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Abstract Background Radiographically, ground-glass nodules (GGN) and part-solid nodules (PSN) in lung adenocarcinoma (LUAD) have significant heterogeneity in their clinical manifestations, biological characteristics, and prognosis. This study aimed to explore the heterogeneity of LUAD in different radiological phenotypes and associated factors influencing tumor evolution. Methods We performed single-cell RNA sequencing (scRNA-seq) on tumor tissues from eight and seven cases of GGN– and PSN–LUAD, respectively, at different disease stages, including minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC), and metastatic lung cancer (MLC). Additionally, we analyzed adjacent normal tissues from four cases. Immunohistochemistry, multiplex immunofluorescence, and external scRNA-seq data were employed to confirm the expression of signature genes as well as the distribution patterns of CXCL9 + TAMs and TREM2 + TAMs. A LUAD mouse model was generated using gene editing, organoid culture, and orthotopic transplantation techniques, and comprehensive analyses such as histopathology, RNA sequencing, and Western blotting were performed to validate key pathways. Results Diverse cellular compositions were observed in the tumor microenvironment (TME) during GGN– and PSN–LUAD invasion and metastasis. Notably, CXCL9 + and TREM2 + tumor-associated macrophages (TAMs) exhibited the most significant enrichment changes. It was found that GGN–LUAD exhibited a stronger immune response than PSN–LUAD, with increased interaction between CXCL9 + TAMs and CD8 + tissue-resident memory T cells during invasion stage (MIA–IAC). Conversely, greater interactions between TREM2 + TAMs and tumor cells were observed in PSN–LUAD during the MLC stage. Additionally, TREM2 + TAMs were found to differentiate into TREM2 + /SPP1 + and TREM2 + /SPP1– TAMs at different stages, which promotes tumor progression. This study also emphasizes that during the transdifferentiation process of GGN– and PSN–LUAD, IFN-γ activates the STAT1 signaling pathway to regulate the activation of CXCL9 + TAMs, and further recruiting CD8 + Trm cells and activating T cells through MHC class I antigen presentation. The role of the IFN-γ/STAT1 pathway in the occurrence and development of LUAD was further validated by animal experiments. Conclusions Our findings offer a potential therapeutic strategy to maintain a dynamic balance within the TME and improve the immunotherapy efficacy by modulating the relative proportions and functional states of CXCL9 + TAMs and TREM2 + TAMs.

Abstract Background and introduction In comparison to other physical assessment methods, the inconsistency in respiratory evaluations continues to pose a major issue and challenge. Objectives This study aims to evaluate the difference in the identification ability of different breath sound. Methods/description In this prospective study, breath sounds from the Formosa Archive of Breath Sound were labeled by five physicians. Six artificial intelligence (AI) breath sound interpretation models were developed based on all labeled data and the labels from the five physicians, respectively. After labeling by AIs and physicians, labels with discrepancy were considered doubtful and relabeled by two additional physicians. The final labels were determined by a majority vote among the physicians. The capability of breath sound identification for humans and AI was evaluated using sensitivity, specificity and the area under the receiver-operating characteristic curve (AUROC). Results/outcome A total of 11,532 breath sound files were labeled, with 579 doubtful labels identified. After relabeling and exclusion, there were 305 labels with gold standard. For wheezing, both human physicians and the AI model demonstrated good sensitivities (89.5% vs. 86.0%) and good specificities (96.4% vs. 95.2%). For crackles, both human physicians and the AI model showed good sensitivities (93.9% vs. 80.3%) but poor specificities (56.6% vs. 65.9%). Lower AUROC values were noted in crackles identification for both physicians and the AI model compared to wheezing. Conclusion Even with the assistance of artificial intelligence tools, accurately identifying crackles compared to wheezing remains challenging. Consequently, crackles are unreliable for medical decision-making, and further examination is warranted.

Abstract Studies on the piezoelectric materials capable of efficiently outputting high electrostrains at low electric fields are driven by the demand for precise actuation in a wide range of applications. Large electrostrains of piezoceramics in operation require high driving fields, which limits their practical application due to undesirable nonlinearities and high energy consumption. Herein, a strategy is developed to enhance the electrostrains of piezoceramics while maintaining low hysteresis by incorporating lead magnesium niobate relaxors into lead zirconate titanium at the morphotropic phase boundary. An ultrahigh inverse piezoelectric coefficient $${d}_{33}^{*}$$ d 33 * of 1380 pm/V with a reduced hysteresis of 11.5% is achieved under a low electric field of 1 kV/mm, outperforming the major lead-based piezoelectric materials. In situ synchrotron X-ray diffraction and domain wall dynamics characterization with sub-microsecond temporal resolution reveal that the outstanding performances originate from facilitated domain wall movement, which in turn is due to reduced lattice distortion and miniaturized domain structures. These findings not only address the pending challenges of effective actuation under reduced driving conditions but also lay the foundation for a more systematic approach to exploring the origin of large electrostrains.

