Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element.

Noncoding mutations in cancer genomes are frequent but challenging to interpret. PVT1 encodes an oncogenic lncRNA, but recurrent translocations and deletions in human cancers suggest alternative mechanisms. Here, we show that the PVT1 promoter has a tumor-suppressor function that is independent of PVT1 lncRNA. CRISPR interference of PVT1 promoter enhances breast cancer cell competition and growth in vivo. The promoters of the PVT1 and the MYC oncogenes, located 55 kb apart on chromosome 8q24, compete for engagement with four intragenic enhancers in the PVT1 locus, thereby allowing the PVT1 promoter to regulate pause release of MYC transcription. PVT1 undergoes developmentally regulated monoallelic expression, and the PVT1 promoter inhibits MYC expression only from the same chromosome via promoter competition. Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements.

Fizeau drag in graphene plasmonics.

Dragging of light by moving media was predicted by Fresnel1 and verified by Fizeau's celebrated experiments2 with flowing water. This momentous discovery is among the experimental cornerstones of Einstein's special relativity theory and is well understood3,4 in the context of relativistic kinematics. By contrast, experiments on dragging photons by an electron flow in solids are riddled with inconsistencies and have so far eluded agreement with the theory5-7. Here we report on the electron flow dragging surface plasmon polaritons8,9 (SPPs): hybrid quasiparticles of infrared photons and electrons in graphene. The drag is visualized directly through infrared nano-imaging of propagating plasmonic waves in the presence of a high-density current. The polaritons in graphene shorten their wavelength when propagating against the drifting carriers. Unlike the Fizeau effect for light, the SPP drag by electrical currents defies explanation by simple kinematics and is linked to the nonlinear electrodynamics of Dirac electrons in graphene. The observed plasmonic Fizeau drag enables breaking of time-reversal symmetry and reciprocity10 at infrared frequencies without resorting to magnetic fields11,12 or chiral optical pumping13,14. The Fizeau drag also provides a tool with which to study interactions and nonequilibrium effects in electron liquids.

CRISPRi screens identify the lncRNA, LOUP, as a multifunctional locus regulating macrophage differentiation and inflammatory signaling.

Long noncoding RNAs (lncRNAs) account for the largest portion of RNA from the transcriptome, yet most of their functions remain unknown. Here, we performed two independent high-throughput CRISPRi screens to understand the role of lncRNAs in monocyte function and differentiation. The first was a reporter-based screen to identify lncRNAs that regulate TLR4-NFkB signaling in human monocytes and the second screen identified lncRNAs involved in monocyte to macrophage differentiation. We successfully identified numerous noncoding and protein-coding genes that can positively or negatively regulate inflammation and differentiation. To understand the functional roles of lncRNAs in both processes, we chose to further study the lncRNA LOUP [lncRNA originating from upstream regulatory element of SPI1 (also known as PU.1)], as it emerged as a top hit in both screens. Not only does LOUP regulate its neighboring gene, the myeloid fate-determining factor SPI1, thereby affecting monocyte to macrophage differentiation, but knockdown of LOUP leads to a broad upregulation of NFkB-targeted genes at baseline and upon TLR4-NFkB activation. LOUP also harbors three small open reading frames capable of being translated and are responsible for LOUP's ability to negatively regulate TLR4/NFkB signaling. This work emphasizes the value of high-throughput screening to rapidly identify functional lncRNAs in the innate immune system.

Development of High-Throughput Experimentation Approaches for Rapid Radiochemical Exploration.

Positron emission tomography is a widely used imaging platform for studying physiological processes. Despite the proliferation of modern synthetic methodologies for radiolabeling, the optimization of these reactions still primarily relies on inefficient one-factor-at-a-time approaches. High-throughput experimentation (HTE) has proven to be a powerful approach for optimizing reactions in many areas of chemical synthesis. However, to date, HTE has rarely been applied to radiochemistry. This is largely because of the short lifetime of common radioisotopes, which presents major challenges for efficient parallel reaction setup and analysis using standard equipment and workflows. Herein, we demonstrate an effective HTE workflow and apply it to the optimization of copper-mediated radiofluorination of pharmaceutically relevant boronate ester substrates. The workflow utilizes commercial equipment and allows for rapid analysis of reactions for optimizing reactions, exploring chemical space using pharmaceutically relevant aryl boronates for radiofluorinations, and constructing large radiochemistry data sets.

