Case report: Cardiac neuroendocrine carcinoma and squamous cell carcinoma treated with MR-guided adaptive stereotactic radiation therapy.

We present two cases of cardiac metastases adjacent to the right ventricle in a 55-year-old male and a 61-year-old female, both treated with magnetic resonance (MR)-guided adaptive stereotactic radiation therapy (SBRT). The prescribed regimen was 30Gy delivered in 3 fractions using a 1.5 Tesla magnetic resonance linear accelerator (MR-linac). Patients exhibited favorable tolerance to the treatment, with no observed acute toxicity.

Stable or at least once HER2-low status during neoadjuvant chemotherapy confers survival benefit in patients with breast cancer.

BACKGROUND: Temporal heterogeneity in human epidermal growth factor receptor 2 (HER2) status may be associated with the prognosis of breast cancer. We aimed to clarify the relationship of HER2-low transition during neoadjuvant therapy with survival outcomes under the new classification of HER2 status. METHODS: This retrospective study was conducted based on the prospective database of breast cancer patients treated with neoadjuvant therapy from September 2013 to August 2020. RESULTS: This analysis enrolled 185 patients, including 44 patients with HER2-zero tumours, 93 patients with HER2-low tumours and 48 patients with HER2-positive tumours after neoadjuvant therapy. Nearly, 57.6% of HER2-zero tumours turned into HER2-low tumours after neoadjuvant therapy, while 25.0% of HER2-low patients changed to HER2-zero or HER2-positive tumours. We found that at least once diagnosis as HER2-low breast cancer was related to hormone receptor status (p < .001) and Ki-67 expression (p = .036). Patients ever diagnosed as HER2-low tumours had favourable clinicopathological features (less Ki-67 expression, lower pathological staging, etc.) as well as significantly better locoregional relapse-free survival (LRFS; p = .007) and overall survival (OS; p = .026) compared with those never exhibiting HER2-low expression. Furthermore, the 6-year OS rates were 94.2% (95% confidence interval (CI) 83.1-98.1), 88.7% (74.4-95.2) and 78.1% (65.4-86.6) for patients with stable, once and none HER2-low expression, respectively (adjusted HR, 0.514 [95%CI, 0.294-0.897], p = .019). CONCLUSIONS: Our study first indicated in patients across all expression levels of HER2 that stable or at least once HER2-low status may confer favourable attributes including less malignant biological behaviour and long-term survival benefit for breast cancer receiving neoadjuvant therapy.

Stable or at least once HER2-low status may confer favourable attributes including less malignant biological behaviour and long-term survival benefit for breast cancer receiving neoadjuvant therapy.HER2-low expression was highly instable during disease evolution from primary lesion to residual tumour and was associated with hormone receptor status, which warrants HER2 re-test in residual lesion, especially for patients with HER2-zero disease at initial diagnosis, so as to give a clear picture of not only prognostic significance but also treatment availability.

Knockdown of SlYTHDF2 Accelerates Dark-Induced Tomato Leaf Senescence by Affecting the ABA Pathway.

N6-methyladenosine (m6A) is a widespread post-transcriptional modification in eukaryotic mRNAs. Proteins with the YTH structural domain act as m6A-binding proteins by recognizing the m6A modification and regulating mRNA through this recognition. In this study, SlYTHDF2, a prototypical m6A -binding protein gene in the YTH family was expressed in various tissues, and subcellular localization analyses indicated that the SlYTHDF2 protein was localized in the nucleus and cytoplasm. SlYTHDF2 knockout lines were obtained using CRISPR/Cas9 technology and showed the senesced leaves prematurely increased endogenous ABA accumulation compared with the wild type. Moreover, we found that dark promoted leaf senescence in SlYTHDF2 knockout lines and exogenous ABA further accelerated leaf senescence under dark conditions. The qRT-PCR analysis revealed significant alterations in the expression of genes associated with the ABA pathway. Relative to the wild type, the CR-slythdf2 plants exhibited reduced levels of photosynthetic pigments, higher accumulation of reactive oxygen species, and increased damage to cell membranes. Additionally, we discovered that SlYTHDF2 interacts with the chloroplast-binding protein SlRBCS3 through yeast two-hybrid and BiFC experiments. Overall, our data suggest the important role of SlYTHDF2 in regulating tomato leaf senescence.

