Impact of SUSAN Denoising and ComBat Harmonization on Machine Learning Model Performance for Malignant Brain Neoplasms.

BACKGROUND AND PURPOSE: Feature variability in radiomics studies due to technical and magnet strength parameters is well known and may be addressed through various pre-processing methods. However, very few studies have evaluated downstream impact of variable pre-processing on model classification performance in a multi-class setting. We sought to evaluate the impact of SUSAN denoising and ComBat harmonization on model classification performance. MATERIALS AND METHODS: A total of 493 cases (410 internal and 83 external dataset) of glioblastoma (GB), intracranial metastatic disease (IMD) and primary CNS lymphoma (PCNSL) underwent semi-automated 3D-segmentation post baseline image processing (BIP) consisting of resampling, realignment, co-registration, skull stripping and image normalization. Post BIP, two sets were generated, one with and another without SUSAN denoising (SD). Radiomics features were extracted from both datasets and batch corrected to produce four datasets: (a) BIP, (b) BIP with SD, (c) BIP with ComBat and (d) BIP with both SD and ComBat harmonization. Performance was then summarized for models using a combination of six feature selection techniques and six machine learning models across four mask-sequence combinations with features derived from one-three (multi-parametric) MRI sequences. RESULTS: Most top performing models on the external test set used BIP+SD derived features. Overall, use of SD and ComBat harmonization led to a slight but generally consistent improvement in model performance on the external test set. CONCLUSIONS: The use of image pre-processing steps such as SD and ComBat harmonization may be more useful in a multiinstitutional setting and improve model generalizability. Models derived from only T1-CE images showed comparable performance to models derived from multiparametric MRI.

Green Nanopesticide: pH Response and Molybdenum Selenide Carrier with Photothermal Effect to Transport Prochloraz to Inhibit Sclerotinia Disease.

Accurate pesticide delivery is a key factor in improving pesticide utilization, which can effectively reduce the use of pesticides and environmental risks. In this study, we developed a nanocarrier preparation method which can be controlled by pH/near-infrared response. Mesoporous molybdenum selenide (MoSe2) with a high loading rate was used as the core, poly(acrylic acid) (PAA) with acid response was used as the shell, and prochloraz (Pro) was loaded to form a pH-/near-infrared-responsive core-shell nanosystem (Pro@MoSe2@PAA NPs, abbreviated as PMP). Sclerotinia sclerotiorum infection secretes oxalic acid, forming an acidic microenvironment. In an acidic environment, PMP could quickly release Pro, and the cumulative release amount of Pro at pH = 5.0 was 3.1 times higher than that at pH = 7.4, and the efficiency of releasing Pro in the acidic environment was significantly enhanced. In addition, the release rate of PMP under near-infrared light irradiation was also significantly improved, and the cumulative release of Pro under simulated sunlight was 2.35 times higher than that under no light. The contact angles of PMP droplets on rapeseeds were reduced by 31.2 and 13.9% compared to Pro and MoSe2, respectively, which proved that the nanosystems had good wettability. In addition, PMP shows excellent adhesion and resistance to simulated rain washout. In the plate antibacterial experiment, the inhibitory effect of 0.5 µg/mL PMP on S. sclerotiorum was as high as 75.2% after 6 days, which showed a higher bactericidal activity than Pro. More importantly, PMP shows excellent biocompatibility and safety to plants, microorganisms, and cells. In a word, PMP is a green nanopesticide with a dual response of pH/near-infrared light, which provides a new strategy for the sustainable development of agriculture.

Survivin as a potential biomarker in the diagnosis of bladder cancer: A systematic review and meta-analysis.

