COVID-19 trends at the University of Tennessee: predictive insights from raw sewage SARS-CoV-2 detection and evaluation and PMMoV as an indicator for human waste.

Wastewater-based epidemiology (WBE) has become a valuable tool for monitoring the prevalence of SARS-CoV-2 on university campuses. However, concerns about effectiveness of raw sewage as a COVID-19 early warning system still exist, and it's not clear how useful normalization by simultaneous comparison of Pepper Mild Mottle Virus (PMMoV) is in addressing variations resulting from fecal discharge dilution. This study aims to contribute insights into these aspects by conducting an academic-year field trial at the student residences on the University of Tennessee, Knoxville campus, raw sewage. This was done to investigate the correlations between SARS-CoV-2 RNA load, both with and without PMMoV normalization, and various parameters, including active COVID-19 cases, self-isolations, and their combination among all student residents. Significant positive correlations between SARS-CoV-2 RNA load a week prior, during the monitoring week, and the subsequent week with active cases. Despite these correlations, normalization by PMMoV does not enhance these associations. These findings suggest the potential utility of SARS-CoV-2 RNA load as an early warning indicator and provide valuable insights into the application and limitations of WBE for COVID-19 surveillance specifically within the context of raw sewage on university campuses.

Identification and characterization of the critical genes encoding Cd-induced enhancement of SOD isozymes activities in Zhe-Maidong (Ophiopogon japonicus).

Superoxide dismutase (SOD) protects plants from abiotic stress-induced reactive oxygen species (ROS) damage. Here, the effects of cadmium (Cd) exposure on ROS accumulation and SOD isozymes, as well as the identification of significant SOD isozyme genes, were investigated under different Cd stress treatments to Zhe-Maidong (Ophiopogon japonicus). The exposure to Cd stress resulted in a notable elevation in the SOD activity in roots. Cu/ZnSODa and Cu/ZnSODb were the most critical SOD isozymes in response to Cd stress, as indicated by the detection results for SOD isozymes. A total of 22 OjSOD genes were identified and classified into three subgroups, including 10 OjCu/ZnSODs, 6 OjMnSODs, and 6 OjFeSODs, based on the analysis of conserved motif and phylogenetic tree. Cu/ZnSOD-15, Cu/ZnSOD-18, Cu/ZnSOD-20, and Cu/ZnSOD-22 were the main genes that control the increase in SOD activity under Cd stress, as revealed via quantitative PCR and transcriptome analysis. Additionally, under various heavy metal stress (Cu2+, Fe2+, Zn2+, Mn2+), Cu/ZnSOD-15, Cu/ZnSOD-18, and Cu/ZnSOD-22 gene expression were significantly upregulated, indicating that these three genes play a critical part in resisting heavy metal stress. The molecular docking experiments performed on the interaction between oxygen ion (O2•-) and OjSOD protein have revealed that the critical amino acid residues involved in the binding of Cu/ZnSOD-22 to the substrate were Pro135, Ile136, Ile140, and Arg144. Our findings provide a solid foundation for additional functional investigations on the OjSOD genes, as well as suggestions for improving genetic breeding and agricultural management strategies to increase Cd resistance in O. japonicus.

A variable speed limit control approach for freeway tunnels based on the model-based reinforcement learning framework with safety perception.

To improve the traffic safety and efficiency of freeway tunnels, this study proposes a novel variable speed limit (VSL) control strategy based on the model-based reinforcement learning framework (MBRL) with safety perception. The MBRL framework is designed by developing a multi-lane cell transmission model for freeway tunnels as an environment model, which is built so that agents can interact with the environment model while interacting with the real environment to improve the sampling efficiency of reinforcement learning. Based on a real-time crash risk prediction model for freeway tunnels that uses random deep and cross networks, the safety perception function inside the MBRL framework is developed. The reinforcement learning components fully account for most current tunnels' application conditions, and the VSL control agent is trained using a deep dyna-Q method. The control process uses a safety trigger mechanism to reduce the likelihood of crashes caused by frequent changes in speed. The efficacy of the proposed VSL strategies is validated through simulation experiments. The results show that the proposed VSL strategies significantly increase traffic safety performance by between 16.00% and 20.00% and traffic efficiency by between 3.00% and 6.50% compared to a fixed speed limit approach. Notably, the proposed strategies outperform traditional VSL strategy based on the traffic flow prediction model in terms of traffic safety and efficiency improvement, and they also outperform the VSL strategy based on model-free reinforcement learning framework when sampling efficiency is considered together. In addition, the proposed strategies with safety triggers are safer than those without safety triggers. These findings demonstrate the potential for MBRL-based VSL strategies to improve traffic safety and efficiency within freeway tunnels.

