Divergent sensory pathways of sneezing and coughing.

Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.

Cellulose as a sustainable scaffold material in cultivated meat production.

The rapid progress in cultivated meat research has engendered considerable attention towards the edible scaffolding biomaterials employed in the production. Cellulose has the advantages in availability, edibility, animal-free origin, etc., which show its potential in wide fields. This review begins by presenting the fundamental physical and chemical properties of cellulose from different sources, including plant and bacterial cellulose. Subsequently, we summarize the application of cellulose especially in cultivated meat and tissue engineering. Furthermore, we explore various methods for preparing cellulose-based scaffolds for cultivated meat, encompassing five specific structural variations. In the end, associated with utilizing cellulose in cultivated meat production, we address several primary challenges surrounding to cell adhesion, scaling up, processibility and mechanical properties, and provide potential innovations. This review underscores the potential of cellulose as a versatile biomaterial in the cultivated meat industry and provides insight into addressing critical challenges for its integration.

Comprehensive multi-omics analysis reveals a combination of lncRNAs that synergistically regulate glycolysis and immunotherapeutic effects in renal clear cell carcinoma.

BACKGROUND: Clear cell renal carcinoma is a common urological malignancy with poor prognosis and treatment outcomes. lncRNAs are important in metabolic reprogramming and the tumor immune microenvironment, but their role in clear cell renal carcinoma is unclear. METHODS: Renal clear cell carcinoma sample data from The Cancer Genome Atlas was used to establish a new risk profile by glycolysis-associated lncRNAs via machine learning. Risk profile-associated column-line plots were constructed to provide a quantitative tool for clinical practice. Patients with renal clear cell carcinoma were divided into high- and low-risk groups. Clinical features, tumor immune microenvironments, and immunotherapy responses were systematically analyzed. We experimentally confirmed the role of LINC01138 and LINC01605 in renal clear cell carcinoma. RESULTS: The risk profile, consisting of LUCAT1, LINC01138, LINC01605, and HOTAIR, reliably predicted survival in patients with renal clear cell carcinoma and was validated in multiple external datasets. The high-risk group presented higher levels of immune cell infiltration and better immunotherapy responses than the low-risk group. LINC01138 and LINC01605 knockdown inhibited the proliferation of renal clear cell carcinoma. CONCLUSIONS: The identified risk profiles can accurately assess the prognosis of patients with clear cell renal carcinoma and identify patient populations that would benefit from immunotherapy, providing valuable insights and therapeutic targets for the clinical management of clear cell renal carcinoma.

Non-volatile 2D MoS2/black phosphorus heterojunction photodiodes in the near- to mid-infrared region.

Cutting-edge mid-wavelength infrared (MWIR) sensing technologies leverage infrared photodetectors, memory units, and computing units to enhance machine vision. Real-time processing and decision-making challenges emerge with the increasing number of intelligent pixels. However, current operations are limited to in-sensor computing capabilities for near-infrared technology, and high-performance MWIR detectors for multi-state switching functions are lacking. Here, we demonstrate a non-volatile MoS2/black phosphorus (BP) heterojunction MWIR photovoltaic detector featuring a semi-floating gate structure design, integrating near- to mid-infrared photodetection, memory and computing (PMC) functionalities. The PMC device exhibits the property of being able to store a stable responsivity, which varies linearly with the stored conductance state. Significantly, device weights (stable responsivity) can be programmed with power consumption as low as 1.8 fJ, and the blackbody peak responsivity can reach 1.68 A/W for the MWIR band. In the simulation of Faster Region with convolution neural network (CNN) based on the FLIR dataset, the PMC hardware responsivity weights can reach 89% mean Average Precision index of the feature extraction network software weights. This MWIR photovoltaic detector, with its versatile functionalities, holds significant promise for applications in advanced infrared object detection and recognition systems.

B, N co-doped carbon dots as efficient nanozymes for colorimetric and fluorometric dual-mode detection of cholesterol.

In this work, the B, N co-doped carbon dots (B, N-CDs) were synthesized via facile hydrothermal approach with 6-aminopyridine boronic acid as precursor. In addition to emitting intense blue luminescence when exposed to ultraviolet light, the prepared B, N-CDs displayed remarkable peroxidase-like activity, which could efficiently catalyze the oxidation of 3, 3', 5, 5' -tetramethylbenzidine (TMB) to blue ox-TMB in the presence of hydrogen peroxide (H2O2). Furthermore, the fluorescence intensity of B, N-CDs increased gradually upon the addition of H2O2. Since cholesterol oxidase (ChOx) can catalyze the oxidation of cholesterol to form H2O2, the as-prepared B, N-CDs was then used as both colorimetric and fluorometric sensors for the detection of cholesterol with detection limit of 0.87 and 2.31 µM, respectively. Finally, the dual-mode approach based on B, N-CDs was effectively utilized for detecting cholesterol levels in serum samples, proving the potential application of B, N-CDs in the field of biological assay.