Early detection, diagnosis, and treatment take on critical significance in preventing and treating bladder cancer. As indicated by numerous studies, survivin can serve as a biomarker of bladder cancer, whereas the results of a wide variety of studies have been controversial. This paper is to assess the accuracy of survivin in the diagnosis of bladder cancer by a meta-analysis. The studies regarding the diagnosis of bladder cancer using survivin were systematically retrieved from the CNKI, WanFang, CBM, VIP, Web of science, cochrane library and pubmed were extracted, and the literature quality was assessed. Meta-analysis was conducted using STATA 16.0 MP. 2,082 relevant studies were searched, and 40 studies were finally covered for meta-analysis. The pooled specificity and pooled sensitivity of survivin mRNA was 0.95 (95%CI: 0.91, 0.97) and 0.94 (95%CI: 0.88, 0.97). The pooled specificity and pooled sensitivity of survivin protein reached 0.95 (95%CI: 0.90, 0.97) and 0.87 (95%CI: 0.78, 0.92). The pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the curve, and diagnostic odds ratio for survivin mRNA reached 17.7 (95%CI: 10.3, 30.6), 0.07 (95%CI: 0.04, 0.12), 0.98 (95%CI: 0.97, 0.99) and 266 (95%CI: 114, 621), respectively. For survivin protein was 16.4 (95%CI: 7.9, 33.9), 0.14 (95%CI: 0.08, 0.24), 0.97 (95%CI: 0.95, 0.98) and 117 (95%CI: 38, 357), respectively. Survivin takes on great significance in diagnosing bladder cancer. However, due to some limitations in the number and quality of covered studies, this conclusion should be validated through additional higher quality clinical studies.

IFN-γ decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3ß signaling pathway.

Post-COVID-19 syndrome may be associated with the abnormal immune status. Compared with the unexposed age-matched elder group, PD-1 in the CD8+ T cells from recovered COVID-19 patients was significantly lower. IFN-γ in the plasma of COVID-19 convalescent patients was increased, which inhibited PD-1 expression in CD8+ T cells from COVID-19 convalescent patients. scRNA-seq bioinformatics analysis revealed that AKT/GSK3ß may regulate the INF-γ/PD-1 axis in CD8+ T cells from COVID-19 convalescent patients. In parallel, an IFN-γ neutralizing antibody reduced AKT and increased GSK3ß in PBMCs. An AKT agonist (SC79) significantly decreased p-GSK3ß. Moreover, AKT decreased PD-1 on CD8+ T cells, and GSK3ß increased PD-1 on CD8+ T cells according to flow cytometry analysis. Collectively, we demonstrated that recovered COVID-19 patients may develop long COVID. Increased IFN-γ in the plasma of recovered Wuhan COVID-19 patients contributed to PD-1 downregulation on CD8+ T cells by regulating the AKT/GSK3ß signaling pathway.

SlPHL1 positively modulates acid phosphatase in response to phosphate starvation by directly activating the genes SlPAP10b and SlPAP15 in tomato.

Increased acid phosphatase (APase) activity is a prominent feature of tomato (Solanum lycopersicum) responses to inorganic phosphate (Pi) restriction. SlPHL1, a phosphate starvation response (PHR) transcription factor, has been identified as a positive regulator of low Pi (LP)-induced APase activity in tomato. However, the molecular mechanism underlying this regulation remains to be elucidated. Here, SlPHL1 was found to positively regulate the LP-induced expression of five potential purple acid phosphatase (PAP) genes, namely SlPAP7, SlPAP10b, SlPAP12, SlPAP15, and SlPAP17b. Furthermore, we provide evidence that SlPHL1 can stimulate transcription of these five genes by binding directly to the PHR1 binding sequence (P1BS) located on their promoters. The P1BS mutation notably weakened SlPHL1 binding to the promoters of SlPAP7, SlPAP12, and SlPAP17b but almost completely abolished SlPHL1 binding to the promoters of SlPAP10b and SlPAP15. As a result, the transcriptional activation of SlPHL1 on SlPAP10b and SlPAP15 was substantially diminished. In addition, not only did transient overexpression of either SlPAP10b or SlPAP15 in tobacco leaves increase APase activity, but overexpression of SlPAP15 in Arabidopsis and tomato also increased APase activity and promoted plant growth. Subsequently, two SPX proteins, SlSPX1 and SlSPX4, were shown to physically interact with SlPHL1. Moreover, SlSPX1 inhibited the transcriptional activation of SlPHL1 on SlPAP10b and SlPAP15 and negatively regulated the activity of APase. Taken together, these results demonstrate that SlPHL1-mediated LP signaling promotes APase activity by activating the transcription of SlPAP10b and SlPAP15, which may provide valuable insights into the mechanisms of tomato response to Pi-limited stress.

