Comparative time-dependent proteomics reveal the tolerance of cancer cells to magnetic iron oxide nanoparticles.

Cancer is one of the most challenging diseases in the world. Recently, iron oxide nanoparticles (IONPs) are emerging materials with rapid development and high application value, and have shown great potential on tumor therapy due to their unique magnetic and biocompatible properties. However, some data hint us that IONPs were toxic to normal cells and vital organs. Thus, more data on biosafety evaluation is urgently needed. In this study, we compared the effects of silicon-coated IONPs (Si-IONPs) on two cell types: the tumor cells (Hela) and the normal cells (HEK293T, as 293 T for short), compared differences of protein composition, allocation and physical characteristics between these two cells. The major findings of our study pointed out that 293 T cells death occurred more significant than that of Hela cells after Si-IONPs treatment, and the rate and content of endocytosis of Si-IONPs in 293 T cells was more prominent than in Hela cells. Our results also showed Si-IONPs significant promoted the production of reactive oxygen species and disturbed pathways related to oxidative stress, iron homeostasis, apoptosis and ferroptosis in both two types of cells, however, Hela cells recovered from these disturbances more easily than 293 T. In conclusion, compared with Hela cells, IONPs are more likely to induce 293 T cells death and Hela cells have their own unique mechanisms to defense invaders, reminding scientists that future in vivo and in vitro studies of nanoparticles need to be cautious, and more safety data are needed for further clinical treatment.

Cardiovascular disease: Mitochondrial dynamics and mitophagy crosstalk mechanisms with novel programmed cell death and macrophage polarisation.

Several cardiovascular illnesses are associated with aberrant activation of cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis, and macrophage polarisation as hallmarks contributing to vascular damage and abnormal cardiac function. Meanwhile, these three novel forms of cellular dysfunction are closely related to mitochondrial homeostasis. Mitochondria are the main organelles that supply energy and maintain cellular homeostasis. Mitochondrial stability is maintained through a series of regulatory pathways, such as mitochondrial fission, mitochondrial fusion and mitophagy. Studies have shown that mitochondrial dysfunction (e.g., impaired mitochondrial dynamics and mitophagy) promotes ROS production, leading to oxidative stress, which induces cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage M1 phenotypic polarisation. Therefore, an in-depth knowledge of the dynamic regulation of mitochondria during cellular pyroptosis, ferroptosis, necroptosis, cuproptosis, disulfidptosis and macrophage polarisation is necessary to understand cardiovascular disease development. This paper systematically summarises the impact of changes in mitochondrial dynamics and mitophagy on regulating novel cellular dysfunctions and macrophage polarisation to promote an in-depth understanding of the pathogenesis of cardiovascular diseases and provide corresponding theoretical references for treating cardiovascular diseases.

A flexible, stretchable and wearable strain sensor based on physical eutectogels for deep learning-assisted motion identification.

Physical eutectogels as a newly emerging type of conductive gel have gained extensive interest for the next generation multifunctional electronic devices. Nevertheless, some obstacles, including weak mechanical performance, low self-adhesive strength, lack of self-healing capacity, and low conductivity, hinder their practical use in wearable strain sensors. Herein, lignin as a green filler and a multifunctional hydrogen bond donor was directly dissolved in a deep eutectic solvent (DES) composed of acrylic acid (AA) and choline chloride, and lignin-reinforced physical eutectogels (DESL) were obtained by the polymerization of AA. Due to the unique features of lignin and DES, the prepared DESL eutectogels exhibit good transparency, UV shielding capacity, excellent mechanical performance, outstanding self-adhesiveness, superior self-healing properties, and high conductivity. Based on the aforementioned integrated functions, a wearable strain sensor displaying a wide working range (0-1500%), high sensitivity (GF = 18.15), rapid responsiveness, and excellent stability and durability (1000 cycles) and capable of detecting diverse human motions was fabricated. Additionally, by combining DESL sensors with a deep learning technique, a gesture recognition system with accuracy as high as 98.8% was achieved. Overall, this work provides an innovative idea for constructing multifunction-integrated physical eutectogels for application in wearable electronics.

High hyperdiploid karyotype with ≥ 49 chromosomes represents a heterogeneous subgroup of acute myeloid leukemia with differential TP53 mutation status and prognosis: a single-center study from China.

