Field performance of 15 rain gardens in different cities in Taiwan.

Rain gardens are widely used for low impact development (LID) or as a nature-based solution (NbS). They help to reduce runoff, mitigate hot temperatures, create habitats for plants and insects, and beautify landscapes. Rain gardens are increasingly being established in urban areas. In Taiwan, the Ministry of Environment (MoE) initiated a rain garden project in Taipei city in 2018, and 15 rain gardens have since been constructed in different cities. These Taiwanese-style rain gardens contain an underground storage tank to collect the filtrated rainwater, which can be used for irrigation. Moreover, the 15 rain gardens are equipped with sensors to monitor temperature, rainfall, and underground water levels. The monitoring data were transmitted with Internet of Things (IoT) technology, enabling the capture and export of real-time values. The water retention, temperature mitigation, water quality, and ecological indices of the rain gardens were quantified using field data. The results from the young rain gardens (1-3 years) showed that nearly 100 % of the rainfall was retained onsite and did not flow out from the rain gardens; however, if the stored water was not used and the tanks were full, the rainwater from subsequent storms could not be stored, and the tanks overflowed. The surface temperatures of the rain garden and nearby impermeable pavement differed by an average of 2-4 °C. This difference exceeded 20 °C in summer at noon. The water in the underground storage tanks had very low levels of SS and BOD, with averages of 1.6 mg/L and 5.6 mg/L, respectively. However, the E. coli concentrations were high, and the average was 6283 CFU/100 mL; therefore, washing or drinking water is not recommended. The ecological indices, i.e., the Shannon and Simpson indices, demonstrated the good flora status of the rain gardens after one year. Although the weather differed by city, the performance of the rain gardens in terms of water retention, temperature mitigation, rainwater harvesting, and providing biological habitats was consistent. However, maintenance influences rain garden performance. If the stored water is not frequently used, the stored volume is reduced, and the stored water quality degrades.

Mesonephric-type adenocarcinomas of the ovary: prevalence, diagnostic reproducibility, outcome, and value of PAX2.

Mesonephric-type (or -like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four-marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four-marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (κ = 0.376-0.727) with the integration of the four-marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first-line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62-5.85; p < 0.0001) compared with patients with EC, when adjusted for age, stage, and p53 status. A diagnosis of MA has prognostic implications for stage I disease, and due to the subtlety of morphological features in some tumors, a low threshold for ancillary testing is recommended.

Preclinical 3D model screening reveals digoxin as an effective therapy for a rare and aggressive type of endometrial cancer.

OBJECTIVE: Dedifferentiated endometrial carcinoma (DDEC) characterized by SWItch/Sucrose Non-Fermentable (SWI/SNF) complex inactivation is a highly aggressive type of endometrial cancer without effective systemic therapy options. Its uncommon nature and aggressive disease trajectory pose significant challenges for therapeutic progress. To address this obstacle, we focused on developing preclinical models tailored to this tumor type and established patient tumor-derived three-dimensional (3D) spheroid models of DDEC. METHODS: High-throughput drug repurposing screens were performed on in vitro 3D spheroid models of DDEC cell lines (SMARCA4-inactivated DDEC-1 and ARID1A/ARID1B co-inactivated DDEC-2). The dose-response relationships of the identified candidate drugs were evaluated in vitro, followed by in vivo evaluation using xenograft models of DDEC-1 and DDEC-2. RESULTS: Drug screen in 3D models identified multiple cardiac glycosides including digoxin and digitoxin as candidate drugs in both DDEC-1 and DDEC-2. Subsequent in vitro dose-response analyses confirmed the inhibitory activity of digoxin and digitoxin with both drugs showing lower IC50 in DDEC cells compared to non-DDEC endometrial cancer cells. In in vivo xenograft models, digoxin significantly suppressed the growth of DDEC tumors at clinically relevant serum concentrations. CONCLUSION: Using biologically precise preclinical models of DDEC derived from patient tumor samples, our study identified digoxin as an effective drug in suppressing DDEC tumor growth. These findings provide compelling preclinical evidence for the use of digoxin as systemic therapy for SWI/SNF-inactivated DDEC, which may also be applicable to other SWI/SNF-inactivated tumor types.