The Pharmacokinetic Interaction of Tirabrutinib with Voriconazole, Itraconazole, and Fluconazole in SD Rats by UPLC-MS/MS.

BACKGROUND: Tirabrutinib is an orally effective, approved, and highly selective second-generation Bruton's tyrosine kinase (BTK) inhibitor for the treatment of recurrent or refractory primary central nervous system lymphoma (PCNSL). OBJECTIVE: This study aimed to develop an ultra-high performance liquid chromatography- tandem mass spectrometry (UPLC-MS/MS) method for the determination of tirabrutinib concentration in rat plasma, where zanubrutinib was used as an internal standard (IS). This method was also applied to study whether tirabrutinib would interact with voriconazole, itraconazole, and fluconazole in rats, providing a reference value for clinical medication guidance. METHODS: In the current study, the organic solvent protein precipitation method was used to treat plasma samples, which is simple and reproducible. Tirabrutinib (m/z 455.32 → 320.21) and zanubrutinib (m/z 472.13 → 455.04) were separated on a Waters Acquity BEH C18 column (2.1 × 50 mm, 1.7 µm) and detected by multiple reaction monitoring (MRM) in positive ionization mode. RESULTS: The method showed good linearity in the range of 5-3000 ng/mL for tirabrutinib with the lower limit of quantification (LLOQ) of 5 ng/mL. The recovery and matrix effects were 85.7-91.0% and 102.0-113.3%, respectively. The accuracy, precision, stability, and carry-over effect were also acceptable. The method could also be used for determining the pharmacokinetic interaction of tirabrutinib in rats. The results showed AUC0→∞ of tirabrutinib to be increased by 139.3% and 83.9% in the presence of voriconazole and fluconazole, respectively, while itraconazole had little effect. CONCLUSION: It is necessary to monitor the concentration of tirabrutinib in patients when it is combined with voriconazole and fluconazole to achieve a better therapeutic effect and reduce the risk of adverse reaction. Further research should be conducted in the future.

A systematic strategy for investigating the pharmacological effects and mechanism of traditional Chinese medicinal formula: Guilin Xiguashuang as a case.

BACKGROUND: Traditional Chinese medicinal formula (TCMF) has specific advantages in treating diseases. However, the pharmacological effects and mechanism of TCMF composed of traditional Chinese medicines (TCM) with unclear active components or targets have not yet been fully elucidated. OBJECTIVES: This research proposed a strategy for elucidating the pharmacological effects and mechanism to address this issue systematically. METHODS: With Guilin Xiguashuang (GLXGS) taken as a case, this study newly provided the multi-level assays, which decomposes TCMF into components, TCM, and TCMF levels. The main pharmacological effects were acquired through a comprehensive analysis based on the active components, pharmacological effects of TCM, and clinical efficacy of TCMF, respectively. The core targets and pathways were further identified and verified to elucidate the mechanism. RESULTS: The main pharmacological effects of GLXGS were anti-inflammatory, analgesic, antibacterial, immunoregulatory, and wound healing. Moreover, the mechanism analysis demonstrated that GLXGS was involved in the regulation of NF-κB and VEGF signaling pathways and core targets, such as IL-6 and TNF-α. Finally, unproven immunomodulatory and anti-inflammatory mechanism were verified using RAW264.7 and THP-1 cells. GLXGS was verified to down-regulate IL-6, IL-1ß, TNF-α, and CD86 in lipopolysaccharides-stimulated RAW264.7 cells, while enhancing polarization in both RAW264.7 and THP-1 cells, which were consistent with analysis results. CONCLUSION: The present research provides a systematic strategy for the pharmacological effect prediction and mechanism analysis of TCMF, which is of great significance for studying complex TCMF.

