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.

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.

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.

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.

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.

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.

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.

Clinical efficacy of duloxetine in the treatment of axial symptoms after posterior cervical spine surgery: a retrospective study.

PURPOSE: To evaluate the efficacy of duloxetine in the treatment of patients with axial symptoms after posterior cervical spine surgery. METHODS: Patients with axial symptoms after posterior cervical spine surgery treated by duloxetine or non-drug therapy from 2018 to 2021 were reviewed. Duloxetine was administered gradually, with oral administration of 30 mg in the first week and oral administration of 60 mg from the second week. Visual analogue scale (VAS), 36-Item Short-Form Health Survey questionnaire (SF-36) and EuroQol-5 Dimensions (EQ-5D) questionnaire were used to evaluate the severity of AS at baseline and 1 week, 2 weeks, 1 month, 3 months and 6 months after medication. The occurrence of adverse reactions was recorded. RESULTS: A total of 63 eligible patients who received duloxetine therapy (n = 35) or non-drug therapy (n = 28) were included. All patients were followed up for 6 months. Significant improvements were found in VAS score compared with baseline in both groups (1.87 ± 0.81 vs 6.61 ± 1.16, 3.18 ± 0.67 vs 6.31 ± 1.40; P < 0.05 for all). Meanwhile, the VAS score of the duloxetine group was significantly better than that of the non-drug therapy group at 1 week, 2 weeks, 1 month, 3 months and 6 months (P < 0.05). Besides, according to 36-Item Short-Form Health Survey questionnaire (SF-36), the PCS score and MCS score are significantly higher than before the treatment in duloxetine group (PCS 62.82 ± 6.04 vs 44.36 ± 7.25, MCS 65.50 ± 4.53 vs 55.55 ± 6.06; P < 0.05 for all). And when we compared variables between the two groups, the PCS score of the duloxetine group was significantly better than that of the non-drug therapy group (P < 0.05), but there was no significant difference in MCS score between the two groups (P > 0.05). What's more, EQ-5D score had significant improvements in the duloxetine group compared with the non-drug therapy group at 1 week, 2 weeks, 1 month, 3 months and 6 months (P < 0.05). CONCLUSION: Oral duloxetine has a better short-term outcome than conventional non-drug therapy in patients with axial symptoms following posterior decompression surgery in the cervical spine.

A Potential Neuroprotective Role for Pyruvate Kinase 2 in Retinal Degeneration.

Retinitis pigmentosa (RP) is an inherited disorder that results in vision impairment that specific therapeutic strategies are not available. However, it is widely regarded that the cGMP system, including cGMP and its interactor cGMP-dependent protein kinase (PKG), acts as a crucial effector during retinal degeneration. We have previously identified a list of cGMP-PKG-dependent genes in the context of RP, and in this study, we further validated one of the targets, namely, pyruvate kinase 2 (PKM2), and investigated the potential role of PKM2 for the photoreceptors' well-being during RP. With the aid of organotypic retinal explant cultures, we pharmacologically manipulated the PKM2 activities in different RP mouse models via the addition of TEPP-46 (a PKM2 activator) and found that activation of PKM2 alleviates the progress of photoreceptor death in the rd10 mouse model. This observation provides supportive evidence that PKM2 may serve as a novel potential molecular target in RP.

GNG4, as a potential predictor of prognosis, is correlated with immune infiltrates in colon adenocarcinoma.

