A versatile attention-based neural network for chemical perturbation analysis and its potential to aid surgical treatment: A experimental study.

Deep learning models have emerged as rapid, accurate, and effective approaches for clinical decisions. Through a combination of drug screening and deep learning models, drugs that may benefit patients before and after surgery can be discovered to reduce the risk of complications or speed recovery. However, most existing drug prediction methods have high data requirements and lack interpretability, which has a limited role in adjuvant surgical treatment. To address these limitations, we propose the attention-based convolution transpositional interfusion network (ACTIN) for flexible and efficient drug discovery. ACTIN leverages the graph convolution and the transformer mechanism, utilizing drug and transcriptome data to assess the impact of chemical pharmacophores containing certain elements on gene expression. Remarkably, just with only 393 training instances, only one-tenth of the other models, ACTIN achieves state-of-the-art performance, demonstrating its effectiveness even with limited data. By incorporating chemical element embedding disparity and attention mechanism-based parameter analysis, it identifies the possible pharmacophore containing certain elements that could interfere with specific cell lines, which is particularly valuable for screening useful pharmacophores for new drugs tailored to adjuvant surgical treatment. To validate its reliability, we conducted comprehensive examinations by utilizing transcriptome data from the lung tissue of fatal COVID-19 patients as additional input for ACTIN, we generated novel lead chemicals that align with clinical evidence. In summary, ACTIN offers insights into the perturbation biases of elements within pharmacophore on gene expression, which holds the potential for guiding the development of new drugs that benefit surgical treatment.

Molecular characterization, clinical value, and cancer-immune interactions of genes related to disulfidptosis and ferroptosis in colorectal cancer.

BACKGROUND: This research strived to construct a new signature utilizing disulfidptosis-related ferroptosis (SRF) genes to anticipate response to immunotherapy, prognosis, and drug sensitivity in individuals with colorectal cancer (CRC). METHODS: The data for RNA sequencing as well as corresponding clinical information of individuals with CRC, were extracted from The Cancer Genome Atlas (TCGA) dataset. SRF were constructed with the help of the random forest (RF), least absolute shrinkage and selection operator (LASSO), and stepwise regression algorithms. To validate the SRF model, we applied it to an external cohort, GSE38832. Prognosis, immunotherapy response, drug sensitivity, molecular functions of genes, and somatic mutations of genes were compared across the high- and low-risk groups (categories). Following this, all statistical analyses were conducted with the aid of the R (version 4.23) software and various packages of the Cytoscape (version 3.8.0) tool. RESULTS: SRF was developed based on five genes (ATG7, USP7, MMD, PLIN4, and THDC2). Both univariate and multivariate Cox regression analyses established SRF as an independent, prognosis-related risk factor. Individuals from the high-risk category had a more unfavorable prognosis, elevated tumor mutational burden (TMB), and significant immunosuppressive status. Hence, they might have better outcomes post-immunotherapy and might benefit from the administration of pazopanib, lapatinib, and sunitinib. CONCLUSION: In conclusion, SRF can act as a new biomarker for prognosis assessment. Moreover, it is also a good predictor of drug sensitivity and immunotherapy response in CRC but should undergo optimization before implementation in clinical settings.

Identification of the shared gene signature and biological mechanism between type 2 diabetes and colorectal cancer.

Background: The correlation of type 2 diabetes mellitus (T2DM) with colorectal cancer (CRC) has garnered considerable attention in the scientific community. Despite this, the molecular mechanisms underlying the interaction between these two diseases are yet to be elucidated. Hence, the present investigation aims to explore the shared gene signatures, immune profiles, and drug sensitivity patterns that exist between CRC and T2DM. Methods: RNA sequences and characteristics of patients with CRC and T2DM were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus databases. These were investigated using weighted gene co-expression network analysis (WGCNA) to determine the co-expression networks linked to the conditions. Genes shared between CRC and T2DM were analyzed by univariate regression, followed by risk prognosis assessment using the LASSO regression model. Various parameters were assessed through different software such as the ESTIMATE, CIBERSORT, AND SSGSEA utilized for tumor immune infiltration assessment in the high- and low-risk groups. Additionally, pRRophetic was utilized to assess the sensitivity to chemotherapeutic agents in both groups. This was followed by diagnostic modeling using logistic modeling and clinical prediction modeling using the nomogram. Results: WGCNA recognized four and five modules that displayed a high correlation with T2DM and CRC, respectively. In total, 868 genes were shared between CRC and T2DM, with 14 key shared genes being identified in the follow-up analysis. The overall survival (OS) of patients in the low-risk group was better than that of patients in the high-risk group. In contrast, the high-risk group exhibited higher expression levels of immune checkpoints The Cox regression analyses established that the risk-score model possessed independent prognostic value in predicting OS. To facilitate the prediction of OS and cause-specific survival, the nomogram was established utilizing the Cox regression model. Conclusion: The T2DM + CRC risk-score model enabled independent prediction of OS in individuals with CRC. Moreover, these findings revealed novel genes that hold promise as therapeutic targets or biomarkers in clinical settings.