The role of circular RNA during the urological cancer metastasis: exploring regulatory mechanisms and potential therapeutic targets.

Metastasis is a major contributor to treatment failure and death in urological cancers, representing an important biomedical challenge at present. Metastases form as a result of cancer cells leaving the primary site, entering the vasculature and lymphatic vessels, and colonizing clones elsewhere in the body. However, the specific regulatory mechanisms of action underlying the metastatic process of urological cancers remain incompletely elucidated. With the deepening of research, circular RNAs (circRNAs) have been found to not only play a significant role in tumor progression and prognosis but also show aberrant expression in various tumor metastases, consequently impacting tumor metastasis through multiple pathways. Therefore, circRNAs are emerging as potential tumor markers and treatment targets. This review summarizes the research progress on elucidating how circRNAs regulate the urological cancer invasion-metastasis cascade response and related processes, as well as their role in immune microenvironment remodeling and circRNA vaccines. This body of work highlights circRNA regulation as an emerging therapeutic target for urological cancers, which should motivate further specific research in this regard.

Comparison of the Profile and Management of Chronic Pancreatitis between China and Western Countries: A Single-Center Experience and Literature Review.

OBJECTIVE: The etiology, clinical presentation, diagnosis, and treatment strategies of chronic pancreatitis (CP) vary significantly between countries. Specifically, the etiology and surgical approaches to treating CP differ between China and Western countries. Therefore, this study aims to compare the disparities in CP profiles and management based on our single-center experience and recent data from the West. METHODS: From January 2007 to December 2017, a total of 130 consecutive patients with histologically confirmed chronic pancreatitis (CP) underwent surgical treatment at the First Affiliated Hospital of Nanjing Medical University. The clinical features, etiology, risk factors, and operative procedures of these CP patients were analyzed and compared with recent data from Western countries. RESULTS: Our patient cohort was predominantly male (3.19:1), with a median age of 50.2 ± 9.8 years. Upper abdominal pain was the most common symptom, present in 102 patients (78.5%). The most common etiology was obstructive factors (47.7%), followed by alcohol (34.6%). The incidence of genic mutation was 2%, significantly lower than rates reported in Western research. Steatorrhea, weight loss, and jaundice were present in 6.9%, 18.5%, and 17.7% of patients, respectively. Pancreatic cysts or pseudocysts were diagnosed in 7 patients (5.4%). The following procedures were performed: Partington procedure in 33 patients (25.4%), Frey procedure in 17 patients (13.2%), Berne procedure in 5 patients (3.9%), Beger procedure in 1 patient (0.8%), pancreaticoduodenectomy in 17 patients (13.1%), pylorus-preserving pancreaticoduodenectomy in 18 patients (13.9%), middle pancreatectomy in 1 patient (0.8%), and distal pancreatectomy in 9 patients (6.9%). Choledochojejunostomy was performed in 14 patients (10.8%), gastroenterostomy in 2 (1.5%), and 15 patients (11.5%) underwent aspiration biopsy. CONCLUSION: Our study confirms that, etiologically, obstructive chronic pancreatitis (CP) is more frequent in the Chinese population than in Western populations. Although diagnostic instruments and operative procedures in China and Western countries are roughly comparable, slight differences exist in relation to diagnostic flowcharts/criteria and the indications and optimal timing of surgery.

Non-volatile rippled-assisted optoelectronic array for all-day motion detection and recognition.

In-sensor processing has the potential to reduce the energy consumption and hardware complexity of motion detection and recognition. However, the state-of-the-art all-in-one array integration technologies with simultaneous broadband spectrum image capture (sensory), image memory (storage) and image processing (computation) functions are still insufficient. Here, macroscale (2 × 2 mm2) integration of a rippled-assisted optoelectronic array (18 × 18 pixels) for all-day motion detection and recognition. The rippled-assisted optoelectronic array exhibits remarkable uniformity in the memory window, optically stimulated non-volatile positive and negative photoconductance. Importantly, the array achieves an extensive optical storage dynamic range exceeding 106, and exceptionally high room-temperature mobility up to 406.7 cm2 V-1 s-1, four times higher than the International Roadmap for Device and Systems 2028 target. Additionally, the spectral range of each rippled-assisted optoelectronic processor covers visible to near-infrared (405 nm-940 nm), achieving function of motion detection and recognition.