NOBILETIN AMELIORATES HEATSTROKE-INDUCED ACUTE LUNG INJURY BY INHIBITING FERROPTOSIS VIA P53/SLC7A11 PATHWAY.

ABSTRACT: The molecular mechanism for nobiletin's protective effect against heatstroke-induced acute lung injury (HS-ALI) remains largely unknown. Previous research has demonstrated that ferroptosis is an important pathogenic event in HS-ALI. Nobiletin is a natural polymethoxylated flavonoid. Herein, we investigated the potential contribution of nobiletin to HS-ALI by inhibiting ferroptosis. Heat stress was used to induce HS-ALI in mice, and mouse lung epithelial-12 (MLE-12) cells were stimulated by heat stress in vitro . Nobiletin was administrated by gavage for 2 h before HS induction. Biochemical kits, immunofluorescence staining, and western blotting were performed on the markers of ferroptosis. Our results showed that nobiletin administration significantly attenuated HS-induced lung injury and ferroptosis. Moreover, nobiletin pretreatment significantly reversed HS-induced p53 upregulation in vivo and in vitro . Pretreatment with a p53 agonist, tenovin-6, partly abolished the protective effect of nobiletin in mice with HS-ALI. Meanwhile, p53 knockdown significantly increased GPX4 and SLC7A11 expression levels compared with the HS group in HS-induced MLE-12 cells. Subsequently, nobiletin ameliorated HS-induced MLE-12 cells ferroptosis by activating the SLC7A11/GPX4 pathway, whereas p53 overexpression effectively abolished the protective effect of nobiletin. Taken together, our findings reveal that nobiletin attenuates HS-ALI by inhibiting ferroptosis through the p53/SLC7A11 pathway, indicating it to be a potential therapeutic agent for HS-ALI prevention and treatment.

Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance.

Introduction: Adenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive. Methods: 119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice. Results: In AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of Akkermansia, Oscillospiraceae and Eubacterium coprostanoligenes genera and increased abundances of Bacteroides, Faecalibacterium, Ruminococcus gnavus genera were revealed in AH patients. The abundance of Bacteroides remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT. Conclusion: These findings highlight the effect of the altered gut microbiota in the AH pathogenesis.

Inhibitory effect of napabucasin on arbidol metabolism and its mechanism research.

As a broad-spectrum antiviral, and especially as a popular drug for treating coronavirus disease 2019 (COVID-19) today, arbidol often involves drug-drug interactions (DDI) when treating critical patients. This study established a rapid and effective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to detect arbidol and its metabolite arbidol sulfoxide (M6-1) levels in vivo and in vitro. In this study, a 200 µL incubation system was used to study the inhibitory effect of the antitumor drug napabucasin on arbidol in vitro, with IC50 values of 2.25, 3.91, and 67.79 µM in rat liver microsomes (RLMs), human liver microsomes (HLMs), and CYP3A4.1, respectively. In addition, we found that the mechanism of inhibition was non-competitive inhibition in RLM and mixed inhibition in HLM. In pharmacokinetic experiments, it was observed that after gavage administration of 48 mg/kg napabucasin and 20 mg/kg arbidol, napabucasin inhibited the metabolism of arbidol in vivo and significantly changed the pharmacokinetic parameters of arbidol, such as AUC(0-t) and AUC(0-∞), in rats. We also found that napabucasin increased the AUC(0-t) and AUC(0-∞) of M6-1, the main metabolite of arbidol. This study provides a reference for the combined use of napabucasin and arbidol in clinical practice.

Direct Enol Ether Metalation-Negishi Coupling Strategy To Prepare α-Heteroaryl Enol Ethers.

A robust direct enol ether metalation-Negishi coupling using heteroaryl halides catalyzed by the palladium-Cy-DPEPhos system is reported. This method, which was demonstrated with a broad substrate scope, is a highly complementary method to the existing Heck coupling of synthesizing challenging α-heteroaryl-α-alkoxy alkenes.

