Gamma-glutamyl transferase to aspartate aminotransferase ratio (GSR) predicts prognoses in patients with colorectal cancer with liver metastasis after microwave ablation.

BACKGROUND: Microwave ablation (MWA) is widely used to eliminate colorectal liver metastases (CRLM). However, the risk of tumor recurrence is difficult to predict due to lack of reliable clinical and biological markers. Elevation of gamma-glutamyl transferase (GGT) and aspartate transaminase (AST) provides signals for liver inflammation and cancer progression. The present study evaluated the association between pre-ablation GGT to AST ratio index (GSR) and hepatic recurrence in patients with CRLM after MWA. METHODS: A retrospectively analyzed 192 CRLM patients who underwent MWA from January 2013 to December 2017. Pre-ablation GSR was classified into high (≤ 2.34) or low (> 2.34) using the upper quartile value. The prognostic value of GSR and other risk factors for liver progression-free survival (LPFS) and cancer-specific survival (CSS) were evaluated by univariate and multivariate analyses. RESULTS: High GSR was significantly associated with males (P = 0.041), the presence of cholelithiasis (P = 0.012), but not pre-ablation chemotherapy (P = 0.355), which caused significantly increased levels of GGT (P = 0.015) and AST (P = 0.008). GSR showed a significant association with LPFS and CSS through univariate analysis (P = 0.002 and 0.006) and multivariate analysis (P = 0.043 and 0.037). The subgroup analysis demonstrated no interaction between GSR and all variables except for distribution in the sub-analysis of LPFS. CONCLUSIONS: Our findings suggest that the pre-ablation GSR can be considered as a promising prognostic indicator for poor prognosis of patients with CRLM underwent MWA. TRIAL REGISTRATION: Not applicable.

Association of mixed exposure to microplastics with sperm dysfunction: a multi-site study in China.

BACKGROUND: Microplastics are environmental pollutants detected in various human organs and tissues. These particles originate from multiple sources including the degradation of larger plastic items and the intentional inclusion in consumer goods. Potential risks for human health resulting from microplastics exposure have also been reported. However, the distribution in the male reproductive system and its effect remains largely unknown. This study aims to investigate the presence of multiple microplastics in human semen and urine and their association with sperm quality in a multi-site study across China. METHODS: We conducted a cross-sectional study involving 113 male participants from three regions in China. Semen and urine samples were collected and analysed using Raman microscopy to detect eight types of microplastics: polystyrene (PS), polypropylene (PP), polycarbonate (PC), polyethylene (PE), polyvinyl chloride (PVC), polytetrafluoroethylene (PTFE), polyethylene terephthalate (PET), and acrylonitrile butadiene styrene (ABS). Semen quality parameters, including total sperm count, concentration, motility, and morphology, were assessed. Statistical analyses, including single and multi-variable models, were used to evaluate the relationship between microplastic exposure and semen quality, with a focus on PTFE, after adjusting confounding factors of age, body mass index (BMI), smoking, alcohol drinking, and sites. FINDINGS: Microplastics were detected in all semen and urine samples, with participants typically exposed to 3-5 different types. The detection rates of PS, PP and PE were the highest. Notably, PTFE exposure was significantly associated with decreased semen quality. Participants exposed to PTFE showed reductions in total sperm count [188.90 ± 163.71 vs. 207.67 ± 132.36 million, p = 0.091], sperm concentration [52.13 ± 47.47 vs. 58.32 ± 37.26 million/mL, p = 0.041], and progressive motility [40.29% ± 19.06 vs. 34.11% ± 17.02, p = 0.083]. The multi-linear regression analysis indicated that each additional type of microplastic exposure was associated with a significant decrease in total sperm number [ß = -15.4 (95% CI: -25.6, -5.2)], sperm concentration [ß = -7.2 (95% CI: -12.4, -2.0)], and progressive motility [ß = -8.3 (95% CI: -13.5, -3.1)]. Latent category analysis further refined these groups by types of microplastic exposure, highlighting specific types more strongly associated with decreased semen quality (OR = 3.5, 95% CI: 1.8, 6.9, p < 0.001). The nomogram can be used to assess the risk of sperm damage by combining the type of microplastic exposure in urine with age and BMI. INTERPRETATION: Our findings highlight the potential reproductive health risks posed by microplastic contamination, particularly PTFE, a non-stick pan coating material, and raise concerns about the potential of urine testing as an indicator of male reproductive microplastic exposure. Future research is warranted to further elucidate the mechanisms underlying the adverse effects of microplastics on male fertility and cross-generational effects. FUNDING: This study was funded by the Clinical Research Project of Shanghai Municipal Commission of Health and Family planning (20224Y0085), Open Fund Project of Guangdong Academy of Medical Sciences (YKY-KF202202), CAMS Innovation Fund for Medical Sciences (2019-I2M-5-064), Shanghai Clinical Research Center for Gynecological Diseases (22MC1940200), Shanghai Urogenital System Diseases Research Centre (2022ZZ01012), Key Discipline Construction Project (2023-2025) of Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai (GWVI-11.1-35, GWVI-11.2-YQ29) and Shanghai Frontiers Science Research Base of Reproduction and Development.

