SENP3 mediates the deSUMOylation and degradation of YAP1 to regulate the progression of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a prevalent malignancy in women, casting a formidable shadow on their well-being. Positioned within the nucleolus, SUMO-specific protease 3 (SENP3) assumes a pivotal role in the realms of development and tumorigenesis. However, the participation of SENP3 in TNBC remains a mystery. Here, we elucidate that SENP3 exerts inhibitory effects on migration and invasion capacities, as well as on the stem cell-like phenotype, within TNBC cells. Further experiments showed that YAP1 is the downstream target of SENP3, and SENP3 regulates tumorigenesis in a YAP1-dependent manner. YAP1 is found to be SUMOylated and SENP3 deconjugates SUMOylated YAP1 and promotes degradation mediated by the ubiquitin-proteasome system. More importantly, YAP1 with a mutation at the SUMOylation site impedes the capacity of WT YAP1 in TNBC tumorigenesis. Taken together, our findings firmly establish the pivotal role of SENP3 in the modulation of YAP1 deSUMOylation, unveiling novel mechanistic insight into the important role of SENP3 in the regulation of TNBC tumorigenesis in a YAP1-dependent manner.

Amino acids and their roles in tumor immunotherapy of breast cancer.

Breast cancer is the most commonly diagnosed cancer among women. The primary treatment options include surgery, radiotherapy, chemotherapy, targeted therapy and hormone therapy. The effectiveness of breast cancer therapy varies depending on the stage and aggressiveness of the cancer, as well as individual factors. Advances in early detection and improved treatments have significantly increased survival rates for breast cancer patients. Nevertheless, specific subtypes of breast cancer, particularly triple-negative breast cancer, still lack effective treatment strategies. Thus, novel and effective therapeutic targets for breast cancer need to be explored. As substrates of protein synthesis, amino acids are important sources of energy and nutrition, only secondly to glucose. The rich supply of amino acids enables the tumor to maintain its proliferative competence through participation in energy generation, nucleoside synthesis and maintenance of cellular redox balance. Amino acids also play an important role in immune-suppressive microenvironment formation. Thus, the biological effects of amino acids may change unexpectedly in tumor-specific or oncogene-dependent manners. In recent years, there has been significant progress in the study of amino acid metabolism, particularly in their potential application as therapeutic targets in breast cancer. In this review, we provide an update on amino acid metabolism and discuss the therapeutic implications of amino acids in breast cancer.

Fantastic beasts and how to study them: rethinking experimental animal behavior.

Humans have been trying to understand animal behavior at least since recorded history. Recent rapid development of new technologies has allowed us to make significant progress in understanding the physiological and molecular mechanisms underlying behavior, a key goal of neuroethology. However, there is a tradeoff when studying animal behavior and its underlying biological mechanisms: common behavior protocols in the laboratory are designed to be replicable and controlled, but they often fail to encompass the variability and breadth of natural behavior. This Commentary proposes a framework of 10 key questions that aim to guide researchers in incorporating a rich natural context into their experimental design or in choosing a new animal study system. The 10 questions cover overarching experimental considerations that can provide a template for interspecies comparisons, enable us to develop studies in new model organisms and unlock new experiments in our quest to understand behavior.

The Preparation and Dust Suppression Performance Evaluation of Iron Ore Tailing-Based Cementitious Composites.

In order to comprehensively utilize iron ore tailings (IOTs), the possibility of using IOTs as raw materials for the preparation of cementitious composites (IOTCCs) was investigated, and IOTCC was further applied to mine interface pollution control. The mechanical properties, hydration products, wind erosion resistance, and freeze-thaw (F-T) cycle resistance of IOTCCs were evaluated rigorously. The activity index of iron tailings increased from 42% to 78% after grinding for 20 s. The IOTCC was prepared by blending 86% IOT, 10% ground granulated blast-furnace slag (GGBS), and 4% cement clinker. Meanwhile, the hydration products mainly comprised ettringite, calcium hydroxide, and C-S-H gel, and they were characterized via XRD, IR, and SEM. It was observed that ettringite and C-S-H gel were principally responsible for the strength development of IOTCC mortars with an increase in curing time. The results show that the kaolinite of the tailings was decomposed largely after mechanical activation, which promoted the cementitious property of IOT.