The Epstein-Barr virus small capsid protein BFRF3 disrupts the NF-кB signaling pathway by inhibiting p65 activity.

Epstein-Barr virus (EBV), a common gamma herpesvirus, establishes a life-long latent infection in the host to defend against innate immune recognition, which is closely related to a variety of malignant tumors, but its specific mechanism is unclear. BFRF3, an EBV-encoded small capsid protein, is mainly involved in the assembly of the viral capsid structure and the maintenance of its stability. Here, we showed that BFRF3 can inhibit TNF-α-mediated NF-кB promoter activation. Moreover, BFRF3 downregulates NF-кB-mediated promoter activation and transcription of inflammatory cytokines, including IL-6 and IL-8. Dual-luciferase reporter assay demonstrated that BFRF3 restrains NF-кB promoter activity at or below the p65 level, and coimmunoprecipitation analysis revealed that BFRF3 not only interacts with p65 but also binds to its critical truncated Rel homology domain (RHD) and transcriptional activation domain (TAD). However, BFRF3 does not affect the dimerization of p65-p50, but overexpression of BFRF3 reduces the nuclear accumulation of p65, and the phosphorylation of p65 (Ser536) is repressed during BFRF3 transfection and EBV lytic infection, which promotes the proliferation of EBV. Overall, our study suggested that BFRF3 may play a crucial role in antiviral immunity to defend against EBV infection by inhibiting NF-κB activity.

Photodynamic Therapy for Condyloma Acuminatum and Cervical Intraepithelial Neoplasia Grade I in a Young Female Patient with Systemic Lupus Erythematosus: A Case Report.

Condyloma acuminatum (CA), commonly known as anogenital warts, is a prevalent sexually transmitted disease primarily caused by low risk human papillomavirus (HPV) types 6 and 11. This case report outlines the successful use of photodynamic therapy (PDT) to treat extensive condyloma acuminatum in a young female patient with systemic lupus erythematosus (SLE) undergoing immunosuppressive treatment. The patient also had cervical intraepithelial neoplasia grade I. Carbon dioxide laser treatment were initially used to remove some surface warts, followed by PDT, resulting in satisfactory outcomes. After seven sessions, the warty growths were successfully removed. Interdisciplinary collaboration, involving rheumatology, gynecology, and dermatology, facilitated comprehensive management. This case highlights the efficacy and safety of PDT in treating condyloma acuminatum and suggests its potential as an alternative treatment for young SLE patients with similar conditions.

Prognostic role of dynamic changes in inflammatory indicators in patients with non-small cell lung cancer treated with immune checkpoint inhibitors-a retrospective cohort study.