The equitable impact of sugary drink taxation structures on sugary drink consumption among Canadians: a modelling study using the 2015 Canadian Community Health Survey-Nutrition.

OBJECTIVE: Estimate the impact of 20% flat-rate and tiered sugary drink tax structures on the consumption of sugary drinks, sugar-sweetened beverages, and 100% juice by age, sex, and socioeconomic position. DESIGN: We modelled the impact of price changes -for each tax structure- on the demand for sugary drinks by applying own- and cross-price elasticities to self-report sugary drink consumption measured using single day 24-hour dietary recalls from the cross-sectional, nationally-representative 2015 Canadian Community Health Survey-Nutrition. For both 20% flat-rate and tiered sugary drink tax scenarios, we used linear regression to estimate differences in mean energy intake and proportion of energy intake from sugary drinks by age, sex, education, food security and income. SETTING: Canada. PARTICIPANTS: 19,742 respondents aged 2 and over. RESULTS: In the 20% flat-rate scenario, we estimated mean energy intake and proportion of daily energy intake from sugary drinks on a given day would be reduced by 29 kcal/day (95%UI: 18, 41) and 1.3% (95%UI: 0.8, 1.8), respectively. Similarly, in the tiered tax scenario, additional small, but meaningful reductions were estimated in mean energy intake (40 kcal/day, 95%UI: 24, 55) and proportion of daily energy intake (1.8%, 95%UI: 1.1, 2.5). Both tax structures reduced, but did not eliminate, inequities in mean energy intake from sugary drinks despite larger consumption reductions in children/adolescents, males and individuals with lower education, food security and income. CONCLUSIONS: Sugary drink taxation, including an additional benefit of taxing 100% juice, could reduce overall and inequities in mean energy intake from sugary drinks in Canada.

Preparation of a Porous Geopolymer (SPG) to be Used as an Adsorbent for Cu2+ Removal.

A porous geopolymer was synthesized using steel slag (accounting for 71.6 wt %) with the aim of effectively removing Cu2+ ions. The chemical composition and microstructure of this material were investigated using X-ray diffraction spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscope analysis, and BET method. The effects of H2O2 doping, H2O doping, and the curing temperature on the properties of this porous geopolymer were systematically investigated. Subsequently, the adsorption behavior of the porous geopolymer toward Cu2+ was explored through static adsorption experiments. The findings reveal that there are a higher specific surface area and pore capacity for the porous geopolymer compared to the original steel slag, with a total porosity of 90.3%, compressive strength of 0.29 MPa, and volume water absorption rate of 69.4%. The adsorption capacity of this material toward Cu2+ is found to be 36.8 mg·g-1, which is slightly superior to that of commercial spherical 4A molecular sieves. The adsorption process follows the quasi-first-order kinetic model, while the isothermal adsorption conforms to the Freundlich model.

Colorectal cancer cells with stably expressed SIRT3 demonstrate proliferating retardation by Wnt/ß-catenin cascade inactivation.

Colorectal cancer (CRC) is a typical and lethal digestive system malignancy. In this study, we investigated the effect of sirtuin 3 (SIRT3) expression, a fidelity mitochondrial protein, on the proliferation of CRC cells and the mechanisms involved. Using the University of Alabama at Birmingham Cancer Data Analysis Portal database and the Clinical Proteomic Tumour Analysis Consortium database, we discovered that low expression of SIRT3 in CRC was a negative factor for survival prognosis (P < .05). Meanwhile, SIRT3 expression was correlated with distant metastasis and tumour, node, metastasis stage of CRC patients (P < .05). Subsequently, we observed that CRC cells with stable SIRT3 expression exhibited a significant decrease in proliferative capacities both in vitro and in vivo, compared to their counterparts (P < .05). Further investigation using western blot, immunoprecipitation and TOPflash/FOPflash assay showed the mechanism of growth retardation of these cells was highly associated with the degradation of ß-catenin in cytosol, and the localization of ß-catenin/α-catenin complex in the nucleus. In conclusion, our findings suggest that the inhibition of CRC cell proliferation by SIRT3 is closely associated with the inactivation of the Wnt/ß-catenin signalling pathway.