Global prevalence, clinical characteristics, surveillance, treatment allocation, and outcomes of alcohol-associated hepatocellular carcinoma.

BACKGROUND AND AIMS: Although the burden of alcohol-associated hepatocellular carcinoma (HCC) is increasing with rising alcohol consumption, clinical presentation and outcomes of alcohol-associated HCC have not been systematically assessed. We aimed to determine the prevalence, clinical characteristics, surveillance rates, treatment allocation, and outcomes of alcohol-associated HCC. METHODS: Medline and Embase were searched from inception to January 2023. Proportional data were analyzed using a generalized linear mixed model. The odds ratio (OR) or mean difference comparing alcohol-associated HCC and other causes was obtained with pairwise meta-analysis. Survival outcomes were evaluated using a pooled analysis of hazard ratios. RESULTS: Of 4,824 records identified, 55 articles (86,345 patients) were included. Overall, 30.4% (CI: 24.0%-37.7%) of HCC were alcohol-associated, with the highest proportion in Europe and the lowest in the Americas. People with alcohol-associated HCC were more likely male, but similar in age and comorbidities, compared to other causes. 20.8% (CI: 11.4%-34.9%) of people with alcohol-associated HCC underwent surveillance compared to 35.0%, 31.6%, and 21.4% in hepatitis B virus, hepatitis C virus, and metabolic dysfunction-associated HCC, respectively (all P<0.05). Alcohol-associated HCC had a lower likelihood of BCLC stage (0/A) (OR: 0.7, CI: 0.6-0.9; P=0.018) and curative therapy (24.5% vs 33.9%; OR 0.7, CI: 0.5-0.9; P=0.003), and higher mortality (HR: 1.3, CI: 1.1-1.5, P=0.012) when compared to other causes. CONCLUSIONS: Alcohol-associated HCC is associated with lower surveillance rates, more advanced BCLC stage, lower likelihood of receiving curative therapy, and poorer survival. These data call for measures to reduce heavy alcohol consumption and improve strategies for effective HCC surveillance in high-risk individuals.

The Burden of Overweight and Obesity-Associated Gastrointestinal Cancers in Low and Lower-Middle-Income Countries: A Global Burden of Disease 2019 Analysis.

INTRODUCTION: Obesity is associated with cancer, including gastrointestinal (GI). Data from low (LICs) and lower-middle-income countries (MICs) are limited. METHODS: We utilized data from the Global Burden of Disease Study 2019 to determine the mortality from GI cancer risk of high body mass index (BMI) in these countries. RESULTS: Mortality rates of GI cancers from high BMI increased in LICs and lower MICs, while burdens decreased or remained stable in high and middle-income countries. DISCUSSION: The GI cancer-related burden from high BMI increased in LICs and lower MICs, necessitating a concerted effort to tackle the obesity pandemic.

The Impact of Neoadjuvant Chemotherapy on Patients With T1N0M0 Triple-Negative and HER-2 Positive Breast Cancer: A Retrospective Analysis Based on the SEER Database.

BACKGROUND: The utilization of neoadjuvant chemotherapy (NAC) originated in the treatment of locally advanced breast cancer (BC). Our study is designed to elucidate the effects of NAC on patients with T1N0M0 triple-negative and HER-2 positive BC. METHODS: This study involved the selection of 10,614 patients diagnosed with T1N0M0 triple-negative and HER-2 positive breast cancer (BC) from the surveillance, epidemiology, and end results (SEER) database. To ascertain the impact of neoadjuvant chemotherapy (NAC) on T1a, T1b, and T1c N0M0 BC, we conducted multivariate Cox regression analyses. Similarly, we performed multivariate Cox regression analyses to compare the effects of neoadjuvant chemotherapy against adjuvant chemotherapy on T1N0M0 BC. The Kaplan-Meier method was employed to delineate survival curves for different molecular subtypes and clinical stages. RESULTS: The data results from the SEER database reveal a significant enhancement of overall survival (OS) in T1c BC patients as a result of NAC. For T1b BC patients, NAC does not present any significant effect. Contrarily, NAC seems to adversely impact the OS of T1a triple-negative BC patients. However, the prognosis comparison between neoadjuvant and adjuvant chemotherapy for T1N0M0 breast cancer did not show any significant difference, with the exception of T1a triple-negative BC. CONCLUSIONS: Patients with T1cN0M0 triple-negative and HER-2 positive BC may derive OS benefits from NAC. Additionally, NAC could be detrimental to T1a triple-negative BC.