High hyperdiploid karyotype with ≥ 49 chromosomes (which will be referred to as HHK) is rare in acute myeloid leukemia (AML). The European leukemia network (ELN) excluded those harboring only numerical changes (with ≥ 3 chromosome gains) from CK and listed them in the intermediate risk group, while the UK National Cancer Research Institute Adult Leukaemia Working Group classification defined ≥ 4 unrelated chromosome abnormalities as the cutoff for a poorer prognosis. Controversies occurred among studies on the clinical outcome of HHK AML, and their molecular characteristics remained unstudied. We identified 1.31% (133/10,131) HHK cases within our center, among which 48 cases only had numerical changes (NUM), 42 had ELN defined adverse abnormalities (ADV) and 43 had other structural abnormalities (STR). Our study demonstrated that: (1) No statistical significance for overall survival (OS) was observed among three cytogenetic subgroups (NUM, STR and ADV) and HHK AML should be assigned to the adverse cytogenetic risk group. (2) The OS was significantly worse in HHK AML with ≥ 51 chromosomes compared with those with 49-50 chromosomes. (3) The clinical characteristics were similar between NUM and STR group compared to ADV group. The former two groups had higher white blood cell counts and blasts, lower platelet counts, and mutations associated with signaling, while the ADV group exhibited older age, higher chromosome counts, higher percentage of myelodysplastic syndrome (MDS) history, and a dominant TP53 mutation.

Associations of life's essential 8 with extent of multi-territorial atherosclerotic plaques and stenosis: a cross-sectional study.

BACKGROUND: Life's Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. METHODS: Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (< 60), moderate (60-<80), and high (≥ 80) groups. Vascular magnetic resonance imaging was used to evaluate intracranial and extracranial arteries; thoracoabdominal computed tomography angiography to evaluate coronary, subclavian, aorta, renal, ilio-femoral arteries; and ankle-brachial index to evaluate peripheral arteries. The presence of atherosclerotic plaque or stenosis in any territory was defined as plaque or vascular stenosis with 1 territory affected or more in these arteries. The extent of atherosclerotic plaques or stenosis was assessed according to the number of these 8 vascular sites affected, and graded as four grades (none, single territory, 2-3 territories, 4-8 territories). RESULTS: Of 3065 included participants, the average age was 61.2 ± 6.7 years, and 53.5% were women (n = 1639). The moderate and high overall LE8 groups were associated with lower extent of multi-territorial plaques [common odds ratio (cOR) 0.44, 95% confidence interval (CI), 0.35-0.55; cOR 0.16, 95%CI, 0.12-0.21; respectively] and stenosis (cOR 0.51, 95%CI, 0.42-0.62; cOR 0.16, 95%CI, 0.12-0.21; respectively) after adjustment for potential covariates. Similar results were observed for medical LE8 score with the extent of multi-territorial plaques and stenosis (P < 0.05). We also found the association between behavior LE8 score and the extent of multi-territorial stenosis (P < 0.05). CONCLUSIONS: The higher LE8 scores, indicating healthier lifestyle, were associated with lower presence and extent of atherosclerotic plaque and stenosis in southern Chinese adults. Prospective studies are needed to further validate these findings.

Rapid production of COVID-19 subunit vaccine candidates and their immunogenicity evaluation in pigs.

The emergence of various variants of concern (VOCs) necessitates the development of more efficient vaccines for COVID-19. In this study, we established a rapid and robust production platform for a novel subunit vaccine candidate based on eukaryotic HEK-293 T cells. The immunogenicity of the vaccine candidate was evaluated in pigs. The results demonstrated that the pseudovirus neutralizing antibody (pNAb) titers reached 7751 and 306 for the SARS-CoV-2 Delta and Omicron variants, respectively, after the first boost. Subsequently, pNAb titers further increased to 10,201 and 1350, respectively, after the second boost. Additionally, ELISPOT analysis revealed a robust T-cell response characterized by IFN-γ (171 SFCs/106 cells) and IL-2 (101 SFCs/106 cells) production. Our study demonstrates that a vaccine candidate based on the Delta variant spike protein may provide strong and broad protection against the prototype SARS-CoV-2 and VOCs. Moreover, the strategy for the efficient and stable expression of recombinant proteins utilizing HEK-293 T cells can be employed as a universal platform for future vaccine development.