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells.

Background: A decrease in the number and activity of thymic epithelial cells (TECs) is an important factor in thymic degeneration. Mesenchymal stem cells (MSCs) treating thymic ageing is a promising strategy, but the DNA methylation modification mechanism in TECs remains unclear. Methods: Aged rhesus monkeys were treated with MSCs to establish a thymic senescence model, and hematoxylin-eosin (HE) staining, immunofluorescence staining, and ELISA were performed to observe the structure and function of the thymus. TEC aging model and MSCs co-culture system were established to detect DNA methylation modification and transcriptomic changes, correlation analysis between transcription factor methylation and mRNA expression, and q-PCR, immunofluorescence staining, and Western blot were used to identified key genes. Results: MSCs improved the structure and function of thymus in elderly macaque monkeys; reduced the expression levels of ß-Gal, P16, and P21; and increased the activity of aging TECs. There were 501 genes with increased methylation in the promoter region in the treated group compared with the untreated group, among which 23 genes were involved in the negative regulation of cell growth, proliferation and apoptosis, while 591 genes had decreased methylation, among which 37 genes were associated with promoting cell growth and proliferation and inhibiting apoptosis. Furthermore, 66 genes showed a negative correlation between promoter methylation levels and gene transcription; specifically, PDE5A, DUOX2, LAMP1 and SVIL were downregulated with increased methylation, inhibiting growth and development, while POLR3G, PGF, CHTF18, KRT17, FOXJ1, NGF, DYRK3, LRP8, CDT1, PRELID1, F2R, KNTC1 and TRIM3 were upregulated with decreased methylation, promoting cell growth. Conclusion: MSCs improve the structure and function of aged thymus, which involves the regulation of DNA methylation profiles and a decrease in the methylation level of the transcription factor NGF to specifically upregulate KRT17 and FOXJ1 to promote the proliferation of TECs.

PET brain imaging in neurological disorders.

Brain disorders are a series of conditions with damage or loss of neurons, such as Parkinson's disease (PD), Alzheimer's disease (AD), or drug dependence. These individuals have gradual deterioration of cognitive, motor, and other central nervous system functions affected. This degenerative trajectory is intricately associated with dysregulations in neurotransmitter systems. Positron Emission Tomography (PET) imaging, employing radiopharmaceuticals and molecular imaging techniques, emerges as a crucial tool for detecting brain biomarkers. It offers invaluable insights for early diagnosis and distinguishing brain disorders. This article comprehensively reviews the application and progress of conventional and novel PET imaging agents in diagnosing brain disorders. Furthermore, it conducts a thorough analysis on merits and limitations. The article also provides a forward-looking perspective in the future development directions of PET imaging agents for diagnosing brain disorders and proposes potential innovative strategies. It aims to furnish clinicians and researchers with an all-encompassing overview of the latest advancements and forthcoming trends in the utilization of PET imaging for diagnosing brain disorders.

SNHG4-mediated PTEN destabilization confers oxaliplatin resistance in colorectal cancer cells by inhibiting ferroptosis.

Oxaliplatin resistance poses a significant challenge in colorectal cancer (CRC) therapy, necessitating further investigation into the underlying molecular mechanisms. This study aimed to elucidate the regulatory role of SNHG4 in oxaliplatin resistance and ferroptosis in CRC. Our findings revealed that treatment with oxaliplatin led to downregulation of SNHG4 expression in CRC cells, while resistant CRC cells exhibited higher levels of SNHG4 compared to parental cells. Silencing SNHG4 attenuated oxaliplatin resistance and reduced the expression of resistance-related proteins MRD1 and MPR1. Furthermore, induction of ferroptosis effectively diminished oxaliplatin resistance in both parental and resistant CRC cells. Notably, ferroptosis induction resulted in decreased SNHG4 expression, whereas SNHG4 overexpression suppressed ferroptosis. Through FISH, RIP, and RNA pull-down assays, we identified the cytoplasmic localization of both SNHG4 and PTEN, establishing that SNHG4 directly targets PTEN, thereby reducing mRNA stability in CRC cells. Silencing PTEN abrogated the impact of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells. In vivo experiments further validated the influence of SNHG4 on oxaliplatin resistance and ferroptosis in CRC cells through PTEN regulation. In conclusion, SNHG4 promotes resistance to oxaliplatin in CRC cells by suppressing ferroptosis through instability of PTEN, thus serves as a target for patients with oxaliplatin-base chemoresistance.