Background: Immune checkpoint inhibitors (ICIs) have become one of the standard treatments for non-small cell lung cancer (NSCLC) patients without driver mutations. However, a considerable proportion of patients suffer from severe immune side effects and fail to respond to ICIs. As effective biomarkers, programmed cell death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) require invasive procedures that place heavy physical and psychological burdens on patients. This study aims to identify simple and effective markers to optimize patient selection through therapeutic decisions and outcome prediction. Methods: This retrospective study comprised 95 patients with metastatic NSCLC who were treated with ICIs either as the standard of care or in a clinical trial. The following data were extracted from the medical records. The baseline and dynamic neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated in the present study. Responses were assessed by computed tomography (CT) imaging and classified according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 every 6-12 weeks during treatment. Results: In total, 95 patients were included in the present study. The median age of patients was 61 years, 83.2% (79/95) patients were male, 62.1% (59/95) were former or current smokers, 66.3% (63/95) had adenocarcinoma, 93.7% (89/95) had stage IV disease, and 87.4% were without molecular alterations. A higher overall response rate (ORR) and prolonged median progression-free survival (PFS) was observed in patients with a lower cycle 3 (C3) NLR [7.7 vs. 5.5 months, hazard ratio (HR): 1.70, 95% confidence interval (CI): 0.90-3.22; P=0.12] and derived NLR (dNLR) (8.2 vs. 5.6 months, HR: 1.67, 95% CI: 0.94-2.97; P=0.08). After two cycles of ICI treatment, patients who had an increased NLR, dNLR, and PLR had a lower ORR and an inferior median PFS than those with a decreased NLR (5.5 vs. 8.5 months, HR: 1.87, 95% CI: 1.09-3.21; P=0.02), dNLR (5.6 vs. 8.4 months, HR: 1.49, 95% CI: 0.87-2.57; P=0.15), and PLR (11.8 vs. 5.5 months, HR: 2.28, 95% CI: 1.32-3.94; P=0.003). Moreover, patients with both an increased NLR and PLR had a worse ORR and median PFS than those with either an increased NLR or PLR, or both an increased NLR and PLR (11.8 vs. 5.5 vs. 5.6 months, P=0.003). In addition, the dynamic changes in the PLR could serve as an independent predictive factor of PFS in NSCLC patients treated with ICIs. Conclusions: Elevated dynamic changes in the NLR and PLR were associated with lower response rates and shorter PFS in the patients with NSCLC treated with ICIs. Our results also highlight the role of dynamic changes in the PLR in identifying patients with NSCLC who could benefit from ICIs.

Associations of objective sleep duration and physical activity with risk of heart failure: A prospective cohort study.

OBJECTIVE: This study aimed to investigate the independent and joint associations of accelerometer-derived sleep duration and physical activity (PA) in different intensities with the risk of incident heart failure (HF). METHODS: The study included 89,572 participants (mean age 62.2 ± 7.8 years, 42.8% male) from the UK Biobank. Sleep duration (short: <6 h/day; normal: 6-8 h/day; long: >8 h/day) and PA [total PA, light PA (LPA), moderate-to-vigorous PA (MVPA), vigorous PA (VPA)] were measured using accelerometers over 7 days. MVPA and VPA were categorized according to the World Health Organization's recommended levels, while LPA and total PA were categorized based on the median. HF cases were identified through hospital records or death registries. RESULTS: Over a 7-year follow-up period, 1324 participants (2.1%; incidence rate, 2.1 per 1000 person-years) developed HF. Short, but not long, sleep duration was linked to a 33% increased risk of HF [hazard ratio (HR) 1.33, 95% confidence interval (CI): 1.11-1.59]. This increased risk associated with short sleep could be mitigated by increasing PA, especially to the levels of recommended MVPA or VPA. In joint analyses, compared to participants meeting the recommended MVPA and with normal sleep duration, those not meeting the MVPA recommendation and with short sleep had the highest HF risk (HR 1.78, 95% CI: 1.42-2.25). CONCLUSIONS: Accelerometer-derived short, but not long, sleep duration was associated with a higher risk of incident HF. Engaging in sufficient PA, especially recommended MVPA or VPA, can partially mitigate this risk.

Fluctuations in serum lipid levels during neoadjuvant treatment as novel predictive and prognostic biomarkers for locally advanced breast cancer: a retrospective analysis based on a prospective cohort.

