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π-Extended pyrene compounds possess remarkable luminescent and semiconducting properties and are being intensively investigated as electroluminescent materials for potential uses in organic light-emitting diodes, transistors, and solar cells. Here, the synthesis of two sets of pyrene-containing π-conjugated polyaromatic regioisomers, namely 2,3,10,11,14,15,20,21-octaalkyloxypentabenzo[a,c,m,o,rst]pentaphene (BBPn) and 2,3,6,7,13,14,17,18-octaalkyloxydibenzo[j,tuv]phenanthro [9,10-b]picene (DBPn), is reported. They were obtained using the Suzuki–Miyaura cross-coupling in tandem with Scholl oxidative cyclodehydrogenation reactions from the easily accessible precursors 1,8- and 1,6-dibromopyrene, respectively. Both sets of compounds, equipped with eight peripheral aliphatic chains, self-assemble into a single hexagonal columnar mesophase, with one short-chain BBPn homolog also exhibiting another columnar mesophase at a lower temperature, with a rectangular symmetry; BBPn isomers also possess wider mesophase ranges and higher mesophases’ stability than their DBPn homologs. These polycyclic aromatic hydrocarbons all show a strong tendency of face-on orientation on the substrate and could be controlled to edge-on alignment through mechanical shearing of interest for their implementation in photoelectronic devices. In addition, both series BBPn and DBPn display green-yellow luminescence, with high fluorescence quantum yields, around 30%. In particular, BBPn exhibit a blue shift phenomenon in both absorption and emission with respect to their DBPn isomers. DFT results were in good agreement with the optical properties and with the stability ranges of the mesophases by confirming the higher divergence from the flatness of DBPn compared with BBPn. Based on these interesting properties, these isomers could be potentially applied not only in the field of fluorescent dyes but also in the field of organic photoelectric semiconductor materials as electron transport materials.

Previous studies reported microplastics (MPs), antibiotics, and antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs). There is still a lack of research progress on the origin, fate, impact and hazards of MPs and ARGs in WWTPs. This paper fills a gap in this regard. In our search, we used “microplastics”, “antibiotic resistance genes”, and “wastewater treatment plant” as topic terms in Web of Science, checking the returned results for relevance by examining paper titles and abstracts. This study mainly explores the following points: (1) the origins and fate of MPs, antibiotics and ARGs in WWTPs; (2) the mechanisms of action of MPs, antibiotics and ARGs in sludge biochemical pools; (3) the impacts of MPs in WWTPs and the spread of ARGs; (4) and the harm inflicted by MPs and ARGs on the environment and human body. Contaminants in sewage sludge such as MPs, ARGs, and antibiotic-resistant bacteria enter the soil and water. Contaminants can travel through the food chain and thus reach humans, leading to increased illness, hospitalization, and even mortality. This study will enhance our understanding of the mechanisms of action among MPs, antibiotics, ARGs, and the harm they inflict on the human body.

Background The third-line treatment options recommended by guidelines for metastatic colorectal cancer (mCRC) are limited with unsatisfactory efficacy. Immune checkpoint inhibitor (ICI)-based strategies have been extensively explored for microsatellite stable (MSS) mCRC at third-line and above settings. This study aimed to evaluate the efficacy and safety of ICI versus non-ICI-based treatments for MSS mCRC patients in third-line setting. Methods Electronic medical records of MSS mCRC patients who received at least third-line therapies at Renmin Hospital of Wuhan University between September 2019 and April 2024 were reviewed retrospectively. Propensity score matching (PSM) was used to balance potential confounding factors. The primary outcomes of interest were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and adverse events (TRAEs). Results Of 243 eligible patients, 93 received third-line ICI therapy and 150 treated with non-ICI therapy. The ORR were 12.9% vs 9.3% and DCR were 80.6% vs 72.0%, respectively. After PSM, an improved median PFS was exhibited in the ICI cohort (5.0 vs 3.6 months; HR = 0.55; 95% CI, 0.39–0.78; P  < 0.001), with a directional improvement of OS (13.8 vs 12.4 months; HR = 0.70; 95% CI, 0.47–1.05; P  = 0.086). In addition, a more significant survival benefit was found in the triplet regimen of ICI, chemotherapy and target therapy, with a median PFS of 8.2 months and OS of 20.2 months. Patients > 60 years of age, male, with liver metastasis, prior anti-VEGF(R) therapy, and wild-type RAS/BRAF could obtain PFS benefit from third-line ICI over non-ICI treatment. Thirty-six (38.7%) patients developed at least once cross-line immunotherapy in ICI cohort, resulting a directional OS improvement. Grade ≥ 3 AEs occurred in 39.8% and 43.3% of patients in each cohort. Immune-related AEs (irAEs) was 38.7%, and grade ≥ 3 irAEs was 14.0% in ICI cohort. Conclusion ICI is a beneficial addition to third-line treatment for some MSS mCRC patients, providing improved survival benefit and controllable safety.