HybAVPnet: a Novel Hybrid Network Architecture for Antiviral Peptides Prediction.

Viruses pose a great threat to human production and life, thus the research and development of antiviral drugs is urgently needed. Antiviral peptides play an important role in drug design and development. Compared with the time-consuming and laborious wet chemical experiment methods, it is critical to use computational methods to predict antiviral peptides accurately and rapidly. However, due to limited data, accurate prediction of antiviral peptides is still challenging and extracting effective feature representations from sequences is crucial for creating accurate models. This study introduces a novel two-step approach, named HybAVPnet, to predict antiviral peptides with a hybrid network architecture based on neural networks and traditional machine learning methods. We adopted a stacking-like structure to capture both the long-term dependencies and local evolution information to achieve a comprehensive and diverse prediction using the predicted labels and probabilities. Using an ensemble technique with the different kinds of features can reduce the variance without increasing the bias. The experimental result shows HybAVPnet can achieve better and more robust performance compared with the state-of-the-art methods, which makes it useful for the research and development of antiviral drugs. Meanwhile, it can also be extended to other peptide recognition problems because of its generalization ability.

Investigation of HLA susceptibility alleles and genotypes with hematological disease among Chinese Han population.

Several genes involved in the pathogenesis have been identified, with the human leukocyte antigen (HLA) system playing an essential role. However, the relationship between HLA and a cluster of hematological diseases has received little attention in China. Blood samples (n = 123913) from 43568 patients and 80345 individuals without known pathology were genotyped for HLA class I and II using sequencing-based typing. We discovered that HLA-A*11:01, B*40:01, C*01:02, DQB1*03:01, and DRB1*09:01 were prevalent in China. Furthermore, three high-frequency alleles (DQB1*03:01, DQB1*06:02, and DRB1*15:01) were found to be hazardous in malignant hematologic diseases when compared to controls. In addition, for benign hematologic disorders, 7 high-frequency risk alleles (A*01:01, B*46:01, C*01:02, DQB1*03:03, DQB1*05:02, DRB1*09:01, and DRB1*14:54) and 8 high-frequency susceptible genotypes (A*11:01-A*11:01, B*46:01-B*58:01, B*46:01-B*46:01, C*01:02-C*03:04, DQB1*03:01-DQB1*05:02, DQB1*03:03-DQB1*06:01, DRB1*09:01-DRB1*15:01, and DRB1*14:54-DRB1*15:01) were observed. To summarize, our findings indicate the association between HLA alleles/genotypes and a variety of hematological disorders, which is critical for disease surveillance.

Critically ill children with SARS-COV-2 Omicron infection at a national children medical center, Guangdong, China.

BACKGROUND: SARS-CoV-2 infection is described as asymptomatic, mild, or moderate disease in most children. SARS-CoV-2 infection related death in children and adolescents is rare according to the current reports. COVID-19 cases increased significantly in China during the omicron surge, clinical data regarding pediatric critical patients infected with the omicron variant is limited. In this study, we aim to provide an overview of the clinical characteristics and outcomes of critically ill children admitted to a national children's medical center in Guangdong Province, China, during the outbreak of the omicron variant infection. METHODS: We conducted a retrospective study from November 25, 2022, to February 8, 2023, which included 63 critically ill children, under the age of 18, diagnosed with SARS-CoV-2 infection. The patients were referred from medical institutions of Guangdong province. The medical records of these patients were analyzed and summarized. RESULTS: The median age of patients was 2 years (Interquartile Range, IQR: 1.0-8.0), sex-ratio (male/female) was 1.52. 12 (19%) patients (age ≥ 3 years) were vaccinated. The median length of hospital stay was 14 days (IQR: 6.5-23) in 63 cases, and duration of fever was 5 days (IQR: 3-8.5), pediatric intensive care unit (PICU) stay was 8 days (IQR 4.0-14.0) in 57 cases. 30 (48%) cases had clear contact history with family members who were infected with SARS-CoV-2. Three children who tested positive for SARS-CoV-2 infection did not show any abnormalities on chest imaging examination. Out of the total patients, 33 (52%) had a bacterial co-infection, with Staphylococcus aureus being the most commonly detected bacterial pathogen. Our cohort exhibited respiratory and nervous system involvement as the primary features. Furthermore, fifty (79%) patients required mechanical ventilation, with a median duration of 7 days (IQR 3.75-13.0). Among these patients, 35 (56%) developed respiratory failure, 16 (25%) patients experienced a deteriorating progression of symptoms and ultimately succumbed to the illness, septic shock was the most common condition among these patients (15 cases), followed by multiple organ failure in 12 cases, and encephalopathy identified in 7 cases. CONCLUSION: We present a case series of critically ill children infected with the SARS-CoV-2 omicron variant. While there is evidence suggesting that Omicron may cause less severe symptoms, it is important to continue striving for measures that can minimize the pathogenic impact of SARS-CoV-2 infection in children.