The significance of serum Klotho to hearing loss: a potential protector under noise pollution.

The issue of hearing protection in the presence of noise pollution is of great importance in the fields of environmental science and clinical medicine. Currently, the clinical significance of Klotho in relation to hearing has not been revealed. The aim of this study was to examine the correlation between serum Klotho levels and Pure Tone Average (PTA) hearing thresholds among individuals in the U.S.. The analysis involved a sample of 1,781 individuals aged 20 to 69, obtained from the 2007-2012 National Health and Nutrition Examination Survey. Various methods were utilized for the analysis, including univariate and multivariate linear regression, stratified analysis, smooth curve fitting, a two-segment linear regression model, and log-likelihood ratio analysis. The results of the univariate analysis indicated that serum Klotho concentration, age, education level, hypertension, diabetes, and smoking all exhibited a significant influence on PTAs. After adjusting for potential confounding factors, it was observed that a decrease in serum Klotho was significantly associated with PTA thresholds at low frequency (ß = -0.002; 95% CI: -0.003, -0.001; P = 0.004), speech frequency (ß = -0.002; 95% CI: -0.003, -0.001; P = 0.007), and high frequency (ß = -0.002; 95% CI: -0.003, -0.001; P = 0.045). Specifically, for every 1 pg/ml decrease in serum Klotho concentration, the PTAs increased by 0.002 dB. Moreover, age and gender-specific analyses revealed significant associations. For individuals aged 59-69, a significant association was found between serum Klotho concentration and high-frequency PTA (ß = -4.153; 95% CI: -7.948, -0.358; P = 0.032). Additionally, among females, significant associations were observed between serum Klotho concentration and speech-frequency PTA (ß = -1.648, 95% CI: -3.197, -0.099; P = 0.037) as well as high-frequency PTA (ß = -3.046; 95% CI: -5.319, -0.772; P = 0.009). Finally, the results of smooth curve fitting and threshold effect analyses indicated a potential negative linear correlation between serum Klotho concentration and PTA thresholds. In conclusion, a lower level of serum Klotho was found to be associated with increased hearing thresholds, particularly among the elderly population. This finding has significant implications for the prevention and treatment of hearing damage.

Management of esophagogastric fistula caused by adjustable gastric band erosion: A case report and literature review.

Laparoscopic adjustable gastric banding (LAGB) is commonly used in the treatment of morbid obesity. However, with clinical application and long-term follow-up, the shortcomings of this procedure were also exposed, bringing about surgery-related complications include dysphagia, intragastric band migration, slippage, and gastric band erosion. Lower esophageal and gastric fistula is a rare but dangerous complication after LAGB. We describe a case of esophagogastric fistula occurring twelve years after a laparoscopic band procedure and its successful management in a multidisciplinary and staged manner, followed by a short review of the literature.

Molecular subtypes identified by multiomics analysis based on cuproptosis-related genes precisely predict response to immunotherapy and chemotherapy in colorectal cancer.