Investigation into the Synergistic Effect of the Zinc Peroxide/Peroxymonosulfate Double-Oxidation System for the Efficient Degradation of Tetracycline.

The increasingly severe antibiotic pollution has become one of the most critical issues. In this study, a zinc peroxide/peroxymonosulfate (ZnO2/PMS) double-oxidation system was developed for tetracycline (TC) degradation. A small amount of ZnO2 (10 mg) and PMS (30 mg) could effectively degrade 82.8% of TC (100 mL, 50 mg/L), and the degradation process could be well described by the pseudo-second-order kinetic model. Meanwhile, the ZnO2/PMS double-oxidation system showed high adaptability in terms of reaction temperature (2-40 °C), initial pH value (4-12), common inorganic anions (Cl-, NO3-, SO42- and HCO3-), natural water source and organic pollutant type. The quenching experiment and electron paramagnetic resonance (EPR) characterization results confirmed that the main reactive oxygen species (ROS) was singlet oxygen (1O2). Moreover, three possible pathways of TC degradation were deduced according to the analyses of intermediates. On the basis of comparative characterization and experiment results, a synergistic activation mechanism was further proposed for the ZnO2/PMS double-oxidation system, accounting for the superior degradation performance. The released OH- and H2O2 from ZnO2 could activate PMS to produce major 1O2 and minor superoxide radicals (•O2-), respectively.

Neutrophils in triple-negative breast cancer: an underestimated player with increasingly recognized importance.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer, with limited therapeutic options readily available. Immunotherapy such as immune checkpoint inhibition has been investigated in TNBC but still encounters low overall response. Neutrophils, the most abundant leukocytes in the body, are increasingly recognized as an active cancer-modulating entity. In the bloodstream, neutrophils escort circulating tumor cells to promote their survival and stimulate their proliferation and metastasis. In the tumor microenvironment, neutrophils modulate the immune milieu through polarization between the anti-tumor and the pro-tumor phenotypes. Through a comprehensive review of recently published literature, it is evident that neutrophils are an important player in TNBC immunobiology and can be used as an important prognostic marker of TNBC. Particularly, in their pro-tumor form, neutrophils facilitate TNBC metastasis through formation of neutrophil extracellular traps and the pre-metastatic niche. These findings will help advance the potential utilization of neutrophils as a therapeutic target in TNBC.

Development and validation of a patient satisfaction survey for pharmaceutical service at primary care settings.

Patient satisfaction is a key quality indicator of pharmacy service. However, there are few studies that develop and validate patient satisfaction surveys applied to pharmaceutical services in primary care settings. It is imperative to establish a well-validated multidimensional instrument for evaluating the viability and sustainability of pharmacy service across geographically diverse regions in low- and middle-income countries. To develop and validate a patient satisfaction instrument for community pharmaceutical services, we carried out a cross-sectional survey in seven provinces across China. The study was conducted in four phases: (i) literature review-based item generation, (ii) expert panel-endorsed questionnaire refinement, (iii) pilot questionnaire development, and (iv) psychometric validation. Survey respondents were standard patients recruited locally and trained to conduct unannounced visits to preselected primary care centers. Between December 2020 and November 2021, the pilot survey comprised a total of 166 unannounced standard patient visits from 125 health-care facilities. The final 24-item Likert-type instrument encompassed five domains: relationship, medication counseling, empathy, accessibility, and overall satisfaction. The satisfactory survey revealed excellent internal consistency. Factor analyses resulted in a 4-factor solution that accounted for 70.7% variance. The results suggest that the questionnaire is a valid and reliable instrument, which has been taken an important step to evaluate patient satisfaction with pharmaceutical services in Chinese primary care settings. Further research on its cross-culture adaptation and applicability in urban retail pharmacy settings is warranted.

Anastrozole and related glucuronic acid conjugate are electrophilic species.