Adipose-derived stem cells promote glycolysis and peritoneal metastasis via TGF-ß1/SMAD3/ANGPTL4 axis in colorectal cancer.

Peritoneal metastasis, the third most common metastasis in colorectal cancer (CRC), has a poor prognosis for the rapid progression and limited therapeutic strategy. However, the molecular characteristics and pathogenesis of CRC peritoneal metastasis are poorly understood. Here, we aimed to elucidate the action and mechanism of adipose-derived stem cells (ADSCs), a prominent component of the peritoneal microenvironment, in CRC peritoneal metastasis formation. Database analysis indicated that ADSCs infiltration was increased in CRC peritoneal metastases, and high expression levels of ADSCs marker genes predicted a poor prognosis. Then we investigated the effect of ADSCs on CRC cells in vitro and in vivo. The results revealed that CRC cells co-cultured with ADSCs exhibited stronger metastatic property and anoikis resistance, and ADSCs boosted the intraperitoneal seeding of CRC cells. Furthermore, RNA sequencing was carried out to identify the key target gene, angiopoietin like 4 (ANGPTL4), which was upregulated in CRC specimens, especially in peritoneal metastases. Mechanistically, TGF-ß1 secreted by ADSCs activated SMAD3 in CRC cells, and chromatin immunoprecipitation assay showed that SMAD3 facilitated ANGPTL4 transcription by directly binding to ANGPTL4 promoter. The ANGPTL4 upregulation was essential for ADSCs to promote glycolysis and anoikis resistance in CRC. Importantly, simultaneously targeting TGF-ß signaling and ANGPTL4 efficiently reduced intraperitoneal seeding in vivo. In conclusion, this study indicates that tumor-infiltrating ADSCs promote glycolysis and anoikis resistance in CRC cells and ultimately facilitate peritoneal metastasis via the TGF-ß1/SMAD3/ANGPTL4 axis. The dual-targeting of TGF-ß signaling and ANGPTL4 may be a feasible therapeutic strategy for CRC peritoneal metastasis.

Comparison of seven anthropometric indexes to predict hypertension plus hyperuricemia among U.S. adults.

Purpose: This study aims to compare the association of hypertension plus hyperuricemia (HTN-HUA) with seven anthropometric indexes. These include the atherogenic index of plasma (AIP), lipid accumulation product (LAP), visceral adiposity index (VAI), triglyceride-glucose index (TyG), body roundness index (BRI), a body shape index (ABSI), and the cardiometabolic index (CMI). Methods: Data was procured from the National Health and Nutrition Examination Survey (NHANES), which recruited a representative population aged 18 years and above to calculate these seven indexes. Logistic regression analysis was employed to delineate their correlation and to compute the odds ratios (OR). Concurrently, receiver operating characteristic (ROC) curves were utilized to evaluate the predictive power of the seven indexes. Results: A total of 23,478 subjects were included in the study. Among these, 6,537 (27.84%) were patients with HUA alone, 2,015 (8.58%) had HTN alone, and 2,836 (12.08%) had HTN-HUA. The multivariate logistic regression analysis showed that the AIP, LAP, VAI, TyG, BRI, ABSI, and CMI were all significantly associated with concurrent HTN-HUA. The OR for the highest quartile of the seven indexes for HTN-HUA were as follows: AIP was 4.45 (95% CI 3.82-5.18), LAP was 9.52 (95% CI 7.82-11.59), VAI was 4.53 (95% CI 38.9-5.28), TyG was 4.91 (95% CI 4.15-5.80), BRI was 9.08 (95% CI 7.45-11.07), ABSI was 1.71 (95% CI 1.45 -2.02), and CMI was 6.57 (95% CI 5.56-7.76). Notably, LAP and BRI demonstrated significant discriminatory abilities for HTN-HUA, with area under the curve (AUC) values of 0.72 (95% CI 0.71 - 0.73) and 0.73 (95% CI 0.72 - 0.74) respectively. Conclusion: The AIP, LAP, VAI, TyG, BRI, ABSI, and CMI all show significant correlation with HTN-HUA. Notably, both LAP and BRI demonstrate the capability to differentiate cases of HTN-HUA. Among these, BRI is underscored for its effective, non-invasive nature in predicting HTN-HUA, making it a superior choice for early detection and management strategies.