BACKGROUND: With increasing attention given to host-specific lipid metabolism status, it is of urgent need to identify lipid metabolism indices with predictive or prognostic value in locally advanced breast cancer patients treated with neoadjuvant chemotherapy (NAC), and to evaluate the performance improvement by incorporating them into the existing Neo-Bioscore staging system. METHODS: Patients from a prospectively maintained database of locally advanced breast cancer patients who received radical surgery after NAC between January 2014 to December 2020 were enrolled in this study. The enrolled patients were randomly divided into a training set and a test set at a ratio of 6:4. The random forest algorithm was applied to rank the importance of prognostic factors, top-ranked lipid metabolism indices of which were then incorporated into Neo-Bioscore to construct an updated prognostic model. The performances of these two models were compared in both training set and test set from multiple perspectives. Study outcomes included disease-free survival (DFS), relapse-free survival (RFS), distance-recurrence-free survival (DRFS), locoregional-recurrence-free survival (LRFS) and overall survival (OS). RESULTS: A total of 200 eligible patients were included in this study. After a median follow-up of 4.73 years, it was demonstrated that the relative increase in total cholesterol (TC; DFS: HR = 4.782, 95%CI 1.410 ~ 16.217, P = 0.012) and low-density lipoprotein (LDL; DFS: HR = 4.622, 95%CI 1.517 ~ 14.088, P = 0.007) during NAC led to poorer survival outcomes. Patients with either a higher body mass index (BMI) or elevated LDL during NAC had a worse prognosis (DFS: HR = 6.351, 95%CI 1.938 ~ 20.809, P = 0.002; OS, HR = 6.919, 95%CI 1.296 ~ 36.932, P = 0.024). Incorporating BMI and LDL fluctuations during NAC into Neo-Bioscore improved the prognostic stratification, especially in terms of LRFS (P = 0.046 vs. P = 0.65) and OS (P = 0.013 vs. P = 0.61). Multidimensional evaluation confirmed the improvement in model fit and clinical use for the updated model in both training set and test set. CONCLUSIONS: This is the first study to illustrate the relative elevation of LDL and TC levels during NAC as independent prognosticators for locally advanced breast cancer. This is also the first attempt to incorporate lipid metabolism indices into the original Neo-Bioscore staging system, which further improves the prognostic stratification of patients receiving NAC.

COLEC10 inhibits the stemness of hepatocellular carcinoma by suppressing the activity of ß-catenin signaling.

BACKGROUND: Liver cancer stem cells (CSCs) contribute to tumor initiation, progression, and recurrence in hepatocellular carcinoma (HCC). The Wnt/ß-catenin pathway plays a crucial role in liver cancer stemness, progression, metastasis, and drug resistance, but no clinically approved drugs have targeted this pathway efficiently so far. We aimed to elucidate the role of COLEC10 in HCC stemness. METHODS: The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases were employed to search for the association between COLEC10 expression and HCC stemness. Colony formation, sphere formation, side population, and limiting dilution tumor initiation assays were used to identify the regulatory role of COLEC10 overexpression in the stemness of HCC cell lines. Wnt/ß-catenin reporter assay and immunoprecipitation were performed to explore the underlying mechanism. RESULTS: COLEC10 level was negatively correlated with HCC stemness. Elevated COLEC10 led to decreased expressions of EpCAM and AFP (alpha-fetoprotein), two common markers of liver CSCs. Overexpression of COLEC10 inhibited HCC cells from forming colonies and spheres, and reduced the side population numbers in vitro, as well as the tumorigenic capacity in vivo. Mechanically, we demonstrated that overexpression of COLEC10 suppressed the activity of Wnt/ß-catenin signaling by upregulating Wnt inhibitory factor WIF1 and reducing the level of cytoplasmic ß-catenin. COLEC10 overexpression promoted the interaction of ß-catenin with the component of destruction complex CK1α. In addition, KLHL22 (Kelch Like Family Member 22), a reported E3 ligase adaptor predicted to interact with CK1α, could facilitate COLEC10 monoubiquitination and degradation. CONCLUSION: COLEC10 inhibits HCC stemness by downregulating the Wnt/ß-catenin pathway, which is a promising target for liver CSC therapy.

Successful Treatment of Generalized Facial Verrucae Vulgaris with a Combination of Curettage and Photodynamic Therapy in an Adolescent: A Case Report.

