Silencing Lnc-HES1-10 Inhibits Osteosarcoma Cells Proliferation, Invasive Ability, and Metastasis.

BACKGROUND: Long noncoding RNA (LncRNA) play a vital role in the development and pathophysiology of osteosarcoma (OS). However, the LncRNA activated by HES1-10 in OS has not been furthered investigated. This present study aims to show the possible function of Lnc-HES1-10 in OS. METHODS: Cell proliferation in vitro were assessed by the MTT assay, whereas the migration and invasion abilities of OS cell lines were measured by wound-healing migration assay and transwell invasion assay, respectively. Quantitative reverse transcriptase polymerase chain reaction and western blot analysis was used to detected the expression level of HES1-10. RESULTS: The present study demonstrated that the Lnc-HES1-10 is overexpressed in OS and associated with poor prognosis of patients. In addition, the results revealed that Lnc-HES1-10 is overexpressed in MG63 and 143B OS cell lines and promote proliferation on both cell lines in vitro. Furthermore, migration and invasion abilities of MG63 and 143B cells are suppressed after silencing Lnc-HES1-10. CONCLUSION: Our finding demonstrates that HES1-10 plays a crucial role in regulating OS growth and metastasis.

Comparison of Conservative Treatment and Surgery Treatment for Acute Scaphoid Fracture: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: This meta-analysis aimed to investigate the effectiveness of conservative and surgical treatments of scaphoid fracture. METHODS: The literature databases of Pubmed, Cochrane library, and Embase were searched in March 2022. This work extracted the data based on healing time, grip strength, range of wrist motion, nonunion, time before returning to work, and complications (including persistent pain, malunion of the fracture, wound infection, scar sensitivity, hypertrophic scar, and implant-related complications). Stata 14.0 software was used for statistical analysis. RESULTS: Twelve RCTs studies met our inclusion criteria. The surgical group had a shorter healing-time and time before returning to work than the conservative group. In addition, the surgical group had significantly better grip strength and range of wrist motion than the conservative group (P < 0.01). However, there was no significant difference between nonunion (P = 0.538) and complications (P = 0.661) between the two groups. CONCLUSION: This meta-analysis showed that surgical treatment of scaphoid fracture achieved better grip strength and range of wrist motion, and had a lower healing time and time before returning to work than the conservative treatment. The two treatments had similar results in nonunion and complications. Further RCTs were required for the research.

Factors influencing the prevalence of frailty in older adults with fractures: the association of nutritional status with frailty.

BACKGROUND AND OBJECTIVES: To investigate the association between frailty, malnutrition, comorbid medical conditions and activities of daily living (ADL) in older adult patients with fractures, and to analyse the influential factors of frailty. METHODS AND STUDY DESIGN: The FRAIL scale including five components: fatigue, resistance, ambulation, illness, and loss of weight, was used to evaluate frailty. Participants were divided into frailty, pre-frailty and non-frailty groups. The ADL was assessed using the Barthel Index, while the nutrition risk screening tool, NRS-2002, was used to assess the nutritional risk, and the Global Leadership Initiative on Malnutrition diagnostic criteria were used to diagnose the nutritional status. Statistical analysis was performed using univariate and multivariate logistic regression to determine the factors associated with frailty. RESULTS: A total of 166 patients were included in the study, and the incidences of frailty, pre-frailty and non-frailty were 39.2%, 33.1% and 27.7%, respectively. The severe dependence rate (ADL scale of <40) in the frailty, pre-frailty and non-frailty groups was 49.2%, 20.0% and 6.52%, respectively. The prevalence of nutritional risk was 33.7% (56/166), including 56.9% (31/65) in the frailty group and 32.7% (18/55) in the pre-frailty group. Of the 166 patients, 45 (27.1%) were diagnosed with malnutrition, including 47.7% (31/65) in the frailty group and 23.6% (13/55) in the pre-frailty group. CONCLUSIONS: Frailty in older adult patients with fractures is widespread, and the prevalence of malnutrition is high. The occurrence of frailty may be related to an advanced age, increased medical comorbidity and impairment in ADL.

Exosomal hsa_circ_0125310 promotes cell proliferation and fibrosis in diabetic nephropathy via sponging miR-422a and targeting the IGF1R/p38 axis.

