Jailed Balloon Technique Versus Jailed Wire Technique for Side Branch Ostium Protection in Bifurcation Lesions: Evidence from Three-dimensional Optical Coherence Tomography Analysis.

Background: There is controversy regarding the effectiveness the of jailed wire technique (JWT) and jailed balloon technique (JBT) in preserving the side branch (SB) during treatment. This study compares the protective effect of JBT versus JWT on the SB ostium area in coronary bifurcation lesions using three-dimensional optical coherence tomography (3D-OCT). Methods: We obtained data from coronary heart disease patients who received OCT-guided percutaneous coronary intervention (PCI) for bifurcation lesions. The SB protection strategies were divided into JWT and JBT, with the latter further subdivided into active JBT (A-JBT) and conventional JBT (C-JBT). The primary endpoint was the SB ostium area difference measured by 3D-OCT before and after PCI. Partial correlation analysis and propensity score matching (PSM) was used to mitigate confounding biases. Results: A total of 207 bifurcation lesions from 191 patients were analyzed, including 136 lesions treated with JWT and 71 lesions treated with JBT. The SB ostium area was significantly greater in the JBT group compared to the JWT group (0.41 ± 1.22 mm2 vs. -0.25 ± 1.40 mm2, p = 0.001). Following 1:1 PSM to adjust for 60 pairs, the difference between groups was not statistically significant (0.28 ± 1.06 mm2 vs. -0.02 ± 1.29 mm2, p = 0.165). Subgroup analysis revealed that A-JBT provided superior protection in both true (0.47 ± 1.22 mm2 vs. -0.10 ± 1.10 mm2, p = 0.011) and non-true bifurcation lesions (0.56 ± 1.43 mm2 vs. -0.38 ± 1.62 mm2, p = 0.030) over JWT, while C-JBT provided protection similar to JWT. A positive partial correlation was observed between the diameter of the jailed balloon and the increase in SB ostium area (r = 0.296, p = 0.013). Conclusions: Overall, A-JBT, but not C-JBT, provided better protection in bifurcation lesions compared to JWT. The larger diameter of the jailed balloon, rather than the application of higher pressure, enhanced the SB protection.

Macrophage WDFY3, a protector against autoimmunity.

Efficient efferocytosis is essential for maintaining homeostasis. Excessive apoptotic cell (AC) death and impaired macrophage efferocytosis lead to autoantigen release and autoantibody production, immune activation, and organ damage. It remains unclear whether these immunogenic autoantigens are the sole cause of increased autoimmunity or if efferocytosis of ACs directly influences macrophage function, impacting their ability to activate T cells and potentially amplifying autoimmune responses. Additionally, it has not been established if enhancing macrophage efferocytosis or modulating macrophage responses to AC engulfment can be protective in autoimmune-like disorders. Our previous work showed WDFY3 is crucial for efficient macrophage efferocytosis. This study reveals that myeloid knockout of Wdfy3 exacerbates autoimmunity in young mice with increased AC burden by systemic injections of ACs and in middle-aged mice developing spontaneous autoimmunity, whereas ectopic overexpression of WDFY3 suppresses autoimmunity in these models. Macrophages, as efferocytes, can activate T cells and the inflammasome upon engulfing ACs, which are suppressed by overexpressing WDFY3. This work uncovered the role of WDFY3 as a protector against autoimmunity by promoting macrophage efferocytosis thus limiting autoantigen production, as well as mitigating T cell activation and inflammasome activation.

Association between preoperative neutrophil-to-lymphocyte ratio and the survival outcomes of esophageal cancer patients underwent esophagectomy: a systematic review and meta-analysis.

Objectives: The purpose of this study was to assess the association between preoperative neutrophil-to-lymphocyte ratio (NLR) and the survival outcomes of esophageal cancer patients who underwent esophagectomy, the latest and comprehensive systematic review performed. Methods: Related literature retrieved from PubMed, Web of Science, Embase, and Cochrane before January 2024, according to the inclusion criteria. Outcomes measured were overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), and cancer-specific survival (CSS). Results: Eighteen studies with 6,119 esophageal cancer patients were retained for analysis. Meta-analysis demonstrated that OS (HR: 1.47; 95% CI: 1.29, 1.67; P < 0.00001), DFS (HR: 1.62; 95% CI: 1.29, 2.05; P < 0.0001), and CSS (HR: 1.62; 95% CI: 1.29, 2.05; P < 0.0001) were significantly shorter in the high NLR group compared with the low NLR group. In addition, meta-analysis revealed a similar RFS (HR: 1.47; 95% CI: 0.92, 2.35; P = 0.10) among the two groups. Subgroup analysis of OS and DFS based on mean/median age, NLR cutoff, and region found that all subgroups remained significant difference between two groups. Conclusion: Among esophageal cancer patients who underwent esophagectomy, preoperative NLR can be used as prognostic factor independently. High-preoperative NLR is associated with poor prognosis. More large-scale, multicenter prospective clinical studies are needed to further validate the relationship between preoperative NLR and prognosis of esophageal cancer.

SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.

Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.

Digital Surgical Guides in Mandibular Genioplasty: Evaluating Precision Against Conventional Techniques.

BACKGROUND: Mandibular genioplasty, a central procedure in oral and maxillofacial surgery, has traditionally relied on surgeon experience with potential limitations in precision. The advent of digital methods, particularly computer-aided design/computer-aided manufacturing (CAD/CAM), offers a promising alternative. This study aims to evaluate the efficacy of digital surgical guides in improving the precision of mandibular genioplasty. METHODS: A prospective analysis of 50 patients undergoing genioplasty was performed, 30 in the experimental group using digital surgical guides and 20 in the control group using traditional methods. Three-dimensional reconstructions were obtained using cone-beam computed tomography (CBCT) and digital scans. Osteotomy guides were 3D-printed based on group assignment. Postoperatively, accuracy was assessed by measuring distances between landmarks. RESULTS: The experimental group showed significantly reduced horizontal positioning errors in genioplasty advancement, with no significant differences in vertical errors. For genioplasty retraction, the experimental group showed fewer vertical positioning errors, while horizontal errors remained consistent. CONCLUSIONS: The use of digital surgical guides in mandibular genioplasty significantly improves surgical accuracy, resulting in improved outcomes and patient satisfaction. This study highlights the potential of digital methods in refining oral and maxillofacial surgical procedures. LEVEL OF EVIDENCE III: 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.

Efferocytosis assay to quantify the engulfment and acidification of apoptotic cells by macrophages using flow cytometry.

Efficient macrophage efferocytosis maintains homeostasis and resolves inflammation. Here, we provide a protocol to assess the engulfment and acidification of apoptotic cells (ACs) by macrophages. We describe steps for preparing bone marrow-derived macrophages (BMDMs) and peritoneal macrophages (PMs), fluorescent labeling of ACs using both a pH-sensitive dye, pHrodo-Red succinimidyl ester, and a pH-insensitive dye, Hoechst, and subsequent incubation with macrophages for efferocytosis. We then detail procedures for flow cytometry-based quantification of engulfment and acidification. For complete details on the use and execution of this protocol, please refer to Shi and Wu et al.1.

Validation of the Cut-Plane Method for Accurate Measurement of Side-Branch Ostium Area in Coronary Bifurcation Lesions: A 3D-OCT Analysis.

Objective: This study aimed to validate the effectiveness, accuracy, and feasibility of the cut-plane method for measuring the side branch (SB) ostium area in three-dimensional optical coherence tomography (3D-OCT) pullbacks performed in the main branch (MB). Methods: A total of 109 sets of OCT pullbacks from the MB and SB of coronary artery bifurcation lesions were analyzed using Vivolight OCT software. Measurements of the SB ostium area from the MB and SB pullbacks were analyzed. Measurements of the SB ostium area from the actual SB pullback were used as a reference. 3D cut-plane analysis was used to estimate the correlations and mean errors with the reference measurements. Results: Thirty-four sets of OCT images from the C7XR system and 75 sets from the CornarisTM system were analyzed using Vivolight software. There was a strong correlation between the reference measurements of the SB ostium area and the measurements obtained through 3D cut-plane analysis in the overall dataset (r = 0.925). This correlation was observed consistently with both the C7XR system (r = 0.955) and CornarisTM system (r = 0.900). Similar results were found in subset analyses of true and nontrue bifurcations (r = 0.936; r = 0.898, respectively) and in left main (LM) or non-LM bifurcation subsets (r = 0.932; r = 0.873, respectively). Conclusions: There were strong correlations between measurements of the SB ostium area by 3D-OCT and the reference measurements, and thus may be a reliable and accurate alternative to direct OCT pullback examinations of the SB.