Sex-based Disparities in Liver Transplantation for Hepatocellular Carcinoma and the Impact of the Growing Burden of NASH.

Background: The cause of liver disease is changing, but its impact on liver transplantation (LT) for hepatocellular carcinoma (HCC) in women and men is unclear. We performed a nationwide study to assess the prevalence and posttransplant survival outcomes of the various causes of liver disease in women and men with HCC. Methods: Data were obtained from the United Network for Organ Sharing database from 2000 to 2022. Data related to the listing, transplant, waitlist mortality, and posttransplant mortality for HCC were extracted. The proportion of HCC related to the various causes of liver disease among LT candidates and recipients and posttransplant survival were compared between women and men. Results: A total of 51 721 individuals (39 465 men, 12 256 women) with HCC were included. From 2000 to 2022, nonalcoholic steatohepatitis (NASH) was the fastest-growing cause of liver disease among female LT candidates with HCC (P < 0.01), followed by alcohol-associated liver disease. NASH overtook chronic hepatitis C as the leading cause of liver disease in 2020 and 2022 among waitlisted women and men with HCC, respectively. Female patients with HCC spent a significantly longer time on the LT waitlist compared with male patients (ß: 8.73; 95% confidence interval [CI], 2.91-14.54). Female patients with HCC from alcohol-associated liver disease also have a lower probability of receiving LT (subdistribution hazard ratio: 0.90; 95% CI, 0.82-0.99). Among transplant recipients with NASH HCC, female sex was associated with lower posttransplant mortality compared with male sex (hazard ratio: 0.79; 95% CI, 0.70-0.89; P < 0.01). Conclusions: Women have a significantly longer waitlist duration compared with men. NASH is now the leading cause of liver disease among both female and male LT candidates and recipients with HCC.

Thermoelectric-Feedback Nanocomposite Hydrogel for Temperature-Synchronized Monitoring and Regulation in Accurate Photothermal Therapy.

Photothermal therapy (PTT) is a promising approach for tumor ablation and cancer treatment. However, controlling the therapeutic temperature during treatment remains challenging, and imprecise thermal regulation can harm adjacent healthy tissues, reduce therapeutic accuracy, and promote the thermotolerance of cellular phenotypes, potentially leading to tumor invasion and recurrence. Although existing methods provide basic temperature control by adjusting irradiation power and photothermal agent dosing, they lack real-time temperature monitoring and feedback control capabilities, underscoring the urgent need for more integrated and precise PTT systems. In this context, an innovative photothermoelectric (PTE) cobalt-infused chitosan (CS) nanocomposite hydrogel (PTE-Co@CS) is developed for precise temperature-regulated PTT, exhibiting desirable mechanical properties and exceptional biocompatibility. Enhanced by embedded nanoparticles, PTE-Co@CS demonstrates superior photothermal conversion efficiency compared with existing methods, while also featuring thermoelectric responsiveness and increased sensitivity to photostimuli. Its advantageous PTE response characteristics ensure a linear correlation between temperature shifts and resistance changes (e.g., R2 = 0.99919 at 0.5 W cm⁻2), enabling synchronized qualitative and quantitative control of PTT temperature through electrical signal monitoring. This allows for real-time monitoring and regulation during PTT, effectively addressing the issue of uncontrollable temperatures and improving therapeutic efficacy.

Concurrent RB1 Loss and BRCA-Deficiency Predicts Enhanced Immunological Response and Long-Term Survival in Tubo-Ovarian High-Grade Serous Carcinoma.

PURPOSE: To evaluate RB1 expression and survival across ovarian carcinoma histotypes, and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). EXPERIMENTAL DESIGN: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 primary HGSC to characterize tumors with concurrent BRCA-deficiency and RB1 loss. RESULTS: RB1 loss was associated with longer OS in HGSC, but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared to patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA-deficiency correlated with transcriptional markers of enhanced interferon response, cell-cycle deregulation, and reduced epithelial-mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. CONCLUSIONS: Co-occurrence of RB1 loss and BRCA-deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Obesity induces PD-1 on macrophages to suppress anti-tumour immunity.