Verrucae vulgaris are highly contagious keratotic lesions occurring on the skin caused by human papillomavirus. Generally, verrucae vulgaris are harmless to the body, but when they occur in specific areas such as the face or soles of the feet, they can profoundly impact an individual's quality of life and necessitate therapeutic intervention. Although several pharmacological and physical topical treatments are available, the results are often unsatisfactory in terms of efficacy and cosmetic outcome. Verrucae which typically occur widely on the face are usually Verrucae Planae. When Verrucae vulgaris does occur, it usually presents as single or occasional multiple lesions, rather than covering almost the entire face. In immunocompromised situations, verruca vulgaris can exhibit rare proliferative behavior. In this report, we present a 17-year-old male adolescent who was successfully treated for generalized facial verrucae vulgaris by using a combination of curettage and photodynamic therapy (PDT). The patient's prolonged use of topical corticosteroids and tacrolimus ointment on the face for eczema over several years is believed to have led to a localized immunosuppressive state of the facial skin, which is considered a significant factor in the outbreak of verrucae vulgaris. Additionally, the patient has a history of acne and frequently scratched face. The appearance of the Koebner phenomenon following scratching is considered another potential reason. This treatment achieved complete resolution and improved the patient's pre-existing acne problem, resulting in a satisfactory cosmetic outcome without any notable adverse effects or recurrence during the follow-up period. This highlighted that pre-treatment with curettage before PDT enhanced the efficiency of verrucae vulgaris treatment and reduced the cost.

In Vivo Detection of Abscisic Acid in Tomato Leaves Based on a Disposable Stainless Steel Electrochemical Immunosensor.

Abscisic acid (ABA) plays an important regulatory role in plants. It is very critical to obtain the dynamic changes of ABA in situ for botanical research. Herein, coupled with paper-based analysis devices, electrochemical immunoelectrodes based on disposable stainless steels sheet were developed for ABA detection in plants in situ. The stainless steel sheets were modified with carbon cement, ferrocene-graphene oxide-multi walled carbon nanotubes nanocomposites, and ABA antibodies. The system can detect the ABA in the range of 1 nM to 100 µM, with a limit of detection of 100 pM. The ABA content in tomato leaves under high salinity was detected in situ. The trend of ABA changes was similar to the expression of SlNCED1 and SlNCED2. Overall, this study offers an approach for in situ detection of ABA in plants, which will help to study the regulation mechanism of ABA in plants and to promote the development of precision agriculture.

Multi-modal segmentation with missing image data for automatic delineation of gross tumor volumes in head and neck cancers.

BACKGROUND: Head and neck (HN) gross tumor volume (GTV) auto-segmentation is challenging due to the morphological complexity and low image contrast of targets. Multi-modality images, including computed tomography (CT) and positron emission tomography (PET), are used in the routine clinic to assist radiation oncologists for accurate GTV delineation. However, the availability of PET imaging may not always be guaranteed. PURPOSE: To develop a deep learning segmentation framework for automated GTV delineation of HN cancers using a combination of PET/CT images, while addressing the challenge of missing PET data. METHODS: Two datasets were included for this study: Dataset I: 524 (training) and 359 (testing) oropharyngeal cancer patients from different institutions with their PET/CT pairs provided by the HECKTOR Challenge; Dataset II: 90 HN patients(testing) from a local institution with their planning CT, PET/CT pairs. To handle potentially missing PET images, a model training strategy named the "Blank Channel" method was implemented. To simulate the absence of a PET image, a blank array with the same dimensions as the CT image was generated to meet the dual-channel input requirement of the deep learning model. During the model training process, the model was randomly presented with either a real PET/CT pair or a blank/CT pair. This allowed the model to learn the relationship between the CT image and the corresponding GTV delineation based on available modalities. As a result, our model had the ability to handle flexible inputs during prediction, making it suitable for cases where PET images are missing. To evaluate the performance of our proposed model, we trained it using training patients from Dataset I and tested it with Dataset II. We compared our model (Model 1) with two other models which were trained for specific modality segmentations: Model 2 trained with only CT images, and Model 3 trained with real PET/CT pairs. The performance of the models was evaluated using quantitative metrics, including Dice similarity coefficient (DSC), mean surface distance (MSD), and 95% Hausdorff Distance (HD95). In addition, we evaluated our Model 1 and Model 3 using the 359 test cases in Dataset I. RESULTS: Our proposed model(Model 1) achieved promising results for GTV auto-segmentation using PET/CT images, with the flexibility of missing PET images. Specifically, when assessed with only CT images in Dataset II, Model 1 achieved DSC of 0.56 ± 0.16, MSD of 3.4 ± 2.1 mm, and HD95 of 13.9 ± 7.6 mm. When the PET images were included, the performance of our model was improved to DSC of 0.62 ± 0.14, MSD of 2.8 ± 1.7 mm, and HD95 of 10.5 ± 6.5 mm. These results are comparable to those achieved by Model 2 and Model 3, illustrating Model 1's effectiveness in utilizing flexible input modalities. Further analysis using the test dataset from Dataset I showed that Model 1 achieved an average DSC of 0.77, surpassing the overall average DSC of 0.72 among all participants in the HECKTOR Challenge. CONCLUSIONS: We successfully refined a multi-modal segmentation tool for accurate GTV delineation for HN cancer. Our method addressed the issue of missing PET images by allowing flexible data input, thereby providing a practical solution for clinical settings where access to PET imaging may be limited.