Abstract The relationship between exposure to ambient air pollutants and emergency attendance for upper gastrointestinal bleeding (UGIB) remains inconclusive. This study examines the association between short‐term exposure to various ambient pollutants and the risk of UGIB emergency attendance. Data on daily UGIB emergency attendance, ambient pollutants, and meteorological conditions in Hong Kong were collected from 2017 to 2022. A time‐series study using a distributed lag non‐linear model to analyze the data, considering lag days. Stratified analysis was performed based on sex, seasons, and the COVID‐19 pandemic period. The burden was quantified using attributable fraction (AF) and number (AN). The study included 31,577 UGIB emergency records. Exposure to high levels of PM2.5 significantly increased the risk of UGIB emergency attendance from lag day 3 (RR: 1.012) to day 6 (RR: 1.008). High NO2 exposure also posed a significant risk from lag day 0 (RR: 1.026) to day 2 (RR: 1.014), and from lag day 5 (RR: 1.013) to day 7 (RR: 1.024). However, there was no association between UGIB and high O3 levels. The attributable burden of high‐concentration NO2 exposure was higher compared to those of PM2.5. Males and elderly individuals (≥65 years) faced a higher risk of UGIB emergencies, particularly during cold seasons. Our study suggests that both PM2.5 and NO2 exposure are associated with an increased risk of emergency attendance for UGIB. Ambient pollutant exposure has a stronger effect on UGIB in males and the elderly, particularly during cold seasons.

Temperature measurement of devices in working state is of critical importance. In this work, GaN-based thermistors and a thermopile are monolithically integrated with a III-nitride blue light-emitting diode (LED) for the on-chip temperature measurement of the LED. The thermistor is based on the temperature-dependent resistance, and the stacked thermopile is based on the Seebeck effect. The measured results indicate that both thermistors and the thermopile can monitor the temperature of the LED sensitively. Due to the advantages of higher sensitivity and easier signal processing, the thermopile is more suitable for real-time monitoring.

Objective To understand the current status of occupational stress, occupational burn-out and sleep quality among ambulance drivers in Hengyang, China and to analyse the relationship between occupational stress, occupational burn-out and sleep quality of ambulance drivers.Design A cross-sectional study.Setting Prehospital emergency centre of third-class hospital in Hengyang, China.Participants From October 2023 to December 2023, a cross-sectional survey was conducted, with 213 ambulance drivers from Hengyang, China, selected as participants.Methods General demographic questionnaires, the Chinese Occupational Stress Inventory, the Maslach Burnout Inventory and the Pittsburgh Sleep Quality Index were used for data collection and analysis.Results Occupational stress among ambulance drivers was positively correlated with occupational burn-out and sleep quality (r=0.528, 0.447, both p

Recent discoveries in mRNA modification have highlighted N1-methyladenosine (m1A), but its role in preeclampsia (PE) pathogenesis remains unclear. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to identify m1A peaks and the expression profile of mRNA in the decidua of humans with early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP). We assessed the m1A modification patterns in preeclamptic decidua using 10 m1A modulators. Our bioinformatic analysis focused on differentially methylated mRNAs (DMGs) and differentially expressed mRNAs (DEGs) in pairwise comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE, as well as m1A-related DEGs. The comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE identified 3110, 2801, and 2818 DMGs, respectively. We discerned three different m1A modification patterns from this data. Further analysis revealed that key PE-related DMGs and m1A-related DEGs predominantly influence signaling pathways critical for decidualization, including cAMP, MAPK, PI3K-Akt, Notch, and TGF-β pathways. Additionally, these modifications impact pathways related to vascular smooth muscle contraction, estrogen signaling, and relaxin signaling, contributing to vascular dysfunction. Our findings demonstrate that preeclamptic decidua exhibits unique mRNA m1A modification patterns and gene expression profiles that significantly alter signaling pathways essential for both decidualization and vascular dysfunction. These differences in m1A modification patterns provide valuable insights into the molecular mechanisms influencing the decidualization process and vascular function in the pathogenesis of PE. These m1A modification regulators could potentially serve as potent biomarkers or therapeutic targets for PE, warranting further investigation.

