Radiomics-based nomogram guides adaptive de-intensification in locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy.

OBJECTIVES: This study aimed to construct a radiomics-based model for prognosis and benefit prediction of concurrent chemoradiotherapy (CCRT) versus intensity-modulated radiotherapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) following induction chemotherapy (IC). MATERIALS AND METHODS: A cohort of 718 LANPC patients treated with IC + IMRT or IC + CCRT were retrospectively enrolled and assigned to a training set (n = 503) and a validation set (n = 215). Radiomic features were extracted from pre-IC and post-IC MRI. After feature selection, a delta-radiomics signature was built with LASSO-Cox regression. A nomogram incorporating independent clinical indicators and the delta-radiomics signature was then developed and evaluated for calibration and discrimination. Risk stratification by the nomogram was evaluated with Kaplan-Meier methods. RESULTS: The delta-radiomics signature, which comprised 19 selected features, was independently associated with prognosis. The nomogram, composed of the delta-radiomics signature, age, T category, N category, treatment, and pre-treatment EBV DNA, showed great calibration and discrimination with an area under the receiver operator characteristic curve of 0.80 (95% CI 0.75-0.85) and 0.75 (95% CI 0.64-0.85) in the training and validation sets. Risk stratification by the nomogram, excluding the treatment factor, resulted in two groups with distinct overall survival. Significantly better outcomes were observed in the high-risk patients with IC + CCRT compared to those with IC + IMRT, while comparable outcomes between IC + IMRT and IC + CCRT were shown for low-risk patients. CONCLUSION: The radiomics-based nomogram can predict prognosis and survival benefits from concurrent chemotherapy for LANPC following IC. Low-risk patients determined by the nomogram may be potential candidates for omitting concurrent chemotherapy during IMRT. CLINICAL RELEVANCE STATEMENT: The radiomics-based nomogram was constructed for risk stratification and patient selection. It can help guide clinical decision-making for patients with locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy, and avoid unnecessary toxicity caused by overtreatment. KEY POINTS: • The benefits from concurrent chemotherapy remained controversial for locoregionally advanced nasopharyngeal carcinoma following induction chemotherapy. • Radiomics-based nomogram achieved prognosis and benefits prediction of concurrent chemotherapy. • Low-risk patients defined by the nomogram were candidates for de-intensification.

Identification of difficult laryngoscopy using an optimized hybrid architecture.

BACKGROUND: Identification of difficult laryngoscopy is a frequent demand in cervical spondylosis clinical surgery. This work aims to develop a hybrid architecture for identifying difficult laryngoscopy based on new indexes. METHODS: Initially, two new indexes for identifying difficult laryngoscopy are proposed, and their efficacy for predicting difficult laryngoscopy is compared to that of two conventional indexes. Second, a hybrid adaptive architecture with convolutional layers, spatial extraction, and a vision transformer is proposed for predicting difficult laryngoscopy. The proposed adaptive hybrid architecture is then optimized by determining the optimal location for extracting spatial information. RESULTS: The test accuracy of four indexes using simple model is 0.8320. The test accuracy of optimized hybrid architecture using four indexes is 0.8482. CONCLUSION: The newly proposed two indexes, the angle between the lower margins of the second and sixth cervical spines and the vertical direction, are validated to be effective for recognizing difficult laryngoscopy. In addition, the optimized hybrid architecture employing four indexes demonstrates improved efficacy in detecting difficult laryngoscopy. TRIAL REGISTRATION: Ethics permission for this research was obtained from the Medical Scientific Research Ethics Committee of Peking University Third Hospital (IRB00006761-2015021) on 30 March 2015. A well-informed agreement has been received from all participants. Patients were enrolled in this research at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , identifier: ChiCTR-ROC-16008598) on 6 June 2016.

ARRB1 downregulates acetaminophen-induced hepatoxicity through binding to p-eIF2α to inhibit ER stress signaling.