Anastrozole (ANA), is an inhibitor of non-steroidal aromatase, widely employed for the treatment of breast cancer. However, ANA-associated liver injury cases have been documented in the application of the drug.The major purposes of the present study were to identify the structure of reactive metabolites derived from ANA and to study related metabolic pathways of ANA.We found ANA itself is an electrophilic species reactive to GSH. ANA can be metabolised to ANA-N+-glucuronide (1) catalysed by UGT1A4. An ANA GSH conjugate (2) was detected in bile and livers of rats treated with ANA. UGT1A4 participated in the phase II metabolic pathway.This work allowed us to better understand the mechanisms of the hepatotoxicity of ANA and provided new avenue to define the possible role of metabolic activation in hepatotoxicity.

Wogonin Increases Cisplatin Sensitivity in Ovarian Cancer Cells Through Inhibition of the Phosphatidylinositol 3-Kinase (PI3K)/Akt Pathway.

BACKGROUND Wogonin (5,7-dihydroxy-8-methoxyflavone), one of flavonoids isolated from the Scutellaria baicalensis, has been regarded as an anticancer candidate because of its maximal efficacy in cancer cells. This study aimed to explore the possible mechanism that wogonin uses to enhance the sensitivity of ovarian cancer cells to cisplatin chemotherapy. MATERIAL AND METHODS The growth inhibition rates of ovarian cancer cells SKOV3/DDP and C13* were assessed by Cell Counting Kit-8 (CCK-8) assay. The apoptosis was assessed under a fluorescence microscope following staining with Hoechst. We further analyzed the expression of Bcl-2, cleaved caspases-3, cleaved-PARP, and phospho-Akt by western blotting. RESULTS In the present study, we found that wogonin reduced proliferation of ovarian cancer cells SKOV3, SKOV3/DDP, OV2008, and C13* in dose- and time-dependent manners and it sensitized cisplatin-induced cytotoxicity. Moreover, treatment with wogonin also increased cisplatin-resistant SKOV3/DDP and C13* cells to low dose cisplatin-induced cell apoptosis. Additionally, such treatment resulted in a significant decrease in phosphorylated Akt. CONCLUSIONS Wogonin could significantly increase the sensitivity of cisplatin-resistant ovarian cancer cells to cisplatin by downregulating the PI3K/Akt pathway.

Death anxiety, sense of meaning in life, and willingness to body donation among nursing students in anatomy course: An explanatory sequential mixed study.

BACKGROUND: Anatomy education is a fundamental part of clinical nursing, but anatomy courses may lead to a range of psychological changes, such as death anxiety and sense of meaning in life. Such experiences and changes may influence student's willingness to donate their body. There is insufficient evidence on whether anatomy courses bring about these changes, and the reasons behind experiences are unclear. Focusing on these changes is essential to improve anatomy education in nursing and to promote the mental health of students in the nursing field. OBJECTIVES: To explore changes and underlying reasons for death anxiety, sense of meaning in life, and the willingness to donate a body before and after anatomy courses. DESIGN: An explanatory sequential explanatory mixed-methods study. PARTICIPANTS: A total of 60 students completed quantitative surveys and 16 students from the sub-samples of the quantitative stage were included in the qualitative interviews. All students were from a comprehensive university in Changsha, Hunan Province, China. METHODS: Data were collected from September 2022 to April 2023, including two rounds of questionnaire surveys and one interview. The questionnaires included sociodemographic data, the Death Anxiety Scale (CT-DAS), the Meaning of Life Scale (MLQ), and a body donation willingness question. Interviews were conducted based on the research objectives. The statistical methods included descriptive statistics, z-tests, and thematic analysis. RESULTS: Quantitative results showed a decrease in emotional dimension of death anxiety (z = -2.534, P < 0.05) and an increase in body donation willingness (z = -3.183, P < 0.05). Qualitative analysis revealed cognitive experience and value assessment may relate to the changes. Based on the two themes, the reduction of death anxiety in emotional dimension can be further attributed to four factors: demystification, instrumentalization, desensitization, and respect and gratitude towards donors. The increase in willingness to donate bodies can be further attributed to two aspects: increase in knowledge of body donation and the affirmation of the value of donation. CONCLUSION: The study found that students experience a decrease in death anxiety in the emotional dimension and an increased inclination to donate their bodies after anatomy courses, which may be related to cognitive experience and value assessment. Future nursing anatomy education could delve deeper into these two perspectives and support students to positively cope with death anxiety and rethink body donation through enriching death education activities such as donor memorial ceremonies. These results provide a basis for designing anatomy courses and improving the psychological well-being and professional competence of nursing students.

