Motifs-based link prediction for heterogeneous multilayer networks.

Link prediction has a wide range of applications in the study of complex networks, and the current research on link prediction based on single-layer networks has achieved fruitful results, while link prediction methods for multilayer networks have to be further developed. Existing research on link prediction for multilayer networks mainly focuses on multiplexed networks with homogeneous nodes and heterogeneous edges, while there are relatively few studies on general multilayer networks with heterogeneous nodes and edges. In this context, this paper proposes a method for heterogeneous multilayer networks based on motifs for link prediction. The method considers not only the effect of heterogeneity of edges on network links but also the effect of heterogeneous and homogeneous nodes on the existence of links between nodes. In addition, we use the role function of nodes to measure the contribution of nodes to form the motifs with links in different layers of the network, thus enabling the prediction of intra- and inter-layer links on heterogeneous multilayer networks. Finally, we apply the method to several empirical networks and find that our method has better link prediction performance than several other link prediction methods on multilayer networks.

The dynamic response mechanism of crops to manganese uptake and transfer mediated by different intercropping crop attributes.

BACKGROUND: An issue of pressing concern is the manganese contamination in farmland soils adjacent to industrial areas. To address this, intercropping hyperaccumulator plants with crops emerges as a sustainable approach to ensuring food security. This study aims to investigate the influence of intercropping Sedum alfredii with maize or soybean on their growth and the dynamics of manganese accumulation through field experiments. RESULTS: The results showed that compared with monoculture, the Sedum alfredii-maize intercropping system exhibited a land equivalent ratio (LER) of 1.89, signifying a 71.13% augmentation in bioaccumulation amount (BCA). Additionally, it led to a significant reduction in manganese content in various organs, ranging from 17.05% to 25.50%. However, the Sedum alfredii-soybean intercropping system demonstrated a LER of 1.94, accompanied by a 66.11% increase in BCA, but did not significantly reduce the manganese content in the roots, stems, and pods of soybeans. Furthermore, manganese accumulation in maize and soybean grains was primarily attributed to the aboveground translocation of manganese. The intercropping effect on blocking manganese absorption of maize during growth and maturity is primarily attributed to the earlier manganese accumulation in intercropped maize by 2.63 to 4.35 days, and a reduction of 21.95% in the maximum manganese accumulation rate. CONCLUSIONS: The study found that manganese accumulation dynamics vary significantly depending on the crop family. Intercropping Sedum alfredii with maize enhances land-use efficiency and reduces manganese uptake by crops, making it a promising strategy for remediating manganese-contaminated farmland near industrial areas. © 2024 Society of Chemical Industry.

Radiological assessment of immunotherapy effects and immune checkpoint-related pneumonitis for lung cancer.

Immune checkpoint inhibitors (ICIs) therapy have revolutionized advanced lung cancer care. Interestingly, the host responses for patients received ICIs therapy are distinguishing from those with cytotoxic drugs, showing potential initial transient worsening of disease burden, pseudoprogression and delayed time to treatment response. Thus, a new imaging criterion to evaluate the response for immunotherapy should be developed. ICIs treatment is associated with unique adverse events, including potential life-threatening immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis) if treated patients are not managed promptly. Currently, the diagnosis and clinical management of ICI-pneumonitis remain challenging. As the clinical manifestation is often nonspecific, computed tomography (CT) scan and X-ray films play important roles in diagnosis and triage. This article reviews the complications of immunotherapy in lung cancer and illustrates various radiologic patterns of ICI-pneumonitis. Additionally, it is tried to differentiate ICI-pneumonitis from other pulmonary pathologies common to lung cancer such as radiation pneumonitis, bacterial pneumonia and coronavirus disease of 2019 (COVID-19) infection in recent months. Maybe it is challenging to distinguish radiologically but clinical presentation may help.

Subarachnoid hemorrhage following wasp stings.