Acetaminophen (APAP) stands as the predominant contributor to drug-induced liver injury (DILI), and limited options are available. ß-Arrestin1 (ARRB1) is involved in numerous liver diseases. However, the role of ARRB1 in APAP-induced liver injury remained uncertain. Wild-type (WT) and ARRB1 knockout (KO) mice were injected with APAP and sacrificed at the indicated times. The histological changes, inflammation, endoplasmic reticulum (ER) stress, and apoptosis were then evaluated. Hepatic cell lines AML-12 and primary hepatocytes were used for in vitro analyses. Systemic ARRB1-KO mice were susceptible to APAP-induced hepatotoxicity, as indicated by larger areas of centrilobular necrosis area and higher levels of ALT, AST, and inflammation level. Moreover, ARRB1-KO mice exhibited increased ER stress (indicated by phosphorylated α subunit of eukaryotic initiation factor 2 (p-eIF2α)-activating transcription factor 4 (ATF4)-CCAAT-enhancer-binding protein homologous protein (CHOP)) and apoptosis (indicated by cleaved caspase 3). Further rescue experiments demonstrated that the induction of apoptosis was partially mediated by ER stress. Overexpression of ARRB1 alleviated APAP-induced ER stress and apoptosis. Moreover, co-IP analysis revealed that ARRB1 directly bound to p-eIF2α and eIF2α. ARRB1 protected against APAP-induced hepatoxicity through targeting ER stress and apoptosis. ARRB1 is a prospective target for treating APAP-induced DILI.

Controlled Synthesis of MOF-Derived Nano-Microstructure toward Lightweight and Wideband Microwave Absorption.

Correlating metal-organic framework (MOF) synthesis processes and microwave absorption (MA) enhancement mechanisms is a pioneer project. Nevertheless, the correlation process still relies mainly on empirical doctrine, which hardly corresponds to the specific mechanism of the effect on the dielectric properties. Hereby, after the strategy of modulation of protonation engineering and solvothermal temperature in the synthesis route, the obtained sheet-like self-assembled nanoflowers were constructed. Porous structures with multiple heterointerfaces, abundant defects, and vacancies are obtained by controlled design of the synthesis procedure. The rearrangement of charges and enhanced polarization can be promoted. The designed electromagnetic properties and special nano-microstructures of functional materials have significant impact on their electromagnetic wave energy conversion effects. As a consequence, the MA performance of the samples has been enhanced toward broadband absorption (6.07 GHz), low thickness (2.0 mm), low filling (20%), and efficient loss (-25 dB), as well as being suitable for practical environmental applications. This work establishes the connection between the MOF-derived materials synthesis process and the MA enhancement mechanism, which provides insight into various microscopic microwave loss mechanisms.

Integration and interplay of machine learning and bioinformatics approach to identify genetic interaction related to ovarian cancer chemoresistance.

Although chemotherapy is the first-line treatment for ovarian cancer (OCa) patients, chemoresistance (CR) decreases their progression-free survival. This paper investigates the genetic interaction (GI) related to OCa-CR. To decrease the complexity of establishing gene networks, individual signature genes related to OCa-CR are identified using a gradient boosting decision tree algorithm. Additionally, the genetic interaction coefficient (GIC) is proposed to measure the correlation of two signature genes quantitatively and explain their joint influence on OCa-CR. Gene pair that possesses high GIC is identified as signature pair. A total of 24 signature gene pairs are selected that include 10 individual signature genes and the influence of signature gene pairs on OCa-CR is explored. Finally, a signature gene pair-based prediction of OCa-CR is identified. The area under curve (AUC) is a widely used performance measure for machine learning prediction. The AUC of signature gene pair reaches 0.9658, whereas the AUC of individual signature gene-based prediction is 0.6823 only. The identified signature gene pairs not only build an efficient GI network of OCa-CR but also provide an interesting way for OCa-CR prediction. This improvement shows that our proposed method is a useful tool to investigate GI related to OCa-CR.

A potential correlation between adipokines, skeletal muscle function and bone mineral density in middle-aged and elderly individuals.