Cuproptosis is a newly reported type of programmed cell death that is involved in the progression of various diseases. Some studies have reported its potential significance in multiple tumors. Colorectal cancer (CRC) is one of the malignant tumors with high incidence and mortality. The purpose of this study was to further explore the importance of cuproptosis in the CRC development and treatment. We analyzed the expression, alterations, and promoter methylation of cuproptosis-related genes (CRGs) in patients with CRC. Three machine learning methods was used to determine cuproptosis-related feature genes and a diagnostic model was built based on them. Using the unsupervised clustering, patients with CRC were classified into distinct clusters. Then, the LASSO method was used to establish a cuproptosis risk model. We analyzed the association of risk scores with outcomes, immune microenvironment, response to immunotherapy, and sensitivity to chemotherapeutic drugs. The results showed that the expression of CRGs was dysregulated in CRC. The diagnostic model based on cuproptosis-related feature genes showed great clinical value. The patients in two clusters displayed different prognosis and microenvironment. Furthermore, the risk score was correlated with clinical characteristics, immune infiltration and response to immunotherapy and chemotherapy. Above all, the present findings revealed the involvement of cuproptosis in CRC development and provided a diagnostic tool to evaluate CRC occurrence risk. The immune infiltration and drug sensitivity analysis results helped to predict the response of patients in different subtypes of CRC to immunotherapy and chemotherapy.

The risk factors of postoperative nausea and vomiting in patients undergoing laparoscopic sleeve gastrectomy and laparoscopic distal gastrectomy: a propensity score matching analysis.

Postoperative nausea and vomiting (PONV) is a common side effect after laparoscopic surgery. The aim of the study is to investigate the variables that could predict PONV in patients who underwent laparoscopic gastrectomy. We divided patients who underwent laparoscopic gastrectomy into PONV and No-PONV groups. Propensity score matching (PSM) was applied to adjust confounding factors for further validation, and ordinal logistic regression analysis was used to identify predictors for PONV. In the ordinal logistic regression analysis, the preoperative neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR]: 3.19, 95% confidence interval [CI]: 1.38-7.38; p < 0.01) was identified as an independent risk factor for the presence of PONV and a predictor of the severity of PONV (OR: 3.44, 95% CI: 1.67-5.20; p < 0.01) in 94 PSM patients. Besides, NLR was positively correlated with the PONV score (r = 0.534, p < 0.001). In the receiver-operating characteristic (ROC) curve analysis, an NLR with an optimal cutoff value of 1.59 predicted severe PONV with a sensitivity of 72% and specificity of 81%. The NLR was an independent risk factor for the presence of PONV, and a high NLR tends to be positively associated with the severity of PONV after laparoscopic gastrectomy.

The knock-on effects of different wastewater feeding modes: Change in microbial communities versus resistance genes in pilot-scale aerobic sludge granulation reactors.

To explore the effects of wastewater feeding modes on the formation of aerobic granular sludge (AGS) and the complex relationships between resistance genes and bacteria, two pilot-scale sequencing batch reactors (SBRs) were established. The SBR with influent wastewater introduced uniformly through pipes at bottom was designated as BSBR, and the SBR with inlet wastewater flowing directly from top was TSBR. BSBR formed dense AGS due to uniform wastewater feeding at bottom, while TSBR failed to cultivate AGS. Metagenomic sequencing illustrated that rapid growth of AGS in BSBR was accompanied with increase of antibiotic resistance genes (ARGs) abundance, but ARGs diminished when the size of AGS was stable. The ARGs continued to elevate in TSBR, and abundance of metal resistance genes (MRGs) was always higher than that in BSBR. Two reactors had markedly different bacterial community, microbes in BSBR owned stronger activity, conferred greater potential to proliferate. AdeF in two systems had the most complex gene-bacteria relationships which would undergo HGT within bacterial genus. The different feeding modes of wastewater directly led to the changing size of sludge, which caused knock-on effects of variations in the abundance of microbial communities and resistance genes. This study provided promising suggestions for the rapid cultivation of AGS and control of resistance genes at pilot-scale.

The association between the body roundness index and the risk of colorectal cancer: a cross-sectional study.