Trends in injury-related mortality among residents of Jiangsu Province from 2012 to 2021: an age-period-cohort analysis.

Objective: We investigated the temporal trends and examined age-, period-, and cohort-specific effects of injury-related deaths among residents in Jiangsu to provide evidence for future injury prevention. Methods: This study included 406,936 injury deaths from the Jiangsu provincial population death registration system. The average annual percent change (AAPC) in age-standardized mortality rates (ASMRs) was analyzed using joinpoint regression. Age-period-cohort models were generated to explore the effects of age, period, and birth cohort effects on mortality risk. Results: ASMRs for all injuries (AAPC = -2.3%), road traffic accidents (AAPC = -5.3%), suicide (AAPC = -3.8%), and drowning (AAPC = -3.9%) showed a downward trend during 2012-2021(all p < 0.05), while unintentional falls showed an upward trend (AAPC = 5.1%, p < 0.05). From 2012 to 2021, the age-standardized mortality rates (ASMRs) for four primary types of injuries consistently exhibited higher among males compared to females, with rural regions displaying higher ASMRs than urban areas. Trends in ASMRs for road traffic accidents, drowning, and unintentional falls by sex and urban/rural areas were consistent with overall trends. Significant age, cohort, and period effects were identified in the trends of injury-related deaths for both sexes in Jiangsu. The age effect showed that the highest age effect for injury-related deaths was for the ages of 85 years and above, except for suicide, which was for the ages 80-84 years. Between 2012 and 2021, the period effect on road traffic accidents declined, while that on accidental falls increased. Initially, the period effect on suicide decreased but then rose, peaking in 2012 with a Relative Risk (RR) of 1.11 (95% CI: 1.04-1.19). Similarly, the period effect on drowning initially declined before rising, with the highest effect observed in 2013, at an RR of 1.12 (95% CI: 1.07-1.19). The highest cohort effects for road traffic accidents were observed in the 1957-1961 group, for accidental falls in the 1952-1956 group, and for both drowning and suicide in the 1927-1931 group. Conclusion: The mortality rate of unintentional falls has been increasing. Older adults are at high risk for the four leading injuries. The improvements in mortality rates can be attributed to advancements in education, urbanization, and the promulgation and implementation of laws and policies.

The m6A methyltransferase METTL3 drives neuroinflammation and neurotoxicity through stabilizing BATF mRNA in microglia.

Persistent neuroinflammation and progressive neuronal loss are defining features of acute brain injury including traumatic brain injury (TBI) and cerebral stroke. Microglia, the most abundant type of brain-resident immune cells, continuously surveil the environment and play a central role in shaping the inflammatory state of the central nervous system (CNS). In the study, we discovered that the protein expression of METTL3 (a m6A methyltransferase) was upregulated in inflammatory microglia independent of increased Mettl3 gene transcription following TBI in both human and mouse subjects. Subsequently, we identified TRIP12, a HECT-domain E3 ubiquitin ligase, as a negative regulator of METTL3 protein expression by facilitating METTL3 K48-linked polyubiquitination. Importantly, selective ablation of Mettl3 inhibited microglial pathogenic activities, diminished neutrophil infiltration, rescued neuronal loss and facilitated functional recovery post-TBI. Using MeRIP-seq and CUT&Tag sequencing, we identified that METTL3 promoted the expression of Basic Leucine Zipper Transcriptional Factor ATF-Like (BATF), which in turn directly bound to a cohort of characteristic inflammatory cytokines and chemokine genes. Enhanced activities of BATF in microglia elicited TNF-dependent neurotoxicity and can also promote neutrophil recruitment through releasing CXCL2. Pharmacological inhibition of METTL3 using a BBB-penetrating drug-loaded nano-system showed satisfactory therapeutic effects in both TBI and stroke mouse models. Collectively, our findings identified METTL3-m6A-BATF axis as a potential therapeutic target for terminating detrimental neuroinflammation and progressive neuronal loss following acute brain injury. METTL3 protein is significantly up-regulated in inflammatory microglia due to the decreased proteasomal degradation mediated by TRIP12 and ERK-USP5 pathways. METTL3 stabilized BATF mRNA stability and promoted BATF expression through the m6A-IGF2BP2-dependent mechanism. Elevated expression of BATF elicits a pro-inflammatory gene program in microglia, and aggravates neuroinflammatory response including local immune responses and peripheral immune cell infiltration. Genetic deletion or pharmaceutically targeting METTL3-BATF axis suppressed microglial pro-inflammatory activities and promoted neurological recovery following TBI and stroke.