Oridonin inhibits bladder cancer survival and immune escape by covalently targeting HK1.

BACKGROUND: Hexokinase I (HK1) is highly expressed in a variety of malignancies, regulates glycolytic pathway in cancer cells, and thus considered to be one of the promising molecular targets for cancer therapy. Nonetheless, the development of a specific inhibitor against HK1 remains elusive. PURPOSE: This study aims to elucidate the mechanism by which oridonin inhibits the proliferation and immune evasion of bladder cancer cells, specifically through the suppression of HK1. METHODS: To examine the mechanisms by which oridonin directly binds to cysteines of HK1 and inhibits bladder cancer growth, this study utilized a variety of methods. These included the Human Proteome Microarray, Streptavidin-agarose affinity assay, Biolayer Interferometry (BLI) ainding analysis, Mass Spectrometry, Cellular Thermal Shift Assay, Extracellular Acidification Rate measurement, and Xenotransplant mouse models. RESULTS: As indicated by our current findings, oridonin forms a covalent bond with Cys-813, located adjacently to glucose-binding domain of HK1. This suppresses the enzymatic activity of HK1, leading to an effective reduction of glycolysis, which triggers cell death via apoptosis in cells derived from human bladder cancer. Significantly, oridonin also inhibits lactate-induced PD-L1 expression in bladder cancer. Furthermore, pairing oridonin with a PD-L1 inhibitor amplifies the cytotoxicity of CD8+ T cells against bladder cancer. CONCLUSION: This research strongly suggests that oridonin serves as a covalent inhibitor of HK1. Moreover, it indicates that functional cysteine residue of HK1 could operate as viable targets for selective inhibition. Consequently, oridonin exhibits substantial potential for the evolution of anti-cancer agents targeting the potential therapeutic target HK1 via metabolism immunomodulation.

Diabetes-associated neutrophil NETosis: pathogenesis and interventional target of diabetic complications.

Neutrophil extracellular traps (NETs) are known as extracellular fibers networks consisting of antimicrobial proteins and decondensated chromatin DNA released by activated neutrophils. NETosis is a NETs-induced neutrophilic cell death which is unique from necrosis or apoptosis. Besides its neutralizing pathogen, NETosis plays a crucial role in diabetes and diabetes-related complications. In patients with diabetes, NETs-releasing products are significantly elevated in blood, and these findings confirm the association of NETosis and diabetic complications, including diabetic wound healing, diabetic retinopathy, and atherosclerosis. This article briefly summarizes the mechanisms of NETosis and discusses its contribution to the pathogenesis of diabetes-related complications and suggests new therapeutic targets by some small molecule compounds.

Coffee grounds-derived carbon quantum dots as peroxidase mimetics for colorimetric and fluorometric detection of ascorbic acid.

In this study, we reported the eco-responsible synthesis of iron-doped carbon quantum dots (Fe-CQDs) from waste coffee grounds through a simple hydrothermal method. The Fe-CQDs exhibited high peroxidase-like activity, which could convert 3,3',5,5'-tetramethylbenzidine (TMB) into blue ox-TMB in the presence of H2O2. After adding ascorbic acid (AA) to above system, the blue solution faded. Based on this phenomenon, a colorimetric method for visual monitoring of H2O2 and AA was developed. Meanwhile, the fluorescence of Fe-CQDs can be quenched by the formed ox-TMB via inner filter effect (IFE), followed by the recovery upon the addition of AA. Therefore, Fe-CQDs can be acted as a fluorescent probe to detect H2O2 and AA through the "on-off-on" mode. Furthermore, the dual-recognition methods based on Fe-CQDs were used to measure AA content in beverage samples. Thus, this work would shed much light on converting waste into biomass CQDs and their potential applications in biomolecular detection.

Cancer-keeper genes as therapeutic targets.