Aeration Alleviated the Adverse Effects of Nitrogen Topdressing Reduction on Tomato Root Vigor, Photosynthetic Performance, and Fruit Development.

To explore the compensation effect of aeration on tomato vegetative and reproductive growth in arid and semi-arid areas, a two-year field experiment was conducted with four micro-nano aeration ratios (0%, 5%, 10%, and 15%) and three nitrogen topdressing levels (80, 60, and 40 kg·ha-1) during the tomato growth period in Ningxia, China. The results showed that increasing the aeration ratio in the range of 0-15% was conducive to the enhancement of tomato root vigor (the ability of triphenyltetrazolium chloride to be reduced, 3-104%) and the leaf net photosynthetic rate (14-63%), favorable to the facilitation of plant dry matter accumulation (3-59%) and plant nitrogen accumulation (2-70%), and beneficial to the improvement of tomato yield (12-44%) and fruit quality. Interestingly, since the aeration ratio exceeded 10%, the increase in the aeration ratio showed no significant effects on the single-fruit weight, tomato yield, and fruit quality. Moreover, with aerated underground drip irrigation, properly reducing the traditional nitrogen topdressing level (80 kg·ha-1) by 25% was favorable for enhancing tomato root vigor (5-31%), increasing tomato yield (0.5-9%), and improving fruit soluble solid accumulation (2-5%) and soluble sugar formation (4-9%). Importantly, increasing the aeration ratio by 5% could compensate for the adverse effects of reducing the nitrogen topdressing level by 25% by improving the leaf photosynthetic rate, promoting plant dry matter accumulation, increasing tomato yield, and enhancing the soluble solid and soluble sugar accumulation in tomato fruits. Synthetically considering the decrease in the nitrogen topdressing amount, leading to plant growth promotion, a tomato yield increase, and fruit quality improvement, a favorable nitrogen topdressing level of 60 kg·ha-1 and the corresponding proper aeration ratio of 10% were suggested for tomato underground drip irrigation in the Yinbei Irrigation District of Ningxia.

Incorporating Inflammation Biomarker-Driven Multivariate Predictive Model for Coronary Microcirculatory Dysfunction in Acute Myocardial Infarction Following Emergency Percutaneous Coronary Intervention.

BACKGROUND: Despite patients with successful revascularization as evidenced by angiographic findings, inadequate clinical management of coronary microcirculatory dysfunction (CMD) may result in preventable adverse outcomes. Therefore, it is imperative to use a multimodal data­driven predictive model for the occurrence of CMD in patients with acute myocardial infarction (AMI) following emergency percutaneous coronary intervention (PCI). METHODS: A prospective case-control analysis was conducted on a cohort of 77 patients with AMI who underwent PCI. The most informative predictors were selected for the predictive model through the application of LASSO analysis and multi-factor logistic regression. The diagnosis of CMD is based on findings from cardiac magnetic resonance (CMR). RESULTS: Based on the findings from LASSO analysis and multi-factor logistic regression, variables including sex, neutrophil-to-lymphocyte ratio (NLR), Gensini score, and diabetes mellitus were identified as independent predictors for the development of CMD in AMI patients who underwent emergency PCI. The predictive model was evaluated using bootstrap self-sampling 500 times. The resulting predictive model demonstrated an AUC value of 0.897 (95% CI: 0.827-0.958). The calibration curves exhibited good concordance between the predictions generated by the model and the CMR analysis. Furthermore, decision curve analysis revealed that the predictive model provided valuable clinical benefit in predicting CMD. CONCLUSIONS: The multivariate predictive model, constructed using readily available clinical variables in patients with AMI who underwent PCI, demonstrates satisfactory predictability for identifying comorbid CMD, thereby facilitating the identification of high-risk patients.