BACKGROUND: Evidence exists of a strong association between inflammation and a decrease in skeletal muscle function and bone mineral density (BMD); however, the specific mechanisms of these associations remain unclear. Adipokines, as key regulators of the inflammatory response, may be implicated in these processes. The objective of this study was to explore the potential correlation between adipokines, skeletal muscle function and BMD in middle-aged and elderly individuals. METHODS: A comparative cross-sectional study was carried out at the Huadong Hospital Affiliated with Fudan University (Shanghai, China). A total of 460 middle-aged and elderly individuals were recruited, and 125 were enrolled in the analysis. Their biochemical indices, body composition, skeletal muscle function and BMD were measured. Bioinformatic analysis was also employed to identify potential adipokine targets linked to skeletal muscle function and BMD. To validate these targets, plasma and peripheral blood mononuclear cells (PBMCs) were harvested from these individuals and subjected to western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Individuals in this cross-sectional study were categorized into 2 groups according to their median skeletal muscle mass (SMM) (28.8 kg for males and 20.6 kg for females). Individuals with lower SMM exhibited poorer grip strength (P = 0.017), longer 5-Times-Sit-to-Stand Test (FTSST) duration (P = 0.029), lower total hip BMD (P = 0.043), lower femoral neck BMD (P = 0.011) and higher levels of inflammatory markers in comparison with individuals with higher SMM. Bioinformatics analysis identified LEP, ADIPOQ, RBP4, and DPP4 as potential adipokine targets associated with skeletal muscle function and BMD. In vitro experiments demonstrated that individuals with decreased skeletal muscle function and BMD expressed higher levels of these adipokines. CONCLUSIONS: Skeletal muscle function is positively correlated with BMD and negatively correlated with levels of inflammatory markers among middle-aged and elderly individuals. Those with lower skeletal muscle function and BMD tend to have a higher expression of LEP, ADIPOQ, RBP4 and DPP4.

Selective Photocatalytic Reduction of CO2 to CO Mediated by Silver Single Atoms Anchored on Tubular Carbon Nitride.

Artificial photosynthesis is a promising strategy for converting carbon dioxide (CO2 ) and water (H2 O) into fuels and value-added chemical products. However, photocatalysts usually suffered from low activity and product selectivity due to the sluggish dynamic transfer of photoexcited charge carriers. Herein, we describe anchoring of Ag single atoms on hollow porous polygonal C3 N4 nanotubes (PCN) to form the photocatalyst Ag1 @PCN with Ag-N3 coordination for CO2 photoreduction using H2 O as the reductant. The as-synthesized Ag1 @PCN exhibits a high CO production rate of 0.32 µmol h-1 (mass of catalyst: 2 mg), a high selectivity (>94 %), and an excellent stability in the long term. Experiments and density functional theory (DFT) reveal that the strong metal-support interactions (Ag-N3 ) favor *CO2 adsorption, *COOH generation and desorption, and accelerate dynamic transfer of photoexcited charge carriers between C3 N4 and Ag single atoms, thereby accounting for the enhanced CO2 photoreduction activity with a high CO selectivity. This work provides a deep insight into the important role of strong metal-support interactions in enhancing the photoactivity and CO selectivity of CO2 photoreduction.

Resveratrol attenuates retinal ganglion cell loss in a mouse model of retinal ischemia reperfusion injury via multiple pathways.

BACKGROUND: Resveratrol (RES) is a natural polyphenol that has been shown to protect retinal ganglion cells (RGCs) following retinal ischemia reperfusion (I/R) injury. However, the molecular mechanisms of resveratrol function are yet to be fully elucidated. Thus, this study explored the potential mechanisms of resveratrol in vivo. METHODS: A retinal ischemia reperfusion injury model was established in adult male C57BL/6 J mice. Intraperitoneal injection of resveratrol was administered continuously for 5 days. RGC survival was determined by immunofluorescence staining with Brn3a. Flash electroretinography (ERG) was conducted to assess visual function. Proteins of HIF-1a, VEGF, p38, p53, PI3K, Akt, Bax, Bcl2, and Cleaved Caspase3 were detected using Western blot. RESULTS: RES administration significantly ameliorated retinal thickness damage and increased Brn3a stained RGCs 7 days after I/R injury. We also found that administration of RES remarkably inhibited the upregulation of mitochondrial apoptosis-related protein Bax and Cleaved Caspase3, as well as increased the expression of Bcl2. Furthermore, RES administration significantly suppressed the I/R injury-induced upregulation of the HIF-1a/VEGF and p38/p53 pathways, while activating the I/R injury-induced downregulation of the PI3K/Akt pathway. Moreover, RES administration remarkably improved retinal function after I/R injury-induced functional impairment. CONCLUSIONS: Our data demonstrated that resveratrol can mitigate retinal ischemic injury induced RGC loss and retinal function impairment by inhibiting the HIF-1a/VEGF and p38/p53 pathways while activating the PI3K/Akt pathway. Therefore, our results further reinforce that resveratrol has potential for treating glaucoma.

Use of neural networks to predict vault values after implantable collamer lens surgery.