Visualizing Triplet Energy Transfer in Organic Near-Infrared Phosphorescent Host-Guest Materials.

Limited by the energy gap law, purely organic materials with efficient near-infrared room temperature phosphorescence are rare and difficult to achieve. Additionally, the exciton transition process among different emitting species in host-guest phosphorescent materials remains elusive, presenting a significant academic challenge. Herein, using a modular nonbonding orbital-π bridge-nonbonding orbital (n-π-n) molecular design strategy, we develop a series of heavy atom-free phosphors. Systematic modification of the π-conjugated cores enables the construction of a library with tunable near-infrared phosphorescence from 655 to 710 nm. These phosphors exhibit excellent performance under ambient conditions when dispersed into a 4-bromobenzophenone host matrix, achieving an extended lifetime of 11.25 ms and a maximum phosphorescence efficiency of 4.2 %. Notably, by eliminating the interference from host phosphorescence, the exciton transition process in hybrid materials can be visualized under various excitation conditions. Spectroscopic analysis reveals that the improved phosphorescent performance of the guest originates from the triplet-triplet energy transfer of abundant triplet excitons generated independently by the host, rather than from enhanced intersystem crossing efficiency between the guest singlet state and the host triplet state. The findings provide in-depth insights into constructing novel near-infrared phosphors and exploring emission mechanisms of host-guest materials.

No bidirectional association between serum 25-hydroxyvitamin D and erectile dysfunction: Mendelian randomization and genetic association studies.

Background: The causal relationship between the level of serum 25-hydroxyvitamin D [25(OH)D] and the risk of erectile dysfunction (ED) is still unclear. Aim: We tried to determine the causal relationship between the level of serum 25(OH)D and ED risk. Methods: In this study, we used genome-wide association study data from the UK Biobank to analyse the relationship between serum 25(OH)D (as the exposure) and ED (as the outcome). Linkage disequilibrium score regression (LDSC) was used to assess the genetic correlation between 2 traits. The CAUSE (Causal Analysis using Summary Effect estimates) method and Mendelian randomization (MR) were employed to evaluate the bidirectional causal relationship. The MRlap method was utilized to assess the impact of sample overlap on the results. To assess potential heterogeneity and horizontal pleiotropy, we utilized methods such as MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy Residual Sum and Outlier), weighted median, and others. Outcomes: The primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED. Results: The LDSC analysis did not reveal a significant genetic correlation between serum 25(OH)D and ED (rg = 0.2787, P = .3536). Additionally, the CAUSE (P value testing that the causal model is a better fit >.05) and MR analyses (odds ratio, 0.8951; 95% confidence interval, 0.7480-1.0710; P = .2260) did not support a causal relationship between 25(OH)D and ED, and our study did not detect any heterogeneity and pleiotropy. Clinical implications: This study provides evidence on whether vitamin D needs to be ingested to prevent or treat ED. Strengths and limitations: We used LDSC and MR to avoid bias. However, the population in this study was limited to European ancestry. Conclusion: No causal relationship was found between 25(OH)D and ED.