Abstract Background This study assessed the impact of pressure-controlled ventilation (PCV) focusing on end-inspiratory flow rate on the incidence of postoperative pulmonary complications (PPCs) and inflammation levels in patients undergoing spinal surgery in the prone position. Methods A total of 187 patients who underwent posterior spinal surgery were enrolled and randomly divided into 3 groups: 61 in the volume-controlled ventilation (VCV) group (group V), 62 in the PCV-volume-guaranteed (VG) group (group P1), and 64 in the PCV-VG end-expiratory zero flow rate group (group P2). Indicators including tidal volume (VT), peak airway pressure (Ppeak), and dynamic lung compliance (Cdyn) were recorded. The Ppeak, Cdyn, PETCO2, and oxygenation index (PaO2/FiO2) after intubation (T0), after prone position (T1), 60 min after prone position (T2), and after supine position at the end of surgery (T3) of the three groups were collected. Results In the within-group comparison, compared with T0, Ppeak increased at T1 − 2 in groups V and P1 (P

Abstract Over the years, lead‐based piezoelectric ceramics found extensive use in vital fields such as sensors and actuators. Despite their exceptional electromechanical properties, lead‐containing materials pose severe environmental risks and foster a new era of lead‐free piezoelectric materials after decades of research. However, recent comparative assessments of potassium sodium niobate (KNN) versus lead zirconate titanate (PZT) piezoelectric materials proposed that the environmental damage already presented before use due to raw material extraction and processing, invoking concerns on the true greenness of the lead‐free alternatives. Nevertheless, many other factors deserve further consideration, for example, reference geometry and life cycle stage. Herein, the comprehensive life cycle assessment is undertaken on PZT and KNN‐based ceramics with a unit volume of 0.001 m3 from cradle to gate. Results show that PZT exhibits higher negative impacts than KNN‐based counterparts, attributed to lead extraction, processing, and associated environmental emissions. Across primary quantitative impact indicators from toxicity, environmental, and resource aspects, KNN‐based ceramics impose fewer risks on the environment and human health, with the overall impact being only 28% of PZT ceramics. Still, more efficient methods are required for KNN‐based ceramics to reduce the high energy consumption and emission during extraction and purification of raw material Nb2O5. This work not only offers critical insights for material development but also serves as a multifaceted reference for advanced fabrication technologies.

BackgroundThe rise in e-cigarette use among youth is a significant global public health issue. It is important to identify those at increased risk and implement effective strategies to reduce e-cigarette popularity among the youth.ObjectiveThis study aims to identify predictors of e-cigarette uptake in youths with no prior tobacco use, considering individual, familial and the broader societal environmental factors.MethodsFor this investigation, a group of 2,487 tobacco-free youths was selected from 15 high schools in Shenzhen, China. Susceptibility to e-cigarettes was determined by assessing the possibility of future use and the openness to trying e-cigarettes if presented by friends. Both chi-square tests and logistic regression were applied to identify factors linked to susceptibility to e-cigarette use.ResultsAmong the respondents, 5.5% (n = 136) were found to be susceptible to e-cigarette use. The analysis revealed factors tied to this risk: perceptions of e-cigarettes, the impact of vaping peers, paternal parenting styles, the extent of social support, exposure to messages both for and against e-cigarettes use, and secondhand smoke (SHS) exposure. Youths who downplayed the addictive nature of e-cigarettes (aOR = 2.01; 95% CI: 1.14–3.55; p = 0.016), those with friends who engaged in vaping (aOR = 3.43–7.64; 95%CI: 2.36–20.42; p

Abstract Background The purpose of this study was to explore the relationship between quantitative epicardial adipose tissue (EAT) based on coronary computed tomography angiography (CCTA) and coronary slow flow (CSF). Methods A total of 85 patients with 0.05). Multivariate logistic regression analysis showed that EAT volume was independently related to CSF [odds ratio (OR) = 4.82, 95% confidence interval (CI): 3.06–7.27, P

Abstract Background Studies on coronary slow flow are receiving increasing attention, but objective evaluations are still lacking. The purpose of this study was to visualize the current status and research hotspots of coronary slow flow through bibliometric analysis. Methods All relevant publications on coronary slow flow from 2003 to 2022 were extracted from the Web of Science Core Collection database and analyzed by VOSviewer and CiteSpace visualization software. Year of publication, journal, country/region, institution, and first author of each paper, as well as research hotspots were identified. Results A total of 913 publications were retrieved. The journal with the most publications was Coronary Artery Disease. The country/region with the most publications was Turkey, followed by China and the United States. The institution with the largest publication volume was Turkey Specialized Higher Education Research Hospital. The author with the largest publication volume was Chun-Yan Ma from China. Keyword analysis indicated that “treatment and prognosis”, “pathogenesis and risk factors” and “diagnosis” were the clustering centers of coronary slow flow, and the research hotspots gradually changed with time, from pathogenesis to treatment and prognosis. Conclusion Future research will focus on the search for effective and non-invasive detection indicators and treatments of coronary slow flow. Collaboration needs to be enhanced between different institutions or countries/regions, which would improve clinical outcomes for patients with coronary slow flow.