Finding cancer-driver genes has been a central theme of cancer research. We took a different perspective; instead of considering normal cells, we focused on cancerous cells and genes that maintained abnormal cell growth, which we named cancer-keeper genes (CKGs). Intervening CKGs may rectify aberrant cell growth, making them potential cancer therapeutic targets. We introduced control-hub genes and developed an efficient algorithm by extending network controllability theory. Control hub are essential for maintaining cancerous states and thus can be taken as CKGs. We applied our CKG-based approach to bladder cancer (BLCA). All genes on the cell-cycle and p53 pathways in BLCA were identified as CKGs, showing their importance in cancer. We discovered that sensitive CKGs - genes easily altered by structural perturbation - were particularly suitable therapeutic targets. Experiments on cell lines and a mouse model confirmed that six sensitive CKGs effectively suppressed cancer cell growth, demonstrating the immense therapeutic potential of CKGs.

The shift of percent excess mortality from zero-COVID policy to living-with-COVID policy in Singapore, South Korea, Australia, New Zealand and Hong Kong SAR.

Introduction: With the economic recession and pandemic fatigue, milder viral variants and higher vaccine coverage along the time lay the basis for lifting anti-COVID policies to restore COVID-19 normalcy. However, when and how to adjust the anti-COVID policies remain under debate in many countries. Methods: In this study, four countries (Singapore, South Korea, Australia, and New Zealand) and one region (Hong Kong SAR), that have shifted from the zero-COVID (ZC) policy to or close to the living-with-COVID (LWC) during or after the Omicron outbreak, were selected as research objects. All-cause mortality data were collected for these objects from 2009 to 2019. The expected mortality was estimated by a simple linear regression method. Excess mortality over time was calculated as the difference between the expected mortality and the observed mortality. Finally, percent excess mortality (PEM) was calculated as the excess mortality divided by the expected mortality. Results: In the examined four countries, PEM fluctuated around 0% and was lower than 10% most of the time under the ZC policy before 2022. After shifting to the LWC policy, all the examined countries increased the PEM. Briefly, countries with high population density (Singapore and South Korea) experienced an average PEM of 20-40% during the first half of 2022, and followed by a lower average PEM of 15-18% during the second half of 2022. For countries with low population density under the LWC policy, Australia experienced an average PEM of 39.85% during the first half of 2022, while New Zealand was the only country in our analysis that achieved no more than 10% in average PEM all the time. On the contrary, Hong Kong SAR under their ZC policy attained an average PEM of 71.14% during the first half of 2022, while its average PEM decreased to 9.19% in the second half of 2022 with LWC-like policy. Conclusion: PEM under different policies within each country/region overtime demonstrated that the mortality burden caused by COVID-19 had been reduced overtime. Moreover, anti-COVID policies are suggested to control the excess mortality to achieve as low as 10% in PEM.

Identification of a glutamine metabolism reprogramming signature for predicting prognosis, immunotherapy efficacy, and drug candidates in bladder cancer.

Background: Bladder cancer is the most common malignancy of the urinary system. However, patient prognosis and treatment outcomes in bladder cancer are difficult to predict owing to high tumor heterogeneity. Given that abnormal glutamine metabolism has been identified as a key factor driving the progression of bladder cancer, it is necessary to assess the prognosis and therapeutic efficacy of bladder cancer treatments based on an analysis of glutamine metabolism-related genes. Methods: We used bladder cancer sample data downloaded from The Cancer Genome Atlas to identify glutamine metabolism-related genes as prognostic markers, and established a novel Glutamine Metabolism Immunity Index (GMII) based on univariate and multivariate COX regression analyses. On the basis of GMII values, bladder cancer patients were divided into high- and low-risk groups, and systematic analysis was conducted for clinical features, somatic mutations, immune cell infiltration, chemotherapeutic response, and immunotherapeutic efficacy. Candidate small-molecule drugs targeting the GMII core target proteins were identified based on molecular docking analysis. Results: The GMII consisting of eight independent prognostic genes was established to be an excellent tool for predicting the survival in patients with bladder cancer and was validated using multiple datasets. Compared with patients in the high-risk group, those in the low-risk group had significantly better responses to gemcitabine and immune checkpoint blockade. In addition, we predicted 12 potential small-molecule drugs that could bind to three of the GMII core target proteins. Conclusions: The GMII can be used to accurately predict the prognosis and immunotherapeutic response of bladder cancer patients, as well as candidate small-molecule drugs. Furthermore, the novel "Glutamine Metabolism-related Gene"-guided strategy for predicting survival and chemo-immunotherapeutic efficacy may also be applicable for cancers other than bladder cancer.

HES1-mediated down-regulation of miR-138 sustains NOTCH1 activation and promotes proliferation and invasion in renal cell carcinoma.

