Influence of intelligent management mode based on Internet of Things on self-management ability and prognosis of elderly patients with hypertensive heart disease: An observational study.

Hypertensive heart disease was difficult to cure with drugs, and most patients had poor compliance, leading to recurrent disease and poor quality of life. The intelligent management mode based on the Internet of Things avoided the excessive dependence of the elderly patients on medical institutions in the traditional medical model and enabled patients to monitor themselves. This study aimed to explore the impact on self-management ability and prognosis of elderly patients with hypertensive heart disease. A total of 150 elderly patients with hypertensive heart disease who received treatment from April 2020 to April 2022 were selected and divided into control group (n = 75 cases) and observation group (n = 75 cases) by random number table method. The control group was given routine intervention, and the observation group was given intelligent management mode based on the Internet of Things. Blood pressure fluctuation, self-management ability, and prognosis of the 2 groups were compared after intervention. After the intervention of the intelligent management mode based on the Internet of Things, the systolic and diastolic blood pressure levels in the observation group were lower than those in the control group (P < .05). After intervention, the scores of self-management ability in diet control, self-care skills, rehabilitation exercise, and self-monitoring in observation group were higher than those in control group (P < .05). After intervention, the total incidence of chest tightness, dyspnea, arrhythmia, edema, and nausea in the observation group was 5 (6.67%), which was significantly lower than that in the control group 12 (16.00%) (P < .05). The application of intelligent management mode based on the Internet of Things could effectively improve patients' blood pressure level, improve patients' self-management ability, and significantly improve the prognosis, which was worthy of popularization and application.

Training on contrast-enhanced ultrasound LI-RADS classification for resident radiologists: a retrospective comparison of performance after training.

OBJECTIVES: To evaluate the effects and benefits of training radiology residents on contrast-enhanced ultrasound (CEUS) according to the Liver Imaging Reporting and Data System (LI-RADS). METHODS: In total, 234 patients at high risk of hepatocellular carcinoma (HCC) who underwent CEUS were enrolled, including 27 lesions in the education set and 207 lesions in the test sets (a-d). Forty-five radiology residents and 4 radiology experts involved in CEUS LI-RADS training individually reviewed the test sets before, immediately after, and 3-months after training. The consistency with kappa values of the description of CEUS features, the classification of focal liver lesions (FLLs), and the diagnostic performance were evaluated. RESULTS: The level of agreement between the radiology experts and residents improved after training (all p < 0.05), while there were no significant differences between the post-training and 3-months post-training results (all p > 0.05). The sensitivity, specificity, positive predictive value, and area under the curve (AUC) based on the CEUS LI-RADS classification of the radiology experts in the diagnosis of HCC were 62.9%, 96.4%, 96.3%, and 0.796, respectively. The diagnostic performance of the radiology residents significantly improved after training (all p < 0.05). Misunderstanding of definitions and subjective interpretation of images were the main reasons for disagreement with multiple responses. CONCLUSION: Dedicated CEUS LI-RADS training improved the performance of radiology residents in diagnosing FLLs and their agreement with radiology experts on CEUS features. Images and videos to explain typical features of the training were essential to improve agreement between the radiology experts and residents. CRITICAL RELEVANCE STATEMENT: Agreement on lesion descriptors between radiology experts and residents can improve with training. KEY POINTS: The diagnostic performance of less experienced radiologists for diagnosing HCC could be improved by training. Images and videos to explain typical features during training were essential. Agreement on lesion descriptors between radiology experts and residents improved after training.

Combined UTMD-Nanoplatform for the Effective Delivery of Drugs to Treat Renal Cell Carcinoma.