Diabetic nephropathy (DN) is still on the rise worldwide, and millions of patients have to be treated through dialysis or transplant because of kidney failure caused by DN. Recent reports have highlighted circRNAs in the treatment of DN. Herein, we aimed to investigate the mechanism by which high glucose-induced exo-circ_0125310 promotes diabetic nephropathy progression. circ_0125310 is highly expressed in diabetic nephropathy and exosomes isolated from high glucose-induced mesangial cells (MCs). High glucose-induced exosomes promote the proliferation and fibrosis of MCs. However, results showed that the effects of exosomes on MCs can be reversed by the knockdown of circ_0125310. miR-422a, which targets IGF1R, was the direct target of circ_0125310. circ_0125310 regulated IGF1R/p38 axis by sponging miR-422a. Exo-circ_0125310 increased the luciferase activity of the WT-IGF1R reporter in the dual-luciferase reporter gene assays and upregulated the expression level of IGF1R and p38. Finally, in vivo research indicated that the overexpression of circ_0125310 promoted the diabetic nephropathy progression. Above results demonstrated that the high glucose-induced exo-circ_0125310 promoted cell proliferation and fibrosis in diabetic nephropathy via sponging miR-422a and targeting the IGF1R/p38 axis.

Photogenerated reactive oxygen species and hyperthermia by Cu3SnS4 nanoflakes for advanced photocatalytic and photothermal antibacterial therapy.

BACKGROUND: The rapid spread of infectious bacteria has brought great challenges to public health. It is imperative to explore effective and environment-friendly antibacterial modality to defeat antibiotic-resistant bacteria with high biosafety and broad-spectrum antibacterial property. RESULTS: Herein, biocompatible Cu3SnS4 nanoflakes (NFs) were prepared by a facile and low-cost fabrication procedure. These Cu3SnS4 NFs could be activated by visible light, leading to visible light-mediated photocatalytic generation of a myriad of reactive oxygen species (ROS). Besides, the plasmonic Cu3SnS4 NFs exhibit strong near infrared (NIR) absorption and a high photothermal conversion efficiency of 55.7%. The ROS mediated cellular oxidative damage and the NIR mediated photothermal disruption of bacterial membranes collaboratively contributed to the advanced antibacterial therapy, which has been validated by the efficient eradication of both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus strains in vitro and in vivo. Meanwhile, the exogenous copper ions metabolism from the Cu3SnS4 NFs facilitated the endothelial cell angiogenesis and collagen deposition, thus expediting the wound healing. Importantly, the inherent localized surface plasmon resonance effect of Cu3SnS4 NFs empowered them as an active substrate for surface-enhanced Raman scattering (SERS) imaging and SERS-labeled bacteria detection. CONCLUSIONS: The low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu3SnS4 NFs make them a candidate for sensitive bacteria detection and effective antibacterial treatment.

The relationship between serum oestrogen levels and clinical outcomes of hormone replacement therapy-frozen embryo transfer: a retrospective clinical study.

BACKGROUND: This study aimed to explore the relationship between serum oestrogen (E2) levels before endometrial transformation and pregnancy outcomes of hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles, which has been investigated for years without any consensus. METHODS: A retrospective cohort study of 10,209 cycles HRT-FET cycles was conducted at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from March 2017 to December 2020. A smooth fitting curve was constructed to identify the relationship between serum E2 levels before endometrial transformation and the clinical pregnancy rate. Then, threshold and saturation effect analysis was employed to explore the cut-off value of serum E2 levels. In addition, patients were divided into 2 groups based on their levels of serum E2 measured before progesterone-induced endometrial transformation: Group 1, < 300 pg/mL (n = 6251) and Group 2, ≥ 300 pg/mL (n = 3958). The clinical pregnancy and miscarriage rates of all groups were compared. Further smooth fitting curve analysis was employed by different subgroups segmented according to different endometrial thicknesses. RESULTS: When the serum E2 level was greater than 300 pg/mL, the clinical pregnancy rate decreased significantly (62.9% vs. 59.8%, p < 0.01), but the miscarriage rates were similar (13.5% vs. 15.6%, p = 0.14). While serum E2 level reached or exceeded 1400 pg/mL, there was no significant correlation between the clinical pregnancy rate and E2 level. The clinical pregnancy rate reached its higher level at lower E2 levels, regardless of the different endometrail thicknesses. CONCLUSIONS: Patients with a lower pretransformation serum E2 level (less than 300 pg/mL) have a higher clinical pregnancy rate and there was no correlation between the clinical pregnancy rate and a higher serum E2 level (greater than 1400 pg/mL) in HRT-FET cycles.