Three days after being stung by wasps in a rural area, a 60-year-old man was admitted to the emergency department with headaches. The physical examination showed that the patient was conscious, had moderate pain, had four head and back stings with local edema and erythema around the wounds, and had a stiff neck. Brain computed tomography upon admission revealed no abnormalities. Following lumbar puncture, the patient was diagnosed with subarachnoid hemorrhage (SAH) induced by wasp stings. No obvious aneurysms were found by either computed tomography angiography or three-dimensional rotational angiography. He received symptomatic treatment including antiallergy medication (chlorpheniramine and intravenous hydrocortisone), nimodipine for possible vasospasm, fluid infusion, and mannitol for intracranial pressure reduction and was discharged on the 14th day. This case of wasp sting-induced SAH is being reported to improve doctors' diagnostic abilities when encountering patients with wasp stings. It is important for emergency physicians to be aware that patients stung by wasps may develop rare complications such as SAH. Hymenoptera-induced SAH is an example of such a case.

Jugular Venous Pulse Waveform Extraction From a Wearable Radio Frequency Sensor.

Many prevalent heart diseases can be indicated by the features of the jugular venous pulse (JVP), an efficacious indicator of right heart health. However, JVP dynamics are not widely utilized in clinical settings as its observation and sensing remain cumbersome. Non-invasive measures of cardiac behavior, including the JVP, are of growing interest to enable continuous and at-home monitoring of cardiac disorders. In this work, we propose a wearable near-field radio-frequency (RF) sensor affixed with a neck collar on the clavicle over the internal jugular vein to enable non-invasive JVP sensing. We employed a complex vector injection signal processing method to extract repeatable JVP waveform features in multiple postures. With a 21-subject human study, we demonstrated morphologically consistent JVP sensing with consistent a-, c-, and v-wave feature timings, benchmarked by synchronous electrocardiogram and phonocardiogram. Further, inter-postural experiments demonstrated the capability of the proposed system to quantify morphological changes to the JVP which are present in many cardiac disorders. The results of this work suggest the proposed near-field RF sensor is capable of non-invasive JVP monitoring, potentially enabling improved sensing in both clinical and ambulatory environments.

Deduced Respiratory Scores on COVID-19 Patients Learning from Exertion-Induced Dyspnea.

Dyspnea is one of the most common symptoms of many respiratory diseases, including COVID-19. Clinical assessment of dyspnea relies mainly on self-reporting, which contains subjective biases and is problematic for frequent inquiries. This study aims to determine if a respiratory score in COVID-19 patients can be assessed using a wearable sensor and if this score can be deduced from a learning model based on physiologically induced dyspnea in healthy subjects. Noninvasive wearable respiratory sensors were employed to retrieve continuous respiratory characteristics with user comfort and convenience. Overnight respiratory waveforms were collected on 12 COVID-19 patients, and a benchmark on 13 healthy subjects with exertion-induced dyspnea was also performed for blind comparison. The learning model was built from the self-reported respiratory features of 32 healthy subjects under exertion and airway blockage. A high similarity between respiratory features in COVID-19 patients and physiologically induced dyspnea in healthy subjects was observed. Learning from our previous dyspnea model of healthy subjects, we deduced that COVID-19 patients have consistently highly correlated respiratory scores in comparison with normal breathing of healthy subjects. We also performed a continuous assessment of the patient's respiratory scores for 12-16 h. This study offers a useful system for the symptomatic evaluation of patients with active or chronic respiratory disorders, especially the patient population that refuses to cooperate or cannot communicate due to deterioration or loss of cognitive functions. The proposed system can help identify dyspneic exacerbation, leading to early intervention and possible outcome improvement. Our approach can be potentially applied to other pulmonary disorders, such as asthma, emphysema, and other types of pneumonia.