Background: This study explored neutralizing IgG antibody levels against COVID-19 decline over time post-vaccination. We conducted this prospective cohort study to investigate the function of gut microbiota in the host immune response following three doses of BNT162b2. Methods: Subjects who received three doses of BNT162b2 were recruited from three centers in Hong Kong. Blood samples were obtained before the first dose and at the one-year timepoint for IgG ELISA to determine the level of neutralizing antibody (NAb). The primary outcome was a high immune response (NAb > 600 AU/mL). We performed shotgun DNA metagenomic sequencing on baseline fecal samples to identify bacterial species and metabolic pathways associated with high immune response using linear discriminant analysis effect size analysis. Results: A total of 125 subjects were recruited (median age: 52 years [IQR: 46.2–59.0]; male: 43 [34.4%]), and 20 were regarded as low responders at the one-year timepoint. Streptococcus parasanguinis (log10LDA score = 2.38, p = 0.003; relative abundance of 2.97 × 10−5 vs. 0.03%, p = 0.001), Bacteroides stercoris (log10LDA score = 4.29, p = 0.024; relative abundance of 0.14% vs. 2.40%, p = 0.014) and Haemophilus parainfluenzae (log10LDA score = 2.15, p = 0.022; relative abundance of 0.01% vs. 0, p = 0.010) were enriched in low responders. Bifidobacterium pseudocatenulatum (log10LDA score = 2.99, p = 0.048; relative abundance of 0.09% vs. 0.36%, p = 0.049) and Clostridium leptum (log10LDA score = 2.38, p = 0.014; relative abundance of 1.2 × 10−5% vs. 0, p = 0.044) were enriched in high responders. S. parasanguinis was negatively correlated with the superpathway of pyrimidine ribonucleotides de novo biosynthesis (log10LDA score = 2.63), which contributes to inflammation and antibody production. H. parainfluenzae was positively correlated with pathways related to anti-inflammatory processes, including the superpathway of histidine, purine, and pyrimidine biosynthesis (log10LDA score = 2.14). Conclusion: Among three-dose BNT162b2 recipients, S. parasanguinis, B. stercoris and H. parainfluenzae were associated with poorer immunogenicity at one year, while B. pseudocatenulatum and C. leptum was associated with a better response.

Abstract Background Triple negative breast cancer (TNBC), the most aggressive subtype of breast cancer, is characterized by a high incidence of brain metastasis (BrM) and a poor prognosis. As the most lethal form of breast cancer, BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies. Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis (BCBrM), but the underlying mechanisms are far from being fully elucidated. Methods Through analysis of BCBrM transcriptome data from mice and patients, and immunohistochemical validation on patient tissues, we identified and verified the specific down-regulation of retinoic acid receptor responder 2 (RARRES2), a multifunctional adipokine and chemokine, in BrM of TNBC. We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies. Key signaling pathway components were evaluated using multi-omics approaches. Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2. Results We found that down-regulation of RARRES2 is specifically associated with BCBrM, and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming. Mechanistically, reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue (PTEN)-mammalian target of rapamycin (mTOR)-sterol regulatory element-binding protein 1 (SREBP1) signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment. Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM. RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

Abstract Background To investigate the impact of the coronavirus disease 2019 (COVID-19) outbreak on the prevalence of respiratory viruses among pediatric patients with acute respiratory infections in Xuzhou from 2015–2021. Methods Severe acute respiratory infection (SARI) cases in hospitalized children were collected from 2015–2021 in Xuzhou, China. Influenza virus(IFV), respiratory syncytial virus (RSV), human parainfluenza virus type 3(hPIV-3), human rhinovirus (hRV), human adenovirus(hAdV), human coronavirus(hCoV) were detected by real-time fluorescence polymerase chain reaction(RT-qPCR), and the results were statistically analyzed by SPSS 23.0 software. Results A total of 1663 samples with SARI were collected from 2015–2021, with a male-to-female ratio of 1.67:1 and a total virus detection rate of 38.5% (641/1663). The total detection rate of respiratory viruses decreased from 46.2% (2015–2019) to 36% (2020–2021) under the control measures for COVID-19 (P 0.05). After the control measures, the detection rate of hPIV-3 decreased in all age groups, and the detection rate of hCoV increased in all except the 1 ~ 3 years old group. Conclusions Implementing control measures for COVID-19 outbreak curbed the spread of respiratory viruses among children as a whole. However, the epidemic of RV and RSV was not affected by the COVID-19 control policy.