ERK1/2 pro-survival signalling is suppressed by pirtobrutinib in ibrutinib-resistant MYD88-mutated lymphoma cells.

Covalent Bruton's tyrosine kinase-inhibitors (cBTK-i) are highly active in MYD88-mutated (MYD88Mut) Waldenstrom's macroglobulinaemia and suppress nuclear factor kappa-light-chain-enhancer of activated B cells and extracellular signal-regulated kinases-1/2 (ERK1/2)-related signalling. BTKCys481 mutations are associated with cBTK-i acquired resistance and are accompanied by reactivation of ERK1/2 that promotes inflammatory cytokine secretion and paracrine-mediated resistance of BTK wild-type (BTKWT) tumour cells. Pirtobrutinib is a non-covalent BTK-inhibitor that binds at non-BTKCys481 sites. We show that pirtobrutinib blocked p-ERK1/2, ERK1/2-driven inflammatory cytokines, and overcame paracrine-mediated resistance in MYD88Mut lymphoma cells expressing mutated BTKCys481. Our results provide important mechanistic insights for the activity of pirtobrutinib in MYD88Mut lymphomas carrying BTKCys481 mutations.

Lung Cancer Research and Treatment: Global Perspectives and Strategic Calls to Action.

BACKGROUND: Lung cancer remains a critical public health issue, presenting multifaceted challenges in prevention, diagnosis, and treatment. This article aims to review the current landscape of lung cancer research and management, delineate the persistent challenges, and outline pragmatic solutions. MATERIALS AND METHODS: Global experts from academia, regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA), the National Cancer Institute (NCI), professional societies, the pharmaceutical and biotech industries, and patient advocacy groups were gathered by the New York Lung Cancer Foundation to review the state of the art in lung cancer and to formulate calls to action. RESULTS: Improving lung cancer management and research involves promoting tobacco cessation, identifying individuals at risk who could benefit from early detection programs, and addressing treatment-related toxicities. Efforts should focus on conducting well-designed trials to determine the optimal treatment sequence. Research into innovative biomarkers and therapies is crucial for more personalized treatment. Ensuring access to appropriate care for all patients, whether enrolled in clinical trials or not, must remain a priority. CONCLUSIONS: Lung cancer is a major health burden worldwide, and its treatment has become increasingly complex over the past two decades. Improvement in lung cancer management and research requires unified messaging and global collaboration, expanded education, and greater access to screening, biomarker testing, treatment, as well as increased representativeness, participation, and diversity in clinical trials.

Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

Acceleration of electrons in the plasma wakefield of a proton bunch.

High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.

Application research on asthma-COPD overlap using low-dose CT scan and quantitative analysis.

PURPOSE: The aim of this study was to assess the proximal airway remodeling, emphysema, and air trapping of asthma-COPD Overlap. MATERIALS AND METHODS: 20 ACO patients, 55 mild to moderate COPD patients and 38 non-severe asthma patients were participated in low-dose dual phase CT scanning and pulmonary function test, comparative analysis was performed to identify differences in CT measurements among three groups. RESULTS: (Ⅰ) The average age and smoking index of ACO and mild to moderate COPD were both higher than non-severe asthma. ACO and mild to moderate COPD group had a higher proportion of males than non-severe asthma. (Ⅱ) In terms of pulmonary function test, FEV1 (%Pred), FEV1/FVC%, MEF25% (%Pred), MEF 50% (%Pred), MMEF (%Pred), and PEF (%Pred) in ACO were significantly reduced than those in non-severe asthma. (Ⅲ) On proximal airway parameters, ACO exhibited higher WA% and Pi10 compared to mild to moderate COPD. However, there was no statistically significant difference in WA% and Pi10 between ACO and non-severe asthma. (Ⅳ) On CT lung function, the emphysema index VI-910ex of ACO was significantly higher than non-severe asthma.Additionally, ACO demonstrated higher MLDex and VI-856ex compared to non-severe asthma. CONCLUSIONS: Compared with non-severe asthma, ACO is more common in male patients with older age and a longer history of smoking, which had more severe airflow obstruction and airway dysfunction than non-severe asthma.ACO showed more obvious proximal airway remodeling than mild to moderate COPD, and was more similar to non-severe asthma.The extent of emphysema and air trapping in ACO were more pronounced compared to non-severe asthma.