FNDC5 prevents oxidative stress and neuronal apoptosis after traumatic brain injury through SIRT3-dependent regulation of mitochondrial quality control.

Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.

Assessing the Impact of Charged Particle Radiation Therapy for Head and Neck Adenoid Cystic Carcinoma: A Systematic Review and Meta-Analysis.

Purpose: Head and neck adenoid cystic carcinoma (HNACC) is a radioresistant tumor. Particle therapy, primarily proton beam therapy and carbon-ion radiation, is a potential radiotherapy treatment for radioresistant malignancies. This study aims to conduct a meta-analysis to evaluate the impact of charged particle radiation therapy on HNACC. Methods: A comprehensive search was conducted in Pubmed, Cochrane Library, Web of Science, Embase, and Medline until December 31, 2022. The primary endpoints were overall survival (OS), local control (LC), and progression-free survival (PFS), while secondary outcomes included treatment-related toxicity. Version 17.0 of STATA was used for all analyses. Results: A total of 14 studies, involving 1297 patients, were included in the analysis. The pooled 5-year OS and PFS rates for primary HNACC were 78% (95% confidence interval [CI] = 66-91%) and 62% (95% CI = 47-77%), respectively. For all patients included, the pooled 2-year and 5-year OS, LC, and PFS rates were as follows: 86.1% (95% CI = 95-100%) and 77% (95% CI = 73-82%), 92% (95% CI = 84-100%) and 73% (95% CI = 61-85%), and 76% (95% CI = 68-84%) and 55% (95% CI = 48-62%), respectively. The rates of grade 3 and above acute toxicity were 22% (95% CI = 13-32%), while late toxicity rates were 8% (95% CI = 3-13%). Conclusions: Particle therapy has the potential to improve treatment outcomes and raise the quality of life for HNACC patients. However, further research and optimization are needed due to the limited availability and cost considerations associated with this treatment modality.

Intelligent perceptual textiles based on ionic-conductive and strong silk fibers.

Endowing textiles with perceptual function, similar to human skin, is crucial for the development of next-generation smart wearables. To date, the creation of perceptual textiles capable of sensing potential dangers and accurately pinpointing finger touch remains elusive. In this study, we present the design and fabrication of intelligent perceptual textiles capable of electrically responding to external dangers and precisely detecting human touch, based on conductive silk fibroin-based ionic hydrogel (SIH) fibers. These fibers possess excellent fracture strength (55 MPa), extensibility (530%), stable and good conductivity (0.45 S·m-1) due to oriented structures and ionic incorporation. We fabricated SIH fiber-based protective textiles that can respond to fire, water, and sharp objects, protecting robots from potential injuries. Additionally, we designed perceptual textiles that can specifically pinpoint finger touch, serving as convenient human-machine interfaces. Our work sheds new light on the design of next-generation smart wearables and the reshaping of human-machine interfaces.

[Preliminarily study of arthrocentesis combined with liquid phase concentrated growth factor injection in the treatment of unilateral temporomandibular joint osteoarthritis].

OBJECTIVE: To observe the clinical effect of arthrocentesis combined with liquid phase concentrated growth factor (CGF) injection in the treatment of unilateral temporomandibular joint osteoarthritis (TMJOA), in order to provide a new treatment option for TMJOA patients. METHODS: In this non-randomized controlled study, patients diagnosed with unilateral TMJOA who visited the center for temporomandibular joint disorder and orofacial pain of Peking University School and Hospital of Stomatology from June 2021 to January 2023 were selected as research objects. The patients were divided into experimental group and control group, which were selected by patients themselves. The experimental group received arthrocentesis combined with liquid phase CGF injection and the control group received arthrocentesis combined with HA injection. Both groups were treated 3 times, once every two weeks. The clinical effect was evaluated by the maximum mouth opening, pain value and the degree of mandibular function limitation 6 months after treatment. The change of condylar bone was evaluated by cone beam CT (CBCT) image fusion technology before and after treatment. RESULTS: A total of 20 patients were included in the experimental group, including 3 males and 17 females, with an average age of (34.40±8.41) years. A total of 15 patients were included in the control group, including 1 male and 14 females, with an average age of (32.20±12.00) years. There was no statistical difference in general information between the two groups (P > 0.05). There were no statistical differences in the mouth opening, pain value and the degree of jaw function limitation between the two groups before treatment (P > 0.05), and all of them improved 6 months after treatment compared with before treatment (P < 0.05). However, the mouth opening of experimental group was significantly higher than that of control group 6 months after treatment (P < 0.05), and the degree of jaw function limitation was significantly lower than that of control group (P < 0.05). CBCT 2D images showed that the condylar bone of both groups was smoother after treatment than before treatment, and image fusion results showed that 10 patients (50.0%) in the experimental group and 5 patients (33.3%) in the control group had reparative remodeling area of condylar bone, and there was no statistical difference between them (P > 0.05). Except for one CGF patient, the other patients in both groups had some absorption areas of condylar bone. CONCLUSION: The arthrocentesis combined with liquid phase CGF injection can improve the clinical symptoms and signs of unilateral TMJOA patients in short term, and is better than HA in increasing mouth opening and improving jaw function. CBCT fusion images of both patient groups show some cases of condylar bone reparative remodeling and its relevance to treatment plans still requires further study.