Defect Induced Charge Redistribution and Enhanced Adsorption of Lysozyme on Hydroxyapatite for Efficient Antibacterial Activity.

Defects in hydroxyapatite (HA) have attracted increasing research interest due to their significant functions to increase the bioactivity and antibacterial ability of hard-tissue implants. However, little is known about the natural property and functional mechanism of the defects in HA. Herein, we reported on the defect property concerned with the coordination state and charge distribution in Al doped HA, as well as the consequent interface and protein capture ability for improved antibacterial activity. Systemic investigations suggested that Al replacing Ca in HA induced coordination defect with decreased coordination number and bond distance, caused charge transfer and redistribution of surrounding O atom and resulted in an increase in negative charge of coordinated O atoms. These O atoms coordinated with Al further served as docking sites for lysozyme molecules via electrostatic and H-bonding interaction. The capacity of lysozyme adsorption for Al-HA increased approximately 10-fold more than that of HA, which significantly increased the antibacterial activity through lysozyme-catalyzed splitting of cell wall of bacteria. Moreover, in vitro studies indicated that Al-HA materials showed good cytocompatibility. These findings not only provided new insights into the important effect of defects on the performances of HA biomaterials by modulation of the coordination state, charge distribution, and chemical activity, but also proposed a promising method for efficient antibacterial activity of HA biomaterials.

Genome-Wide Identification and Characterization of the Trehalose-6-phosphate Synthetase (TPS) Gene Family in Watermelon (Citrullus lanatus) and Their Transcriptional Responses to Salt Stress.

With the increase in watermelon cultivation area, there is an urgent need to explore enzymatic and genetic resources for the sustainable development of watermelon, especially under salt stress. Among the various compounds known, trehalose plays an important role in regulating abiotic stress tolerances in diverse organisms, including plants. Therefore, the present study comprehensively analyzed the trehalose-6-phosphate synthase (TPS) gene family in watermelon. The study analyzed the functional classification, evolutionary characteristics, and expression patterns of the watermelon TPS genes family. Seven ClTPSs were identified and classified into two distinct classes according to gene structure and phylogeny. Evolutionary analysis suggested the role of purifying selection in the evolution of the TPS family members. Further, cis-acting elements related to plant hormones and abiotic stress were identified in the promoter region of the TPS genes. The tissue-specific expression analysis showed that ClTPS genes were widely expressed in roots, stems, leaves, flowers, and fruits, while ClTPS3 was significantly induced under salt stress. The overexpression of ClTPS3 in Arabidopsis thaliana significantly improved salt tolerance. Finally, the STRING functional protein association networks suggested that the transcription factor ClMYB and ClbHLH regulate ClTPS3. Thus, the study indicates the critical role of ClTPS3 in watermelon response to salt stress.

Downregulation of XIST ameliorates acute kidney injury by sponging miR-142-5p and targeting PDCD4.

Acute kidney injury (AKI) is a common kidney disease that markedly affects public health. To date, the roles of long noncoding RNA XIST in AKI are poorly understood. Here, we investigated the biological functions of XIST in AKI. We observed that XIST expression increased in patients with AKI and HK-2 cells stimulated by CoCl2 . In addition, a rat AKI model induced by ischemia-reperfusion was established. Tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 messenger RNA expression were induced in vivo; moreover, XIST expression was upregulated. Knockdown of XIST significantly repressed CoCl2 -triggered injury in HK-2 cells. However, microRNA (miR)-142-5p, a downstream target of XIST, was downregulated in AKI. miR-142-5p was repressed by XIST and miR-142-5p could inhibit CoCl2 -induced injury in HK-2 cells. Moreover, PDCD4 expression was significantly increased in AKI. PDCD4 was predicted to be the target of miR-142-5p. Subsequently, loss of PDCD4 was able to retard injury in HK-2 cells exposed to CoCl2. Thus, we suggest that XIST regulates miR-142-5p and PDCD4, and it has the potential to function as a biomarker in therapeutic strategies for AKI.