Cardiac magnetic resonance imaging-derived pathophysiology and prognosis of diabetes mellitus with acute myocardial infarction after revascularization: a prospective cohort study.

BACKGROUND: Little is known about the underlying factors contributing to unfavourable clinical outcomes in patients with diabetes mellitus (DM) complicated by new-onset acute myocardial infarction (AMI). The aim of this study was to investigate the impact of DM on the pathophysiologic features and prognosis of patients with new-onset AMI following successful revascularization by utilizing cardiac magnetic resonance (CMR). METHODS: Consecutive patients diagnosed with new-onset AMI between June 2022 and January 2024 were included. All patients underwent culprit vessel revascularization upon admission and CMR imaging 3-7 days later. The primary clinical endpoint of this study was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), for which the average follow-up was 10 months. RESULTS: A total of 72 patients were divided into a DM group (n = 23) and a non-DM group (n = 49). Multivariate logistic regression analysis revealed that DM was an independent risk factor for the occurrence of microvascular obstruction. Multivariate linear regression analysis found that DM was the influencing factor of global radial strain (B = -4.107, t = -2.328, p = 0.023), while fasting blood glucose influenced infarct segment myocardial radial strain (B = -0.622, t = -2.032, p = 0.046). DM independently contributed to the risk of MACCEs following successful revascularization in patients with AMI (p < 0.05). CONCLUSION: Comprehensive phenotypic characterization of myocardial injury and microcirculatory status could enable reliable identification of high-risk MACCEs in DM patients with new-onset AMI following successful revascularization.

Dysregulated Ribosome Biogenesis Is a Targetable Vulnerability in Triple-Negative Breast Cancer: MRPS27 as a Key Mediator of the Stemness-inhibitory Effect of Lovastatin.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited effective therapeutic options readily available. We have previously demonstrated that lovastatin, an FDA-approved lipid-lowering drug, selectively inhibits the stemness properties of TNBC. However, the intracellular targets of lovastatin in TNBC remain largely unknown. Here, we unexpectedly uncovered ribosome biogenesis as the predominant pathway targeted by lovastatin in TNBC. Lovastatin induced the translocation of ribosome biogenesis-related proteins including nucleophosmin (NPM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and the ribosomal protein RPL3. Lovastatin also suppressed the transcript levels of rRNAs and increased the nuclear protein level and transcriptional activity of p53, a master mediator of nucleolar stress. A prognostic model generated from 10 ribosome biogenesis-related genes showed outstanding performance in predicting the survival of TNBC patients. Mitochondrial ribosomal protein S27 (MRPS27), the top-ranked risky model gene, was highly expressed and correlated with tumor stage and lymph node involvement in TNBC. Mechanistically, MRPS27 knockdown inhibited the stemness properties and the malignant phenotypes of TNBC. Overexpression of MRPS27 attenuated the stemness-inhibitory effect of lovastatin in TNBC cells. Our findings reveal that dysregulated ribosome biogenesis is a targetable vulnerability and targeting MRPS27 could be a novel therapeutic strategy for TNBC patients.

A highly conductive gel electrolyte with favorable ion transfer channels for long-lived zinc-iodine batteries.

Aqueous rechargeable zinc-iodine batteries (ARZIBs), as a powerful energy alternative, have inherent advantages, such as low cost, good safety and environmental friendliness. Unfortunately, uneven Zn deposition with dendrite growth and undesirable side reactions seriously compromises the safety and stability of ARZIBs. Herein, a novel strategy is demonstrated to fabricate highly conductive iota-carrageenan (IC) gel electrolyte. The unique double helix structure with good mechanical properties provides favorable Zn2+ channels guided by sulfate groups, which enables confinement effect and orderly guidance of Zn deposition. Additionally, the activity of water molecules confined in the gel electrolyte is reduced, thus inhibiting the corrosion reactions of the zinc electrode. As a result, the gel electrolyte with remarkable ionic conductivity (42.95 mS cm-1) showed a good cycling stability over 1000 h. Importantly, the Zn-I2 batteries with the IC-Zn gel electrolyte demonstrated remarkable reversibility with an impressive capacity retention (91.9%) over 5000 cycles and high average coulombic efficiency (99.86%). This work provides a reliable strategy to develop natural polymer gel electrolytes to regulate the Zn deposition for advanced rechargeable Zn-I2 batteries.