Preoperative CT histogram analysis to predict the expression of Ki-67 in solid pseudopapillary tumours of the pancreas.

AIM: To explore the value of preoperative computed tomography (CT) histogram features in predicting the expression status of Ki-67 in patients with solid pseudopapillary pancreatic tumours (SPTP). MATERIALS AND METHODS: This retrospective study analysed venous phase CT images of 39 patients with SPTP confirmed at surgery and histopathology and measured using the Ki-67 proliferation index from November 2015 to February 2022. According to the Ki-67 proliferation index, they were divided into high expression (Ki-67 ≥ 4%) and low expression (Ki-67 < 4%) groups. The histogram features of quantitative parameters were extracted using MaZda software, and the quantitative parameters of CT histograms were compared between groups. The receiver operating characteristic (ROC) curves of the patients were plotted according to the parameters, with statistically significant differences. The area under the curve (AUC), sensitivity, and specificity were calculated, and the effectiveness of the histogram parameters in predicting Ki-67 expression was analysed and evaluated. RESULTS: In total, 27 SPTP patients were enrolled, including 11 with high expression of Ki-67 and 16 with low expression. Comparative analysis of the Ki-67 high- and low-expression groups revealed a statistically significant in necrosis and variance (p<0.05). ROC curve analysis showed that the AUC of necrosis and variance predicting Ki-67 expression status were 0.753 and 0.841, the sensitivities were 81.8% and 81.3%, and the specificities were 68.7% and 81.8%, respectively. CONCLUSION: Preoperative CT histogram features help predict Ki-67 expression status in patients with SPTP.

Asprosin: its function as a novel endocrine factor in metabolic-related diseases.

BACKGROUND AND PURPOSE: Asprosin was discovered as a new endocrine hormone originating from fibrillin-1 cleavage that plays a crucial role in various metabolic-related diseases, such as obesity, nonalcoholic fatty liver disease (NAFLD), diabetes, polycystic ovary syndrome (PCOS), and cardiovascular diseases. The purpose of this review is to describe the recent advancements of asprosin. METHOD: Narrative review. RESULT: This comprehensive review explores its tissue-specific functions, focusing on white adipose tissue, liver, hypothalamus, testis, ovary, heart, pancreas, skeletal muscle, and kidney. CONCLUSION: Asprosin is a multifaceted protein with tissue-specific roles in various physiological and pathological processes. Further research is needed to fully understand the mechanisms and potential of asprosin as a therapeutic target. These insights could provide new directions for treatments targeting metabolic-related diseases.

Competing risk nomogram and risk classification system for evaluating overall and cancer-specific survival in neuroendocrine carcinoma of the cervix: a population-based retrospective study.

OBJECTIVE: Neuroendocrine carcinoma of the cervix (NECC) is a rare malignancy with poor clinical prognosis due to limited therapeutic options. This study aimed to establish a risk-stratification score and nomogram models to predict prognosis in NECC patients. METHODS: Data on individuals diagnosed with NECC between 2000 and 2019 were retrieved from the Surveillance Epidemiology and End Results (SEER) database and then randomly classified into training and validation cohorts (7:3). Univariate and multivariate Cox regression analyses evaluated independent indicators of prognosis. Least absolute shrinkage and selection operator (LASSO) regression analysis further assisted in confirming candidate variables. Based on these factors, cancer-specific survival (CSS) and overall survival (OS) nomograms that predict survival over 1, 3, and 5 years were constructed. The receiver operating characteristic (ROC) curve, the concordance index (C-index), and the calibration curve estimated the precision and discriminability of the competing risk nomogram for both cohorts. Finally, we assessed the clinical value of the nomograms using decision curve analysis (DCA). RESULTS: Data from 2348 patients were obtained from the SEER database. Age, tumor stage, T stage, N stage, chemotherapy, radiotherapy, and surgery predicted OS. Additionally, histological type was another standalone indicator of CSS prognosis. For predicting CSS, the C-index was 0.751 (95% CI 0.731 ~ 0.770) and 0.740 (95% CI 0.710 ~ 0.770) for the training and validation cohorts, respectively. Furthermore, the C-index in OS prediction was 0.757 (95% CI 0.738 ~ 0.776) and 0.747 (95% CI 0.718 ~ 0.776) for both cohorts. The proposed model had an excellent discriminative ability. Good accuracy and discriminability were also demonstrated using the AUC and calibration curves. Additionally, DCA demonstrated the high clinical potential of the nomograms for CSS and OS prediction. We constructed a corresponding risk classification system using nomogram scores. For the whole cohort, the median CSS times for the low-, moderate-, and high-risk groups were 59.3, 19.5, and 7.4 months, respectively. CONCLUSION: New competing risk nomograms and a risk classification system were successfully developed to predict the 1-, 3-, and 5-year CSS and OS of NECC patients. The models are internally accurate and reliable and may guide clinicians toward better clinical decisions and the development of personalized treatment plans.