Introduction: The effective accumulation of nanoparticles (NPs) in the tumour area is an important goals of current nanotechnology research, and a targeted nanoplatform is an effective solution. So we designed a multifunctional sound-sensitive targeted NP that combines a sonosensitizer to enable precisely targeted, deep-penetration sonodynamic therapy (SDT) in combination with multimodal imaging for the diagnosis and monitoring of renal cell carcinoma (RCC). Methods: ZnPP@PP NPs (ZnPP@PLGA- PFP NPs) were prepared via a double emulsion method, and G250 was covalently attached to the NPs shell via the carbon diimide method. Physicochemical property tests were conducted on the ZnPP@G-PP NPs, including tests of particle size, potential distribution, encapsulation efficiency and drug loading capability. We assessed the targeting ability, the production of reactive oxygen species (ROS) and permeability of the NPs in vitro. Moreover, we evaluated the nanoparticle's multimodal imaging capabilities and therapeutic ability against RCC, both in vitro and in vivo. Results: The Znpp@G-PP NPs were successfully constructed, and their general properties showed uniform particle size, negative potential and good stability. The nanoparticles were successfully loaded with ZnPP and connected with G250, showing tumor-specific targeting ability. Under LIFU irradiation, the nanoparticles produced 1O2 by SDT. For RCC, PA/US multi-modal imaging of Znpp@G-PP NPs provide diagnostic information and monitor therapies in real time in 786-O RCC xenografts, with good biocompatibility. With the UTMD, nanoparticles can be effectively targeted into the tumor cells and penetrate into the tumor interior, significantly improving the SDT effect. Experiments in vitro and in vivo showed that the combination of the nanoparticles and LIFU could suppress the tumor, and the therapeutic effect was confirmed by immunohistochemistry. Conclusion: ZnPP@G-PP NPs provide a promising theranostic strategy for RCC and a platform for further research on improving the efficacy of diagnosis and treatment.

Terphenyllin induces CASP3-dependent apoptosis and pyroptosis in A375 cells through upregulation of p53.

BACKGROUND: Melanoma, one of the most lethal forms of skin cancer, has the potential to develop in any area where melanocytes are present. Currently, postoperative recurrence due to the emergence of systemic drug resistance represents a significant challenge in the treatment of melanoma. In this study, terphenyllin (TER), a distinctive inhibitory impact on melanoma cells was identified from the natural p-terphenyl metabolite. This study aimed to elucidate the intrinsic mechanism of this inhibitory effect, which may facilitate the discovery of novel chemotherapeutic agents. METHODS: A transcriptome sequencing and metabolomic analysis of TER-treated A375 cells was conducted to identify potential pathways of action. The key proteins were knocked out and backfilled using CRISPR-Cas9 technology and molecular cloning. Subsequently, the results of cytosolic viability, LDH release, immunofluorescence and flow cytometry were employed to demonstrate the cell death status of the drug-treated cells. RESULTS: The p53 signalling pathway was markedly upregulated following TER treatment, leading to the activation of CASP3 via the intrinsic apoptotic pathway. The activated CASP3 initiated apoptosis, while simultaneously continuing to cleave the GSDME, thereby triggering pyroptosis. The knockout of p53, a key protein situated upstream of this pathway, resulted in a significant rescue of TER-induced cell death, as well as an alleviation of the decrease in cell viability. However, the knockout of key proteins situated downstream of the pathway (CASP3 and GSDME) did not result in a rescue of TER-induced cell death, but rather a transformation of the cells from apoptosis and pyroptosis. CONCLUSIONS: The induction of apoptosis and pyroptosis in A375 cells by TER is mediated via the p53-BAX/FAS-CASP3-GSDME signalling pathway. This lays the foundation for TER as a potential anti-melanoma drug in the future. It should be noted that CASP3 and GSDME in this pathway solely regulate the mode of cell death, rather than determine whether cell death occurs. This distinction may prove valuable in future studies of apoptosis and pyroptosis.

Consecutive palmitoylation and phosphorylation orchestrates NLRP3 membrane trafficking and inflammasome activation.

NLRP3 inflammasome activation, essential for cytokine secretion and pyroptosis in response to diverse stimuli, is closely associated with various diseases. Upon stimulation, NLRP3 undergoes subcellular membrane trafficking and conformational rearrangements, preparing itself for inflammasome assembly at the microtubule-organizing center (MTOC). Here, we elucidate an orchestrated mechanism underlying these ordered processes using human and murine cells. Specifically, NLRP3 undergoes palmitoylation at two sites by palmitoyl transferase zDHHC1, facilitating its trafficking between subcellular membranes, including the mitochondria, trans-Golgi network (TGN), and endosome. This dynamic trafficking culminates in the localization of NLRP3 to the MTOC, where LATS1/2, pre-recruited to MTOC during priming, phosphorylates NLRP3 to further facilitate its interaction with NIMA-related kinase 7 (NEK7), ultimately leading to full NLRP3 activation. Consistently, Zdhhc1-deficiency mitigated LPS-induced inflammation and conferred protection against mortality in mice. Altogether, our findings provide valuable insights into the regulation of NLRP3 membrane trafficking and inflammasome activation, governed by palmitoylation and phosphorylation events.