The SNHG1-Centered ceRNA Network Regulates Cell Cycle and Is a Potential Prognostic Biomarker for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and lethal types of cancer. This study aimed to identify the expression regulatory network and a prognostic signature of HCC. RNA-seq data from The Cancer Genome Atlas were used to identify the differentially expressed genes (DEGs) between HCC and normal liver tissues. DEGs were subjected to the construction of protein-protein interaction (PPI) network and enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The results showed that most of the DEGs were enriched in the cell cycle pathway, and the top 10 hub genes in the PPI network belong to the cell cycle pathway. A ceRNA network was constructed using starBase database, including one lncRNA (SNHG1), seven miRNAs (miR-195-5p, miR-199a-3p, miR-199a-5p, miR-199b-3p, miR-383-5p, miR-424-5p and miR-654-3p) and six of the top 10 hub genes (BUB1, CCNA2, CCNB1, KIF11, NCAPG, and TOP2A). In vitro experiments showed that knockdown of SNHG1 in the HCC cell lines (Huh7 and HepG2) decreased the expression of the six hub genes and cell viability, leading to cell cycle arrest at the G1 phase. These findings indicate that SNHG1 promotes cell proliferation by regulating cell cycle-related genes as a ceRNA. Additionally, Kaplan-Meier's survival and multivariate Cox regression analysis identified a prognostic signature of seven genes (including SNHG1 and the six SNHG1-regulated hub genes) for overall survival of HCC patients. In conclusion, this study identified a novel regulatory network in HCC and a potential independent prognostic factor for overall survival of HCC patients.

Circular RNA circANKRD36 regulates Casz1 by targeting miR-599 to prevent osteoarthritis chondrocyte apoptosis and inflammation.

Osteoarthritis (OA) is an ageing-related disease characterized by articular cartilage degradation and joint inflammation. circRNA has been known to involve in the regulation of multiple inflammatory diseases including OA. However, the mechanism underlying how circRNA regulates OA remains to be elucidated. Here, we report circANKRD36 prevents OA chondrocyte apoptosis and inflammation by targeting miR-599, which specifically degrades Casz1. We performed circRNA sequencing in normal and OA tissues and found the expression of circANKRD36 is decreased in OA tissues. circANKRD36 is also reduced in IL-1ß-treated human chondrocytes. FACS analysis and Western blot showed that the knockdown of circANKRD36 promotes the apoptosis and inflammation of chondrocytes in IL-1ß stress. We then found miR-599 to be the target of circANKRD36 and correlate well with circANKRD36 both in vitro and in vivo. By database analysis and luciferase assay, Casz1 was found to be the direct target of miR-599. Casz1 helps to prevent apoptosis and inflammation of chondrocytes in response to IL-1ß. In conclusion, our results proved circANKRD36 sponge miR-599 to up-regulate the expression of Casz1 and thus prevent apoptosis and inflammation in OA.

Furniture-Integrated Respiration Sensors by Notched Transmission Lines.

Non-invasive respiration sensors integrated into furniture can be invisible to the user and greatly enhance comfort and convenience to facilitate many applications. Current sensors often require user cooperation or fitting, which discourages frequent usage. We present a new respiration sensor integrated into a bed or a chair by modifying a radio-frequency (RF) coaxial cable structure with a designed notch. The lung motion is coupled to the electromagnetic leakage at the notch through near-field coherent sensing (NCS). The sensors, covered with fabrics and positioned under the abdomen and thorax, can capture the respiratory waveforms and derive the breath rate. The heart rate can also be evaluated in the same setup with proper filtering. The sensor design can tolerate large position variation to accommodate user uncertainties. Various voluntary exercises of normal, deep, fast, held and blocked breathing were measured under different postures of supine, recumbent and sitting by the carrier frequency range between 900MHz and 2.4GHz. The breath rate from 10 participants compare well with the synchronous commercial chest-belt sensors in all breathing routines.

Effect of Genetic Variation of NAT2 on Isoniazid and SLCO1B1 and CES2 on Rifampin Pharmacokinetics in Ghanaian Children with Tuberculosis.