The system of radiological protection and the UN sustainable development goals.

In 2015 the United Nations issued 17 Sustainable Development Goals (SDGs) addressing a wide range of global social, economic, and environmental challenges. The main goal of this paper is to provide an understanding of how the current System of Radiological Protection relates to these SDGs. In the first part it is proposed that the current System of Radiological Protection is implicitly linked to sustainable development. This is substantiated by analysing the features of the current System as set out by the International Commission on Radiological Protection (ICRP) in its publications. In the second part it is proposed that sustainability should be considered and more explicitly addressed in the next ICRP general recommendations, as part of the currently ongoing review and revision of the current System. A few examples are given of how this could be realised, and it is proposed that this issue should be discussed and developed together with the international community interested in radiological protection.

Birth Cohort Studies of Long-Term Exposure to Ambient Air Pollution in Early Life and Development of Asthma in Children and Adolescents from Denmark.

INTRODUCTION: Exposure to ambient air pollution from combustion-source emissions contributes to the prevalence of asthma, but the role of early-life exposure in asthma development is not well understood. The objective was to examine the effects of early-life exposure to multiple specific ambient air pollutants on incidence and prevalence of asthma and to determine the mechanistic basis for these effects. METHODS: The study included all live-born singletons in Denmark during 1998-2016 (N = 1,060,154), participants in the Danish National Birth Cohort (DNBC3, N = 22,084), and participants in the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC, N = 803). We modeled the concentrations of particulate matter ≤2.5 and ≤10 µm in aerodynamic diameter (PM2.5 and PM10), PM-related elemental carbon (EC), organic carbon (OC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), secondary organic aerosols (SOA), and sea salt as well as nitrogen dioxide (NO2), nitrogen oxides (NOx), sulfur dioxide (SO2), and ozone (O3) - from all sources. Prenatal and postnatal time-weighted mean exposures were calculated for all residential addresses.We defined asthma incidence as the first registered asthma diagnosis for all and used parental recall at child aged 7 to determine the prevalence of doctor-diagnosed asthma ever and active asthma for the DNBC participants. For the COPSAC participants, we analyzed inflammatory markers in blood collected at 6 months of age; at 6 years of age, we analyzed nasal epithelial deoxyribonucleic acid (DNA) methylation, gene expression, immune mediators, and forced expiratory volume in 1 second (FEV1).Cox proportional hazard models were fitted with fixed prenatal means and time-varying running annual means of a year before the event for the postnatal follow-up period for asthma incidence. Logistic regression models with cluster-robust standard errors and generalized estimating equations for dependence between women being included more than once were used for asthma prevalence. Mixed-effect linear regression models with random intercept for cohort were used to examine changes in lung function, and linear regression models were used to examine changes in biomarkers. RESULTS: The prenatal mean and interquartile range (IQR) concentrations of PM2.5 and NO2 were 10.5 (2.4) and 17.5 (8.7) µg/m3. In the nationwide study the risk of asthma incidence increased with increasing prenatal exposure to all pollutants except for O3 and sea salt. An IQR increase in prenatal exposure was associated with an adjusted hazard ratio (HR) and 95% confidence interval (CI) of 1.06 (95% CI: 1.04-1.08) for PM2.5 and 1.04 (1.02-1.05) for NO2. The corresponding estimates for postnatal exposures were 1.08 (1.05-1.10) and 1.02 (1.01-1.04), respectively.In the DNBC participants, the asthma incidence results from models further adjusted with cohort-specific covariates were similar to models adjusted for register-based covariates only. Prenatal exposure to PM2.5, PM10, NO2, NOx, EC, SO42-, and sea salt were weakly associated with elevated risk for asthma incidence. There was no evidence of associations with asthma prevalence.For the COPSAC children, an IQR of PM2.5 and of NH4+ was each associated with a 2%-3% (95% CI: 1%-5%) reduction in mean FEV1, consistently for prenatal and postnatal exposures. Prenatal exposure to PM and NO2 was associated with immunological changes in blood and the airways but not with DNA methylation or gene expression changes. CONCLUSIONS: The results of these studies strengthen the evidence that long-term exposure to ambient air pollution contributes to the development of asthma in early life through an altered immune profile, even at these relatively low concentrations.