Ascorbic acid (AsA) is an essential nutritional component and powerful antioxidant in vegetables, and in plants, AsA levels are regulated by light. AsA levels in the leaves of Chinese chive (Allium tuberosum Rottler ex Spr), a popular vegetable, are poorly understood. Thus, this study was performed to assess the influence of light on AsA biosynthesis in chive and select related genes (AtuGGP1 and AtuGME1); in addition, bioinformatic analyses and gene expression level assays were performed. The biological information obtained for AtuGGP1 and AtuGME1 was analysed with several tools, including NCBI, DNAMAN, and MEGA11. After different light treatments were performed, the Chive AsA content and AtuGGP1 and AtuGME1 expression levels were determined. These results suggest that 1) compared with natural light, continuous darkness inhibited AsA synthesis in chives. 2) The amino acid sequences of AtuGGP1 and AtuGME1 are very similar to those of other plants. 3) The trends observed for the expression levels of AtuGGP1 and AtuGME1 were consistent with the AsA content observed in chives. Hence, we speculated that light controls AsA biosynthesis in chives by regulating AtuGGP1 and AtuGME1 expression. This study provided impactful and informative evidence regarding the functions of GGP and GME in chives.

Hazardous impacts caused by harmful algal blooms (HABs) have facilitated the development of novel effective approaches for controlling the frequent HABs. Recently, bacteria with algicidal effects, as a promising alternative tool for eliminating the HABs-forming species have received wide concerns. In the present study, a marine bacterial strain 6A1 with potent algicidal activity was successfully isolated from a bloom of Akashiwo sanguinea, and the characteristics related to its algicidal action were systematically investigated. Sequencing results of 16S rDNA suggested that this bacterium belongs to the genus Arenibacter in the family Flavobacteriaceae, while the phylogenetic analysis revealed that Arenibacter sp. strain 6A1 was the only algicidal bacterium in Arenibacter to date, according to the best of our knowledge. Arenibacter sp. strain 6A1 had an extraordinarily high algicidal performance when it was added to A. sanguinea culture with a volume fraction of 1.5% for 2 h. The algicidal performance of strain 6A1 was concentration-dependent and time-dependent. The best algicidal efficacy of strain 6A1 was seen during the stationary phase, while the resistance of A. sanguinea to strain 6A1 declined as the growth cycle progressed. Subsequently, the indirect algicidal mode of Arenibacter sp. strain 6A1 was verified and the algicidal compounds produced by strain 6A1 were proved to be heat-resistant. Further research showed that strain 6A1 caused a severe damage in photosynthesis, oxidative stress, and also damage in three HABs-forming algae to varying degrees. The greatest algicidal performance was found on unarmored dinoflagellate A. sanguinea, followed by raphidophyte Chattonella antiqua and armored dinoflagellate Alexandrium tamarense. The Arenibacter sp. strain 6A1 exhibited selective algicidal activity on a wide range of algal species, primarily targeting Pyrrophyta and Ochrophyta. The proposed bacteria (strain 6A1) can be a powerful and eco-friendly tool for emergency treatment of HABs caused by certain algal species in coastal water bodies.

PurposeThe purpose of this study was to explore the relationship between education level and health behavior including sleep, work activity, exercise activity, and sedentary behavior among emerging adults.MethodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2007 and 2018. The study sample included 4,484 emerging adults aged 18–25 years and the weighted participants were 30,057,813. Weighted multivariable regression analysis was performed to investigate the association between education level and the aforementioned health behavior, adjusting for age, gender, race/ethnicity, marital status, poverty-income ratio, BMI, smoking, and alcohol drinking status.ResultsThis study revealed that higher education level was associated with shorter sleep duration [Fully adjusted model, β (95% CI): −0.588 (−0.929, −0.246), p < 0.001]. Additionally, those with higher education levels were more likely to allocate time in sedentary behavior [β (95% CI): 90.162 (41.087, 139.238), p < 0.001]. Moreover, higher education level was related to less work activity [β (95% CI): −806.991 (−1,500.280, −113.703), p = 0.023] and more exercise activity time [β (95% CI): 118.196 (−21.992, 258.385), p = 0.097]. Subgroup analysis further verified this trend and detected that males with higher education level tended to participate in less work activity [β (95% CI): −1,139.972 (−2,136.707, −143.237), p = 0.026] while females with higher education level tended to engage in more exercise activity [Fully adjusted model, β (95% CI): 141.709 (45.468, 237.950), p = 0.004].ConclusionThis study highlighted the importance of education level as a significant factor in promoting healthy behavior among emerging adults. The findings underscored the need for the Ministry of Education to prioritize educating this demographic about the significance of maintaining adequate sleep patterns and reducing sedentary habits. Encouraging them to allocate more time for work and physical activities can significantly contribute to their overall wellbeing and success, ultimately fostering a healthier next generation.