Isoniazid and rifampin are essential components of first-line antituberculosis (anti-TB) therapy. Understanding the relationship between genetic factors and the pharmacokinetics of these drugs could be useful in optimizing treatment outcomes, but this is understudied in children. We investigated the relationship between N-acetyltransferase type 2 (NAT2) genotypes and isoniazid pharmacokinetics, as well as that between the solute carrier organic anion transporter family member 1B1 (encoded by SLCO1B1) and carboxylesterase 2 (CES2) single nucleotide polymorphisms (SNPs) and rifampin pharmacokinetics in Ghanaian children. Blood samples were collected at times 0, 1, 2, 4, and 8 h postdose in children with tuberculosis on standard first-line therapy for at least 4 weeks. Isoniazid and rifampin concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and pharmacokinetic parameters were calculated using noncompartmental analysis. Genotyping of NAT2, SLCO1B1, and CES2 SNPs were performed using validated TaqMan genotyping assays. The Kruskal-Wallis test was used to compare pharmacokinetic parameters among the three genotypic groups and was followed by the Wilcoxon rank sum test for pairwise group comparisons. Genotype status inferred by the NAT2 4-SNP and 7-SNP genotyping panels identified children with a slow acetylator phenotype but not the rapid genotype. For rifampin, only the rare SLCO1B1*1b homozygous variant was associated with rifampin pharmacokinetics. Our findings suggest that NAT2 and SCLCO1B1*1b genotyping may have minimal clinical utility in dosing decisions at the population level in Ghanaian children, but it could be useful at the individual level or in populations that have a high frequency of implicated genotypes. Further studies in other populations are warranted.

Surfactant protein D attenuates nitric oxide-stimulated apoptosis in rat chondrocyte by suppressing p38 MAPK signaling.

Innate immune molecule surfactant protein D (SP-D), a member of the C-type lectin protein family, plays an indispensable role in host defense and the regulation of inflammation in the lung and other tissues. Osteoarthritis (OA) is a degenerative disease of cartilage, with inflammation that causes pathologic changes and tissue damage. However, it is unknown whether there exist SP-D expression and its potential role in the pathogenesis of OA. In this study, we examined SP-D expression and explored its biological function in a sodium nitroprusside (SNP)-stimulated rat chondrocytes and surgically-induced rat OA model. We found SP-D expression in both human and rat articular chondrocytes, with higher level in normal chondrocytes compared to in OA chondrocytes. Furthermore, In vivo study demonstrated that recombinant human SP-D (rhSP-D) ameliorated cartilage degeneration in surgically-induced rat OA model. In vitro cell culture study showed that rhSP-D markedly inhibited the expression of caspase-3 as an apoptosis biomarker, and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK), which resulted in maintaining normal nuclear morphology and increasing mitochondrial membrane potential in SNP-stimulated rat chondrocytes. Collectively, these findings indicate that SP-D expresses in articular chondrocytes and suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via suppressing p38 MAPK activity.

Pulsed electromagnetic fields protect the balance between adipogenesis and osteogenesis on steroid-induced osteonecrosis of femoral head at the pre-collapse stage in rats.

This study was designed to investigate the effects of pulsed electromagnetic fields (PEMF) on the balance of adipogenesis and osteogenesis on steroid-induced osteonecrosis of the femoral head (OFH) in rats. Forty-two rats were divided into three groups: Steroid group (S, n = 16); Steroid + PEMF group (S + P, n = 16); and Control group (C, n = 10). For groups S and S + P, all rats were first intravenously given 10 µg/kg lipopolysaccharide on day 1, and then intramuscularly injected with 20 mg/kg methylprednisolone acetate on days 2, 3, and 4, with an interval of 24 h. After 4 weeks, the S + P group was treated with PEMF (4.5-ms square pulse, repeated at 15 Hz, with a peak of 1.2 mT) for 4 h a day for the next 8 weeks. Group S was not exposed to PEMF. Group C was chosen as the control group, without steroid use and exposure to PEMF. After 8 weeks of treatment, the histological changes, and mRNA and protein expressions of PPAR-γ2 and Runx2 were measured and analyzed. Compared with the S group, lower incidence of osteonecrosis (31% vs. 69%, P < 0.05) and empty osteocyte lacuna rate (36.16 ± 15.34 vs. 59.55 ± 21.70, P < 0.01) was observed in the S + P group. Furthermore, PEMF suppressed the expressions of PPAR-γ2 and improved the expressions of Runx2 in the femoral head (P < 0.05). All data suggest that PEMF is an effective physiotherapy in the treatment of steroid-induced ONFH, and the possible underlying mechanisms include protecting the balance between adipogenesis and osteogenesis.