The Association of Serum Complement C1q with Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Coronary artery disease (CAD) is one of the leading causes of death in middle-aged and elderly people, and its incidence has been increasing in recent years. An in-depth understanding of the pathogenesis of CAD is important to ensure the health of CAD patients. Objective: To analyze the association of serum complement C1q with CAD," you could say something like "The objective of this meta-analysis is to investigate the relationship between serum complement C1q levels and the presence of CAD, aiming to provide insights for clinical diagnosis and treatment. Methods: Relevant studies on C1q and CAD were searched in PubMed, Web of Science and other literature databases. Two research team members independently cross-screened the literature according to the inclusion-exclusion criteria and assessed the literature quality. RevMan5.3 software was used for statistical analysis. Results: Three references were finally included, all of which had a Newcastle-Ottawa Scale (NOS) score ≥6, indicating high quality. A total of 2065 subjects were studied, including 1249 in the experimental group (CAD patients) and 816 in the control group (healthy population). Through the meta-analysis, it was found that the experimental group (CAD patients) had higher serum C1q than the control group (healthy controls) (P < .05). According to subgroup analysis, age, sex, sample size, diabetes mellitus (with/without), and serum complement C1q detection methods were not factors affecting the heterogeneity of the literature, and more data are needed for verification. Validation analysis with the fixed-effect model also showed higher C1q expression in the experimental group (P < .05). The graph of the funnel plot was basically symmetrical, suggesting low publication bias. Conclusions: Serum complement C1q is elevated in CAD patients, but its mechanism of action may have a dual effect, but further research is needed to understand its precise role and clinical implications.

Joint-GWAS, Linkage Mapping, and Transcriptome Analysis to Reveal the Genetic Basis of Plant Architecture-Related Traits in Maize.

Plant architecture is one of the key factors affecting maize yield formation and can be divided into secondary traits, such as plant height (PH), ear height (EH), and leaf number (LN). It is a viable approach for exploiting genetic resources to improve plant density. In this study, one natural panel of 226 inbred lines and 150 family lines derived from the offspring of T32 crossed with Qi319 were genotyped by using the MaizeSNP50 chip and the genotyping by sequence (GBS) method and phenotyped under three different environments. Based on the results, a genome-wide association study (GWAS) and linkage mapping were analyzed by using the MLM and ICIM models, respectively. The results showed that 120 QTNs (quantitative trait nucleotides) and 32 QTL (quantitative trait loci) related to plant architecture were identified, including four QTL and 40 QTNs of PH, eight QTL and 41 QTNs of EH, and 20 QTL and 39 QTNs of LN. One dominant QTL, qLN7-2, was identified in the Zhangye environment. Six QTNs were commonly identified to be related to PH, EH, and LN in different environments. The candidate gene analysis revealed that Zm00001d021574 was involved in regulating plant architecture traits through the autophagy pathway, and Zm00001d044730 was predicted to interact with the male sterility-related gene ms26. These results provide abundant genetic resources for improving maize plant architecture traits by using approaches to biological breeding.

Exosomal circ_0000735 contributes to non-small lung cancer malignant progression.