Adverse drug reactions of intravesical instillation therapy for bladder cancer: based on FDA adverse event reporting system.

BACKGROUND: Intravesical chemotherapy and immunotherapy are common adjuvant treatments for non-muscle invasive bladder cancer post-surgery. Analyzing adverse events linked to these therapies, can assist in clinical decision-making and risk assessment. STUDY DESIGN AND METHODS: Disproportionality analysis was conducted to analyze data from the Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the first quarter of 2024, exploring potential positive signals between Bacillus Calmette-Guérin, mitomycin-C, epirubicin, gemcitabine, and adverse events. RESULTS: The database retrieved 2018, 140, 31, and 85 adverse event reports associated with Bacillus Calmette-Guérin, mitomycin-C, epirubicin, and gemcitabine, respectively. Adverse reactions not mentioned in the label, such as aortic aneurysm and ocular congestion, were observed in preferred term level related to Bacillus Calmette-Guérin. Mitomycin-C exhibited specificity in skin and subcutaneous tissue diseases not reflected in the package insert. Gemcitabine-induced adverse drug reactions showed signals in vascular and lymphatic diseases meeting the screening criteria of all 4 indicators, with capillary leakage syndrome being the preferred term with the highest signal intensity. CONCLUSION: This study observed new adverse event signals, providing important assistance for drug selection in adjuvant therapy for non-muscle invasive bladder cancer postoperatively.

Human-Centric Transformer for Domain Adaptive Action Recognition.

We study the domain adaptation task for action recognition, namely domain adaptive action recognition, which aims to effectively transfer action recognition power from a label-sufficient source domain to a label-free target domain. Since actions are performed by humans, it is crucial to exploit human cues in videos when recognizing actions across domains. However, existing methods are prone to losing human cues but prefer to exploit the correlation between non-human contexts and associated actions for recognition, and the contexts of interest agnostic to actions would reduce recognition performance in the target domain. To overcome this problem, we focus on uncovering human-centric action cues for domain adaptive action recognition, and our conception is to investigate two aspects of human-centric action cues, namely human cues and human-context interaction cues. Accordingly, our proposed Human-Centric Transformer (HCTransformer) develops a decoupled human-centric learning paradigm to explicitly concentrate on human-centric action cues in domain-variant video feature learning. Our HCTransformer first conducts human-aware temporal modeling by a human encoder, aiming to avoid a loss of human cues during domain-invariant video feature learning. Then, by a Transformer-like architecture, HCTransformer exploits domain-invariant and action-correlated contexts by a context encoder, and further models domain-invariant interaction between humans and action-correlated contexts. We conduct extensive experiments on three benchmarks, namely UCF-HMDB, Kinetics-NecDrone and EPIC-Kitchens-UDA, and the state-of-the-art performance demonstrates the effectiveness of our proposed HCTransformer.

Tumour-associated and non-tumour-associated bacteria co-abundance groups in colorectal cancer.

BACKGROUND & AIMS: Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between tumor tissue (TT) and normal tissue (NT), as well as their associations with clinical features, are needed to be clarified. METHODS: Bacterial 16 S rRNA sequencing was performed by using TT samples and NT samples of 251 patients with colorectal cancer. Microbial diversity, taxonomic characteristics, microbial composition, and functional pathways were compared between TT and NT. Hierarchical clustering was used to construct CAGs. RESULTS: Four CAGs were grouped in the hierarchical cluster analysis. CAG 2, which was mainly comprised of pathogenic bacteria, was significantly enriched in TT samples (2.27% in TT vs. 0.78% in NT, p < 0.0001). CAG 4, which was mainly comprised of non-pathogenic bacteria, was significantly enriched in NT samples (0.62% in TT vs. 0.79% in NT, p = 0.0004). In addition, CAG 2 was also significantly associated with tumor microsatellite instability (13.2% in unstable vs. 2.0% in stable, p = 0.016), and CAG 4 was positively correlated with the level of CA199 (r = 0.17, p = 0.009). CONCLUSIONS: Our research will deepen our understanding of the interactions among multiple bacteria and offer insights into the potential mechanism of NT to TT transition.