Obesity is a leading risk factor for progression and metastasis of many cancers1,2, yet can in some cases enhance survival3-5 and responses to immune checkpoint blockade therapies, including anti-PD-1, which targets PD-1 (encoded by PDCD1), an inhibitory receptor expressed on immune cells6-8. Although obesity promotes chronic inflammation, the role of the immune system in the obesity-cancer connection and immunotherapy remains unclear. It has been shown that in addition to T cells, macrophages can express PD-19-12. Here we found that obesity selectively induced PD-1 expression on tumour-associated macrophages (TAMs). Type I inflammatory cytokines and molecules linked to obesity, including interferon-γ, tumour necrosis factor, leptin, insulin and palmitate, induced macrophage PD-1 expression in an mTORC1- and glycolysis-dependent manner. PD-1 then provided negative feedback to TAMs that suppressed glycolysis, phagocytosis and T cell stimulatory potential. Conversely, PD-1 blockade increased the level of macrophage glycolysis, which was essential for PD-1 inhibition to augment TAM expression of CD86 and major histocompatibility complex I and II molecules and ability to activate T cells. Myeloid-specific PD-1 deficiency slowed tumour growth, enhanced TAM glycolysis and antigen-presentation capability, and led to increased CD8+ T cell activity with a reduced level of markers of exhaustion. These findings show that obesity-associated metabolic signalling and inflammatory cues cause TAMs to induce PD-1 expression, which then drives a TAM-specific feedback mechanism that impairs tumour immune surveillance. This may contribute to increased cancer risk yet improved response to PD-1 immunotherapy in obesity.

POLE-mutated Endometrial "Carcinosarcoma".

The molecular subtype classification of endometrial carcinomas has conceptually changed our approach to this disease. However, open questions remain about how to integrate certain histotype diagnoses with the molecular subtype. We report 2 cases with morphologic suspicion for endometrial carcinosarcoma, that still fell short of the essential criteria for diagnosing carcinosarcoma. On subsequent molecular testing pathogenic POLE mutations were detected and a descriptive diagnosis of endometrial endometrioid carcinomas, low-grade with a homologous sarcoma component was rendered. This challenges the existence of POLE-mutated "carcinosarcoma."

REDOMA: Bayesian random-effects dose-optimization meta-analysis using spike-and-slab priors.

The rise of cutting-edge precision cancer treatments has led to a growing significance of the optimal biological dose (OBD) in modern oncology trials. These trials now prioritize the consideration of both toxicity and efficacy simultaneously when determining the most desirable dosage for treatment. Traditional approaches in early-phase oncology trials have conventionally relied on the assumption of a monotone relationship between treatment efficacy and dosage. However, this assumption may not hold valid for novel oncology therapies. In reality, the dose-efficacy curve of such treatments may reach a plateau at a specific dose, posing challenges for conventional methods in accurately identifying the OBD. Furthermore, achieving reliable identification of the OBD is typically not possible based on a single small-sample trial. With data from multiple phase I and phase I/II trials, we propose a novel Bayesian random-effects dose-optimization meta-analysis (REDOMA) approach to identify the OBD by synthesizing toxicity and efficacy data from each trial. The REDOMA method can address trials with heterogeneous characteristics. We adopt a curve-free approach based on a Gamma process prior to model the average dose-toxicity relationship. In addition, we utilize a Bayesian model selection framework that uses the spike-and-slab prior as an automatic variable selection technique to eliminate monotonic constraints on the dose-efficacy curve. The good performance of the REDOMA method is confirmed by extensive simulation studies.

Sex and Race-Ethnic Disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease: An Analysis of 40,166 Individuals.