Simultaneous Quantification of Seven Antifungal Agents in Human Serum Using Liquid Chromatography-Tandem Mass Spectrometry.

Systemic antifungal agents are essential for high-risk patients undergoing immunosuppressive therapy or cancer chemotherapy because of the rapid increase in opportunistic fungal infections. Therapeutic drug monitoring is crucial to ensuring the efficacy and safety of antifungal agents owing to their pharmacokinetic variability. In the present study, we developed and validated a quantitative method for the simultaneous detection of seven commonly used antifungal drugs (amphotericin B, isavuconazole, voriconazole, fluconazole, posaconazole, caspofungin, and micafungin) using liquid chromatography-tandem mass spectrometry. Methanol (containing 0.1% formic acid) was used for protein precipitation and only 50 µL of serum was required for the analysis. Chromatographic separation was conducted using a Waters Acquity UPLC C8 column, and one stable isotope-labeled agent and two analogs were used as internal standards. The calibration curves ranged from 0.1 to 50 µg/mL for all agents, and the correlation coefficient (R2) for all calibration curves was above 0.9835. The intra-day precision (1.2-11.2%), inter-day precision (2.4-13.2%), and mean bias values (-10.9 to 13.6%) were within an acceptable range of ±15%. Successful implementation of the developed method in clinical practice would facilitate the effective monitoring of these antifungal agents.

Deltonin enhances gastric carcinoma cell apoptosis and chemosensitivity to cisplatin via inhibiting PI3K/AKT/mTOR and MAPK signaling.

BACKGROUND: As an active ingredient derived from Dioscorea zingiberensis C.H. Wright, deltonin has been reported to show anti-cancer effects in a variety of malignancies. AIM: To investigate the role and mechanism of action of deltonin in promoting gastric carcinoma (GC) cell apoptosis and chemosensitivity to cisplatin. METHODS: The GC cell lines AGS, HGC-27, and MKN-45 were treated with deltonin and then subjected to flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium bromide assays for cell apoptosis and viability determination. Western blot analysis was conducted to examine alterations in the expression of apoptosis-related proteins (Bax, Bid, Bad, and Fas), DNA repair-associated proteins (Rad51 and MDM2), and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/AKT/mTOR) and p38-mitogen-activated protein kinase (MAPK) axis proteins. Additionally, the influence of deltonin on GC cell chemosensitivity to cisplatin was evaluated both in vitro and in vivo. RESULTS: Deltonin treatment weakened viability, enhanced apoptosis, and dampened DNA repair in GC cell lines in a dose-dependent pattern. Furthermore, deltonin mitigated PI3K, AKT, mTOR, and p38-MAPK phosphorylation. HS-173, an inhibitor of PI3K, attenuated GC cell viability and abolished deltonin inhibition of GC cell viability and PI3K/AKT/mTOR and p38-MAPK pathway activation. Deltonin also promoted the chemosensitivity of GC cells to cisplatin via repressing GC cell proliferation and growth and accelerating apoptosis. CONCLUSION: Deltonin can boost the chemosensitivity of GC cells to cisplatin via inactivating p38-MAPK and PI3K/AKT/mTOR signaling.

Differentiation Between Glioblastoma and Metastatic Disease on Conventional MRI Imaging Using 3D-Convolutional Neural Networks: Model Development and Validation.