Tissue Accumulation and Biotransformation of 6PPD-Quinone in Adult Zebrafish and Its Effects on the Intestinal Microbial Community.

The pronounced lethality of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPD-quinone or 6PPDQ) toward specific salmonids, while sparing other fish species, has received considerable attention. However, the underlying cause of this species-specific toxicity remains unresolved. This study explored 6PPDQ toxicokinetics and intestinal microbiota composition in adult zebrafish during a 14-day exposure to environmentally realistic concentrations, followed by a 7-day recovery phase. Predominant accumulation occurred in the brain, intestine, and eyes, with the lowest levels in the liver. Six metabolites were found to undergo hydroxylation, with two additionally undergoing O-sulfonation. Semiquantitative analyses revealed that the predominant metabolite featured a hydroxy group situated on the phenyl ring adjacent to the quinone. This was further validated by assessing enzyme activity and determining in silico binding interactions. Notably, the binding affinity between 6PPDQ and zebrafish phase I and II enzymes exceeded that with the corresponding coho salmon enzymes by 1.04-1.53 times, suggesting a higher potential for 6PPDQ detoxification in tolerant species. Whole-genome sequencing revealed significant increases in the genera Nocardioides and Rhodococcus after exposure to 6PPDQ. Functional annotation and pathway enrichment analyses predicted that these two genera would be responsible for the biodegradation and metabolism of xenobiotics. These findings offer crucial data for comprehending 6PPDQ-induced species-specific toxicity.

Structural insights linking H-bridging of archaeal GDGTs to high temperature.

Isoprenoid glycerol dialkyl glycerol tetraethers (GDGTs), characteristic membrane lipids of archaea, are widely used in ecological and geochemical studies, especially for paleoenvironmental reconstruction. Glycerol monoalkyl glycerol tetraethers (GMGTs, also known as H-GDGTs), a unique variant of GDGTs, have covalent bonds linking the two alkyl chains. Despite some studies suggesting a link between GMGTs and high temperatures, the reliability and mechanisms remain unclear. Using molecular dynamics simulations, we elucidated the mechanism connecting GMGTs to high temperatures. Our findings show that H-bridging linkages reduce the distance between alkyl chains, leading to thicker and denser membranes with lower fluidity and permeability. The diffusion coefficient of GMGTs decreased by approximately 35 % compared to GDGTs, indicating their role as a archaeal high-temperature adaptation. This study provides a mechanistic basis for using archaeal GMGTs in geochemical studies and enhances confidence in their use for paleotemperature reconstruction.

Useful or not? The discussion of traditional Chinese medicine to treat COVID-19 on a Chinese social networking site.

The use of traditional medicine is a global phenomenon, and the WHO advocated its appropriate integration into modern healthcare systems. However, there is a hot debate about the legitimacy of traditional medicine among the general public. Here, we investigated the debate in the Chinese digital context by analysing 1954 responses related to 100 questions about traditional Chinese medicine (TCM) treatment against COVID-19 on the Zhihu platform. Attitude function theory was applied to understand the reasons underlying public attitudes.Results showed that Zhihu users generally held a supportive attitude toward TCM. Their attitudes mainly came from their own experience and traditional media. The general users were more negative while medical professionals were more positive toward TCM. Ego defence (eg, derogating evidence sources) was used the most to support attitudes, followed by value expression (eg, believing in science). Supporters showed fewer expressions of faith (eg, the use of TCM is a kind of faith), politics (eg, supporting TCM is about politics) and science value (eg, TCM is a field of science), fewer ego defence, more patriotism and cultural confidence expressions (eg, TCM is a cultural pride) and more knowledge explanation (eg, TCM accelerates the metabolism of phlegm) than expected. Opposers showed fewer utilitarian and knowledge functions, fewer expressions of patriotism and more expressions of faith, politics and economics, but more ego defence functions than expected. Opposing posts were more likely to attract engagement than supporting and neutral posts. Posts that mentioned attitude functions generally attracted more engagement.Our findings indicate that TCM debate in modern China is not only relevant to medical science and health, but also rooted deeply in cultural ideology, politics and economics. The findings can provide global insights into the development of proactive policies and action plans that will help the integration of traditional medicine into modern healthcare systems.