Coaxial Electrospun Polycaprolactone/Gelatin Nanofiber Membrane Loaded with Salidroside and Cryptotanshinone Synergistically Promotes Vascularization and Osteogenesis.

Background: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized. Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/ß-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery. Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.

Development of a Preoperative Screening Tool to Reduce Morbidity and Mortality of COVID-19-positive Hepatobiliary Patients.

PURPOSE: This study aimed to create a preoperative risk assessment form for COVID-19-positive hepatobiliary patients to guide further prevention of complications after surgery and reduce morbidity and mortality. DESIGN: Based on the literature, focus groups, and case studies, a multidisciplinary panel of 15 experts conducted three rounds of a Delphi study that resulted in the development of a preoperative risk assessment form to be used by healthcare professionals in the treatment of COVID-19-positive hepatobiliary patients. METHODS: A preoperative risk assessment form for health professionals to use among COVID-19-positive hepatobiliary patients was developed based on literature, focus groups, and case studies. A 3-round Delphi study was conducted to validate and revise the risk assessment form using a multidisciplinary panel of 15 experts involved in hepatobiliary surgery. FINDINGS: The experts demonstrated high cooperation and familiarity with the research topic, with positive coefficients ranging from 93.33% to 100% and authority coefficients ranging from 0.83 to 0.86. The coordination coefficients were 0.33, 0.26, and 0.22, respectively, indicating good coordination among expert opinions. The final risk assessment form included 9 primary (first-level) indicators, 38 secondary (second-level) indicators, and 122 tertiary (third-level) indicators. CONCLUSIONS: The preoperative risk assessment form for hepatobiliary surgery patients infected with COVID-19 is scientifically rigorous, reliable, and valid. This screening tool may be used by health providers to identify high-risk patients, prevent postoperative complications, and reduce morbidity and mortality.

Auto-inducible synthetic pathway in E. coli enhanced sustainable indigo production from glucose.

Indigo is widely used in textile industries for denim garments dyeing and is mainly produced by chemical synthesis which, however, raises environmental sustainability issues. Bio-indigo may be produced by fermentation of metabolically engineering bacteria, but current methods are economically incompetent due to low titer and the need for an inducer. To address these problems, we first characterized several synthetic promoters in E. coli and demonstrated the feasibility of inducer-free indigo production from tryptophan using the inducer-free promoter. We next coupled the tryptophan-to-indigo and glucose-to-tryptophan pathways to generate a de novo glucose-to-indigo pathway. By rational design and combinatorial screening, we identified the optimal promoter-gene combinations, which underscored the importance of promoter choice and expression levels of pathway genes. We thus created a new E. coli strain that exploited an indole pathway to enhance the indigo titer to 123 mg/L. We further assessed a panel of heterologous tryptophan synthase homologs and identified a plant indole lyase (TaIGL), which along with modified pathway design, improved the indigo titer to 235 mg/L while reducing the tryptophan byproduct accumulation. The optimal E. coli strain expressed 8 genes essential for rewiring carbon flux from glucose to indole and then to indigo: mFMO, ppsA, tktA, trpD, trpC, TaIGL and feedback-resistant aroG and trpE. Fed-batch fermentation in a 3-L bioreactor with glucose feeding further increased the indigo titer (≈965 mg/L) and total quantity (≈2183 mg) at 72 h. This new synthetic glucose-to-indigo pathway enables high-titer indigo production without the need of inducer and holds promise for bio-indigo production.

The anti-inflammatory role of zDHHC23 through the promotion of macrophage M2 polarization and macrophage necroptosis in large yellow croaker (Larimichthys crocea).