Association of vaspin rs2236242 gene variants with type 2 diabetes and obesity in a Chinese population: A prospective, single-center study.

AIM: Vaspin is an adipokine separated from visceral fat tissues of obese diabetic rats. This study was to investigate the association between vaspin rs2236242 gene polymorphism and type 2 diabetes mellitus (T2DM) or obesity in a Chinese population. MATERIALS AND METHODS: T2DM patients and nondiabetic controls were recruited from Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University (Shanghai, China) from May 1, 2015 to June 30, 2017. Clinicopathologic characteristics were recorded and their blood samples were collected. Serum vaspin levels were detected by enzyme-linked immunosorbent assay and vaspin rs2236242 genotypes by tetra-amplification refractory mutation system-polymerase chain reaction. RESULTS: Two hundred and ninety-nine patients with T2DM and 311 controls were recruited at last. The vaspin genotypes of diabetic patients were distinct from nondiabetic controls (χ 2 = 54.611, p < 0.0001). Genotyping revealed that T2DM patients have a greater prevalence of A allele compared with controls (61.9% vs. 42.1%, p < 0.0001). A allele was associated with an increased risk of T2DM (odds ratio = 2.23, 95% confidence interval = 1.773-2.804, p < 0.0001) compared with T allele. The genotype distribution did not differ among nondiabetic subjects with or without obesity. The serum vaspin levels were higher in T2DM patients and obese controls than the nonobese controls, however, the rs2236242 was not found to be significantly related to serum vaspin levels. CONCLUSIONS: Our findings showed the association between vaspin rs2236242 gene variants with obesity and T2DM in a Chinese population. People with rs2236242 A allele had a 2.23-fold increased risk of T2DM. These findings suggest that vaspin rs2236242 may serve as a potential diagnostic and/or therapeutic targets for T2DM.

LncRNA NEAT1 promotes extracellular matrix accumulation and epithelial-to-mesenchymal transition by targeting miR-27b-3p and ZEB1 in diabetic nephropathy.

Diabetic nephropathy (DN) is a kind of microvascular complications of diabetes. Long noncoding RNAs (lnRNAs) can participate in the development of various diseases, including DN. However, the function of lncRNA NEAT1 is unclear. In our present study, we reported that NEAT1 was significantly increased in streptozotocin-induced DN rat models and high-glucose-induced mice mesangial cells. We observed that knockdown of NEAT1 greatly inhibited renal injury of DN rats. Meanwhile, downregulation of NEAT1-modulated extracellular matrix (ECM) proteins (ASK1, fibronectin, and TGF-ß1) expression and epithelial-mesenchymal transition (EMT) proteins (E-cadherin and N-cadherin) in vitro. Previously, miR-27b-3p has been reported to be involved in diabetes. Here, miR-27b-3p was decreased in DN rats and high-glucose-induced mice mesangial cells. The direct correlation between NEAT1 and miR-27b-3p was validated using the dual-luciferase reporter assay and RNA immunoprecipitation experiments. In addition, zinc finger E-box binding homeobox 1 (ZEB1), which has been identified in the process of EMT clearly contributes to EMT progression. ZEB1 was predicted as a target of miR-27b-3p and overexpression of miR-27b-3p dramatically repressed ZEB1 expression. Therefore, our data implied the potential role of NEAT1 in the fibrogenesis and EMT in DN via targeting miR-27b-3p and ZEB1.

Long noncoding RNA Gm6135 functions as a competitive endogenous RNA to regulate toll-like receptor 4 expression by sponging miR-203-3p in diabetic nephropathy.

We aim to explore the relationship between Gm6135 and diabetic nephropathy. We detected the relative expression levels of Gm6135 and toll-like receptor 4 (TLR4) in diabetic nephropathy mice and high-glucose-cultured mouse mesangial cells SV40-MES-13 by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot detection. Cell proliferation and apoptosis were detected after small interfering RNA (siRNA) interference or plasmid overexpression of Gm6135/TLR4, and bioinformatics method was used to predict and screen miR-203 as an intermediate factor. Through dual-luciferase reporter gene, RNA pull-down, qRT-PCR, and western blot, the binding relationship between Gm6135, miR-203-3p, and TLR4 was confirmed. The possibility of the competing endogenous RNA mechanism was demonstrated by cell localization assays and rip assays. Finally, the proliferation of mouse mesangial cells SV40-MES-13 was detected after mimics and inhibitor of microRNA, which were reversed with TLR4 overexpression and siRNA. The results showed that the relative expression levels of Gm6135 and TLR4 in the kidney and high-glucose-cultured mouse mesangial cells of diabetic nephropathy mice increased significantly. Overexpression or downregulation of Gm6135/TLR4 significantly affected the proliferation and apoptosis of mouse mesangial cells. Gm6135 upregulates TLR4 by competitively binding to miR-203-3p.