Circular RNA circESYT2 serves as a microRNA-665 sponge to promote the progression of hepatocellular carcinoma through ENO2.

Circular RNAs (circRNAs) have emerged as crucial regulators in tumor progression, yet their specific role in hepatocellular carcinoma (HCC) remains largely uncharacterized. In this study, we utilized high-transcriptome sequencing to identify the upregulation of circESYT2 (hsa_circ_002142) in HCC tissues. Functional experiments carried out in vivo and in vitro revealed that circESYT2 played a significant role in maintaining the growth and metastatic behaviors of HCC. Through integrative analysis, we identified enolase 2 (ENO2) as a potential target regulated by circESYT2 through the competitive endogenous RNA sponge mechanism. Additional gain- or loss-of-function experiments indicated that overexpression of circESYT2 led to a tumor-promoting effect, which could be reversed by transfection of microRNA-665 (miR-665) mimic or ENO2 knockdown in HCC cells. Furthermore, the direct interaction between miR-665 and circESYT2 and between miR-665 and ENO2 was confirmed using RNA immunoprecipitation, FISH, RNA pull-down, and dual-luciferase reporter assays, highlighting the involvement of the circESYT2/miR-665/ENO2 axis in promoting HCC progression. These findings shed light on the molecular characteristics of circESYT2 in HCC tissues and suggest its potential as a biomarker or therapeutic target for HCC treatment.

Integrative Kinase Activity Profiling and Phosphoproteomics of rd10 Mouse Retina during cGMP-Dependent Retinal Degeneration.

Inherited retinal degenerative diseases (IRDs) are a group of rare diseases that lead to a progressive loss of photoreceptor cells and, ultimately, blindness. The overactivation of cGMP-dependent protein kinase G (PKG), one of the key effectors of cGMP-signaling, was previously found to be involved in photoreceptor cell death and was studied in murine IRD models to elucidate the pathophysiology of retinal degeneration. However, PKG is a serine/threonine kinase (STK) with several hundred potential phosphorylation targets and, so far, little is known about the specificity of the target interaction and downstream effects of PKG activation. Here, we carried out both the kinome activity and phosphoproteomic profiling of organotypic retinal explant cultures derived from the rd10 mouse model for IRD. After treating the explants with the PKG inhibitor CN03, an overall decrease in peptide phosphorylation was observed, with the most significant decrease occurring in seven peptides, including those from the known PKG substrate cyclic-AMP-response-element-binding CREB, but also Ca2+/calmodulin-dependent kinase (CaMK) peptides and TOP2A. The phosphoproteomic data, in turn, revealed proteins with decreased phosphorylation, as well as proteins with increased phosphorylation. The integration of both datasets identified common biological networks altered by PKG inhibition, which included kinases predominantly from the so-called AGC and CaMK families of kinases (e.g., PKG1, PKG2, PKA, CaMKs, RSKs, and AKTs). A pathway analysis confirmed the role of CREB, Calmodulin, mitogen-activated protein kinase (MAPK) and CREB modulation. Among the peptides and pathways that showed reduced phosphorylation activity, the substrates CREB, CaMK2, and CaMK4 were validated for their retinal localization and activity, using immunostaining and immunoblotting in the rd10 retina. In summary, the integrative analysis of the kinome activity and phosphoproteomic data revealed both known and novel PKG substrates in a murine IRD model. This data establishes a basis for an improved understanding of the biological pathways involved in cGMP-mediated photoreceptor degeneration. Moreover, validated PKG targets like CREB and CaMKs merit exploration as novel (surrogate) biomarkers to determine the effects of a clinical PKG-targeted treatment for IRDs.