Zinc finger Asp-His-His-Cys motif-containing (zDHHC) proteins, known for their palmitoyltransferase (PAT) activity, play crucial roles in diverse cellular processes, including immune regulation. However, their non-palmitoyltransferase immunomodulatory functions and involvement in teleost immune responses remain underexplored. In this study, we systematically characterized the zDHHC family in the large yellow croaker (Larimichthys crocea), identifying 22 members. Phylogenetic analysis unveiled that each of the 22 LczDHHCs formed distinct clusters with their orthologues from other teleost species. Furthermore, all LczDHHCs exhibited a highly conserved DHHC domain, as confirmed by tertiary structure prediction. Notably, LczDHHC23 exhibited the most pronounced upregulation following Pseudomonas plecoglossicida (P. plecoglossicida) infection of macrophage/monocyte cells (MO/MΦ). Silencing LczDHHC23 led to heightened pro-inflammatory cytokine expression and diminished anti-inflammatory cytokine levels in MO/MΦ during infection, indicating its anti-inflammatory role. Functionally, LczDHHC23 facilitated M2-type macrophage polarization, as evidenced by a significant skewing of MO/MΦ towards the pro-inflammatory M1 phenotype upon LczDHHC23 knockdown, along with the inhibition of MO/MΦ necroptosis induced by P. plecoglossicida infection. These findings highlight the non-PAT immunomodulatory function of LczDHHC23 in teleost immune regulation, broadening our understanding of zDHHC proteins in host-pathogen interactions, suggesting LczDHHC23 as a potential therapeutic target for immune modulation in aquatic species.

Laryngopharyngeal reflux disease: Updated examination of mechanisms, pathophysiology, treatment, and association with gastroesophageal reflux disease.

Laryngopharyngeal reflux disease (LPRD) is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus. LPRD commonly presents with sym-ptoms such as hoarseness, cough, sore throat, a feeling of throat obstruction, excessive throat mucus. This complex condition is thought to involve both reflux and reflex mechanisms, but a clear understanding of its molecular mechanisms is still lacking. Currently, there is no standardized diagnosis or treatment protocol. Therapeutic strategies for LPRD mainly include lifestyle modifications, proton pump inhibitors and endoscopic surgery. This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms, patho-physiology and treatment of LPRD. We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

Risk factors of non-arteritic anterior ischaemic optic neuropathy and central retinal artery occlusion.

AIM: To investigate the difference in risk factors between non-arteritic anterior ischaemic optic neuropathy (NAION) and central retinal artery occlusion (CRAO) and develop a predictive diagnostic nomogram. METHODS: The study included 37 patients with monocular NAION, 20 with monocular CRAO, and 24 with hypertension. Gender, age, and systemic diseases were recorded. Blood routine, lipids, hemorheology, carotid and brachial artery doppler ultrasound, and echocardiography were collected. The optic disc area, cup area, and cup-to-disc ratio (C/D) of the unaffected eye in the NAION and CRAO group and the right eye in the hypertension group were measured. RESULTS: The carotid artery intimal medial thickness (C-IMT) of the affected side of the CRAO group was thicker (P=0.039) and its flow-mediated dilation (FMD) was lower (P=0.049) than the NAION group. Compared with hypertension patients, NAION patients had higher whole blood reduced viscosity low-shear (WBRV-L) and erythrocyte aggregation index (EAI; P=0.045, 0.037), and CRAO patients had higher index of rigidity of erythrocyte (IR) and erythrocyte deformation index (EDI; P=0.004, 0.001). The optic cup and the C/D of the NAION group were smaller than the other two groups (P<0.0001). The diagnostic prediction model showed high diagnostic specificity (83.7%) and sensitivity (85.6%), which was highly related to hypertension, the C-IMT of the affected side, FMD, platelet (PLT), EAI, and C/D. CONCLUSION: CRAO patients show thicker C-IMT and worse endothelial function than NAION. NAION and CRAO may be related to abnormal hemorheology. A small cup and small C/D may be involved in NAION. The diagnostic nomogram can be used to preliminarily identify NAION and CRAO.

Mild phototherapy mediated by IR780-Gd-OPN nanomicelles suppresses atherosclerotic plaque progression through the activation of the HSP27-regulated NF-κB pathway.