Microglia in radiation-induced brain injury: Cellular and molecular mechanisms and therapeutic potential.

BACKGROUND: Radiation-induced brain injury is a neurological condition resulting from radiotherapy for malignant tumors, with its underlying pathogenesis still not fully understood. Current hypotheses suggest that immune cells, particularly the excessive activation of microglia in the central nervous system and the migration of peripheral immune cells into the brain, play a critical role in initiating and progressing the injury. This review aimed to summarize the latest advances in the cellular and molecular mechanisms and the therapeutic potential of microglia in radiation-induced brain injury. METHODS: This article critically examines recent developments in understanding the role of microglia activation in radiation-induced brain injury. It elucidates associated mechanisms and explores novel research pathways and therapeutic options for managing this condition. RESULTS: Post-irradiation, activated microglia release numerous inflammatory factors, exacerbating neuroinflammation and facilitating the onset and progression of radiation-induced damage. Therefore, controlling microglial activation and suppressing the secretion of related inflammatory factors is crucial for preventing radiation-induced brain injury. While microglial activation is a primary factor in neuroinflammation, the precise mechanisms by which radiation prompts this activation remain elusive. Multiple signaling pathways likely contribute to microglial activation and the progression of radiation-induced brain injury. CONCLUSIONS: The intricate microenvironment and molecular mechanisms associated with radiation-induced brain injury underscore the crucial roles of immune cells in its onset and progression. By investigating the interplay among microglia, neurons, astrocytes, and peripheral immune cells, potential strategies emerge to mitigate microglial activation, reduce the release of inflammatory agents, and impede the entry of peripheral immune cells into the brain.

Phosphine-Catalyzed γ'-Carbon 1,6-Conjugate Addition of α-Succinimide Substituted Allenoates with Para-Quinone Methides: Synthesis of 4-Diarylmethylated 3,4-Disubstituted Maleimides.

In this paper, an interesting γ'-carbon 1,6-conjugate addition for phosphine-catalyzed α-succinimide substituted allenoates has been disclosed. A wide array of substrates was found to participate in the reaction, resulting in the production of diverse 4-diarylmethylated 3,4-disubstituted maleimides with satisfactory to outstanding yields. Furthermore, a plausible mechanism for the reaction was proposed by the investigators.

Characterize direct protein interactions with enrichable, cleavable and latent bioreactive unnatural amino acids.

Latent bioreactive unnatural amino acids (Uaas) have been widely used in the development of covalent drugs and identification of protein interactors, such as proteins, DNA, RNA and carbohydrates. However, it is challenging to perform high-throughput identification of Uaa cross-linking products due to the complexities of protein samples and the data analysis processes. Enrichable Uaas can effectively reduce the complexities of protein samples and simplify data analysis, but few cross-linked peptides were identified from mammalian cell samples with these Uaas. Here we develop an enrichable and multiple amino acids reactive Uaa, eFSY, and demonstrate that eFSY is MS cleavable when eFSY-Lys and eFSY-His are the cross-linking products. An identification software, AixUaa is developed to decipher eFSY mass cleavable data. We systematically identify direct interactomes of Thioredoxin 1 (Trx1) and Selenoprotein M (SELM) with eFSY and AixUaa.

Randomized trial comparing the effects of a 3D head-up system and microscope eyepiece-assisted simulated vitrectomy with intraocular illumination on the ocular surface of an operator.