Circular RNA is an important regulator for non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be significantly overexpressed in NSCLC tissues. Therefore, its role and mechanism in NSCLC progression need to be further explored. The expression levels of circ_0000735, miR-345-5p and A disintegrin and metalloprotease 19 (ADAM19) were determined using quantitative real-time PCR. EdU staining, wound healing and transwell assays were utilized to detect cell proliferation and metastasis. The protein levels of metastasis markers, exosome markers and ADAM19 were determined using western blot. Animal experiments were performed to confirm the role of circ_0000735 in NSCLC tumorigenesis. The exosomes from cells and serum were identified using transmission electron microscopy and nanoparticle tracking analysis. We found that circ_0000735 was upregulated in NSCLC, and its knockdown repressed NSCLC cell proliferation and metastasis. In terms of mechanism, circ_0000735 targeted miR-345-5p to regulate ADAM19. MiR-345-5p inhibitor reversed the suppressive effect of circ_0000735 knockdown on NSCLC progression, and ADAM19 overexpression abolished the inhibition effect of miR-345-5p on NSCLC progression. Also, animal experiments showed that silencing of circ_0000735 reduced NSCLC tumorigenesis. In addition, exosomes mediated the intercellular transmission of circ_0000735, and serum exosomal circ_0000735 might be an important indicator for the diagnosis of NSCLC. In conclusion, circ_0000735 facilitated NSCLC progression via miR-345-5p/ADAM19 pathway, and serum exosomal circ_0000735 might be a potential biomarker for NSCLC diagnosis.

UV-A radiation increases biomass yield by enhancing energy flow and carbon assimilation in the edible cyanobacterium Nostoc sphaeroides.

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.

Prioritized single vitrified blastocyst to be warmed between grades 3 or 4 blastocyst on day 5 transfer cycles.

PURPOSE: Selecting the optimal blastocyst to implant during cryopreservation and warming is critial for in vitro fertilization success. Therefore, the aim of this study was to explore which blastocyst should be prioritized to be thawed when facing a single vitrified blastocyst on day 5 transfer. METHODS: A retrospective study including 1,976 single vitrified-warmed blastocyst transfer cycles was conducted from January 2016 to December 2020. RESULTS: We found that grade 4 vitrified blastocyst had a higher clinical pregnancy (60.64% vs. 49.48%, P < 0.001) and live birth rates (50.12% vs 39.59%, P < 0.001) than the grade 3 vitrified blastocyst. However, no statistical difference was found between groups in miscarriage rate, birth weight, or gestational age. Besides, the grade 4 vitrified-thawed blastocyst had significant potential to develop into grade 6 blastocyst after further culturing for 16 h (73.68% vs. 48.60%, P < 0.001). The grade 6 transferred blastocyst was markedly higher in both clinical pregnancy rate (61.88% vs. 51.53%, P < 0.001) and live birth rate (50.91% vs. 40.46%, P < 0.001) compared to grade 5 transferred blastocyst. CONCLUSIONS: Grade 4 vitrified blastocyst is recommended when facing single vitrified blastocyst on day 5 transfer. More importantly, the "embryonic escape hypothesis" was firstly proposed to reveal the findings.

Omics Approaches Unveiling the Biology of Human Atherosclerotic Plaques.

Atherosclerosis is a chronic inflammatory disease of the arterial wall, characterized by the buildup of plaques with the accumulation and transformation of lipids, immune cells, vascular smooth muscle cells, and necrotic cell debris. Plaques with collagen-poor thin fibrous caps infiltrated by macrophages and lymphocytes are considered unstable because they are at the greatest risk of rupture and clinical events. However, the current histologic definition of plaque types may not fully capture the complex molecular nature of atherosclerotic plaque biology and the underlying mechanisms contributing to plaque progression, rupture, and erosion. The advances in omics technologies have changed the understanding of atherosclerosis plaque biology, offering new possibilities to improve risk prediction and discover novel therapeutic targets. Genomic studies have shed light on the genetic predisposition to atherosclerosis, and integrative genomic analyses expedite the translation of genomic discoveries. Transcriptomic, proteomic, metabolomic, and lipidomic studies have refined the understanding of the molecular signature of atherosclerotic plaques, aiding in data-driven hypothesis generation for mechanistic studies and offering new prospects for biomarker discovery. Furthermore, advancements in single-cell technologies and emerging spatial analysis techniques have unveiled the heterogeneity and plasticity of plaque cells. This review discusses key omics-based discoveries that have advanced the understanding of human atherosclerotic plaque biology, focusing on insights derived from omics profiling of human atherosclerotic vascular specimens.