BACKGROUND: Appropriate sizing of the implantable collamer lens (ICL) and accurate prediction of the vault are crucial prior to surgery. However, sometimes, the vault value is higher or lower than predicted, necessitating reoperation. The present study aimed to develop neural networks for improving predictions of vault values following ICL implantation based on preoperative biometric data. METHODS: This retrospective study included 137 eyes of 74 patients with ICLs. Linear regression and neural network analyses were used to examine the relationship between vault values at the 6-month follow-up and preoperative parameters (e.g., ICL characteristics and biometrics). RESULTS: Linear regression analysis revealed that vault values were correlated with five variables: ICL size, anterior chamber depth (ACD), angle-to-angle (ATA), white-to-white (WTW), and lens thickness (LT) (adjusted R2 = 0.411). Inclusion of more input variables was associated with better performance in the neural network analysis. The degree of fit when all 11 variables were included in the neural network model was close to 1 (R2 = 0.98). R2 values for the quaternary neural network model enrolling four input variables (ICL size, ATA, ACD, and LT) reached 0.90. CONCLUSIONS: A neural network equation including the ICL size and biometric parameters of the anterior segment (ATA, ACD, and LT) can be used to predict the postoperative vault, aiding in the selection of an appropriate ICL size and reducing the need for reoperation after surgery.

ß-Arrestin1 is involved in hepatocellular carcinoma metastasis via extracellular signal-regulated kinase-mediated epithelial-mesenchymal transition.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is a malignant disease worldwide. It is implicated in high cancer-related mortality rates in humans. ß-Arrestin1 (ARRB1) has been demonstrated to be related to the development of several cancers, while the relationship between ARRB1 and metastasis in HCC is unknown. METHODS: A tissue microarray of 68 tissues from HCC patients with or without metastasis was collected. Wild-type and ARRB1 knockout mice were used to examine the role of ARRB1 in metastasis in vivo. The level of ARRB1 in HCC tissues, mouse liver tissues, and cell lines was determined by quantitative reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry. Migration, invasion, and motility capacities of HCC cells were determined by transwell assay and wound healing assay. Vein injection of nude mice model was used to reveal the metastatic abilities of HCC cell lines. For the mechanism study, we investigated the effects of ARRB1 on the phosphorylation of ERK1/2 and the expression of epithelial-mesenchymal transition (EMT) markers in HCC. RESULTS: We reveal that ARRB1 accelerates metastasis in HCC and that ARRB1 deficiency inhibits hepatocarcinogenesis and reverses EMT in mice. ARRB1 regulates HCC cell migration and invasion and suppresses HCC metastasis in vivo. Furthermore, we show that ARRB1 promotes EMT through the phosphorylation of ERK1/2. CONCLUSIONS: Our data suggest that ARRB1 promotes HCC invasion and metastasis through p-ERK1/2-mediated EMT and that suppression of ARRB1 or p-ERK1/2 may offer potential therapeutic targets for HCC therapy.

ß-Arrestin1 alleviates acute pancreatitis via repression of NF-κBp65 activation.

BACKGROUND AND AIM: ß-Arrestins (ß-arrs) are regulators and mediators of G protein-coupled receptor signaling that are functionally involved in inflammation. Nuclear factor-κB p65 (NF-κBp65) activation has been observed early in the onset of pancreatitis. However, the effect of ß-arrs in acute pancreatitis (AP) is unclear. The aim of this study is to investigate whether ß-arrs are involved in AP through activation of NF-κBp65. METHODS: Acute pancreatitis was induced by either caerulein injection or choline-deficient supplemented with ethionine diet (CDE). ß-arr1 wild-type and ß-arr1 knockout mice were used in the experiment. The survival rate was calculated in the CDE model mice. Histological and western blot analyses were performed in the caerulein model. Inflammatory mediators were detected by real-time polymerase chain reaction in the caerulein-induced AP mice. Furthermore, AR42J and PANC-1 cell lines were used to further study the effects of ß-arr1 in caerulein-induced pancreatic cells. RESULTS: ß-Arr1 but not ß-arr2 is significantly downregulated in caerulein-induced AP in mice. Targeted deletion of ß-arr1 notably upregulated expression of the pancreatic inflammatory mediators including tumor necrosis factor α and interleukin 1ß as well as interleukin 6 and aggravated AP in caerulein-induced mice. ß-Arr1 deficiency increased mortality in mice with CDE-induced AP. Further, ß-arr1 deficiency enhanced caerulein-induced phosphorylation of NF-κBp65 both in vivo and in vitro. CONCLUSION: ß-Arr1 alleviates AP via repression of NF-κBp65 activation, and it is a potentially therapeutic target for AP.