BACKGROUND: Colorectal cancer (CRC), has a link between obesity, especially visceral fat. The body roundness index (BRI) can more accurately assess body fat and visceral fat levels. It is, however, unknown whether BRI is associated with CRC risk. METHODS: 53,766 participants were enrolled from the National Health and Nutrition Examination Survey (NHANES). Analysing the corelation between BRI and CRC risk was performed using logistic regression. Stratified analyses revealed the association based on the population type. Receiver operating characteristic curve (ROC) was performed for predicting CRC risk using different anthropometric indices. RESULTS: The risk of CRC mounting apparently with elevated BRI for participants with CRC compared to normal participants (P-trend < 0.001). The association persisted even after adjusting for all covariates (P-trend = 0.017). In stratified analyses, CRC risk increased with increasing BRI, especially among those who were inactive (OR (95% CI): Q3 3.761 (2.139, 6.610), P < 0.05, Q4 5.972 (3.347, 8.470), P < 0.01), overweight (OR (95% CI): Q3 2.573 (1.012, 7.431), P < 0.05, Q4 3.318 (1.221, 9.020), P < 0.05) or obese (OR (95% CI): Q3 3.889 (1.829, 8.266), P < 0.001, Q4 4.920 (2.349, 10.308), P < 0.001). ROC curve showed that BRI had a better ability in forecasting the risk of CRC than other anthropometric indices such as body weight etc. (all P < 0.05). CONCLUSIONS: CRC risk and BRI have a positive and significant relationship, particularly in inactive participants with BMI ≥ 25 kg/m2. It is hoped that these results will raise awareness of the importance of reducing visceral fat deposition.

The spread of different resistance genes fractions in nitrification system under chronic exposure to varying alkyl chain length benzalkyl dimethylammonium compounds.

Benzalkyl dimethylammonium compounds (BACs) are generally applied as surfactants and disinfectants. In this study, the nitrification systems were exposed to different alkyl chain lengths (C12-C16) and different levels of BACs (0-5 mg/L), respectively, totally 120 days and to explore the chronic effect of BACs on resistance genes (RGs). RGs were classified into four fractions based on activated sludge properties. Ammonia oxidation performance were not significantly affected by BACs, whereas BACs increased the absolute abundance of most intracellular RGs in sludge (si-RGs). Under the exposure of BACs, extracellular RGs in water (we-RGs) showed a decrease trend and si-RGs tended to be converted to we-RGs. Tightly bound-Tyrosine side chain was significantly correlated with most we-RGs, and we-intI1 might contribute to the propagation of RGs. Therefore, the risk of transmission of different fractions of RGs in the nitrification system under the stress of BACs should be taken seriously.

Different acesulfame potassium fate and antibiotic resistance propagation pattern in nitrifying and denitrifying sludge systems.

Acesulfame potassium (ACE-K) is a widely utilized sugar substitute with increasing demand, which is frequently detected in various environmental matrix due to recalcitrance. However, a general consensus on the contribution of nitrifying and denitrifying process to ACE-K removal is lacking. Therefore, ACE-K removal, its effects on antibiotic resistant genes (ARGs) propagation and microbial community in nitrifying sequencing batch reactor (N-SBR) and denitrifying sequencing batch reactor (D-SBR) inoculated with the identical activated sludge were investigated. In this study, ACE-K can be eliminated in N-SBR with satisfying removal efficiency (96.76 ± 8.33 %) after 13 d acclimation, while it remained persistent (average ACE-K removal efficiency of 2.24 ± 1.86 %) in D-SBR during 84 d exposure. Moreover, ACE-K hardly affected the performances of these two types of reactors and had little impact on nitrifying and denitrifying functional genes. However, initial contact with ACE-K would increase ARGs abundance, network analysis showed functional bacteria in each reactor were possible ARGs hosts. Potential ACE-K degrading genera Chelatococcus, Bosea and Aquamicrobium were found in both reactors. LefSe analysis showed that Phyllobacteriaceae containing Aquamicrobium genus was a differentially enriched family in N-SBR. This research might provide a perspective for better understanding factor affecting ACE-K fate in wastewater treatment process and its ecological risks.

Murine neonatal dermal fibroblast acquires a lymphoid tissue organizer cell-like activity upon synergistic activation of TNF-α receptor and LTß receptor.