Ovarian cancer is one of the most common malignant tumours affecting the female reproductive organs. CD147 (BSG) and CD98hc (SLC3A2) are oncogenes that form the CD98hc-CD147 complex, which regulates the proliferation, metastasis, metabolism, and cell cycle of cancer cells. The roles of the CD98hc-CD147 complex in ovarian cancer remain unclear. We analysed the expression and prognostic value of CD147 and CD98hc in ovarian cancer using the TCGA and ICGC databases. The effect of CD147 and CD98hc on the tumour immune response was analysed using the TIMER database. CD98hc was more highly expressed in normal tissues than primary tumour tissues, while CD147 was more highly expressed in primary tumour tissues than normal tissues. CD98hc expression was significantly associated with neutrophil and dendritic cell levels. CD147 and CD98hc were correlated with DNA repair, the cell cycle, and DNA replication. The CD98hc-CD147 complex could serve as a target for ovarian cancer treatment.

Keloid is a pathological scar that is higher than the skin surface following skin damage. Its lesion range often extends beyond the original damage boundary and does not naturally subside over time. Its pathogenesis is very complex, currently the main causes include fibroblast excessive proliferation, collagen and extracellular matrix (Extracellular matrix, ECM) excessive deposition, excessive angiogenesis, and so on. The traditional treatment method primarily involves surgical intervention, but it is associated with a high recurrence rate post-surgery. Consequently, many treatment methods are derived according to the different clinical characteristics of keloid. This paper will review the therapeutic progress in recent years from surgical treatment, physiotherapy, drug therapy, and biological therapy, with the goal of offering valuable insights for the clinical treatment of keloids.

The relationship between cardiac and renal function is complicated. The impact of percutaneous coronary intervention (PCI) on renal function in patients with coronary artery disease is still unclear. The current study sought to assess renal function change, including the time course of renal function, after elective PCI in patients with improved renal function and to identify renal function predictors of major adverse cardiovascular events. We examined data from 1572 CHD patients who had coronary angiography (CAG) or PCI in this retrospective cohort study. Patients receiving elective PCI (n=1240) and CAG (n=332) between January 2013 and December 2018 were included. Pre-PCI and procedural variables associated with post-PCI eGFR, change in renal function after post-PCI follow-up, and post-PCI eGFR association with major adverse cardiovascular events were investigated. Following the procedure, 88.7 percent of PCI group patients had unchanged or improved renal function. The treatment of PCI was found to independently correlate with IRF following coronary angiography in an analysis of patients undergoing PCI [OR 4.561 (95% CI:2 .556-8.139); p

Three metal complexes [Cu(HL)Cl](C2H5OH)2] (complex 1), [Ni4L2(CH3COO)4(C2H5OH)4] (complex 2) and [CoHL2] (complex 3) based on 2,3-dihydroxybenzaldehyde-2-(2-aminophenyl)benzimidazole Schiff base (H2L) were synthesized by solvothermal reaction. The three complexes were characterized by FT-IR spectrometer, elemental analysis, thermogravimetric analysis, and X-ray single-crystal diffraction. X-ray single-crystal diffraction analysis confirmed that complex 1 belongs to monoclinic crystal system with P21/c space group, and complex 3 crystallizes in trigonal crystal system with R-3 space group. However, complex 2 crystallized in triclinic crystal system with P-1 space group and exhibits centrosymmetric tetranuclear crystallographic structure. Besides, MTT assay was studied antitumor activities against different tumor cells. The results show that the three complexes all have fine anticancer activities. Among them, complex 2 has significantly better anticancer properties against CNE-2Z cells than that of cisplatin. Finally, apoptosis and cell migration were studied to prove that complex 2 could inhibit tumor cells from proliferating in the manner of apoptosis and migration.

The pre-and postsynaptic communication is critical for faithful synaptic transmission and induction of synaptic plasticity. Here, the authors found that CaMKII functions at GABAergic neurons to recruit GABAARs by triggering anterograde signals.