[Clinical observation of different intramedullary fixation methods for the treatment of intertrochanteric fracture].

OBJECTIVE: To explore clinical efficacy of proximal femoral nail anti-rotation(PFNA),InterTan and proximal femoral bionic intramedullary nail (PFBN) in treating femoral intertrochanteric fracture. METHODS: Clinical data of 120 patients with intertrochanteric fracture who were underwent closed reduction intramedullary nail-internal fixation from January 2020 to January 2021 were retrospectively analyzed. According to methods of internal fixation,patients were divided into 3 groups. There were 25 patients in PFBN group,including 16 females and 9 males,aged from 69 to 79 years old with an average of (73.67±5.16) years old. There were 55 patients in PFNA group,including 38 females and 17 males,aged from 68 to 80 years old with an average of (74.23±5.57) years old. There were 40 patients in InterTan group,including 26 females and 14 males,aged from 68 to 79 years old with an average of (73.45±5.34) years old. Operative time,intraoperative blood loss,incision length,hospital stay,weight-bearing time,fracture healing time and complications among 3 groups were compared,and clinical effect was evaluated by Harris score of hip function before operation,1,6 and 12 months after opertaion,respectively. RESULTS: Patients among 3 groups were successfully completed operation and were followed up for more than 12 months. There were no significant difference in hospital stay,operative time,intraoperative blood loss and incision length among 3 groups (P>0.05). Weight bearing time of PFBN group (7.98±1.34) d and InterTan group (8.22±0.46) d were earlier than that of PFNA group (10.27±0.66) d(P<0.01). Fracture healing time of PFBN group (10.14±2.33) weeks and InterTan group (11.87±2.48) weeks were earlier than that of PFNA group (13.68±2.36) weeks (P<0.01). One month after operation,Harris score in PFBN group (70.52±5.34) and InterTan group (69.81±6.17) was higher than that of PFNA group (51.46±5.36),and there was no significant difference between PFBN group and InterTan group (P>0.05). There were no significant difference in Harris scores among 3 groups before operation,6 and 12 months after opertaion(P>0.05). Cases of complication of InterTan group and PFNA group were lower than that of PFNA group (P<0.05). CONCLUSION: PFBN and InterTan for the treatment of intertrochanteric fracture have advantages of faster fracture healing,earlier weight-bearing time and fewer postoperative complications than traditional PFNA,but three operations could achieve higher effective rates without significant difference in long-term results.

Elucidation of clinical implications Arising from circadian rhythm and insights into the tumor immune landscape in breast cancer.

Background: Circadian rhythm is an internal timing system generated by circadian-related genes (CRGs). Disruption in this rhythm has been associated with a heightened risk of breast cancer (BC) and regulation of the immune microenvironment of tumors. This study aimed to investigate the clinical significance of CRGs in BC and the immune microenvironment. Methods: CRGs were identified using the GeneCards and MSigDB databases. Through unsupervised clustering, we identified two circadian-related subtypes in patients with BC. We constructed a prognostic model and nomogram for circadian-related risk scores using LASSO and Cox regression analyses. Using multi-omics analysis, the mutation profile and immunological microenvironment of tumors were investigated, and the immunotherapy response in different groups of patients was predicted based on their risk strata. Results: The two circadian-related subtypes of BC that were identified differed significantly in their prognoses, clinical characteristics, and tumor immune microenvironments. Subsequently, we constructed a circadian-related risk score (CRRS) model containing eight signatures (SIAH2, EZR, GSN, TAGLN2, PRDX1, MCM4, EIF4EBP1, and CD248) and a nomogram. High-risk individuals had a greater burden of tumor mutations, richer immune cell infiltration, and higher expression of immune checkpoint genes, than low-risk individuals, indicating a "hot tumor" immune phenotype and a more favorable treatment outcome. Conclusions: Two circadian-related subtypes of BC were identified and used to establish a CRRS prognostic model and nomogram. These will be valuable in providing guidance for forecasting prognosis and developing personalized treatment plans for BC.