Burden and trend of dietary risk-related colorectal cancer in China and its provinces: findings from the Global Burden of Disease Study 2019.

OBJECTIVES: The objective of this experiment was to evaluate the spatial pattern and temporal trend of colorectal cancer (CRC) burden attributed to dietary risk factors in China from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. METHODS: Numbers and age-standardised rates of deaths, disability-adjusted life years (DALYs) and corresponding average annual percentage change (AAPC) were determined. The joinpoint regression analysis was used to assess the temporal trends of CRC deaths and DALYs from 1990 to 2019. RESULTS: In China, the number of diet-attributable CRC deaths and DALYs in 2019 were 90.41 (95% uncertainty interval: 65.69, 114.67) and 2234.06 (1609.96, 2831.24) per-1000 population, marking 2.05% and 1.68% annual increases since 1990, respectively. The region with the highest increase in age-standardised rates (ASRs) of diet-related CRC deaths and DALYs was in Taiwan with an AAPC of 2.00% (1.51, 2.48), whereas the highest decline in ASRs of CRC deaths and DALYs was observed in Hong Kong with an AAPC of -0.63% (-0.90, -0.35) (all P < 0.05). Nationally, men suffered higher CRC deaths and DALY burdens attributable to dietary risks than did women. Regarding the specific diet group, diets low in calcium, milk, and whole grains contributed to CRC deaths and DALYs the most. CONCLUSIONS: Diet is an important contributor to increasing CRC burden in China. Necessary measures should be taken to kerb the growing burden attributed to dietary factors, particularly in males and in regions with middle Socio-demographic Index or lower.

Recommendations for eligibility criteria concerning bariatric and metabolic surgical and endoscopic procedures for obese Hong Kong adults 2024: Hong Kong Society for Metabolic and Bariatric Surgery Position Statement.

The surgical management of obesity in Hong Kong has rapidly evolved over the past 20 years. Despite increasing public awareness and demand concerning bariatric and metabolic surgery, service models generally are not standardised across bariatric practitioners. Therefore, a working group was commissioned by the Hong Kong Society for Metabolic and Bariatric Surgery to review relevant literature and provide recommendations concerning eligibility criteria for bariatric and metabolic interventions within the local population in Hong Kong. The current position statement aims to provide updated guidance regarding the indications and contraindications for bariatric surgery, metabolic surgery, and bariatric endoscopic procedures.

Consensus gene co-expression analysis across multiple intestinal tissues to identify key genes and pathways associated with abdominal fat deposition in broilers.