Abstract Background Hematogenous disseminated tuberculosis predisposes to concurrent tuberculous meningitis (TBM), the most devastating and disabling form of tuberculosis. However, children often have atypical clinical symptoms, difficulty in specimen collection, low specimen content, and an increasing incidence of drug-resistant tuberculosis. Thus, the accurate diagnosis and timely treatment of childhood tuberculosis face monumental challenges. Case presentation The 14-year-old female presented to the hospital with intermittent fever, headache, and blurred vision. Her cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis, an elevated protein level, and a decreased chloride level. And her CSF tested positive for TB-RNA. Xpert MTB/RIF detected Mycobacterium tuberculosis in her CSF, but the rifampin resistance test was unknown. Subsequently, her CSF culture was positive for Mycobacterium tuberculosis. The drug sensitivity test (DST) revealed resistance to isoniazid, rifampin, and fluoroquinolones. A computed tomography (CT) of the chest showed diffuse miliary nodules in both lungs. Intracranial enhanced magnetic resonance imaging (MRI) showed “multiple intensified images of the brain parenchyma, cisterns, and part of the meninges.” The final diagnosis is miliary pulmonary tuberculosis and pre-extensive drug-resistant TBM. After 19 months of an oral, individualized antituberculosis treatment, she recovered with no significant neurological sequelae. Conclusion For patients with miliary pulmonary tuberculosis, especially children, even if there are no typical clinical symptoms, it is necessary to know whether there is TBM and other conditions. Always look for the relevant aetiological basis to clarify whether it is drug-resistant tuberculosis. Only a rapid and accurate diagnosis and timely and effective treatment can improve the prognosis and reduce mortality and disability rates.

With the capability of interconversion between electrical and mechanical energy, piezoelectric materials have been revolutionized by the implementation of perovskite-piezoelectric-ceramic-based studies over 70 years. In particular, the market of piezoelectric ceramics has been dominated by lead zirconate titanate for decades. Nowadays, the research on piezoelectric ceramics is largely driven by cutting-edge technological demand as well as the consideration of a sustainable society. Hence, environmental-friendly lead-free piezoelectric materials have emerged to replace lead-based Pb(Zr,Ti)O3 (PZT) compositions. Owing to the inherent high mechanical quality factor (Qm) and low energy loss, (Li,Na)NbO3 (LNN) materials have recently drawn increasing attention and brought advantages to high-power piezoelectric applications. Although the crystallographic structures of LNN materials were intensively investigated for decades, the technical strategies for electrical performance are still limited. As a result, the property enhancement appears to have approached a plateau. This review traces the progress in the development of LNN materials, starting from the polymorphism in terms of the crystal structures, phase transitions, and local structural distortions. Then, the key milestone works on the functional tunability of LNN are reviewed with emphasis on involved engineering approaches. The exceptional performance at a large vibration velocity makes LNN ceramics promising for high-power applications, such as ultrasonic welding (UW) and ultrasonic osteotomes (UOs). The remaining challenges and some strategic insights for synergistically engineering the functional performance of LNN piezoceramics are also suggested.

Abstract Background Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been found to have a great potential for soft tissue repair due to various biological functions, including pro-angiogenesis and low immunogenicity. However, the low yield and heterogeneity of MSC-EVs limited their clinical transformation. This study was designed to develop a novel adipose-derived stem cell engineered nanovesicles (ADSC-NVs) with high production and explore its pro-angiogenetic effect and application in adipose tissue regeneration. Methods Adipose-derived stem cell-derived extracellular vesicles (ADSC-EVs) were isolated from an EVs-free culture medium for human ADSCs (hADSCs). ADSC-NVs were prepared by sequentially extruding ADSCs followed by iodixanol density gradient ultracentrifugation and were compared with ADSC-EVs in morphology, size distribution, protein contents and yield. The pro-angiogenetic effect of ADSC-NVs in different doses (0, 5, 20 and 80 μg/mL) in vitro was determined using transwell assay, tube formation assay, western blot and qRT-PCR. In vivo, BALB/c nude mice were administered injection of a mixture of fat granules and different dose of ADSC-NVs and grafts were harvested at 12 weeks post-transplantation for further analysis. By analyzing the weight and volume of grafts and histological evaluation, we investigated the effect of ADSC-NVs in vessel formation and adipose tissue regeneration. Results Our results showed yield of purified ADSC-NVs was approximately 20 times more than that of ADSC-EVs secreted by the same number of ADSCs. In vitro, both ADSC-NVs and ADSC-EVs exhibited a dose-dependent pro-angiogenetic effect, despite their distinct miRNA profiles. These effects of ADSC-NVs may be mediated by enriched miR-21-5p via PTEN inhibition and PI3K/p-Akt signaling activation. Furthermore, after a mixed injection of ADSC-NVs, vessel formation and adipose regeneration were observed in vivo in fat implants. Conclusions Our study developed a potent alternative of ADSC-EVs. ADSC-NVs have a high pro-angiogenesis potential and can be used as cell-free therapeutic biomaterials in soft tissue regeneration.