Reducing plaque lipid content and enhancing plaque stability without causing extensive apoptosis of foam cells are ideal requirements for developing a safe and effective treatment of atherosclerosis. In this study, we synthesized IR780-Gd-OPN nanomicelles by conjugating osteopontin (OPN) and loading a gadolinium-macrocyclic ligand (Gd-DOTA) onto near-infrared dye IR780-polyethylene glycol polymer. The nanomicelles were employed for mild phototherapy of atherosclerotic plaques and dual-mode imaging with near-infrared fluorescence and magnetic resonance. In vitro results reveal that the mild phototherapy mediated by IR780-Gd-OPN nanomicelles not only activates heat shock protein (HSP) 27 to protect foam cells against apoptosis but also inhibits the nuclear factor kappa-B (NF-κB) pathway to regulate lipid metabolism and macrophage polarization, thereby diminishing the inflammatory response. In vivo results further validate that mild phototherapy effectively reduces plaque lipid content and size while simultaneously enhancing plaque stability by regulating the ratio of M1 and M2-type macrophages. In summary, this study presents a promising approach for developing a safe and highly efficient method for the precise therapeutic visualization of atherosclerosis. STATEMENT OF SIGNIFICANCE: The rupture of unstable atherosclerotic plaques is a major cause of high mortality rates in cardiovascular diseases. Therefore, the ideal outcome of atherosclerosis treatment is to reduce plaque size while enhancing plaque stability. To address this challenge, we designed IR780-Gd-OPN nanomicelles for mild phototherapy of atherosclerosis. This treatment can effectively reduce plaque size while significantly improving plaque stability by increasing collagen fiber content and elevating the ratio of M2/M1 macrophages, which is mainly attributed to the inhibition of the NF-κB signaling pathway by mild phototherapy-activated HSP27. In summary, our proposed mild phototherapy strategy provides a promising approach for safe and effective treatment of atherosclerosis.

Risk Factors and Risk Assessment for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis.

OBJECTIVE: To analyse the pertinent risk factors associated with post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) and develop a predictive scoring system for assessing the risk of PEP in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) procedures. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Gastroenterology, Nantong First People's Hospital, Jiangsu, China, from January 2022 to January 2023. METHODOLOGY: Clinical data of 375 patients who underwent successful ERCP treatment were collected and organised. Relevant risk factors for PEP were analysed, and a scoring system was established to predict the risk of PEP. RESULTS: Among the 375 patients who underwent ERCP, the incidence of PEP was 9.07% (34/375). Univariate analysis revealed that female gender, pancreatic duct opacification, difficult cannulation, operation time ≥45 minutes, sphincter of Oddi dysfunction (SOD), and biliary stenting were risk factors for PEP. Multivariate analysis showed that female gender, pancreatic duct opacification, difficult cannulation, operation time ≥45 minutes, and SOD were independent risk factors for PEP. A scoring system was developed, and the receiver operating characteristic (ROC) curve analysis determined a cut-off value of 1.5 points. Patients with a score less than 1.5 points had a low probability of developing PEP, while those with a score greater than 1.5 points had a significantly higher probability of PEP. CONCLUSION: Female gender, pancreatic duct opacification, difficult cannulation, operation time ≥45 minutes, and SOD were independent risk factors for PEP. Additionally, a reliable scoring system was established to predict the risk of PEP. Clinicians can use this scoring system to assess the risk of PEP in patients and implement preventive measures to reduce the incidence of PEP. KEY WORDS: Endoscopic retrograde cholangiopancreatography, Post-ERCP pancreatitis, Risk factors, Risk assessment, Preventive measure.

Association of leptin receptor polymorphisms with susceptibility of non-small cell lung cancer: Evidence from 2249 subjects.

Non-small cell lung cancer (NSCLC) is increasing dramatically. It is believed that energy metabolism-related genes could play an important role in etiology of NSCLC. In this study, we sought to assess the correlation between three LEPR single nucleotide polymorphisms (rs1137101, rs1137100 and rs6588147) with NSCLS susceptibility. In total, 1193 NSCLC cases and 1056 controls were included. SNPscan™ genotyping method was used to analyze the genotypes of LEPR polymorphisms. Compared to rs6588147 GG in LEPR gene, this study identified a protective role of LEPR rs6588147 GA and GA/AA for the occurrence of NSCLC (GA vs. GG [p = 0.021] and GA/AA vs. GG [p = 0.030]). As well, we found that a protective role of LEPR rs6588147 for the occurrence of non-SCC subgroup (p < 0.05). By logistic regression analysis, we found that the rs6588147 A allele related genotypes might play a protective role for the occurrence of NSCLC in drinking, BMI ≥24 kg/m2, smoking and male subgroups. We also found that the rs1137101 A allele related genotypes played a protective role for the occurrence of NSCLC in male, younger participants (under 59 years) and overweight/obesity (BMI ≥24 kg/m2) subgroups. We found that LEPR Ars1037100Ars1037101Ars6588147 haplotype might play a protective role for the occurrence of NSCLC (p = 0.013). In addition, our findings indicated that LEPR rs1137100 G>A SNP might increase the risk of lymph node metastases (p = 0.038). This study highlights that LEPR rs6588147, rs1137101 genotypes and LEPR Ars1037100Ars1037101Ars6588147 haplotype are correlated with the occurrence of NSCLC. LEPR rs1137100 G>A SNP increases the risk of lymph node metastases.