BACKGROUND: To compare the effects of a 3D head-up system and microscope eyepiece-assisted simulated vitrectomy intraocular illumination on the ocular surface of an operator. METHODS: This was a prospective randomized controlled study. According to the application system, thirty ophthalmic operators (60 eyes) were randomly divided into 3D and eyepiece groups. Under different intensities of intraocular illumination, operators in both groups viewed the fundus model through a 3D display screen or microscopic eyepiece for 2 h. Objective examinations and a subjective symptom questionnaire were used immediately after the test to evaluate the ocular surface of the operators. Objective examinations included nonintrusion tear meniscus height (NIKTMH), nonintrusion break-up time (NIKBUT), and bulbar redness and strip meniscometry tube (SMTube) measurements. Statistical analyses were performed by using SPSS 26.0 software. RESULTS: After the test, the NIKTMH, NIKBUT and SMTube measurements decreased; however, the degree of change varied among the groups of different systems. The differences between the 3D group and the eyepiece group in NIKTMH measurements, SMTube measurements, subjective symptom scores (eye dryness, difficulty focusing, and cervical pain), and light intensity reaching the ocular surface of the operators were statistically significant (P < 0.05). All of the objective and subjective tests showed that the 3D group had fewer effects on the NIKTMH and SMTube measurements, and the subjective comfort of the 3D group was greater. CONCLUSION: For both 3D screens and eyepieces, simulated vitrectomy with intraocular illumination for two hours can lead to discomfort and abnormalities in the operator's ocular surface; however, these abnormalities are less severe in the 3D group. TRIAL REGISTRATION: This trial was registered on December 22, 2022, at the Chinese Clinical Trials Registry with NO. ChiCTR2200066989.

Is neoadjuvant chemotherapy necessary for T2N0-1M0 hormone receptor-positive/HER2-negative breast cancer patients undergoing breast-conserving surgery?

INTRODUCTION: For HR-positive/HER2-negative patients who can undergo breast-conserving surgery (BCS) but have a tumor size of 2-5 cm or 1-3 lymph node metastases, neoadjuvant chemotherapy (NAC) is still controversial. METHODS: Patients with T2N0-1M0 HR-positive/HER2-negative BC who underwent BCS between 2010 and 2017 were selected from the SEER database. Propensity score matching (PSM) was used to minimize the influence of confounding factors. The overall survival (OS) and breast cancer-specific survival (BCSS) of patients were estimated by Kaplan‒Meier curves and Cox proportional hazard models. Independent prognostic factors were included to construct a nomogram prediction model. RESULTS: A total of 6475 BC patients were enrolled, of whom 553 received NAC and 5922 received adjuvant chemotherapy (AC). In the T2N0-1M0 population and T2N1M0 subgroup, AC patients before PSM had better OS and BCSS than NAC patients. After PSM, there was no significant difference in OS or BCSS between the two groups. However, in the T2N0M0 subgroup, there was no difference in survival between the AC and NAC groups before and after PSM. Stratified analysis revealed that for complete response (CR) patients, survival was roughly equivalent between the NAC and AC groups. However, the survival of no response (NR) and partial response (PR) patients was significantly worse than that of AC patients. Cox analysis revealed that radiotherapy after BCS was an independent protective factor for OS. NAC is an independent risk factor for NR and PR patients. The nomogram has good prediction efficiency. CONCLUSION: NAC before BCS is not necessary for T2N0-1M0 HR-positive/HER2-negative BC patients.

MicroRNA expression profile of chicken liver at different times after Histomonas meleagridis infection.

Histomonas meleagridis, an anaerobic intercellular parasite, is known to infect gallinaceous birds, particularly turkeys and chickens. The resurgence of histomonosis in recent times has resulted in significant financial setbacks due to the prohibition of drugs used for disease treatment. Currently, research on about H. meleagridis primarily concentrate on the examination of its virulence, gene expression analysis, and the innate immunity response of the host organism. However, there is a lack of research on differentially expressed miRNAs (DEMs) related to liver infection induced by H. meleagridis. In this study, the weight gain and pathological changes at various post-infection time points were evaluated through animal experiments to determine the peak and early stages of infection. Next, High-throughput sequencing was used to examine the expression profile of liver miRNA at 10 and 15 days post-infection (DPI) in chickens infected with the Chinese JSYZ-F strain of H. meleagridis. A comparison with uninfected controls revealed the presence of 120 and 118 DEMs in the liver of infected chickens at 10 DPI and 15 DPI, respectively, with 74 DEMs being shared between the two time points. Differentially expressed microRNAs (DEMs) were categorized into three groups based on the time post-infection. The first group (L1) includes 45 miRNAs that were differentially expressed only at 10 DPI and were predicted to target 1646 genes. The second group (L2) includes 43 miRNAs that were differentially expressed only at 15 DPI and were predicted to target 2257 genes. The third group (L3) includes 75 miRNAs that were differentially expressed at both 10 DPI and 15 DPI and were predicted to target 1623 genes. At L1, L2, and L3, there were 89, 87, and 41 significantly enriched Gene Ontology (GO) terms, respectively (p<0.05). The analysis of differentially expressed miRNA target genes using KEGG pathways revealed significant enrichment at L1, L2, and L3, with 3, 4, and 5 pathways identified, respectively (p<0.05). This article suggests that the expression of liver miRNA undergoes dynamic alterations due to H. meleagridis and the host. It showed that the expression pattern of L1 class DEMs was more conducive to regulating the development of the inflammatory response, while the L2 class DEMs were more conducive to augmenting the inflammatory response. The observed patterns of miRNA expression associated with inflammation were in line with the liver's inflammatory process following infection. The results of this study provide a basis for conducting a comprehensive analysis of the pathogenic mechanism of H. meleagridis from the perspective of host miRNAs.