RNF20 promotes the polyubiquitination and proteasome-dependent degradation of AP-2α protein.

Transcription factor activator protein 2α (AP-2α) is a negative regulator of adipogenesis by repressing the transcription of CCAAT/enhancer binding protein (C/EBPα) gene. During adipogenesis, AP-2α is degraded, leading to transcriptional up-regulation of C/EBPα. However, the mechanism for AP-2α degradation is not clear. Here, using immunoprecipitation assay and mass spectrometry, we identified ring finger protein 20 (RNF20) as an AP-2α-interacting protein in 3T3-L1 preadipocytes. RNF20 has been proved to be an E3 ubiquitin ligase for both histone H2B and tumor suppressor ErbB3-binding protein 1 (Ebp1). In this study, we demonstrated that RNF20 co-localized and interacted with AP-2α, and promoted its polyubiquitination and proteasome-dependent degradation. Over-expression of RNF20 inhibited the activity of AP-2α and rescued the C/EBPα expression which was inhibited by AP-2α. These results suggested that RNF20 may play roles in adipocyte differentiation by stimulating ubiquitin-proteasome-dependent degradation of AP-2α.

The influence of a half-course tourniquet strategy on peri-operative blood loss and early functional recovery in primary total knee arthroplasty.

PURPOSE: The aim of this study was to explore the influence of a half-course tourniquet strategy on the peri-operative blood loss and early functional recovery in primary total knee arthroplasty. METHODS: A prospective clinical randomised controlled study was carried out in which 64 patients were equally divided into two groups: half-course group and whole-course group. A series of indicators were observed and recorded. These included operation time, peri-operative blood loss, visual analogue scale (VAS) score of the thigh or knee, limb swelling index, rehabilitation progress and occurrence of deep venous thrombosis cases. RESULTS: There was no significant difference in operation time between the two groups. The intra-operative blood loss was slightly more in the half-course group, while the difference was not significant. The post-operative blood loss and calculated blood loss were less in the half-course group and the difference was significant. The thigh VAS score, limb swelling and time intervals required for patients to achieve straight leg raises and 90° of knee flexion in the half-course group were better than in the whole-course group. No case of symptomatic deep venous thrombosis happened in this study, while occult incidence of deep venous thrombosis happened in both groups, but no significant difference between the groups was confirmed. CONCLUSIONS: The half-course tourniquet strategy could decrease the total peri-operative blood loss in primary total knee arthroplasty. It was beneficial in helping patients to achieve earlier functional recovery by improving the pain experience and limb swelling early in the post-operative period.

The proteasome activator PA28γ, a negative regulator of p53, is transcriptionally up-regulated by p53.

PA28γ (also called REGγ, 11Sγ or PSME3) negatively regulates p53 activity by promoting its nuclear export and/or degradation. Here, using the RNA ligase-mediated rapid amplification of cDNA ends (RLM-RACE) method, we identified the transcription start site of the PA28γ gene. Assessment with the luciferase assay demonstrated that the sequence -193 to +16 is the basal promoter. Three p53 binding sites were found within the PA28γ promoter utilizing a bioinformatics approach and were confirmed by chromatin immunoprecipitation and biotinylated DNA affinity precipitation experiments. The p53 protein promotes PA28γ transcription, and p53-stimulated transcription of PA28γ can be inhibited by PA28γ itself. Our results suggest that PA28γ and p53 form a negative feedback loop, which maintains the balance of p53 and PA28γ in cells.

Fisetin suppresses chondrocyte senescence and attenuates osteoarthritis progression by targeting sirtuin 6.