RATIONALE AND OBJECTIVES: Imaging-based differentiation between glioblastoma (GB) and brain metastases (BM) remains challenging. Our aim was to evaluate the performance of 3D-convolutional neural networks (CNN) to address this binary classification problem. MATERIALS AND METHODS: T1-CE, T2WI, and FLAIR 3D-segmented masks of 307 patients (157 GB and 150 BM) were generated post resampling, co-registration normalization and semi-automated 3D-segmentation and used for internal model development. Subsequent external validation was performed on 59 cases (27 GB and 32 BM) from another institution. Four different mask-sequence combinations were evaluated using area under the curve (AUC), precision, recall and F1-scores. Diagnostic performance of a neuroradiologist and a general radiologist, both without and with the model output available, was also assessed. RESULTS: 3D-model using the T1-CE tumor mask (TM) showed the highest performance [AUC 0.93 (95% CI 0.858-0.995)] on the external test set, followed closely by the model using T1-CE TM and FLAIR mask of peri-tumoral region (PTR) [AUC of 0.91 (95% CI 0.834-0.986)]. Models using T2WI masks showed robust performance on the internal dataset but lower performance on the external set. Both neuroradiologist and general radiologist showed improved performance with model output provided [AUC increased from 0.89 to 0.968 (p = 0.06) and from 0.78 to 0.965 (p = 0.007) respectively], the latter being statistically significant. CONCLUSION: 3D-CNNs showed robust performance for differentiating GB from BMs, with T1-CE TM, either alone or combined with FLAIR-PTR masks. Availability of model output significantly improved the accuracy of the general radiologist.

The impacts of CYP3A4 genetic polymorphism and drug interactions on the metabolism of lurasidone.

The aim of this study was to investigate the impacts of 24 variants of recombinant human CYP3A4 and drug interactions on the metabolism of lurasidone. In vitro, enzymatic reaction incubation system of CYP3A4 was established to determine the kinetic parameters of lurasidone catalyzed by 24 CYP3A4 variants. Then, we constructed rat liver microsomes (RLM) and human liver microsomes (HLM) incubation system to screen potential anti-tumor drugs that could interact with lurasidone and studied its inhibitory mechanism. In vivo, Sprague-Dawley (SD) rats were applied to study the interaction between lurasidone and olmutinib. The concentrations of the analytes were detected by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). As the results, we found that compared with the wild-type CYP3A4, the relative intrinsic clearances vary from 355.77 % in CYP3A4.15 to 14.11 % in CYP3A4.12. A series of drugs were screened based on the incubation system, and compared to without olmutinib, the amount of ID-14283 (the metabolite of lurasidone) in RLM and HLM were reduced to 7.22 % and 7.59 %, and its IC50 were 18.83 ± 1.06 µM and 16.15 ± 0.81 µM, respectively. At the same time, it exerted inhibitory effects both through a mixed mechanism. When co-administration of lurasidone with olmutinib in rats, the AUC(0-t) and AUC(0-∞) of lurasidone were significantly increased by 73.52 % and 69.68 %, respectively, while CLz/F was observably decreased by 43.83 %. In conclusion, CYP3A4 genetic polymorphism and olmutinib can remarkably affect the metabolism of lurasidone.

Decreased risk of radiation pneumonitis with concurrent use of renin-angiotensin system inhibitors in thoracic radiation therapy of lung cancer.

Background: Radiation pneumonitis (RP) is the primary dose-limiting toxicity associated with radiotherapy. This study aimed to observe the effects of renin-angiotensin system inhibitors in Chinese patients with lung cancer who received thoracic radiation. Methods: Patients with lung cancer who received thoracic radiation at a total dose of ≥45 Gray between October 2017 and December 2022 were enrolled in this study. We retrospectively evaluated the factors influencing grade 2 or higher RP. Results: A total of 320 patients were enrolled in this study; 62 patients were identified as angiotensin receptor blockers or angiotensin-converting enzyme inhibitor users. Additionally, 99 patients (30.9%) had grade 2 or higher RP, and the incidence in the renin-angiotensin system inhibitor group was 17.7% (11 out of 62 patients). Patients in the renin-angiotensin system inhibitors (RASi) group were older and had a higher percentage of males, lower percentage of ECOG score 0, higher percentage of hypertension, and higher percentage of adenocarcinoma than those in the non-RASi group. ECOG score [hazard ratio (HR) = 1.69, p = 0.009], history of smoking (HR = 1.76, p = 0.049), mean dose (HR = 3.63, p = 0.01), and RASi (HR = 0.3, p = 0.003) were independent predictive factors for RP. All subgroups benefited from RASi. Conclusion: This study showed that oral RASi administration has the potential to mitigate the incidence of grade 2 or higher RP in patients with lung cancer undergoing thoracic radiotherapy. To validate and further substantiate these findings, additional prospective research is warranted.