Tertiary lymphoid organs (TLOs) are ectopic aggregates of immune cells. As accumulating studies demonstrate TLOs as a predictor of better prognosis in certain cancers, targeting TLO formation, which is tightly regulated by the lymphoid tissue organizer cells (LTOs), has become intriguing in cancer treatment. However, the clinical outcome of these attempts is limited, because the approaches for activating tumor adjacent LTO is lack and little is known about what type of self-cell can be used as LTO to initiate TLO formation. Here we demonstrate that co-stimulation with membrane-bound ligand LTα1ß2 and soluble TNF-α could induced an LTO-like activity in murine neonatal dermal fibroblast, featured by high expression of cell migration-associated chemokines and adhesion molecules that resemble typical LTO gene signature. Furthermore, the LTO-phenotypic dermal fibroblast could enhance the attachment and survival of T and B cell and proliferation of T cell. These findings suggest dermal fibroblast as a promising target for TLO induction to improve cancer immunotherapy.

Partial S(0)-driven autotrophic denitrification process facilitated the quick natural enrichment of anammox bacteria at room temperature.

Anaerobic ammonium oxidation (anammox) is well-known to be an environmental and promising biotechnology. However, the natural enrichment of anammox bacteria is still a challenging topic. In this study, partial S(0)-driven autotrophic denitrification (PSAD) was developed to stably supply nitrite, and natural enrichment of anammox bacteria was rapidly realized in a single sequencing moving bed biofilm reactor at room temperature. With the initiation of PSAD, anammox bacteria spontaneously emerged within 12 days, and PSAD-anammox coupling system was realized successfully. And then, the influent concentration of ammonium continuously increased to the same concentration as the nitrate, and the mean total nitrogen removal efficiency reached 92.77 %, which was mainly contributed by anammox. Moreover, the coupling of PSAD and anammox reduced the risk of sulfate emissions. cDNA high throughput sequencing revealed that the relative abundance of Candidatus Brocadia and Thiobacillus reached 39.03 % and 13.48 % at the 88th day. Oligotyping analysis illustrated that GATTTAAT and GTCCCA were the dominant Ca. Brocadia and Thiobacillus oligotypes in PSAD-anammox coupling system, respectively. DNA-based stable isotope probing further deciphered that Thiobacillus was the actual performer of PSAD and supported the nitrite for anammox bacteria in PSAD-anammox coupling system. Overall, this work provided a new strategy to naturally enrich anammox bacteria.

Comprehensive analysis of the prognostic and immunotherapeutic implications of STAT family members in human colorectal cancer.

Background: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and the second leading cause of cancer mortality. Signal transducer and activator of transcription (STAT) proteins are a group of transcription factors implicated in cell signal transduction and gene transcription in several cancer types. However, the level of expression, genetic alterations, and biological function of different STATs, as well as their prognostic and immunotherapeutic value in CRC remain unclear. Methods: The mRNA and protein expression levels, genetic alterations, prognostic value, gene-gene and protein-protein interaction networks, and biological function of STATs in CRC were studied using the GEPIA, HPA, cBioPortal, PrognoScan, Kaplan-Meier plotter, GeneMANIA, STRING, and Metascape databases. The expression of STATs in CRC was confirmed using immunohistochemistry (IHC). Finally, the relationship between STAT expression and immune infiltration as well as immunotherapy-associated indicators was also investigated. Results: The expression levels of STAT2/5A/5B are downregulated in CRC, and the STAT1/3/4/5B expressions were significantly associated with the tumor stage of patients with CRC. The abnormal expression of STAT2/4/5B in patients with CRC is related to the prognosis of patients with CRC. The STATs and their neighboring proteins are primarily associated with lymphocyte activation, cytokine-mediated signaling pathways, positive regulation of immune response, regulation of cytokine production, and growth hormone receptor signaling pathways in cancer. The expression of STATs was significantly associated with immune infiltration and immunotherapy response-associated indicators. Conclusion: This study may help further understand the molecular mechanism of CRC and provide new prognostic biomarkers and immunotherapy targets in patients with CRC.

Photoactive terahertz metasurfaces for ultrafast switchable sensing of colorectal cells.