Osteoarthritis (OA) is the most common type of arthritis and is an age-related joint disease that is particularly prevalent in subjects over 65 years old. The chronic rise of senescent cells has a close correlation with age-related diseases such as OA, and the senescence-associated secretory phenotype (SASP) is implicated in OA cartilage degeneration pathogenesis. Sirtuin 6 (SIRT6) is likely to be a key senescence-related regulator. Fisetin (FST) is a natural flavonol of the flavonoid family that is recommended as a senolytic drug to extend health and lifespan. However, the potential chondroprotective effects of FST on OA rats are largely unclarified. The aim of this study is to investigate the ameliorative effects of FST on OA joint cartilage and the relationship with SIRT6 and the detailed mechanisms from anti-inflammatory and anti-senescent perspectives. Rats were subjected to destabilization of the medial meniscus (DMM) surgery as a means of inducing the experimental OA model in vivo. Chondrocytes treated with IL-1ß were utilized for mimicking the OA cell model in vitro. Intra-articular injection of FST, OSS_128,167 (OSS, SIRT6 inhibitor), and MDL800 (MDL, SIRT6 agonist) in vivo or administering them in IL-1ß-induced rat chondrocytes in vitro were performed in order to determine the effects FST has on OA and the link with SIRT6. This study found SIRT6 level to be negatively correlated with OA severity. SIRT6 downregulation was validated in the joint cartilages of DMM rats and IL-1ß-treated chondrocytes. It was also notably demonstrated that FST can activate SIRT6. Both the administration of FST and activation of SIRT6 using MDL were found to rescue cartilage erosion, decrease extracellular matrix (ECM) degradation, prevent cartilage from apoptosis, and improve detrimental senescence-related phenotype. The alleviative effects of FST against inflammation, ECM degradation, apoptosis, and senescence in IL-1ß-stimulated chondrocytes were also confirmed. SIRT6 loss occurs in articular cartilage in OA pathogenesis, which is linked to aging. FST attenuates injury-induced aging-related phenotype changes in chondrocytes through the targeting of SIRT6.

Motif-based community detection in heterogeneous multilayer networks.

Multilayer networks composed of intralayer edges and interlayer edges are an important type of complex networks. Considering the heterogeneity of nodes and edges, it is necessary to design more reasonable and diverse community detection methods for multilayer networks. Existing research on community detection in multilayer networks mainly focuses on multiplexing networks (where the nodes are homogeneous and the edges are heterogeneous), but few studies have focused on heterogeneous multilayer networks where both nodes and edges represent different semantics. In this paper, we studied community detection on heterogeneous multilayer networks and proposed a motif-based detection algorithm. First, the communities and motifs of multilayer networks are defined, especially the interlayer motifs. Then, the modularity of multilayer networks based on these motifs is designed, and the community structure of the multilayer network is detected by maximizing the modularity of multilayer networks. Finally, we verify the effectiveness of the detection algorithm on synthetic networks. In the experiments on synthetic networks, comparing with the classical community detection algorithms (without considering interlayer heterogeneity), the motif-based modularity community detection algorithm can obtain better results under different evaluation indexes, and we found that there exists a certain relationship between motifs and communities. In addition, the proposed algorithm is applied in the empirical network, which shows its practicability in the real world. This study provides a solution for the investigation of heterogeneous information in multilayer networks.

Human umbilical cord mesenchymal stem cells promote steroid-induced osteonecrosis of the femoral head repair by improving microvascular endothelial cell function.