Potential and mechanism of disinfection by-products removal in drinking water by bubbling corona discharge.

Disinfection by-products (DBPs) with significant teratogenic and carcinogenic properties have become a growing concern among the public. As an efficient and environmentally friendly technology, non-thermal plasma offers potential for removing emerging micro-pollutants. In this study, the degradation performance of bubbling corona discharge was evaluated on 24 halogenated alicyclic and aliphatic DBPs present in drinking water at concentrations ranging from ng/L to µg/L. The degradation of DBPs followed pseudo-first-order kinetics with rate constants (kobs) in the descending order of halonitromethanes (HNMs), halogenated benzoquinones (HBQs), haloacetonitriles, trihalomethanes (THMs), haloketones, halogenated aldehydes, and haloacetic acids (HAAs). THMs, HNMs, and HBQs were effectively removed within 5 min under a discharge power of 28 W. Degradation rates achieved by plasma treatment surpass those of other conventional treatment technologies. The required energy consumption was in the range of 5-30 kW·h/m3/order. Furthermore, the study investigated the effects of discharge power, initial concentration, and economic analysis on the degradation of four selected DBPs as representatives of mono-, di- and multi-carbon-containing DBPs, namely chloroform (TCM) and bromoform (TBM), tribromoacetic acid (TBAA), and 2,3,5,6-tetrachloro-1,4-benzoquinone (TetraC-BQ). Reactive radicals in the plasma system were investigated using electron paramagnetic resonance, optical emission spectroscopy, fluorimetry, and radical scavengers. Hydrated electrons and hydroxyl radicals played an important role in the removal of DBPs. The intermediates generated during the degradation of TCM, TBM, TBAA, and TetraC-BQ were identified, and the possible degradation pathways for mono- and binary C-DBPs and HBQs were deduced. The breakdown of HBQs did not produce secondary contamination with aliphatic DBPs. The carbon in DBPs was primarily converted to formic acid, acetic acid, and oxalic acid, and the halogens were mainly converted to halogen ions. Additionally, luminescent bacteria toxicity testing confirmed that plasma treatment could reduce the acute toxicity of water samples. These findings demonstrate the potential of plasma treatment as a post-treatment device at the household level.

FSE-Net: feature selection and enhancement network for mammogram classification.

Objective. Early detection and diagnosis allow for intervention and treatment at an early stage of breast cancer. Despite recent advances in computer aided diagnosis systems based on convolutional neural networks for breast cancer diagnosis, improving the classification performance of mammograms remains a challenge due to the various sizes of breast lesions and difficult extraction of small lesion features. To obtain more accurate classification results, many studies choose to directly classify region of interest (ROI) annotations, but labeling ROIs is labor intensive. The purpose of this research is to design a novel network to automatically classify mammogram image as cancer and no cancer, aiming to mitigate or address the above challenges and help radiologists perform mammogram diagnosis more accurately.Approach. We propose a novel feature selection and enhancement network (FSE-Net) to fully exploit the features of mammogram images, which requires only mammogram images and image-level labels without any bounding boxes or masks. Specifically, to obtain more contextual information, an effective feature selection module is proposed to adaptively select the receptive fields and fuse features from receptive fields of different scales. Moreover, a feature enhancement module is designed to explore the correlation between feature maps of different resolutions and to enhance the representation capacity of low-resolution feature maps with high-resolution feature maps.Main results. The performance of the proposed network has been evaluated on the CBIS-DDSM dataset and INbreast dataset. It achieves an accuracy of 0.806 with an AUC of 0.866 on the CBIS-DDSM dataset and an accuracy of 0.956 with an AUC of 0.974 on the INbreast dataset.Significance. Through extensive experiments and saliency map visualization analysis, the proposed network achieves the satisfactory performance in the mammogram classification task, and can roughly locate suspicious regions to assist in the final prediction of the entire images.