BACKGROUND: Although the aberrant activation of NOTCH1 pathway causes a malignant progression of renal cell carcinoma (RCC), the precise molecular mechanisms behind the potential action of pro-oncogenic NOTCH1/HES1 axis remain elusive. Here, we examined the role of tumor suppressive miR-138-2 in the regulation of NOTCH1-HES1-mediated promotion of RCC. METHODS: This study employed bioinformatics, xenotransplant mouse models, ChIP assay, luciferase reporter assay, functional experiments, real-time PCR and Western blot analysis to explore the mechanisms of miR-138-2 in the regulation of NOTCH1-HES1-mediated promotion of RCC, and further explored miR-138-2-containing combination treatment strategies. RESULTS: There existed a positive correlation between down-regulation of miR-138 and the aberrant augmentation of NOTCH1/HES1 regulatory axis. Mechanistically, HES1 directly bound to miR-138-2 promoter region and thereby attenuated the transcription of miR-138-5p as well as miR-138-2-3p. Further analysis revealed that miR-138-5p as well as miR-138-2-3p synergistically impairs pro-oncogenic NOTCH1 pathway through the direct targeting of APH1A, MAML1 and NOTCH1. CONCLUSIONS: Collectively, our current study strongly suggests that miR-138-2 acts as a novel epigenetic regulator of pro-oncogenic NOTCH1 pathway, and that the potential feedback regulatory loop composed of HES1, miR-138-2 and NOTCH1 contributes to the malignant development of RCC. From the clinical point of view, this feedback regulatory loop might be a promising therapeutic target to treat the patients with RCC.

Anticancer effect of a pyrrole-imidazole polyamide-triphenylphosphonium conjugate selectively targeting a common mitochondrial DNA cancer risk variant in cervical cancer cells.

Cervical cancer remains a major threat to women's health, especially in countries with limited medical resources, and new drugs are needed to improve patient survival and minimize adverse effects. Here, we examine the effects of a triphenylphosphonium (TPP)-conjugated pyrrole-imidazole polyamide (CCC-h1005) targeting the common homoplasmic mitochondrial DNA (mtDNA) cancer risk variant (ATP6 8860A>G) on the survival of cervical cancer cell lines, cisplatin-resistant HeLa cells and patient-derived cervical clear cell carcinoma cells as models of cervical cancer treatment. We found that CCC-h1005 induced death in these cells and suppressed the growth of xenografted HeLa tumors with no severe adverse effects. These results suggest that PIP-TPP designed to target mtDNA cancer risk variants can be used to treat many cervical cancers harboring high copies of the target variant, providing a foundation for clinical trials of this class of molecules for treating cervical cancer and other types of cancers.

Integration of multi-omics and clinical treatment data reveals bladder cancer therapeutic vulnerability gene combinations and prognostic risks.

Background: Bladder cancer (BCa) is a common malignancy of the urinary tract. Due to the high heterogeneity of BCa, patients have poor prognosis and treatment outcomes. Immunotherapy has changed the clinical treatment landscape for many advanced malignancies, opening new avenues for the precise treatment of malignancies. However, effective predictors and models to guide clinical treatment and predict immunotherapeutic outcomes are still lacking. Methods: We downloaded BCa sample data from The Cancer Genome Atlas to identify anti-PD-L1 immunotherapy-related genes through an immunotherapy dataset and used machine learning algorithms to build a new PD-L1 multidimensional regulatory index (PMRI) based on these genes. PMRI-related column-line graphs were constructed to provide quantitative tools for clinical practice. We analyzed the clinical characteristics, tumor immune microenvironment, chemotherapy response, and immunotherapy response of patients based on PMRI system. Further, we performed function validation of classical PMRI genes and their correlation with PD-L1 in BCa cells and screening of potential small-molecule drugs targeting PMRI core target proteins through molecular docking. Results: PMRI, which consists of four anti-PD-L1 immunotherapy-associated genes (IGF2BP3, P4HB, RAC3, and CLK2), is a reliable predictor of survival in patients with BCa and has been validated using multiple external datasets. We found higher levels of immune cell infiltration and better responses to immunotherapy and cisplatin chemotherapy in the high PMRI group than in the low PMRI group, which can also be used to predict immune efficacy in a variety of solid tumors other than BCa. Knockdown of IGF2BP3 inhibited BCa cell proliferation and migration, and IGF2BP3 was positively correlated with PD-L1 expression. We performed molecular docking prediction for each of the core proteins comprising PMRI and identified 16 small-molecule drugs with the highest affinity to the target proteins. Conclusions: Our PD-L1 multidimensional expression regulation model based on anti-PD-L1 immunotherapy-related genes can accurately assess the prognosis of patients with BCa and identify patient populations that will benefit from immunotherapy, providing a new tool for the clinical management of intermediate and advanced BCa.