Melatonin confers thermotolerance and antioxidant capacity in Chinese cabbage.

Due to the damaging effect of high temperatures on plant development, global warming is predicted to increase agricultural risks. Chinese cabbage holds considerable importance as a leafy vegetable that is extensively consumed and cultivated worldwide. Its year-round production also encounters severe challenges in the face of high temperatures. In this study, melatonin (MT), a pivotal multifunctional signaling molecule that coordinates responses to diverse environmental stressors was used to mitigate the harmful effects of high temperatures on Chinese cabbage. Through the utilization of growth indices, cytological morphology, physiological and biochemical responses, and RNA-Seq analysis, alongside an examination of the influence of crucial enzymes in the endogenous MT synthesis pathway on the thermotolerance of Chinese cabbage, we revealed that MT pretreatment enhanced photosynthetic activity, maintained signaling pathways associated with endoplasmic reticulum protein processing, and preserved circadian rhythm in Chinese cabbage under high temperatures. Furthermore, pretreatment with MT resulted in increased levels of soluble sugar, vitamin C, proteins, and antioxidant enzyme activity, along with decreased levels of malondialdehyde, nitrate, flavonoids, and bitter glucosinolates, ultimately enhancing the capacity of the organism to mitigate oxidative stress. The knockdown of the tryptophan decarboxylase gene, which encodes a key enzyme responsible for MT biosynthesis, resulted in a significant decline in the ability of transgenic Chinese cabbage to alleviate oxidative damage under high temperatures, further indicating an important role of MT in establishing the thermotolerance. Taken together, these results provide a mechanism for MT to improve the antioxidant capacity of Chinese cabbage under high temperatures and suggest beneficial implications for the management of other plants subjected to global warming.

No-observed adverse effect levels of deoxynivalenol and aflatoxin B1 in combination induced immune inhibition and apoptosis in vivo and in vitro.

Mycotoxins are toxic metabolites produced by fungal species, commonly exist in animal feeds, and pose a serious risk to human as well as animal health. But limited studies have focused on combined effects of no-observed adverse effect levels. In vivo study, 6 weeks old twenty-four mice were individually exposed to Deoxynivalenol (DON) at 0.1 mg/kg BW, Aflatoxin B1 (AFB1) at 0.01 mg/kg BW, and mixture of DON and AFB1 (0.1 mg/kg BW and 0.01 mg/kg BW, respectively) for 28 days. Then, DON at 0.5 µg/mL, AFB1 at 0.04 µg/mL, and mixtures of DON and AFB1 (0.5 µg/mL, 0.04 µg/mL, respectively) were applied to porcine alveolar macrophages (PAMs) in vitro study. Our in vivo results revealed that the combined no-observed adverse effect levels of DON and AFB1 administration decreased IgA and IgG levels in the serum, the splenic TNF-α, IFN-γ, IL-2 and IL-6 mRNA expression and T-lymphocyte subset levels (CD4+ and CD8+) in the spleen. Additionally, the combined administration increased caspase-3, caspase-9, Bax, Cyt-c, and decreased Bcl-2 protein expression. Taken together, the combined no-observed adverse effect levels of DON and AFB1 could induce immunosuppression, which may be related to apoptosis. This study provides new insights into the combined immune toxicity (DON and AFB1).