Conjugated linoleic acid (CLA) as a functional food: Is it beneficial or not?

Conjugated linoleic acid (CLA) has attracted great attention in recent years as a popular class of functional food that is broadly used. It refers to a group of geometric and positional isomers of linoleic acid (LA) with a conjugated double bond. The main natural sources of CLA are dairy products, beef and lamb, whereas only trace amounts occur naturally in plant lipids. CLA has been shown to improve various health issues, having effects on obesity, inflammatory, anti-carcinogenicity, atherogenicity, immunomodulation, and osteosynthesis. Also, compared to studies on humans, many animal researches reveal more positive benefits on health. CLA represents a nutritional avenue to improve lifestyle diseases and metabolic syndrome. Most of these effects are attributed to the two major CLA isomers [conjugated linoleic acid cis-9,trans-11 isomer (c9,t11), and conjugated linoleic acid trans-10,cis-12 isomer (t10,c12)], and their mixture (CLA mix). In contrast, adverse effects of CLA have been also reported, such as glucose homeostasis, insulin resistance, hepatic steatosis and induction of colon carcinogenesis in humans, as well as milk fat inhibition in ruminants, lowering chicken productivity, influencing egg quality and altering growth performance in fish. This review article aims to discuss the health benefits of CLA as a nutraceutical supplement and highlight the possible mechanisms of action that may contribute to its outcome. It also outlines the feasible adverse effects of CLA besides summarizing the recent peer-reviewed publications on CLA to ensure its efficacy and safety for proper application in humans.

Intracavitary cardiac metastasis of cervical squamous cell carcinoma with immune thrombocytopenia: a rare case report.

Cervical cancer is a prevalent gynecological malignancy; however, intracavitary cardiac metastasis of cervical squamous cell carcinoma is exceptionally rare. In addition, the co-occurrence of cervical cancer and right ventricular cancer thrombus with autoimmune diseases is extremely uncommon. Furthermore, the role of immune checkpoint inhibitors in the treatment process of such cases remains controversial. Given the scarcity of reported cases, it is imperative to document and highlight this unique presentation, providing novel insights into diagnosis and management strategies. We present the case of an adult patient diagnosed with cervical cancer and concurrent right ventricular cancer thrombus, accompanied by immune thrombocytopenia (ITP). The patient exhibited resistance to conventional ITP drugs, with suboptimal platelet response. However, upon achieving initial control of the tumor, the patient's platelet counts returned to normal. Notably, the addition of immune checkpoint inhibitors targeting PD-L1 resulted in effective tumor control, accompanied by sustained high platelet levels. Unfortunately, during subsequent anti-tumor therapy, the patient experienced a prolonged platelet rise time, rendering continuous effective anti-tumor therapy and anticoagulant therapy unattainable. This led to a gradual increase in intraventricular thrombosis, ultimately resulting in the patient's demise due to circulatory failure. This rare case sheds light on the potential alleviation of ITP in patients with tumor complications through effective antitumor therapy. The successful control of ITP after tumor management highlights the importance of integrated treatment approaches. Furthermore, the inclusion of immune checkpoint inhibitors demonstrated their potential role in achieving tumor control and maintaining platelet levels. However, the prolonged platelet rise time observed during subsequent therapy underscores the challenges in maintaining both effective anti-tumor therapy and anticoagulant therapy, necessitating careful management strategies. This case report emphasizes the need for a comprehensive evaluation and tailored therapeutic interventions in similar complex scenarios. In summary, this case report offers valuable clinical insights into the management of intracavitary cardiac metastasis of cervical squamous cell carcinoma, the coexistence of immune thrombocytopenia, and the potential implications of immune checkpoint inhibitors in such cases. Understanding these rare occurrences and their clinical impact can contribute to improved diagnostic approaches, therapeutic decision-making, and patient outcomes.