Efficient Homolytic Cleavage of H2O2 on Hydroxyl-Enriched Spinel CuFe2O4 with Dual Lewis Acid Sites.

Traditional H2O2 cleavage mediated by macroscopic electron transfer (MET) not only has low utilization of H2O2, but also sacrifices the stability of catalysts. We present a non-redox hydroxyl-enriched spinel (CuFe2O4) catalyst with dual Lewis acid sites to realize the homolytic cleavage of H2O2. The results of systematic experiments, in situ characterizations, and theoretical calculations confirm that tetrahedral Cu sites with optimal Lewis acidity and strong electron delocalization can synergistically elongate the O-O bonds (1.47 Š→ 1.87 Å) in collaboration with adjacent bridging hydroxyl (another Lewis acid site). As a result, the free energy of H2O2 homolytic cleavage is decreased (1.28 eV → 0.98 eV). H2O2 can be efficiently split into ⋅OH induced by hydroxyl-enriched CuFe2O4 without MET, which greatly improves the catalyst stability and the H2O2 utilization (65.2 %, nearly 2 times than traditional catalysts). The system assembled with hydroxyl-enriched CuFe2O4 and H2O2 affords exceptional performance for organic pollutant elimination. The scale-up experiment using a continuous flow reactor realizes long-term stability (up to 600 mL), confirming the tremendous potential of hydroxyl-enriched CuFe2O4 for practical applications.

Regulation of the immune microenvironment by pioglitazone-loaded polylactic glycolic acid nanosphere composite scaffolds to promote vascularization and bone regeneration.

Osteogenesis is caused by multiple factors, and the inflammatory response, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), regeneration of blood vessels, and other factors must be considered in bone tissue engineering. To effectively repair bone defect, it is important to decrease excessive inflammation, enhance the differentiation of mesenchymal stem cells into osteoblasts, and stimulate angiogenesis. Herein, nano-attapulgite (ATP), polyvinyl alcohol (PVA), and gelatin (GEL) scaffolds were produced using 3D printing technology and pioglitazone (PIO)-containing polylactic acid-glycolic acid (PLGA) nanospheres were added. In both in vitro and in vivo studies, material scaffolds with PIO-loaded polylactic acid-glycolic acid nanospheres could reduce the inflammatory response by encouraging macrophage polarization from M1 to M2 and promoting the osteogenic differentiation of BMSCs by activating the BMP2/Smad/RUNX2 signal pathway to repair bone defects. The vascularization of human umbilical vein endothelial cells (HUVECs) through the PI3K/AKT/HIF1-/VEGF pathway was also encouraged. In vivo research using PIO-containing PLGA nanospheres revealed massive collagen deposition in skin models. These findings indicate a potentially effective scaffold for bone healing, when PLGA nanospheres-which contain the drug PIO-are combined with ATP/PVA/GEL scaffolds.

Circular RNA circWNK1 inhibits the progression of gastric cancer via regulating the miR-21-3p/SMAD7 axis.

Gastric cancer (GC) is a highly aggressive malignancy with limited treatment options for advanced-stage patients. Recent studies have highlighted the role of circular RNA (circRNA) as a novel regulator of cancer progression in various malignancies. However, the underlying mechanisms by which circRNA contributes to the development and progression of GC remain poorly understood. In this study, we utilized microarrays and real-time quantitative polymerase chain reaction (qRT-PCR) to identify and validate a downregulated circRNA, hsa_circ_0003251 (referred to as circWNK1), in paired GC and normal tissues. Through a series of in vitro and in vivo gain-of-function and loss-of-function assays, we demonstrated that circWNK1 exerts inhibitory effects on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of GC cells. Additionally, we discovered that circWNK1 acts as a competitive endogenous RNA (ceRNA) for SMAD7 by sequestering miR-21-3p. Our findings were supported by comprehensive biological information analysis, as well as RNA pull-down, luciferase reporter gene, and western blot assays. Notably, the downregulation of circWNK1 in GC cells resulted in reduced SMAD7 expression, subsequently activating the TGF-ß signaling pathway. Collectively, our study reveals that circWNK1 functions as a tumor suppressor in GC by regulating the miR-21-3p/SMAD7-mediated TGF-ß signaling pathway. Furthermore, circWNK1 holds promise as a potential biomarker for the diagnosis and treatment of GC.