1. Abdominal fat deposition (AFD) is regulated by multiple intestinal tissues, and changes in the function of intestinal tissues are associated with AFD. Currently, integration of transcriptomic data across multiple intestinal tissues to explore excessive AFD has rarely been reported in broilers.2. In this study, a consensus gene co-expression network across the duodenum, jejunum, ileum and caecum of high- and low-abdominal fat broiler lines (HL and LL) was constructed using a publicly available transcriptomic data set. Combining the results of functional enrichment analyses and differential gene expression analyses, this investigated the genes and biological pathways across the four intestinal tissues that might influence AFD.3. In one expression module, NDUFA5, NDUFS6, NDUFA4, NDUFS4, ATP5H, ATP5J and ATP5C1 were significantly enriched in the oxidative phosphorylation pathway, with GPX2 and GSR significantly enriched in the glutathione metabolism pathway. These genes were significantly downregulated in the four intestinal tissues of the HL compared to LL chickens, which may be associated with AFD by increasing intestinal permeability.4. Lipid metabolism relevant genes were identified in other modules (ALDH7A1, ACSBG1, THEM4 and DECR1), which may be linked to AFD through regulation of lipid metabolism. Interestingly, in the first module, 12 genes were significantly enriched in the proteasome pathway and significantly downregulated in the four intestinal tissues in HL birds compared to LL birds, indicating a link between the proteasome and AFD.

Effect of goose-derived adiponectin peptide gADP3 on LPS-induced inflammatory injury in goose liver.

1. This study evaluated the effects and mechanisms of action of the peptide gADP3 on hepatic inflammatory injury induced by lipopolysaccharide (LPS).2. Hepatic inflammatory injury was induced in geese by intraperitoneal injection of LPS and gADP3, and the adiponectin receptor agonist AdipoRon (positive control) was used for potential amelioration. Serum inflammatory factor levels, liver function-related biochemical indicators and oxidative stress-related biochemical parameters in the liver tissues were determined. The expression levels of adiponectin and its receptors, inflammation and oxidative stress-related genes and key signalling molecules involved in adiponectin, inflammation and oxidative stress signalling pathways in liver tissues were detected.3. The peptide gADP3 alleviated inflammatory cell infiltration and hepatic inflammatory changes, reversed the decrease in serum albumin (ALB), total protein (TP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) content or activity induced by LPS and increased the activity of the antioxidant enzymes CAT (catalase), SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase).4. The peptide gADP3 upregulated the expression of antioxidant enzyme-related genes GCLC, HO-1 and NQO1 in liver tissues, decreased the levels of inflammatory factors like TNF-α, IL-1ß, IL-6, IFN-γ and TGF-ß and reduced mRNA expression levels of inflammatory-related genes TNF-α, IL-1ß, iNOS and TGF-ß. Additionally, it increased the mRNA and protein expression levels of adiponectin and its receptors, as well as key molecules in the adiponectin signalling pathway like AMPK and PPARα. In addition, gADP3 reversed the changes in mRNA or protein expression of inflammatory and oxidative stress signalling pathway-related genes P38MAPK, NF-κBP65, TLR4 and Nrf2 in liver tissues caused by LPS treatment.5. In conclusion, goose-derived adiponectin peptide gADP3, similar to the adiponectin receptor agonist AdipoRon, attenuated LPS-induced hepatic inflammatory injury in geese.

[Interpretation on the report of global cancer statistics 2022].

In April 2024, the World Health Organization/International Agency for Research on Cancer (IARC) published the global cancer statistics 2022 in the CA: Cancer Journal for Clinicians. This report focuses on the incidence and mortality of 36 cancers in 185 countries or territories worldwide, analyzing the differences of gender, geographic region, and the Human Development Index (HDI) level. It is estimated that in the year 2022, there were 19.96 million new cancer cases and 9.74 million cancer deaths worldwide. Lung cancer (2 480 301, 12.4%) was the most frequently diagnosed cancer in 2022, followed by female breast cancer (2 295 686, 11.5%), colorectal cancer (1 926 118, 9.6%), prostate cancer (1 466 680, 7.3%), and gastric cancer (968 350, 4.9%). Lung cancer (1 817 172, 18.7%) was also the leading cause of cancer death, followed by colorectal cancer (903 859, 9.3%), liver cancer (757 948, 7.8%), female breast cancer (665 684, 6.9%), and gastric cancer (659 853, 6.8%). With demographics-based predictions indicating that the number of new cases of cancer will reach over 35 million by 2050. The Beijing Office for Cancer Prevention and Control team has collated this report and briefly interpreted it in combination with the current situation of cancer incidence and mortality in China.