Catalase (CAT) is an important antioxidant enzyme that breaks down H2O2 into water and oxygen. Inhibitor-modulating CAT activity in cancer cells is emerging as a potential anticancer strategy. However, the discovery of CAT inhibitors towards the heme active center located at the bottom of long and narrow channel has made little progress. Therefore, targeting new binding site is of great importance for the development of efficient CAT inhibitors. Here, the first NADPH-binding site inhibitor of CAT, BT-Br, was designed and synthesized successfully. The cocrystal structure of BT-Br-bound CAT complex was determined with a resolution of 2.2 Å (PDB ID:8HID), which showed clearly that BT-Br bound at the NADPH-binding site. Furthermore, BT-Br was demonstrated to induce ferroptosis in castration-resistant prostate cancer (CRPC) DU145 cells and eventually reduce CRPC tumors in vivo effectively. The work indicates that CAT has potential as a novel target for CRPC therapy based on ferroptosis inducing.

Background: Neutralizing antibody level wanes with time after COVID-19 vaccination. We aimed to study the relationship between baseline gut microbiota and immunogenicity after three doses of CoronaVac. Methods: This was a prospective cohort study recruiting three-dose CoronaVac recipients from two centers in Hong Kong. Blood samples were collected at baseline and one year post-first dose for virus microneutralization (vMN) assays to determine neutralization titers. The primary outcome was high immune response (defined as with vMN titer ≥ 40). Shotgun DNA metagenomic sequencing of baseline fecal samples identified potential bacterial species and metabolic pathways using Linear Discriminant Analysis Effect Size (LEfSe) analysis. Univariate and multivariable logistic regression models were used to identify high response predictors. Results: In total, 36 subjects were recruited (median age: 52.7 years [IQR: 47.9–56.4]; male: 14 [38.9%]), and 18 had low immune response at one year post-first dose vaccination. Eubacterium rectale (log10LDA score = 4.15, p = 0.001; relative abundance of 1.4% vs. 0, p = 0.002), Collinsella aerofaciens (log10LDA score = 3.31, p = 0.037; 0.39% vs. 0.18%, p = 0.038), and Streptococcus salivarius (log10LDA score = 2.79, p = 0.021; 0.05% vs. 0.02%, p = 0.022) were enriched in low responders. The aOR of high immune response with E. rectale, C. aerofaciens, and S. salivarius was 0.03 (95% CI: 9.56 × 10−4–0.32), 0.03 (95% CI: 4.47 × 10−4–0.59), and 10.19 (95% CI: 0.81–323.88), respectively. S. salivarius had a positive correlation with pathways enriched in high responders like incomplete reductive TCA cycle (log10LDA score = 2.23). C. aerofaciens similarly correlated with amino acid biosynthesis-related pathways. These pathways all showed anti-inflammation functions. Conclusion: E. rectale,C. aerofaciens, and S. salivarius correlated with poorer long-term immunogenicity following three doses of CoronaVac.

Due to the influence of the Asian southwest monsoon, seasonal drought is serious and water resources are scarce in the Yunnan province of Southwest China. More effective water-saving irrigation methods should be developed to solve the problem of water scarcity in the dry season. In this study, a subsurface drip irrigation method was used to improve the water productivity of tomato cultivation. Deficit irrigation was conducted. We controlled the lower limit of soil moisture at three different levels (55~65%, 65~75%, and 75~85% of the field capacity). The results indicated that the subsurface drip irrigation treatment significantly increased tomato height in the later stage of tomato growth. Due to the buried pipes, the root/shoot ratio was 8~18% higher for subsurface drip irrigation than for surface drip irrigation methods. Though the yields using subsurface drip irrigation methods were slightly lower than those obtained using surface drip irrigation methods, the tomato quality and water productivity improved significantly. The subsurface drip irrigation methods improved the water productivity by 8.5~21.8% at different soil moisture levels and improved the chlorophyll content by 9.1~17.3%. The VC, soluble sugar, soluble solids, and the ratio of sugar to acid increased by 6.5~15.2%, 7.3~21.6%, 4.1~6.6%, and 3.2~20.8%. This study also indicated that by optimizing the irrigation methods and patterns, water productivity and fruit quality could be improved by more than 50%. This research will be helpful for guiding irrigation during the drought season in the southwest monsoon area in Asia.