Identification and immunological characteristics of chaperonin GroEL in Riemerella anatipestifer.

Riemerella anatipestifer (RA) infections cause major economic losses in the duck industry. In this study, an immunogenic protein, chaperonin GroEL (GroEL), was identified from the outer membrane of RA strain WJ4 by immunoproteomic assay based on matrix-assisted laser desorption/ionization time of flight mass spectrometry. The complete sequence of the encoding gene, chaperonin groEL (groEL) was amplified and determined to be 1,629 base pairs in length. groEL was then cloned into expression vector pGEX-6P-1, and the expression of the recombinant GroEL (rGroEL) in Escherichia coli strain BL21 was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting analysis. Immunization assay showed that ducklings or rabbits immunized with purified rGroEL generated 53- or 160-fold more anti-GroEL antibodies than those with no immunization. Importantly, bactericidal assay showed that rabbit anti-GroEL serum killed 30.0-57.3% of bacteria representing different serotypes, while rabbit anti-bacterin serum killing activity exhibits large serotype-dependent variations between 0.2% and 63.6%. Animal challenge experiment showed that ducklings immunized with rGroEL were 50%, 37.5%, and 37.5% protected from the challenge with RA strains WJ4 (serotype 1), Th4 (serotype 2), and YXb-2 (serotype 10), respectively. In addition, groEL from 34 additional RA strains was amplified by polymerase chain reaction (PCR), and products from nine were sequenced. groEL is highly conserved among RA strains, as the DNA sequence identity was over 97.5% between WJ4 and the nine additional strains. Our results suggest that GroEL may be a good candidate for new RA vaccine development.

Enhanced catalytic performance of spinel-type Cu-Mn oxides for benzene oxidation under microwave irradiation.

Microwave-assisted heterogeneous catalytic oxidation of benzene was investigated over Cu-Mn spinel oxides. The spinel oxides were synthesized by a coprecipitation method from metal nitrate hydrolysis in a solution using tetramethylammonium hydroxide (TMAH) as a precipitation reagent. The catalysts were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, X-ray absorption fine structure, scanning electron microscopy, transmission electron microscope and H2-temperature-programmed reduction studies. Microwave absorption by the Cu-Mn spinel oxide is mainly driven by dielectric losses (dielectric heating). Cu-Mn spinel oxide with a Cu/Mn ratio of 1 exhibited superior activity to single oxides under microwave heating, demonstrating lower apparent activation energy than that obtained under conventional heating. Microwave irradiation lowered the reaction temperature required for benzene oxidation compared with conventional heating. Transient tests were used to investigate the reactivity of oxygen species in the catalytic reaction, and the high reactivity of Cu-Mn spinel oxides was related to the high reactivity of lattice oxygen on the catalyst surface. The reactivity of the oxygen species was enhanced under microwave heating, leading to an enhanced benzene oxidation reaction. The combination of adsorption and catalytic oxidation processes using Cu-Mn spinel oxides and zeolites efficiently decomposed benzene at low concentrations.

Hexokinase 2 Is a Pivot for Lovastatin-induced Glycolysis-to-Autophagy Reprogramming in Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited therapeutic options available. We have recently demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, suppresses TNBC cell proliferation and stemness properties in vitro and in vivo. However, the mechanisms through which lovastatin inhibits TNBC cells are not fully understood. Here, we used 1H NMR-based metabolomic profiling to investigate lovastatin-induced metabolic changes in TNBC cell line MDA-MB-231. Among the 46 metabolites identified, lactate demonstrated the highest variable importance in projection (VIP) score. Glycolysis stress test revealed that lovastatin significantly decreased the extracellular acidification rate (ECAR) in MDA-MB-231 cells. Furthermore, lovastatin treatment down-regulated the levels of glycolysis-related proteins including GLUT1, PFK1, and PKM2 in MDA-MB-231 but not non-TNBC MDA-MB-453 cells. In addition, lovastatin induced autophagy as evidenced by increased LC3 puncta formation and LC3-II/I ratio, increased AMPK phosphorylation, and decreased Akt phosphorylation. We also revealed the interaction between the glycolytic enzyme hexokinase 2 (HK2) and the mitochondrial membrane protein voltage-dependent anion channel 1 (VDAC1), an important regulator of autophagy. Further bioinformatics analysis revealed that VDAC1 was expressed at a higher level in breast cancer than normal tissues and higher level of VDAC1 predicted poorer survival outcomes in breast cancer patients. The present study suggests that lovastatin might exert anti-tumor activity by reprogramming glycolysis toward autophagy in TNBC cells through HK2-VDAC1 interaction.