The insufficiency of CT examination in early detection of central lung squamous cell carcinoma and squamous epithelial precancerous lesions.

BACKGROUND: CT examination for lung cancer has been carried out for more than 20 years and great achievements have been made in the early detection of lung cancer. However, in the clinical work, a large number of advanced central lung squamous cell carcinoma are still detected through bronchoscopy. Meanwhile, a part of CT-occult central lung squamous cell carcinoma and squamous epithelial precancerous lesions are also accidentally detected through bronchoscopy. METHODS: This study retrospectively collects the medical records of patients in the bronchoscopy room of the Endoscopy Department of Zhejiang Cancer Hospital from January 2014 to December 2018. The inclusion criteria for patients includes: 1.Patient medical records completed, 2.Without history of lung cancer before the diagnosis and first pathological diagnosis of primary lung cancer, 3.Have the lung CT data of the same period, 4.Have the bronchoscopy records and related pathological diagnosis, 5.The patients undergoing radical surgical treatment must have a complete postoperative pathological diagnosis. Finally, a total of 10,851 patients with primary lung cancer are included in the study, including 7175 males and 3676 females, aged 22-98 years. Firstly, 130 patients with CT-occult lesions are extracted and their clinical features are analyzed. Then, 604 cases of single central squamous cell carcinoma and 3569 cases of peripheral adenocarcinoma are extracted and compares in postoperative tumor diameter and lymph node metastasis. RESULTS: 115 cases of CT-occult central lung squamous cell carcinoma and 15 cases of squamous epithelial precancerous lesions are found. In the total lung cancer, the proportion of CT-occult lesions is 130/10,851 (1.20%). Meanwhile, all these patients are middle-aged and elderly men with a history of heavy smoking. There are statistically significant differences in postoperative median tumor diameter (3.65 cm vs.1.70 cm, P < 0.0001) and lymph node metastasis rate (50.99% vs.13.06%, P < 0.0001) between 604 patients with operable single central lung squamous cell carcinoma and 3569 patients with operable peripheral lung adenocarcinoma. Of the 604 patients with squamous cell carcinoma, 96.52% (583/604) are male with a history of heavy smoking and aged 40-82 years with a median age of 64 years. CONCLUSIONS: This study indicates that the current lung CT examination of lung cancer is indeed insufficiency for the early diagnosis of central squamous cell carcinoma and squamous epithelial precancerous lesions. Further bronchoscopy in middle-aged and elderly men with a history of heavy smoking can make up for the lack of routine lung CT examination.

Accelerated Selective Li+ Transports Assisted by Microcrack-Free Anionic Network Polymer Membranes for Long Cyclable Lithium Metal Batteries.

Rechargeable Li metal batteries have the potential to meet the demands of high-energy density batteries for electric vehicles and grid-energy storage system applications. Achieving this goal, however, requires resolving not only safety concerns and a shortened battery cycle life arising from a combination of undesirable lithium dendrite and solid-electrolyte interphase formations. Here, a series of microcrack-free anionic network polymer membranes formed by a facile one-step click reaction are reported, displaying a high cation conductivity of 3.1 × 10-5 S cm-1 at high temperature, a wide electrochemical stability window up to 5 V, a remarkable resistance to dendrite growth, and outstanding non-flammability. These enhanced properties are attributed to the presence of tethered borate anions in microcrack-free membranes, which benefits the acceleration of selective Li+ cations transport as well as suppression of dendrite growth. Ultimately, the microcrack-free anionic network polymer membranes render Li metal batteries a safe and long-cyclable energy storage device at high temperatures with a capacity retention of 92.7% and an average coulombic efficiency of 99.867% at 450 cycles.

Switchable Power Generation in Triboelectric Nanogenerator Toward Chip-Less Wearable Power Module Applications.

