptional stability, making it an ideal method to calibrate the SLM with exceptional efficiency and precision in real applications.

Refraction correction for deep-water three-dimensional visual measurement based on multi-objective optimization.

Refraction-induced errors affect the accuracy of three-dimensional visual measurements in deepwater environments. In this study, a binocular camera refractive imaging model was established, and a calibration method for the refraction parameters was proposed for high-accuracy shape and deformation measurements in deep-water environments. First, an initial estimate of the refractive axis was obtained using a three-dimensional calibration target. Then, the errors in the distance between the spatial point pairs and the reprojection errors are taken as the dual optimization objectives, and the Non-dominated Sorting Genetic Algorithm II is applied to optimize the refraction parameters. To efficiently calculate the reprojection error, an improved numerical computation method is proposed to accelerate the calculation of the analytical forward projection. Underwater experiments were conducted to verify the method's effectiveness. The results showed that the average error of the absolute position of the reconstructed points was less than 1.1 mm and the average error of the displacement was less than 0.04 mm. This study provides a sound solution for accurate three-dimensional visual measurement in deep-water environments.

Two cases of successful sirolimus treatment for patients with activated phosphoinositide 3-kinase δ syndrome 1.

BACKGROUND: Activated phosphoinositide3-kinase (PI3K) δ syndrome 1 (APDS1) is a novel inborn errors of immunity (IEIs) caused by heterozygous gain of function mutations in PI3Kδ catalytic p110δ (PIK3CD). APDS1 has a spectrum of clinical manifestations. Recurrent respiratory infections, lymphoproliferation, hepatosplenomegaly, hyper-IgM syndrome and autoimmunity are the common symptoms of this disease. CASE PRESENTATION: Patient 1 presented with recurrent respiratory infections, hepatosplenomegaly and hyper-IgM syndrome. Patient 2 developed early onset systemic lupus erythematosus (SLE)-like disease with resistant thrombocytopenia. c.3061 G > A and c.2314G > A variants in the PIK3CD gene were detected by whole exome sequencing in two patients respectively. c.2314G > A variant in PIK3CD gene of patient 2 is a newly report. After genetic diagnosis, two patients received sirolimus treatment and sirolimus alleviated clinical manifestations, including hepatosplenomegaly in patient 1 and thrombocytopenia in patient 2. CONCLUSION: Genetics diagnosis should be considered in patients with complicated clinical manifestations with no or insufficient response to the conventional therapies. If whole exome sequencing suggests a variant in PIK3CD gene, sirolimus may relieve hepatosplenomegaly and resistant thrombocytopenia. This is the first report of c.2314G > A variant in PIK3CD gene.