Identification of a novel ferroptosis-related gene signature associated with prognosis, the immune landscape, and biomarkers for immunotherapy in ovarian cancer.

Ferroptosis has been implicated in tumor progression and immunoregulation. Identification of ferroptosis-related prognostic gene is important for immunotherapy and prognosis in ovarian cancer (OV). We assessed the potential predictive power of a novel ferroptosis-related gene (FRG) signature for prognosis and immunotherapy in Asian and Caucasian OV populations. We collected gene expression profiles and clinicopathological data from public databases. The least absolute shrinkage and selection operator Cox regression algorithm was used to construct the FRG signature. Receiver operating characteristic (ROC) curve, Kaplan-Meier method, Cox regression model were used to evaluate the clinical benefits of FRG signature. Gene functional and gene set enrichment analyses were used for functional annotation and immune landscape analysis. A 15-FRG signature was constructed and used to stratify patients into two risk groups. Patients in the high-risk group had significantly worse survival. The risk score was a significant independent risk factor for OS. The area under the ROC curve indicated the good prediction performance of the FRG signature. Notably, the low-risk group showed a significant enrichment in immune-related pathways and a "hot" immune status. The risk score was found to be an efficient and robust predictor of response to immunotherapy. In conclusion, our study identified a novel 15-FRG prognostic signature that can be used for prognostic prediction and precision immunotherapy in Asian and Caucasian OV populations.

Oridonin attenuates lung inflammation and fibrosis in silicosis via covalent targeting iNOS.

Silicosis, the most common type of pneumoconiosis, exhibits a high incidence in workers who are chronically exposed to crystalline silica (CS). No specific remedy for cure as yet. The terpenoid oridonin exerts multiple modulatory functions in neoplasms and inflammations as a natural compound. In this study, we explored the effect of oridonin on silicosis and revealed the underlying molecular mechanism. An experimental silicosis mouse model was established to evaluate the effects of oridonin on pneumonia and pulmonary fibrosis. In addition, the impact of oridonin on alveolar macrophages (AMs) was examined in the MH-S cell line. Its molecular target, inducible nitric oxide synthase (iNOS), was identified by chemobiological means, and virus-mediated gene overexpression systems confirmed that oridonin directly restrained iNOS protein levels. Oridonin alleviated pneumonia and pulmonary fibrosis in silicosis mice with no obvious systemic toxicity. These effects were partially related to oridonin inhibition of CS-induced AMs injury and inflammation. Furthermore, oridonin suppressed iNOS enzymatic expression and activity by covalently binding to the Thr109 residue of the iNOS target. Thus, our results indicate oridonin as a potential iNOS enzymatic suppressor in experimental silicosis that attenuates pneumonia and pulmonary fibrosis progression, which provides a therapeutic avenue for silicosis prevention and treatment.

Dietary exposure to polystyrene nanoplastics impairs fasting-induced lipolysis in adipose tissue from high-fat diet fed mice.

The health concerns of microplastics (MPs) and nanoplastics (NPs) surge, but the key indicators to evaluate the adverse risks of MPs/NPs are elusive. Recently, MPs/Ps were found to disturb glucose and lipid metabolism in rodents, suggesting that MPs/NPs may play a role in obesity progression. In this study, we firstly demonstrated that the distribution of fluorescent polystyrene nanoplastics (nPS, 60 nm) white adipose tissue (WAT) of mice. Furthermore, nPS could traffic across adipocytes in vitro and reduced lipolysis under ß-adrenergic stimulation in adipocytes in vitro and ex vivo. Consistently, chronic oral exposure to nPS at the dietary exposure relevant concentrations (3 and 223 µg/kg body weight) impaired fasting-induced lipid mobilization in obese mice and subsequently contributed to larger adipocyte size in the subcutaneous WAT. In addition, the chronic exposure of nPS induced macrophage infiltration in the small intestine and increased lipid accumulation in the liver, accelerating the disruption of systemic metabolism. Collectively, our findings highlight the potential obesogenic role of nPS via diminishing lipid mobilization in WAT of obese mice and suggest that lipolysis relevant parameters may be used for evaluating the adverse effect of MPs/NPs in clinics.