A Multi-Frequencies Micro-Electromagnetic Vibration Energy Harvester with Nonlinearity for Expanding the Frequency Band.

In this paper, we proposed a multi-frequencies electromagnetic vibration energy harvester (EVEH) with a wider operating frequency band. The EVEH contains three different vibration picking-up systems with different natural frequencies. A broadened bandwidth was obtained by combining the structural nonlinearity of the vibration picking-up systems with the multi-frequencies, while the vibration energy harvest was increased by adopting two induction coils in the EVEH system. At an acceleration of 1.5g and frequencies of 45.6, 75 and 146.5 Hz, the peak-peak voltages of the prototype were 336, 270 and 39.8 mV, respectively. The corresponding bandwidths were 10.1, 7.8 and 4.2 Hz, respectively.

Catalyst development for O2-assisted oxidative dehydrogenation of propane to propylene.

O2-Assisted oxidative dehydrogenation of propane (O2-ODHP) could convert abundant shale gas into propylene as an important chemical raw material, meaning O2-ODHP has practical significance. Thermodynamically, high temperature is beneficial for O2-ODHP; however, high reaction temperature always causes the overoxidation of propylene, leading to a decline in its selectivity. In this regard, it is crucial to achieve low temperatures while maintaining high efficiency and selectivity during O2-ODHP. The use of catalytic technology provides more opportunities for achieving high-efficiency O2-ODHP under mild conditions. Up to now, many kinds of catalytic systems have been elaborately designed, including transition metal oxide catalysts (such as vanadium-based catalysts, molybdenum-based catalysts, etc.), transition metal-based catalysts (such as Pt nanoclusters), rare earth metal oxide catalysts (especially CeO2 related catalysts), and non-metallic catalysts (BN, other B-containing catalysts, and C-based catalysts). In this review, we have summarized the development progress of mainstream catalysts in O2-ODHP, aiming at providing a clear picture to the catalysis community and advancing this research field further.

HOPE: Hybrid-Granularity Ordinal Prototype Learning for Progression Prediction of Mild Cognitive Impairment.

Mild cognitive impairment (MCI) is often at high risk of progression to Alzheimer's disease (AD). Existing works to identify the progressive MCI (pMCI) typically require MCI subtype labels, pMCI vs. stable MCI (sMCI), determined by whether or not an MCI patient will progress to AD after a long follow-up. However, prospectively acquiring MCI subtype data is time-consuming and resource-intensive; the resultant small datasets could lead to severe overfitting and difficulty in extracting discriminative information. Inspired by that various longitudinal biomarkers and cognitive measurements present an ordinal pathway on AD progression, we propose a novel Hybrid-granularity Ordinal PrototypE learning (HOPE) method to characterize AD ordinal progression for MCI progression prediction. First, HOPE learns an ordinal metric space that enables progression prediction by prototype comparison. Second, HOPE leverages a novel hybrid-granularity ordinal loss to learn the ordinal nature of AD via effectively integrating instance-to-instance ordinality, instance-to-class compactness, and class-to-class separation. Third, to make the prototype learning more stable, HOPE employs an exponential moving average strategy to learn the global prototypes of NC and AD dynamically. Experimental results on the internal ADNI and the external NACC datasets demonstrate the superiority of the proposed HOPE over existing state-of-the-art methods as well as its interpretability. Source code is made available at https://github.com/thibault-wch/HOPE-for-mild-cognitive-impairment.

Effect of shenmai injection on anthracycline-induced cardiotoxicity: A systematic review and meta-analysis.