Due to rapid socioeconomic development, antibiotic pollution and heavy metal pollution are receiving increasing amounts of attention. Both antibiotics and heavy metals in the environment are persistent and toxic, and the interactions between the pollutants create potential long-term hazards for the ecological environment and human health as mixed pollutants. In this study, the surface water of the Yitong River in Changchun was used as the research object, and the hazards associated with antibiotics and heavy metals in the surface water were assessed by analyzing the spatial and temporal distribution characteristics of antibiotics and heavy metals and by using ecological risk assessment and human health risk assessment models. The results showed that ofloxacin (OFL) and norfloxacin (NOR) varied seasonally according to the seasonal climate, with total concentrations ranging from 17.65 to 902.47 ng/L and ND to 260.49 ng/L for OFL and NOR, respectively, and from 8.30 to 120.40 μg/L, 1.52 to 113.41 μg/L and 0.03 to 0.04 μg/L for copper (Cu), zinc (Zn) and cadmium (Cd), respectively. In terms of spatial distribution, the concentration of antibiotics in the urban sections, which had intensive human activities, was higher than that in the suburban sections, while the concentration of heavy metals in the suburban sections, which had intensive agricultural operations, was greater than that in the urban section. Ecological risk evaluation showed that NOR and OFL were present in the water bodies at a high-risk level, Cd was at a low pollution level, and the heavy metal Cd was the primary pollutant associated with health risks toward for adults and children, and it was mainly at a medium risk level. Additionally, both antibiotics and heavy metals posed higher health risks for children than for adults.

The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, we identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, and find focal amplifications in the GCA cohort are associated with the chromothripsis process and may be induced by accumulated DNA damage due to local dietary habits. We observe diverse correlations between the presence of oncogene focal amplifications and prognosis, where ERBB2 focal amplifications positively correlate with prognosis and EGFR focal amplifications negatively correlate with prognosis. Large-scale ERBB2 immunohistochemistry results from 1668 GCA patients show survival probability of ERBB2 positive patients is lower than that of ERBB2 negative patients when their surviving time is under 2 years, however, the tendency is opposite when their surviving time is longer than 2 years. Our observations indicate that the ERBB2 focal amplifications may represent a good prognostic marker in GCA patients. The role of focal amplifications and extrachromosomal DNA (ecDNA) is unknown in gastric cardia adenocarcinoma (GCA). Here, the authors identify frequent focal amplifications and ecDNAs in Chinese GCA patient samples, as well as the potential associations of these alterations with prognosis and dietary habits.

Increased oxidative stress, which can lead to the retinal pigment epithelium (RPE) cell death by inducing ATP depletion and DNA repair, is believed to be a prominent pathology in age-related macular degeneration (AMD). In the present study, we showed that and 0.1 mM nicotinamide adenine dinucleotide (NAD + ) administration significantly blocked RPE cell death induced by 300 μM H 2 O 2 . Further investigation showed that H 2 O 2 resulted in increased intracellular ROS level, activation of PARP-1 and subsequently necrotic death of RPE cells. Exogenous NAD + administration significantly decreased intracellular and intranuclear ROS levels in H 2 O 2 -treated RPE cells. In addition, NAD + administration to H 2 O 2 -treated RPE cells inhibited the activation of PARP-1 and protected the RPE cells against necrotic death. Moreover, exogenous NAD + administration up-regulated autophagy in the H 2 O 2 -treated RPE cells. Inhibition of autophagy by LY294002 blocked the decrease of intracellular and intranuclear ROS level. Besides, inhibition of autophagy by LY294002 abolished the protection of exogenous NAD + against H 2 O 2 -induced cell necrotic death. Taken together, our findings indicate that that exogenous NAD + administration suppresses H 2 O 2 -induced oxidative stress and protects RPE cells against PARP-1 mediated necrotic death through the up-regulation of autophagy. The results suggest that exogenous NAD + administration might be potential value for the treatment of AMD.