Serum lipid ratios as novel prognostic biomarkers for patients with locally advanced breast cancer treated with neoadjuvant therapy.

OBJECTIVES: To investigate the association between lipid ratios and survival outcomes in patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. METHOD: This retrospective study included patients with LABC receiving neoadjuvant chemotherapy. Serum lipid levels were prospectively measured at baseline. Associations of triglyceride to total cholesterol (TG/TC), triglyceride to high-density lipoprotein (TG/HDL) and triglyceride to low-density lipoprotein (TG/LDL) ratios with prognosis were evaluated. RESULTS: Patients with high TG/TC (adjusted hazard ratio [aHR] = 2.47, 95% CI: 1.10, 5.56, p = 0.029), TG/HDL (aHR = 2.73, 95% CI: 1.16, 6.41, p = 0.021) and TG/LDL (aHR = 2.50, 95% CI: 1.11, 5.65, p = 0.027) ratios were more likely to experience disease-free survival (DFS) events. Subgroup analysis suggested that the prognostic impact of lipid ratios was more pronounced in patients with negative HER2 status or those at a high risk of recurrence (e.g. clinical stage III, Ki67 > 30%). Additionally, higher lipid ratios tended to indicate early DFS events (0 ~ 2 years) (TG/TC p = 0.021, TG/HDL p = 0.046, TG/LDL p < 0.001), and the TG/LDL ratio demonstrated the best predictive efficacy (TG/TC vs. TG/HDL vs. TG/LDL, 1-year AUC: 0.724 vs. 0.676 vs. 0.846, 2-year AUC: 0.653 vs. 0.638 vs. 0.708). CONCLUSION: Baseline serum TG/TC, TG/HDL and TG/LDL ratios were independent prognostic factors in patients with LABC undergoing neoadjuvant therapy. However, their utility in predicting the early DFS events warrants further investigation. CLINICAL TRIAL REGISTRATION: NCT05621564.

Clinical remission of moderate generalized myasthenia gravis through exclusive use of Buzhong Yiqi decoction: A case report.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune neuromuscular disorder with significant morbidity and mortality. Traditional Chinese medicine (TCM) offers an alternative approach to standard pharmacological and surgical interventions, which are often associated with adverse side effects. This case report details the clinical remission of a 50-year-old male with moderate generalized MG following exclusive treatment with a modified Buzhong Yiqi decoction (BYD), a TCM formula, without the use of immunosuppressive agents. CASE SUMMARY: The patient presented with diplopia, bilateral ptosis, weakness in chewing, limb weakness, and other symptoms indicative of spleen and stomach qi deficiency. Modified BYD was prescribed, focusing on strengthening the spleen, nourishing qi and blood, and enhancing immune response. The treatment included ingredients such as Radix Astragali, Angelica sinensis, Atractylodes macrocephala, and others, aiming to restore balance and improve the patient's condition. After two weeks of TCM treatment, the patient showed significant improvement in symptoms of myasthenia. By the second month, all clinical symptoms had disappeared. The patient continued to receive the TCM regimen until the thirtieth month of treatment. At the time of writing this report, the patient has no clinical symptoms and has experienced no relapse. Notably, no obvious adverse effects were reported throughout the treatment. CONCLUSION: The success of this case suggests that TCM may serve as an independent treatment option for moderate MG, offering a steroid-free alternative, which would be particularly valuable for patients who are intolerant of or refuse steroid therapy, potentially with significant clinical implications. However it needs a randomized clinical trial comparing TCM to conventional Western medicine treatment to validate it.

CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Enhanced Replenishment of Active Lattice Oxygen Using Chiral Copper Oxide.

Effective catalytic performance of the transition metal oxide is attributed to high specific surface areas, abundant surface oxygen atoms, and balanced valence ratios. Although the chirality of the transition metal has attracted attention, most studies have focused on optical application. A few chiral transition metal oxides were used as electrocatalysts and photocatalysts. The influence of the chiral catalysts on the thermal catalysis process has been less explored. In this study, Mn-loaded chiral (M/l-CuO and M/d-CuO) and achiral CuO (M/a-CuO) were synthesized and compared in the catalytic oxidization of toluene. Spectrally analyzed Mn was well-dispersed on both chiral and achiral CuO. l-CuO and d-CuO showed nanoflower-like chirality. The angles between each (001) plane of CuO were the source of chirality. The toluene turnover frequency (TOF) of the samples was in the order of Mn/d-CuO (5.6 × 10-5 s-1) > Mn/l-CuO (4.4 × 10-5 s-1) > Mn/a-CuO (3.2 × 10-5 s-1) at 240 °C, consistent with the order of the oxygen replenishment rate. The as-prepared catalysts had similar ratios of lattice oxygen/surface adsorbed oxygen, Mn3+/Mn4+, and Cu+/Cu2+. A higher TOF was attributed to chirality, which increased the lattice oxygen replenishment speed from the gaseous phase to the solid surface. Our study indicates gas-solid catalysis from a structure-activity viewpoint.

Ag/AgBr-oxygen enriched g-C3N4 for efficient photocatalytic degradation of trimethylamine.

In this study, Ag/AgBr-O-gCN samples with ternary Z-type heterojunctions were prepared by in situ photoreduction using water as the reducing agent for generating Ag/AgBr active species and oxygen doping. The experimental results indicated that Ag/AgBr-O-gCN degraded trimethylamine by nearly 100% in half an hour and maintained 90% of its original activity after five cycles. The kinetic constant of Ag/AgBr-O-gCN was excellent at 0.0928 min-1, 3.8 times that of gCN, 2.3 times that of Ag/AgBr-gCN, and 1.9 times that of O-gCN. Unlike Ag/AgBr-gCN photoreduced by methanol, gCN was used as an electron donor in the aqueous solution during the photoreduction process, and oxidation sites between the gCN skeleton and Ag/AgBr were formed for constructing the heterojunction system. The Z-type heterojunction system was established by introducing a suitable size of Ag nanoparticles as the recombination center to keep indirect contact between gCN and AgBr. This effectively reduced the electron-hole recombination rate and caused activity enhancement. This study offers a novel idea for the construction of a ternary heterojunction.

A relatively rare traditional Chinese medicine pattern of primary Sjögren syndrome: A case report.