OBJECTIVE: Shenmai injection is a classic herbal prescription, and is often recommended for the treatment of anthracycline-induced cardiotoxicity. However, the efficacy and safety of Shenmai injection for the treatment of anthracycline-induced cardiotoxicity have not been reported. MATERIALS AND METHODS: We conducted a comprehensive search of eight literature databases and two clinical trial registries, retrieving all randomized controlled trials (RCTs) related to the treatment of anthracycline-induced cardiotoxicity with Shenmai injection from the establishment of the databases to July 1, 2023. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. The GRADE pro3.6.1 software was utilized for assessing the quality of evidence. RESULTS: A total of 16 RCTs including 2140 patients were included in this study. Meta-analysis showed that Shenmai injection had an advantage in improving ST-T segment changes (RR = 0.28; 95 % CI, 0.20 to 0.39; P < 0.0001) (P < 0.01), creatine kinase isoenzyme (SMD = -3.49; 95 % CI, -5.24 to -1.74; P < 0.0001), Prolonged QT interval (RR = 0.46; 95 % CI, 0.28 to 0.75; P = 0.0018), Low QRS Voltage (RR = 0.44; 95 % CI, 0.27 to 0.71; P = 0.0007), sinus tachycardia (RR = 0.41; 95 % CI, 0.28 to 0.60; P < 0.0001), atrial premature beats (RR = 0.55; 95 % CI, 0.35 to 0.87; P = 0.01), Premature Ventricular Contractions (RR = 0.39; 95 % CI, 0.26 to 0.59; P < 0.0001) and creatine kinase (SMD = -1.43; 95 % CI, -2.57 to -0.29; P < 0.0001) in patients with anthracycline-induced cardiotoxicity. advantage, which was supported by sensitivity analyses, but not in improving left ventricular ejection fraction (MD = 16.01; 95 % CI, -3.10 to 35.12; P = 0.10) and atrioventricular block (RR = 0.49; 95 % CI, 0.24 to 1.03; P = 0.06). The literature included in the study did not refer to data regarding the safety aspects of Shenmai injection, so we do not yet know the safety of Shenmai injection. The results of subgroup analyses suggested that heterogeneity was not related to the administered dose and chemotherapy regimen. The publication bias test showed no publication bias. The quality of evidence for the results ranged from "very low" to "moderate." CONCLUSION: This study suggests that Shenmai injection is effective in treating anthracycline-induced cardiotoxicity and is a potential treatment for anthracycline-induced cardiotoxicity. However, due to the poor methodological quality of the included RCTs, we recommend rigorous, high-quality, large-sample trials to confirm our findings.

Mannan-binding lectin inhibits oxidative stress-induced senescence via the NAD+/Sirt1 pathway.

Prolonged or excessive oxidative stress can lead to premature cellular and body aging. Mannan-binding lectin (MBL) is synthesized by the liver and plays an important role in innate immunity, anti-inflammation, and anti-oxidation, and has a positive impact on health and longevity. To date, few studies investigated the role of MBL in attenuating oxidative stress-induced senescence. In this study, we evaluated the role of MBL in oxidative stress-induced premature aging and explored its underlying mechanism in C57BL/6 mice and mouse embryonic fibroblasts (NIH/3T3). First, we established an oxidative premature senescence model induced by D-galactose in C57BL/6 mice. We found that MBL-deficient mice had a marked aging-like appearance, reduced learning and spatial exploration abilities, severe liver pathological damage, and significantly upregulated expression of Senescence-associated proteins (p53 and p21), inflammatory kinesins (IL-1ß and IL-6), and the senescence ß-galactosidase (SA-ß-Gal) positive rate as compared with WT mice. In the H2O2-induced oxidative senescence model of NIH/3T3 cells, consistent results were obtained after MBL intervention. In addition, MBL effectively inhibited G1 phase arrest, ROS levels, DNA damage, and mitochondrial dysfunction in premature senescent cells. Mechanistically, we found that oxidative stress inhibited the nicotinamide adenine dinucleotide (NAD+)/ silent information regulator 1 (Sirt1) signaling pathway, while MBL activated the NAD+/Sirt1 signaling pathway inhibited by oxidative stress. In addition, MBL could activate the NAD+/Sirt1 pathway by upregulating NAMPT, which in turn inhibited p38 phosphorylation by activating the NAD+/Sirt1 pathway. In conclusion, MBL inhibits oxidative aging, which may facilitate the development of therapeutics to delay oxidative aging.

The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing AMOTL2-LATS-YAP pathway.