Metasurfaces with a strongly enhanced local field are envisioned as a powerful platform for ultrasensitive optical sensors to significantly amplify imperceptible differences between compatible bioanalytes. Through the use of phototunable silicon-based terahertz (THz) metasurfaces, we experimentally demonstrate ultrafast switchable sensing functions. It is found that the THz responses of the coupled-resonances in the metasurfaces shift from Lorentz-lattice mode to electromagnetism-induced transparency (EIT) mode under optical pumping within an ultrashort time of 32 ps, enabling an ultrafast sensitive sensor. For the Lorentz-lattice mode, the THz time-domain signal directly shows a highly sensitive response to detect tiny analytes without extra Fourier transformation as the mismatch between the two modes increases. Once the metasurfaces are switched to the EIT mode, the silicon-metal hybrid structure supports frequency-domain sensing ability due to strong field confinement with a sensitivity of 118.4 GHz/RIU. Both of the sensing configurations contribute to more subtle information and guarantee the accuracy of the sensor performance. Combined with the aforementioned advantages, the proposed metasurfaces have successfully identified colorectal cells between normal, adenoma, and cancer states in experiments. This work furnishes a new paradigm of constructing reliable and flexible metasurface sensors and can be extended to other optics applications.

The fate and behavior mechanism of antibiotic resistance genes and microbial communities in flocs, aerobic granular and biofilm sludge under chloroxylenol pressure.

Chloroxylenol (PCMX), an antibacterial agent, has been widely detected in water environment and has toxic effects on biology and ecology. During 270 d, the influence of PCMX on the performance of three nitrification systems was investigated, including floc-based sequencing batch reactor (FSBR), aerobic granule-based SBR (AGSBR) and biofilm SBR (BSBR). The nitrification capability of three systems was inhibited by PCMX, but recovered after domestication, and PCMX made three systems realize partial nitrification for 10, 100 and 35 days, respectively. The extracellular polymeric substances of three systems increased first and then decreased with the increment of PCMX. The granular structure of AGSBR may be conducive to the enrichment of antibiotic resistance genes (ARGs), and almost all ARGs of BSBR were reduced during the addition of 5.0 mg/L PCMX. The microbial community results showed that Rhodococcus as potential degrading bacteria was continuously enriched in three systems. Piscinibacter was regarded as the potential antibiotic resistant bacteria, which was positively associated with multiple ARGs in three systems. Additionally, quaternary ammonium compounds resistance genes had a variety of positive correlations with bacteria in three systems. This study provided a new perspective for the usage and treatment of PCMX.

Colorectal cancer immunotherapy-Recent progress and future directions.

Compared with conventional chemotherapy and targeted therapy, immunotherapy has changed the treatment prospects of various solid tumors and has recently become the main treatment method for metastatic or recurrent solid tumors, including malignant melanoma, non-small-cell lung cancer, and renal cell carcinoma. The application of immune checkpoint inhibitor (ICI)-based immunotherapy in patients with colorectal cancer (CRC) has yielded satisfactory results in terms of safety and efficacy, and several immunotherapeutic agents, including pembrolizumab, nivolumab, and ipilimumab, have been approved for the treatment of advanced CRC. The advent of other immunotherapies, such as chimeric antigen receptor-modified T (CAR-T) cells or cancer vaccines, have also contributed to the development of immunotherapy for CRC. Here, we summarize the findings of recent clinical trials on the efficacy of immunotherapy in CRC and briefly describe the mechanisms associated with tumor-intrinsic resistance to ICIs. We then discuss potential biomarkers for predicting the efficacy of immunotherapy.

The Significance of Neutrophil Extracellular Traps in Colorectal Cancer and Beyond: From Bench to Bedside.

Neutrophil extracellular traps (NETs), products of neutrophil death when exposed to certain stimuli, were first proposed as a type of response to bacterial infection in infectious diseases. Since then, extensive studies have discovered its involvement in other non-infectious inflammatory diseases including thromboembolism, autoimmune diseases, and cancer. Colorectal cancer (CRC) is one of the most common malignancies in the world. NET formation is closely associated with tumorigenesis, progression, and metastasis in CRC. Therefore, the application of NETs in clinical practice as diagnostic biomarkers, therapeutic targets, and prognostic predictors has a promising prospect. In addition, therapeutics targeting NETs are significantly efficient in halting tumor progression in preclinical cancer models, which further indicates its potential clinical utility in cancer treatment. This review focuses on the stimuli of NETosis, its pro-tumorigenic activity, and prospective clinical utility primarily in but not limited to CRC.