RATIONALE: This report presents a unique case of a patient diagnosed with Primary Sjögren's syndrome and a relatively rare traditional Chinese medicine pattern, known as the combined cold and heat pattern and cold-dampness syndrome. The patient's condition was successfully managed using Chinese herbal medicine, specifically the modified Da-Chai-Hu decoction and Linggui Zhugan decoction. PATIENT CONCERNS: A 56-year-old woman had chronic dry eye and mouth for over 10 years. She was initially managed with traditional Chinese herbal medicine (TCHM) prescriptions, including the Zengye decoction, but the therapeutic effects were unsatisfactory. As the disease progressed, she was diagnosed with an anxiety disorder due to symptoms of vexation and insomnia. Treatment with alprazolam and venlafaxine failed to alleviate these symptoms. Recently, her general condition gradually worsened, with symptoms including a bitter taste in her mouth, dizziness, hot flashes, chills, poor appetite, chest discomfort, and constipation. DIAGNOSES: After a series of examinations, including a Schirmer test and labial gland biopsy, she was diagnosed with Sjögren's syndrome. INTERVENTIONS: Despite regular treatment with pilocarpine, sodium hyaluronate eye drops, venlafaxine, and alprazolam, the dry mouth symptoms intensified. Consequently, she sought further intervention through the TCHM. OUTCOMES: After 8 weeks of treatment with the modified Da-Chai-Hu decoction and Linggui Zhugan decoction, she reported a significant improvement in her dryness-related symptoms and sleep quality. LESSONS: This case report demonstrates that TCHM can effectively treat Primary Sjögren's syndrome, and should be considered for broader applications. Furthermore, this underscores the importance of tailoring treatment formulas to patients by identifying their specific syndrome differentiation in a clinical setting.

Chronic Obstructive Pulmonary Disease and Osteoporosis: A Two-Sample Mendelian Randomization Analysis.

Background: There is a global increase in the prevalence of osteoporosis and chronic obstructive pulmonary disease (COPD). Studies based on observation revealed a higher incidence of osteoporosis in patients with COPD. We looked into the genetic relationship between COPD and osteoporosis using the Mendelian randomization (MR) technique. Methods: The inverse variance-weighted (IVW) method was the primary technique used in this MR investigation. The sensitivity was assessed using the simple median, weighted median, penalized weighted median, and MR Egger regression analysis. Results: The IVW model demonstrated that genetically determined COPD is causally associated with an elevated risk of osteoporosis (odds ratio [OR] fixed-effect, 1.010; 95% confidence interval [CI], 1.001-1.019, P=0.021; OR random-effect, 1.010; 95% CI, 1.001-1.020, P=0.039). It was also found that this correlation held valid for the simple and weighted median, Penalized weighted, MR-Egger, and MR Egger (bootstrap) approaches. No heterogeneity was found in the IVW or MR-Egger analysis results (Q=131.374, P=0.061 and Q=128.895, P=0.069, respectively). Furthermore, no pleiotropic influence via genetic variations was revealed by MR-Egger regression (intercept, -0.0002; P=0.160). No one single nucleotide polymorphism was found to have a substantial impact on the relationship between COPD and osteoporosis by the leave-one-out sensitivity analysis. Conclusion: Our MR analysis demonstrated a substantial positive impact of COPD on the risk of osteoporosis.

Promising preclinical models for lung cancer research-lung cancer organoids: a narrative review.

Background and Objective: Traditional cell line models are the commonly used preclinical models for lung cancer research. However, cell lines cannot recapitulate the complex tumor heterogeneity and cannot mimic the microenvironment of human cancer. Recently, 3D multicellular in vitro self-assembled models called "organoids" have been developed at a fast pace in the field of research, which can mimic the actual primary tumor. At present, several studies have reported on protocols of lung cancer organoids (LCOs) generation, and using LCOs can provide novel insight into the basic and translational research of lung cancer. However, the establishment of the LCO models remains challenging due to the complexity of lung cancer and the immaturity of organoid technology, so it is necessary to understand the influences of different methodologies on LCO generation and review the applications and limitations of LCO models. Methods: In this review, we searched the literature in the recent ten years in the field of LCOs. Key Content and Findings: We summarized the methodology, the problems, and the solutions in the LCOs generation, its application and limitations, as well as proposing future challenges and perspectives. Conclusions: Currently, LCOs are successfully generated via exploring the methodology by the researchers. Though there are still challenges in clinical application, LCOs are applied in some cancer studies including investigation of anti-cancer treatment response in vitro, modeling tumor immune microenvironment, and construction of organ chips, which are forging a promising path towards precision medicine.