Metastasis is the major culprit of treatment failure in nasopharyngeal carcinoma (NPC). Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2), a core circadian gene, plays a crucial role in the development of various tumors. Nevertheless, the biological role and mechanism of ARNTL2 are not fully elucidated in NPC. In this study, ARNTL2 expression was significantly upregulated in NPC tissues and cells. Overexpression of ARNTL2 facilitated NPC cell migration and invasion abilities, while inhibition of ARNTL2 in similarly treated cells blunted migration and invasion abilities in vitro. Consistently, in vivo xenograft tumor models revealed that ARNTL2 silencing reduced nude mice inguinal lymph node and lung metastases, as well as tumor growth. Mechanistically, ARNTL2 negatively regulated the transcription expression of AMOTL2 by directly binding to the AMOTL2 promoter, thus reducing the recruitment and stabilization of AMOTL2 to LATS1/2 kinases, which strengthened YAP nuclear translocation by suppressing LATS-dependent YAP phosphorylation. Inhibition of AMOTL2 counteracted the effects of ARNTL2 knockdown on NPC cell migration and invasion abilities. These findings suggest that ARNTL2 may be a promising therapeutic target to combat NPC metastasis and further supports the crucial roles of circadian genes in cancer development.

Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis.

The Chinese tree shrew ( Tupaia belangeri chinensis) has emerged as a promising model for investigating adrenal steroid synthesis, but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans. Here, we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing, spatial transcriptome analysis, mass spectrometry, and immunohistochemistry. We compared the transcriptomes of various adrenal cell types across tree shrews, humans, macaques, and mice. Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans, including CYP11B2, CYP11B1, CYB5A, and CHGA. Biochemical analysis confirmed the production of aldosterone, cortisol, and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands. Furthermore, genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome, primary aldosteronism, hypertension, and related disorders in humans based on genome-wide association studies. Overall, this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland. Our comprehensive results (publicly available at http://gxmujyzmolab.cn:16245/scAGMap/) should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

A retrospective analysis on the diagnostic value of ultrasound-guided percutaneous biopsy for peritoneal lesions.

BACKGROUND: Routine examinations have a low specificity and a low positive rate for the diagnosis of peritoneal lesions. This study aimed to evaluate the diagnostic value and safety of ultrasound-guided percutaneous peritoneal lesion biopsies in patients with ascites and/or abdominal distension with unclear causes. METHODS: A retrospective analysis was performed in 153 consecutive patients with ascites and/or abdominal distension with unclear causes. All of the patients showed abnormalities of the peritoneum or greater omentum after ultrasonography, and underwent ultrasound-guided percutaneous biopsies using a Bard auto-biopsy gun with 18- or 16-gauge biopsy needles. RESULTS: The success rate of the procedures was 100% (153/153) and the satisfaction rate of the tissue specimens in the biopsy was 91.5% (140/153). A specific histopathological diagnosis was made in 142 out of 153 patients, with an overall diagnostic accuracy of 92.8%. Among the diagnosed patients, 62 were peritoneal metastatic adenocarcinoma, 49 were peritoneal tuberculosis, 11 were peritoneal malignant mesothelioma, 8 were chronic peritoneal infections, 7 were pseudomyxoma peritonei, and 5 were primary peritoneal lymphoma. Only 11 patients did not get a pathologic diagnosis due to the lack of sufficient tissue specimen. No serious complications occurred. CONCLUSIONS: Ultrasound-guided percutaneous biopsy could be a simple, safe and accurate diagnostic method in patients with ascites and/or abdominal distension with unclear causes.

Deep Rank-Consistent Pyramid Model for Enhanced Crowd Counting.

Most conventional crowd counting methods utilize a fully-supervised learning framework to establish a mapping between scene images and crowd density maps. They usually rely on a large quantity of costly and time-intensive pixel-level annotations for training supervision. One way to mitigate the intensive labeling effort and improve counting accuracy is to leverage large amounts of unlabeled images. This is attributed to the inherent self-structural information and rank consistency within a single image, offering additional qualitative relation supervision during training. Contrary to earlier methods that utilized the rank relations at the original image level, we explore such rank-consistency relation within the latent feature spaces. This approach enables the incorporation of numerous pyramid partial orders, strengthening the model representation capability. A notable advantage is that it can also increase the utilization ratio of unlabeled samples. Specifically, we propose a Deep Rank-consistEnt pyrAmid Model (), which makes full use of rank consistency across coarse-to-fine pyramid features in latent spaces for enhanced crowd counting with massive unlabeled images. In addition, we have collected a new unlabeled crowd counting dataset, FUDAN-UCC, comprising 4000 images for training purposes. Extensive experiments on four benchmark datasets, namely UCF-QNRF, ShanghaiTech PartA and PartB, and UCF-CC-50, show the effectiveness of our method compared with previous semi-supervised methods. The codes are available at https://github.com/bridgeqiqi/DREAM.