The tumour microenvironment (TME) and immunosuppression play an important role in colon cancer (CC) metastasis, which seriously affects the prognosis of CC. G protein subunit gamma 4 (GNG4) has been shown to participate in tumour progression and the tumour mutation burden (TMB) in colorectal cancer. However, the effect of GNG4 on the CC TME and immunology remains elusive. Weighted gene coexpression network analysis (WGCNA) was employed for screening aberrantly expressed genes associated with the immune score, and GNG4 was then selected through prognostic and immune correlation analysis. Based on RNA sequencing data obtained from the TCGA and GEO databases, the expression pattern and immune characteristics of GNG4 were comprehensively examined using a pan-cancer analysis. Upregulation of GNG4 was linked to an adverse prognosis and immune inhibitory phenotype in CC. Pan-cancer analysis demonstrated higher GNG4 expression in tumours than in paired normal tissue in human cancers. GNG4 expression was closely related to prognosis, TMB, immune checkpoints (ICPs), microsatellite instability (MSI) and neoantigens. GNG4 promoted CC cell proliferation, migration and invasion and participated in immune regulation in the TME. Significantly, GNG4 expression was found to negatively correlate with tumour-infiltrating immune cells, ICP, TMB and MSI in CC. GNG4 expression predicted the immunotherapy response in the IMvigor210 cohort, suggesting that GNG4 could be used as a potential biomarker in CC for prognostication and immunology. Moreover, the expression of GNG4 predicted the immunotherapy response of ICB in CC.

Identifying potential toxic organic substances in leachates from tire wear particles and their mechanisms of toxicity to Scenedesmus obliquus.

Tire wear particles (TWPs) are increasingly being found in the aquatic environment. However, there is limited information available on the environmental consequences of TWP constituents that may be release into water. In this study, TWP leachate samples were obtained by immersing TWPs in ultrapure water. Using high-resolution mass spectrometry and toxicity identification, we identified potentially toxic organic substances in the TWP leachates. Additionally, we investigated their toxicity and underlying mechanisms. Through our established workflow, we structurally identified 13 substances using reference standards. The median effective concentration (EC50) of TWP leachates on Scenedesmus obliquus growth was comparable to that of simulated TWP leachates prepared with consistent concentrations of the 13 identified substances, indicating their dominance in the toxicity of TWP leachates. Among these substances, cyclic amines (EC50: 1.04-3.65 mg/L) were found to be toxic to S. obliquus. We observed significant differential metabolites in TWP leachate-exposed S. obliquus, primarily associated with linoleic acid metabolism and purine metabolism. Oxidative stress was identified as a crucial factor in algal growth inhibition. Our findings shed light on the risk posed by TWP leachable substances to aquatic organisms.

Identification of milling status based on vibration signals using artificial intelligence in robot-assisted cervical laminectomy.

BACKGROUND: With advances in science and technology, the application of artificial intelligence in medicine has significantly progressed. The purpose of this study is to explore whether the k-nearest neighbors (KNN) machine learning method can identify three milling states based on vibration signals: cancellous bone (CCB), ventral cortical bone (VCB), and penetration (PT) in robot-assisted cervical laminectomy. METHODS: Cervical laminectomies were performed on the cervical segments of eight pigs using a robot. First, the bilateral dorsal cortical bone and part of the CCB were milled with a 5 mm blade and then the bilateral laminae were milled to penetration with a 2 mm blade. During the milling process using the 2 mm blade, the vibration signals were collected by the acceleration sensor, and the harmonic components were extracted using fast Fourier transform. The feature vectors were constructed with vibration signal amplitudes of 0.5, 1.0, and 1.5 kHz and the KNN was then trained by the features vector to predict the milling states. RESULTS: The amplitudes of the vibration signals between VCB and PT were statistically different at 0.5, 1.0, and 1.5 kHz (P < 0.05), and the amplitudes of the vibration signals between CCB and VCB were significantly different at 0.5 and 1.5 kHz (P < 0.05). The KNN recognition success rates for the CCB, VCB, and PT were 92%, 98%, and 100%, respectively. A total of 6% and 2% of the CCB cases were identified as VCB and PT, respectively; 2% of VCB cases were identified as PT. CONCLUSIONS: The KNN can distinguish different milling states of a high-speed bur in robot-assisted cervical laminectomy based on vibration signals. This method is feasible for improving the safety of posterior cervical decompression surgery.