BACKGROUND: To overcome the limitations of the term "non-alcoholic fatty liver disease" (NAFLD), the term metabolic-associated steatotic liver disease (MASLD) was introduced. While epidemiologic studies have been conducted on MASLD, there is limited evidence on its associated sex and ethnic variations. AIMS: This study assesses the differences across sex and race-ethnicity on the prevalence, associated risk factors and adverse outcomes in individuals with MASLD. METHODS: Data retrieved from the National Health and Nutrition Examination Survey between 1999 to 2018 was analyzed. Prevalence, clinical characteristics, and outcomes were evaluated according to sex and race-ethnicity. Adverse outcomes and mortality events were analyzed using multivariate analyses. RESULTS: Of 40,166 individuals included, 37.63% had MASLD. There was a significant increase in MASLD prevalence from 1999 to 2018 among Mexican Americans (Annual Percentage Change [APC] + 1.889%, p < 0.001), other Hispanics (APC + 1.661%, p = 0.013), NH Whites (APC + 1.084%, p = 0.018), NH Blacks (APC + 1.108%, p = 0.007), and females (APC + 0.879%, p = 0.030), but not males. Females with MASLD were at lower risk of all-cause (HR: 0.766, 95%CI 0.711 to 0.825, p < 0.001), cardiovascular disease-related (CVD) (SHR: 0.802, 95% CI 0.698 to 0.922, p = 0.002) and cancer-related mortality (SHR: 0.760, 95% CI 0.662 to 0.873, p < 0.001). Significantly, NH Blacks have the highest risk of all-cause and CVD-related mortality followed by NH Whites then Mexican Americans. CONCLUSION: There has been an increase in prevalence in most race-ethnicities over time. While the change in definition shows no significant differences in previous associations found in NAFLD, the increased mortality in NH Whites relative to Mexican Americans remains to be explored.

Molecular Surrogate Subtypes of Ovarian and Peritoneal Low-grade Serous Carcinoma.

Low-grade serous carcinoma (LGSC) is an uncommon histotype of ovarian carcinoma, accounting for ~3% of cases. There is evidence that survival of peritoneal LGSC (pLGSC) is longer than that of ovarian LGSC (oLGSC). Key molecular alterations of LGSC have been established, including loss of CDKN2A and PR expression, MAPK pathway alterations, and loss of USP9X expression. We hypothesized that LGSC could be subclassified into clinically applicable molecular subtypes by a few surrogate tests similar to endometrioid carcinomas using a hierarchical decision tree based on the strength of the prognostic associations of the individual alterations. Our study included 71 LGSCs. Immunohistochemistry for CDKN2A, ER, PR, NF1, and USP9X and sequencing for KRAS, NRAS, and BRAF were performed. Our data showed the co-occurrence of key molecular alterations, and despite suggestive trends, hierarchical molecular subtyping did not provide significantly different stratification of patients according to survival in this cohort. We confirmed that patients diagnosed with pLGSC have a longer survival than high-stage oLGSC, with the intriguing observation that normal CDKN2A and PR status were associated with excellent survival in pLGSC. Therefore, CDKN2A and PR status might aid in the classification of indeterminate implants, where abnormal findings favor pLGSC over noninvasive implants. Molecular subtypes should be further evaluated in larger cohorts for their prognostic and potentially predictive value.

Socio-economic association of alcohol use disorder and cardiovascular and alcohol-associated liver disease from 2010 to 2019.

BACKGROUNDS AND AIMS: Alcohol use leads to disabilities and deaths worldwide. It not only harms the liver but also causes alcohol use disorder (AUD) and heart disease. Additionally, alcohol consumption contributes to health disparities among different socio-economic groups. METHODS: We estimated global and regional trends in the burden of AUD, liver disease, and cardiovascular disease from alcohol using the methodology of the Global Burden of Disease study. RESULTS: In 2019, the highest disability-adjusted life years rate per 100,000 population was due to AUD (207.31 [95% Uncertainty interval (UI) 163.71-261.66]), followed by alcohol-associated liver disease (ALD) (133.31 [95% UI 112.68-156.17]). The prevalence rate decreased for AUD (APC [annual percentage change] -0.38%) and alcohol-induced cardiomyopathy (APC -1.85%) but increased for ALD (APC 0.44%) and liver cancer (APC 0.53%). Although the mortality rate for liver cancer from alcohol increased (APC 0.30%), mortality rates from other diseases decreased. Between 2010 and 2019, the burden of alcohol-associated complications increased in countries with low and low-middle sociodemographic index (SDI), contributing more significantly to the global burden. CONCLUSION: The global burden of AUD, liver, and cardiovascular disease has been high and increasing over the past decade, particularly for liver complications. Lower SDI countries are contributing more to this global burden. There is a pressing need for effective strategies to address this escalating burden.