A conceptual shift toward next-generation wearable electronics is driving research into self-powered electronics technologies that can be independently operated without plugging into the grid for external power feeding. Triboelectric nanogenerators (TENGs) are emerging as a key component of self-powered electronics, but a power type mismatch between supply and demand limits their direct implementation into wearable self-powered electronics. Here, a TENG with switchable power mode capability is reported where the charge flow direction is modulated over the course of slow and random mechanical stimuli, with exceptional rectification capabilities as high as ≈133, stable outputs over the cycles, and design flexibility in different platforms. Importantly, the remarkable switchable power generation with fabric counter materials illuminates a new path for the smooth integration of flexible TENGs into wearable self-powered electronics.

Dynamic Transition between Monomer and Excimer Phosphorescence in Organic Near-Infrared Phosphorescent Crystals.

Achieving efficient near-infrared room-temperature phosphorescence of purely organic phosphors remains scarce and challenging due to strong nonradiative decay. Additionally, the investigation of triplet excimer phosphorescence is rarely reported, despite the fact that excimer, a special emitter commonly formed in crystals with strong π-π interactions, can efficiently change the fluorescent properties of compounds. Herein, a series of dithienopyrrole derivatives with low triplet energy levels and stable triplet states, exhibiting persistent near-infrared room-temperature phosphorescence, is developed. Via the modification of halogen atoms, the crystals display tunable emissions of monomers from 645 to 702 nm, with a maximum lifetime of 3.68 ms under ambient conditions. Notably, excimer phosphorescence can be switched on at low temperatures, enabled by noncovalent interactions rigidifying the matrix and stabilizing triplet excimer. Unprecedentedly, the dynamic transition process is captured between the monomer and excimer phosphorescence with temperature variations, revealing that the unstable triplet excimers in crystals with a tendency to dissociate can result in the effective quench of room-temperature phosphorescence. Excited state transitions across varying environments are elucidated, interpreting the structural dynamics of the triplet excimer and demonstrating strategies for devising novel near-infrared phosphors.

Neurological impairment is crucial for tire rubber-derived contaminant 6PPDQ-induced acute toxicity to rainbow trout.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6PPDQ) has attracted significant attention due to its highly acute lethality to sensitive salmonids. However, studies investigating the mechanisms underlying its acute toxicity have been lacking. In this work, we demonstrated the sensitivity of rainbow trout to 6PPDQ-induced mortality. Moribund trout exhibited significantly higher brain concentrations of 6PPDQ compared to surviving trout. In an in vitro model using human brain microvascular endothelial cells, 6PPDQ can penetrate the blood-brain barrier and enhance blood-brain barrier permeability without compromising cell viability. The time spent in the top of the tank increased with rising 6PPDQ concentrations, as indicated by locomotion behavior tests. Furthermore, 6PPDQ influenced neurotransmitter levels and mRNA expression of neurotransmission-related genes in the brain and exhibited strong binding affinity to target neurotransmission-related proteins using computational simulations. The integrated biomarker response value associated with neurotoxicity showed a positive linear correlation with trout mortality. These findings significantly contribute to filling the knowledge gap between neurological impairments and apical outcomes, including behavioral effects and mortality, induced by 6PPDQ.

The predictive value of the change of the number of pixels under different CT value intervals in the CT-occult central lung squamous cell carcinoma and squamous epithelial precancerous lesions.

BACKGROUND: Due to the fact that the CT-occult central lung squamous cell carcinoma and squamous epithelial precancerous lesions. (CT-occult CLSCC and SEPL) cannot be detected by lung CT screening, early and timely diagnosis of central lung cancer becomes very difficult, which directly affects the prognosis of patients. METHODS: We retrospectively review medical records of patients at the Zhejiang Cancer Hospital and enrolled 41 patients with the CT-occult CLSCC and SEPL and 48 patients without the CT-occult CLSCC and SEPL. We compare the clinical characteristics, imaging features and Changes in the number of pixels under different CT value intervals of patients with and without the CT-occult CLSCC and SEPL and we perform univariate and multivariate logistic regression analysis to explore independent factors for the CT-occult CLSCC and SEPL in the patients. RESULTS: We demonstrate that pack-years ≥ 20 (OR: 3.848, 95% CI: 1.086 ~ 13.633), the number of pixels change of CT value in interval [-850 ~ -750HU] (OR: 5.302, 95% CI: 1.122 ~ 25.057) and in interval [-900 ~ -850HU] (OR: 3.478, 95% CI: 1.167 ~ 10.365) are independently associated with the CT-occult CLSCC and SEPL in the patients. Ultimately, the logistic model obtained is statistically significant (p < 0.05) and an area under the ROC curve is 0.776 (95% CI: 0.682-0.870). The sensitivity of this model is 90.2% and the specificity is 52.1%. CONCLUSION: The results of this study indicate that in the CT value range [-950 ~ -750HU], when the total number of lung pixels tend to increase towards the region with high CT value, the probability of the occurrence of CT-occult CLSCC and SEPL lesions also increases. Meanwhile, these results have guiding significance for the further study of radiomic.