A novel mutation in GPR68 causes hypomaturation amelogenesis imperfecta.

OBJECTIVES: To identify the genetic cause of a Chinese family with hypomaturation amelogenesis imperfecta (AI) and to characterize the structure of GPR68 mutated enamel in order to develop a deeper understanding of the role of the GPR68 protein during the intricate process of amelogenesis. DESIGN: One Chinese family with generalized hypomaturation AI was recruited. Two of the third molars from the proband were subjected to scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Whole exome sequencing (WES) was performed, and the identified mutation was confirmed by Sanger sequencing. Bioinformatics studies were further conducted to analyze the potential deleterious effects of the mutation. RESULTS: The proband presented with a hypomaturation AI phenotype, characterized by fragile and discolored enamel surface. The AI enamel showed prismatic structure, which was sporadically obscured by areas of amorphous material and porous structure. EDX analysis showed the proband's enamel demonstrated a significant decrease in calcium and phosphorus content and a significant increase in oxygen compared with normal enamel. A novel homozygous mutation of G protein-coupled receptor 68 (GPR68) (c .149 T > A, p.Ile50Asn) was identified in the proband. Bioinformatics analysis indicated that the mutation site displayed a high level of evolutionary conservation among species, and the mutation might impact the stability and conformation of the protein. CONCLUSION: The novel homozygous GPR68 mutation resulted in hypomaturation AI. We first described the effect of GPR68 mutation on enamel structure. Our results provide new genetic evidence that mutations involved in GPR68 contribute to hypomaturation AI.

Simple and scalable preparation of lignin based porous carbon coated nano-clay composites and their efficient removal for the diversified iodine.

Here, lignin and nano-clay were used to prepare novel composite adsorbents by one-step carbonization without adding activators for radioactive iodine capture. Specially, 1D nano-clay such as halloysite (Hal), palygorskite (Pal) and sepiolite (Sep) were selected as skeleton components, respectively, enzymatic hydrolysis lignin (EHL) as carbon source, lignin based porous carbon/nano-clay composites (ELC-X) were prepared through ultrasonic impregnation, freeze drying, and carbonization. Characterization results indicated lignin based porous carbon (ELC) well coated on the surface of nano-clay, and made its surface areas increase to 252 m2/g. These composites appeared the micro-mesoporous hierarchical structure, considerable N doping and good chemical stability. Results of adsorption experiments showed that the introduction of ELC could well promote iodine vapor uptake of nano-clay, and up to 435.0 mg/g. Meanwhile, the synergistic effect between lignin based carbon and nano-clay was very significant for the adsorption of iodine/n-hexane and iodine ions, their capacity were far exceed those of a single material, respectively. The relevant adsorption kinetic and thermodynamics, and mechanism of ELC-X composites were clarified. This work provided a class of low-cost and environmentally friendly adsorbents for radioactive iodine capture, and opened up ideas for the comprehensive utilization of waste lignin and natural clay minerals.

Shorter Door-to-ECG Time Is Associated with Improved Mortality in STEMI Patients.

Background: Delayed intervention for ST-segment elevation myocardial infarction (STEMI) is associated with higher mortality. The association of door-to-ECG (D2E) with clinical outcomes has not been directly explored in a contemporary US-based population. Methods: This was a three-year, 10-center, retrospective cohort study of ED-diagnosed patients with STEMI comparing mortality between those who received timely (<10 min) vs. untimely (>10 min) diagnostic ECG. Among survivors, we explored left ventricular ejection fraction (LVEF) dysfunction during the STEMI encounter and recovery upon post-discharge follow-up. Results: Mortality was lower among those who received a timely ECG where one-week mortality was 5% (21/420) vs. 10.2% (26/256) among those with untimely ECGs (p = 0.016), and in-hospital mortality was 6.0% (25/420) vs. 10.9% (28/256) (p = 0.028). Data to compare change in LVEF metrics were available in only 24% of patients during the STEMI encounter and 46.5% on discharge follow-up. Conclusions: D2E within 10 min may be associated with a 50% reduction in mortality among ED STEMI patients. LVEF dysfunction is the primary resultant morbidity among STEMI survivors but was infrequently assessed despite low LVEF being an indication for survival-improving therapy. It will be difficult to assess the impact of STEMI care interventions without more consistent LVEF assessment.