Recently, there has been growing interest in using cell therapy through core decompression (CD) to treat osteonecrosis of the femoral head (ONFH). Our study aimed to investigate the effectiveness and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in treating steroid-induced ONFH. We constructed a steroid-induced ONFH rabbit model as well as dexamethasone (Dex)-treated bone microvascular endothelial cells (BMECs) model of human femoral head. We injected hUCMSCs into the rabbit femoral head via CD. The effects of hUCMSCs on steroid-induced ONFH rabbit model and Dex-treated BMECs were evaluated via micro-CT, microangiography, histology, immunohistochemistry, wound healing, tube formation, and western blotting assay. Furthermore, we conducted single-cell RNA sequencing (scRNA-seq) to examine the characteristics of endothelial cells, the activation of signaling pathways, and inter-cellular communication in ONFH. Our data reveal that hUCMSCs improved the femoral head microstructure and bone repair and promoted angiogenesis in the steroid-induced ONFH rabbit model. Importantly, hUCMSCs improved the migration ability and angioplasty of Dex-treated BMECs by secreting COL6A2 to activate FAK/PI3K/AKT signaling pathway via integrin α1ß1.

A novel cancer-germline gene DAZL promotes progression and cisplatin resistance of non-small cell lung cancer by upregulating JAK2 and MCM8.

Germline-specific genes are usually activated in cancer cells and drive cancer progression; such genes are called cancer-germline or cancer-testis genes. The RNA-binding protein DAZL is predominantly expressed in germ cells and plays a role in gametogenesis as a translational activator or repressor. However, its expression and role in non-small cell lung cancer (NSCLC) are unknown. Here, mining of RNA-sequencing data from public resources and immunohistochemical analysis of tissue microarrays showed that DAZL was expressed exclusively in testis among normal human tissues but ectopically expressed in NSCLC tissues. Testis and NSCLC cells expressed the shorter and longer transcript variants of the DAZL gene, respectively. Overexpression of the longer DAZL transcript promoted tumor growth in a mouse xenograft model. Silencing of DAZL suppressed cell proliferation, colony formation, migration, invasion, and cisplatin resistance in vitro and tumor growth in vivo. Quantitative proteomic analysis based on tandem mass tag and Western blot analysis showed that DAZL upregulated the expression of JAK2 and MCM8. RNA-binding protein immunoprecipitation assays showed that DAZL bound to the mRNA of JAK2 and MCM8. The JAK2 inhibitor fedratinib attenuated the oncogenic outcomes induced by DAZL overexpression, whereas silencing MCM8 counteracted the effects of DAZL overexpression on cisplatin-damaged DNA synthesis and half-maximal inhibitory concentration of cisplatin. In conclusion, DAZL was identified as a novel cancer-germline gene that enhances the translation of JAK2 and MCM8 to promote NSCLC progression and resistance to cisplatin, respectively. These findings suggest that DAZL is a potential therapeutic target in NSCLC.

SIRT3 alleviates high glucose-induced chondrocyte injury through the promotion of autophagy and suppression of apoptosis in osteoarthritis progression.

A growing amount of epidemiological evidence proposes diabetes mellitus (DM) to be an independent risk factor for osteoarthritis (OA). Sirtuin 3 (SIRT3), which is mainly located in mitochondria, belongs to the family of nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases and is involved in the physiological and pathological processes of cell regulation. The aim of this study was to investigate the effects of SIRT3 on diabetic OA and underlying mechanisms in the prevention of type 2 DM (T2DM)-induced articular cartilage damage. High-fat and high-sugar diets combined with streptozotocin (STZ) injection were used for establishing an experimental T2DM rat model. The destabilization of medial meniscus (DMM) surgery was applied to induce the rat OA model. Primary rat chondrocytes were cultivated with a concentration of gradient glucose. Treatment with intra-articular injection of SIRT3 overexpression lentivirus was achieved in vivo, and intervention with SIRT3 knockdown was performed using siRNA transfection in vitro. High glucose content was found to activate inflammatory response, facilitate apoptosis, downregulate autophagy, and exacerbate mitochondrial dysfunction in a dose-dependent manner in rat chondrocytes, which can be deteriorated by SIRT3 knockdown. In addition, articular cartilage damage was found to be more severe in T2DM-OA rats than in DMM-induced OA rats, which can be mitigated by the intra-articular injection of SIRT3 overexpression lentivirus. Targeting SIRT3 is a potential therapeutic strategy for the alleviation of diabetic OA.