Co-Expression and Combined Prognostic Value of CSPG4 and PDL1 in TP53-Aberrant Triple-Negative Breast Cancer.

Background: In triple-negative breast cancer (TNBC), PDL1/PD1-directed immunotherapy is effective in less than 20% of patients. In our preliminary study, we have found CSPG4 to be highly expressed together with PDL1 in TNBCs, particularly those harboring TP53 aberrations. However, the clinical implications of co-expressed CSPG4 and PDL1 in TNBCs remain elusive. Methods: A total of 85 advanced TNBC patients treated in the Hunan Cancer Hospital between January 2017 and August 2019 were recruited. The expressions of CSPG4 and PDL1 in TNBC tissues were investigated using immunohistochemistry (IHC). The RNA-seq dataset from the TCGA-BRCA project was further used to analyze the mRNA expression of CSPG4 and PDL1 in TP53-aberrant TNBCs. Cox proportional hazards model and Kaplan-Meier curves with Logrank test was used to analyze the effects of CSPG4 and PDL1 on survival. TNBC cell lines were further used to investigate the molecular mechanism that were involved. Results: TP53 aberrations occurred in more than 50% of metastatic TNBCs and were related to higher tumor mutation burden (TMB). In TCGA-BRCA RNA-seq dataset analysis, both CSPG4 and PDL1 levels were high in TNBCs, especially in TP53-aberrant TNBCs. IHC assay showed nearly 60% of advanced TNBCs to be CSPG4-positive and about 25% to be both CSPG4-positive and PDL1-positive. The levels of CSPG4 and PDL1 were high in TNBC cell lines as revealed by flow cytometry and immunoblotting compared with non-TNBC cells. Univariate Cox regression analysis indicated that CSPG4 positivity was a significant risk factor for progression-free survival in metastatic TNBCs, with a hazard ratio (HR) of 2.26 (P = 0.05). KM curves with Logrank test also identified high level of CSPG4 as a significant risk factor for overall survival in advanced breast cancers in TCGA-BRCA samples (P = 0.02). The immunoblotting assays showed that EMT-related pathways were involved in CSPG4-mediated invasion. Conclusions: CSPG4 expression level is associated with PDL1 positivity in TP53-aberrant TNBC cells. Patients with CSPG4 expression have poor treatment response and poor overall survival. Co-expressed CSPG4 and PDL1 may have an important prognostic value and provide new therapeutic targets in TNBC patients. CSPG4 might mediate tumor invasion and PDL1 overexpression through EMT-related pathway.

Megapixel camera arrays enable high-resolution animal tracking in multiwell plates.

Tracking small laboratory animals such as flies, fish, and worms is used for phenotyping in neuroscience, genetics, disease modelling, and drug discovery. An imaging system with sufficient throughput and spatiotemporal resolution would be capable of imaging a large number of animals, estimating their pose, and quantifying detailed behavioural differences at a scale where hundreds of treatments could be tested simultaneously. Here we report an array of six 12-megapixel cameras that record all the wells of a 96-well plate with sufficient resolution to estimate the pose of C. elegans worms and to extract high-dimensional phenotypic fingerprints. We use the system to study behavioural variability across wild isolates, the sensitisation of worms to repeated blue light stimulation, the phenotypes of worm disease models, and worms' behavioural responses to drug treatment. Because the system is compatible with standard multiwell plates, it makes computational ethological approaches accessible in existing high-throughput pipelines.