Combined effects of cadmium and sulfamethoxazole on Eisenia fetida: Insights into accumulation, subcellular partitioning, biomarkers and toxicological responses.

Cadmium (Cd) and sulfamethoxazole (SMX) frequently coexist in farmlands, yet their synergistic toxicological impacts on terrestrial invertebrates remain unexplored. In this study, earthworms were exposed to artificial soils percolated with Cd (5 mg/kg), SMX (5 mg/kg) or combination of them for 7 days, followed by a 12-day elimination phase in uncontaminated soil. The uptake of Cd and SMX by the earthworms, along with their subcellular distribution, was meticulously analyzed. Additionally, a suite of biomarkers-including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and weight loss-were evaluated to assess the health status of the earthworms and the toxicological effects of the Cd and SMX mixture. Notably, the cotreatment with Cd and SMX resulted in a significantly higher weight loss in Eisenia fetida (41.25 %) compared to exposure to Cd alone (26.84 %). Moreover, the cotreatment group exhibited substantially higher concentrations of Cd in the total internal body, fraction C (cytosol), and fraction E (tissue fragments and cell membranes) in Eisenia fetida compared to Cd alone counterparts. The combined exposure also significantly elevated the SMX levels in the total body and fraction C compared with the SMX-only treated earthworms. Additionally, Eisenia fetida subjected to the combined treatment showed markedly increased activities of SOD, CAT, and MDA compared to those treated with Cd alone. The effect addition indices (EAIs), ranging from 1.00 to 2.23, unequivocally demonstrated a synergistic effect of the combined treatments. Interestingly, relocating the earthworms to clean soil did not mitigate the observed adverse effects. These findings underscore the increased risk posed by the Cd-SMX complex to terrestrial invertebrates in agricultural areas.

A novel long non-coding RNA MIR4500HG003 promotes tumor metastasis through miR-483-3p-MMP9 axis in triple-negative breast cancer.

Breast cancer (BC) is the most common cancer and the leading cause of cancer-related deaths in women worldwide. The 5-year survival rate is over 90% in BC patients, but once BC cells metastasis into distal organs, it is dramatically decreasing to less than 30%. Especially, triple-negative breast cancer (TNBC) patients usually lead to poor prognosis and survival because of metastasis. Understanding the underline mechanisms of TNBC metastasis is a critical issue. Non-coding RNAs, including of lncRNAs and microRNAs, are non-protein-coding transcripts and have been reported as important regulators in TNBC metastasis. However, the underline mechanisms for non-coding RNAs regulating TNBC metastasis remain largely unclear. Here, we found that lncRNA MIR4500HG003 was highly expressed in highly metastatic MDA-MB-231 TNBC cells and overexpression of MIR4500HG003 enhanced metastasis ability in vitro and in vivo and promoted MMP9 expression. Furthermore, we found MIR4500HG003 physically interacted with miR-483-3p and reporter assay showed miR-483-3p attenuated MMP9 expression. Importantly, endogenous high expressions of MIR4500HG003 were correlated with tumor recurrence in TNBC patients with tumor metastasis. Taken together, our findings suggested that MIR4500HG003 promotes metastasis of TNBC through miR-483-3p-MMP9 signaling axis and may be used as potential prognostic marker for TNBC patients.

Protein lipoylation: mitochondria, cuproptosis, and beyond.

Protein lipoylation, a crucial post-translational modification (PTM), plays a pivotal role in mitochondrial function and emerges as a key player in cell death through cuproptosis. This novel copper-driven cell death pathway is activated by excessive copper ions binding to lipoylated mitochondrial proteins, disrupting energy production and causing lethal protein aggregation and cell death. The intricate relationship among protein lipoylation, cellular energy metabolism, and cuproptosis offers a promising avenue for regulating essential cellular functions. This review focuses on the mechanisms of lipoylation and its significant impact on cell metabolism and cuproptosis, emphasizing the key genes involved and their implications for human diseases. It offers valuable insights into targeting dysregulated cellular metabolism for therapeutic purposes.