On-site rapid detection of multiple pesticide residues in tea leaves by lateral flow immunoassay.

The application of pesticides (mostly insecticides and fungicides) during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea. Thus, it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits. However, the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues. In this study, nine types of lateral flow immunochromatographic strips (LFICSs) were developed to detect the pesticides of interest (fenpropathrin, chlorpyrifos, imidacloprid, thiamethoxam, acetamiprid, carbendazim, chlorothalonil, pyraclostrobin, and iprodione). To reduce the interference of tea substrates on the assay sensitivity, the pretreatment conditions for tea samples, including the extraction solvent, extraction time, and purification agent, were optimized for the simultaneous detection of these pesticides. The entire testing procedure (including pretreatment and detection) could be completed within 30 min. The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.

Design, Synthesis, Biological Evaluation and Molecular Docking of Novel F-18-Labeled Focal Adhesion Kinase Inhibitors as Potential Tumor Radiotracers.

Tumor diagnosis, especially at the early stages, holds immense significance. Focal adhesion kinase (FAK) is often highly expressed across various types of tumors, making it a promising target for both therapy and diagnosis. In this study, seven novel inhibitors were designed and synthesized. The inhibitory activity of these compounds against FAK was notably potent, with an IC50 range of 1.27-1968 nM. In particular, compounds 7a and 7c, with IC50 values of 5.59 nM and 1.27 nM, respectively, were radiolabeled with F-18 and then evaluated with S-180 tumor-bearing mice. Subsequently, they exhibited moderate-to-high tumor uptake values, with [18F]7a showing 1.39 ± 0.30%ID/g at 60 min post injection and [18F]7c demonstrating 6.58 ± 0.46%ID/g at 30 min post injection. In addition, the results from docking studies revealed the binding specifics of the studied compounds. Overall, these findings hold the potential to offer valuable guidance for enhancing the development of radiotracers and enzyme inhibitors.

A prospective phase II clinical trial of total neoadjuvant therapy for locally advanced gastric cancer and gastroesophageal junction adenocarcinoma.

To investigate the safety and efficacy of the neoadjuvant chemoradiotherapy (NCRT) followed by neoadjuvant consolidation chemotherapy (NCCT) and surgery for locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma. Patients diagnosed as locally advanced GC or Siewert II/III GEJ adenocarcinoma with clinical stage T3-4 and/or N positive were prospectively enrolled. Patients underwent NCRT (45 Gy/25 fractions) with concurrent S-1, followed by NCCT (4 to 6 cycles of the SOX regimen) 2 to 4 weeks after NCRT. Gastric cancer radical resection with D2 lymph node dissection was performed 4 to 6 weeks after the total neoadjuvant therapy. The study was conducted from November 2019 to January 2023, enrolling a total of 46 patients. During the NCRT, all patients completed the treatment without dose reduction or delay. During the NCCT, 32 patients (69.6%) completed at least 4 cycles of chemotherapy. Grade 3 or higher adverse events in NCRT (5 cases) were non-hematological. During the course of NCCT, a notable occurrence of hematological toxicities was observed, with grade 3 or higher leukopenia (9.7%) and thrombocytopenia (12.2%) being experienced. A total of 28 patients (60.9%) underwent surgery, achieving R0 resection in all cases. A significant proportion of cases (71.4%) exhibited pathological downstaging to ypT0-2, while 10 patients (35.7%) demonstrated a pathologic complete response (pCR). The total neoadjuvant therapy comprising NCRT followed by NCCT and surgery demonstrates a low severe adverse reactions and promising efficacy, which could be considered as a viable treatment for locally advanced GC or GEJ adenocarcinoma.Trial registration: Clinicaltrials.gov (registration number: NCT04062058); the full date of first trial registration was 20/08/2019.