Melatonin can increase plant resistance to stress, and exogenous melatonin has been reported to promote stress resistance in plants. In this study, a melatonin biosynthesis-related SlCOMT1 gene was cloned from tomato (Solanum lycopersicum Mill. cv. Ailsa Craig), which is highly expressed in fruits compared with other organs. The protein was found to locate in the cytoplasm. Melatonin content in SlCOMT1 overexpression transgenic tomato plants was significantly higher than that in wild-type plants. Under 800 mM NaCl stress, the transcript level of SlCOMT1 in tomato leaf was positively related to the melatonin contents. Furthermore, compared with that in wild-type plants, levels of superoxide and hydrogen peroxide were lower while the content of proline was higher in SlCOMT1 transgenic tomatoes. Therefore, SlCOMT1 was closely associated with melatonin biosynthesis confers the significant salt tolerance, providing a clue to cope with the growing global problem of salination in agricultural production.

Orchids are among the most endangered in the plant kingdom. Lack of endosperm in their seeds renders orchids to depend on nutrients provided by orchid mycorrhizal fungi (OMF) for seed germination and seedling formation in the wild. OMF that parasitize in germination seeds is an essential element for orchid seedling formation, which can also help orchid reintroduction. Considering the limitations of the previous orchid reintroduction technology based on seed germination-promoting OMF (sgOMF) sourced from orchid roots, an innovative approach is proposed here in which orchid seeds are directly co-sown with sgOMF carrying ecological specificity from protocorms/seedlings. Based on this principle, an integrative and practical procedure concerning related ecological factors is further raised for re-constructing long-term and self-sustained orchid populations. We believe that this new approach will benefit the reintroduction of endangered orchids in nature.

Mesenchymal stromal cells (MSCs) are multipotent stem cells well known for repairing tissue, supporting hematopoiesis, and modulating immune and inflammation response. These outstanding properties make MSCs as an attractive candidate for cellular therapy in immune-based disorders, especially hematopoietic stem cell transplantation (HSCT). In this review, we outline the progress of MSCs in preventing and treating engraftment failure (EF), graft-versus-host disease (GVHD) following HSCT and critically discuss unsolved issues in clinical applications.

The deficiency of clinically specific biomarkers has made it difficult to achieve an accurate diagnosis of temporomandibular joint osteoarthritis (TMJ-OA) and the insufficient comprehension of the pathogenesis of the pathogenesis of TMJ-OA has posed challenges in advancing therapeutic measures. The combined use of metabolomics and transcriptomics technologies presents a highly effective method for identifying vital metabolic pathways and key genes in TMJ-OA patients. In this study, an analysis of synovial fluid untargeted metabolomics of 6 TMJ-OA groups and 6 temporomandibular joint reducible anterior disc displacement (TMJ-DD) groups was conducted using liquid and gas chromatography mass spectrometry (LC/GC-MS). The differential metabolites (DMs) between TMJ-OA and TMJ-DD groups were analyzed through multivariate analysis. Meanwhile, a transcriptomic dataset (GSE205389) was obtained from the GEO database to analyze the differential metabolism-related genes (DE-MTGs) between TMJ-OA and TMJ-DD groups. Finally, an integrated analysis of DMs and DE-MTGs was carried out to investigate the molecular mechanisms associated with TMJ-OA. The analysis revealed significant differences in the levels of 46 DMs between TMJ-OA and TMJ-DD groups, of which 3 metabolites (L-carnitine, taurine, and adenosine) were identified as potential biomarkers for TMJ-OA. Collectively, differential expression analysis identified 20 DE-MTGs. Furthermore, the integration of metabolomics and transcriptomics analysis revealed that the tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, ferroptosis were significantly enriched. This study provides valuable insights into the metabolic abnormalities and associated pathogenic mechanisms, improving our understanding of TMJOA etiopathogenesis and facilitating potential target screening for therapeutic intervention.