Tracing conflict-induced cognitive-control adjustments over time using aperiodic EEG activity.

Cognitive-control theories assume that the experience of response conflict can trigger control adjustments. However, while some approaches focus on adjustments that impact the selection of the present response (in trial N), other approaches focus on adjustments in the next upcoming trial (N + 1). We aimed to trace control adjustments over time by quantifying cortical noise by means of the fitting oscillations and one over f algorithm, a measure of aperiodic activity. As predicted, conflict trials increased the aperiodic exponent in a large sample of 171 healthy adults, thus indicating noise reduction. While this adjustment was visible in trial N already, it did not affect response selection before the next trial. This suggests that control adjustments do not affect ongoing response-selection processes but prepare the system for tighter control in the next trial. We interpret the findings in terms of a conflict-induced switch from metacontrol flexibility to metacontrol persistence, accompanied or even implemented by a reduction of cortical noise.

Comprehensive analysis of INTS family related to expression, prognosis, diagnosis and immune features in hepatocellular carcinoma.

Purpose: The integrator subunit (INTS) family, a group exclusive to metazoans, participates in various biologic processes. However, their roles in hepatocellular carcinoma (HCC) remain largely unexplored. Methods: Public databases were utilized to investigate the transcriptional and protein expression, and clinical relevance of the INTS family in HCC. Meanwhile, the effects of INTS13 knockdown and overexpression on cell proliferation and apoptosis were studied using HCC cell lines. Results: The mRNA expression of most INTSs were higher in tumor than normal tissues. Higher expression of INTS1/2/3/4/7/8/9/11/12/13 were correlated with poorer overall survival (OS) in Kaplan-Meier Survival Analysis. Multivariate analysis revealed higher level of INTS13 was an independent prognostic factor for shorter OS. Furthermore, genetic alteration of INTS3/6/7/8/9/10 were found in HCC patients and was associated with shorter disease-free survival and progression-free survival. INTS1/2/3/5/7/11/13/14 were associated with activation of tumor-induced immune response and immune infiltration in HCC. Knockdown of INTS13 inhibited cell proliferation and induced apoptosis in HCC cell lines, while overexpression of INTS13 had the opposite effect. Conclusion: Our results indicate that INTS13 is an independent prognostic biomarker in HCC. Furthermore, INTS13 enhances cell proliferation and decreases cell apoptosis in HCC cell lines leading to a poorer OS in HCC patients.

Efficacy of scleral buckling for the treatment of rhegmatogenous retinal detachment using a novel foldable capsular buckle.

AIM: To evaluate the effectiveness and safety of scleral buckling for the treatment of rhegmatogenous retinal detachment (RRD) using a novel foldable capsular buckle (FCB). METHODS: This was a series of case observation studies. Eighteen patients (18 eyes) who visited our ophthalmology department between August 2020 and August 2022 and were treated for RRD with scleral buckling using FCB were included. The procedure was similar to conventional scleral buckling, while a balloon-like FCB was placed onto the retinal break with balanced salt solution filling for a broad, external indentation instead of the silicone buckle. The retinal reattachment rate, best corrected visual acuity (BCVA), intraocular pressure (IOP), refractive dioptre and astigmatism degree, and complications were evaluated and recorded. RESULTS: There were 7 males and 11 females aged 19-58y. The average time course of RRD was 12d, ranging from 7-20d. The retinal break was located in the superior quadrants in 8 eyes and in the inferior quadrants in 10 eyes, with macula-off detachments in 12 eyes. The patients were followed-up for at least 6mo. The final retinal reattachment rate was 100%. The BCVA was significantly improved compared with the baseline (P<0.05). There was no significant change in refractive dioptre or astigmatism degree at each follow-up (all P>0.05). Three patients had transiently high IOPs within one week after surgery. Mild diplopia occurred in 5 patients after surgery and then disappeared after the balloon fluid was removed. CONCLUSION: The success rate of FCB scleral buckling for RRD is satisfactory. This procedure can be expected to be applied in new, uncomplicated cases of RRD.