Combined RNAi of CTTN and FGF2 Modulates Cell Migration, Invasion and G1/S Transition of Hepatocellular Carcinoma through Ras/ERK Signaling Pathway.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) die of rapid progression and distant metastasis. Gene therapy represents a promising choice for HCC treatment, but the effective targeted methods are still limited. OBJECTIVE: CTTN/cortactin plays a key role in actin polymerization and regulates cytoskeleton remodeling. However, the interaction network of CTTN in HCC is not well understood. METHODS: siRNA was designed for CTTN silencing and Affymetrix GeneChip sequencing was used to obtain the gene profile after CTTN knockdown in the HCC cell line SMMC-7721. Potential interacting genes of CTTN were identified using qRT-PCR. The inhibition on HCC by combined RNA interference (RNAi) of CTTN and fibroblast growth factor 2 (FGF2) was detected. RESULTS: A total of 1,717 significantly altered genes were screened out and 12 potential interacting genes of CTTN were identified. The interaction of CTTN and FGF2 was validated and combined RNAi of CTTN and FGF2 achieved a synergistic effect, leading to better inhibition of HCC cell migration, invasion and G1/S transition than single knockdown of CTTN or FGF2. Mechanistically, combined RNAi of CTTN and FGF2 modulated the Ras/ERK signaling pathway. In addition, the EMT epithelial marker E-cadherin was upregulated while the mesenchymal marker Vimentin and cell cycle protein Cyclin D1 were downregulated after combined RNAi of CTTN and FGF2. Additionally, qRT-PCR and immunohistochemical staining showed that both CTTN and FGF2 were highly expressed in metastatic HCC tissues. CONCLUSION: Combined RNAi of CTTN and FGF2 may be a novel and promising intervention strategy for HCC invasion and metastasis.

Assessment of alterations in the retina and vitreous in pre- and post-COVID-19 patients using swept-source optical coherence tomography and angiography: A comparative study.

Ocular manifestations have been well recognized in coronavirus disease 2019 (COVID-19) outbreak. Several studies have detected ocular manifestations in patients after COVID-19. However, little is known about the retinal and vitreal alterations in patients before and after COVID-19 infection. This study aimed to investigate the retinal and vitreal alterations in patients before and after contracting COVID-19 infection using swept-source optical coherence tomography (SS-OCT) and angiography (SS-OCTA). A total of 38 participants (76 eyes) were enrolled and followed-up 1 month after COVID-19 infection. Then, 26 patients (52 eyes) were evaluated 3 months after COVID-19 infection. Compared with the pre-COVID-19 status, patients with 1- and 3-month post-COVID-19 statuses had significant thinning of ganglion cell and inner plexiform layer, thickening of inner nuclear layer, a decrease in the vessel density (VD) of superficial vascular complex, and an increase in the VD of deep vascular complex. Meanwhile, alteration in parameters of foveal avascular zone (all p < 0.05) and hyper-reflective dots in the vitreous of 27 patients (54 eyes) (71.1% vs. pre-COVID-19, 34.2%, p = 0.006) were observed. These findings suggest significantly retinal and vitreal alterations occurred in patients after COVID-19 infection, possibly due to direct or indirect virus-induced injuries. Further longitudinal studies are required to investigate the long-term effects of COVID-19 infection on the human eyes.