[Repeated superovulation induction after failure in previous IVF-ET cycles with the ultra-long protocol: Analysis of outcomes of clinical pregnancy].

OBJECTIVE: To analyze the clinical outcomes of repeated superovulation induction in patients with adenomyosis or moderate to severe pelvic endometriosis after failure in previous IVF-ET cycles with the ultra-long protocol. METHODS: We retrospectively analyzed the clinical data about 37 patients with adenomyosis or moderate to severe pelvic endometriosis in our center from 2009 to 2013, who underwent repeated IVF-ET after failure in the previous cycles with the ultra-long protocol, namely by injection of 2－6 ampoules of 3.75 mg gonadotropin-releasing hormone agonist (GnRH-a). All the patients met the following requirements: hCG-negative at 14 days after transfer, within 3－7 days after menstruation, and properly down-regulated serum follicle stimulating hormone (FSH) (<10 mIU/ml), luteinizing hormone (LH) (<10 mIU/ml), estradiol (E2) (<30 pg/ml), follicle diameter (<10 mm) and endometrial thickness, and received GnRH (Gonal-F, Serono) for ovulation induction. We compared the clinical and laboratory data and pregnancy outcomes between the first and repeated cycles before and after ovulation induction. RESULTS: The repeated cycles, as compared with previous ones, showed significant increases in the antral follicle count (AFC) on the first day of stimulation (7.55 ± 1.86 vs 6.45 ± 2.5, P<0.05), number of follicles =≥14 mm in diameter on the hCG trigger day (7.81 ± 3.6 vs 5.56 ± 3.68, P<0.05), level of E2 (ï¼»2 362.15 ± 1 210.49ï¼½ vs ï¼»1 749.22 ± 1 139.44ï¼½ pg/ml, P<0.05), and numbers of oocytes retrieved (7.51 ± 3.23 vs 4.78 ± 3.41, P<0.05) and embryos transferred (2.00 ± 0.33 vs 1.50 ± 0.67, P<0.05), exhibited a remarkably reduction in the dose of GnRH (ï¼»1 791.65 ± 1 889.41ï¼½ vs ï¼»3 439.56 ± 1 836.53ï¼½ IU, P<0.05), and achieved a clinical pregnancy rate of 62.16%. CONCLUSIONS: With proper reduction of the FSH, LH and E2 levels and follicle diameter, repeated superovulation induction for IVF-ET can improve the ovarian response and pregnancy outcomes of the patients with adenomyosis or moderate to severe pelvic endometriosis after failure in the previous IVF-ET cycles with the ultra-long protocol.

The crystal structure and chemical state of aluminum-doped hydroxyapatite by experimental and first principles calculation studies.

Aluminum (Al) is a trace element found in hard tissues, and the induction of bone diseases by Al accumulation has generated interest in the role and mechanism of Al in bone metabolism. Because hydroxyapatite (HA) constitutes the main inorganic content of human hard tissues, the biological effect of Al in human hard tissues is closely related to the intrinsic state of Al-doped HA (Al-HA). However, few investigations to date have focused on the crystallography of Al-HA. Herein, we determined the crystallographic characteristics and energy states of Al-HA by conducting theoretical and experimental studies. Al-HA [Ca10-1.5xAlx(PO4)6(OH)2] with a defect structure was synthesized. XRD patterns and morphology images revealed that doping of Al decreased the crystallinity and the HA nanocrystal size. The optimized crystal structure indicated that Al was preferentially substituted for Ca(2) and Ca vacancies appeared at the Ca(2)1 site. Al doping locally distorted the regularity and integrity of the HA crystal structure, leading to the occurrence of Ca(2+) vacancies and the displacement and rotation of OH(-) and [PO4](3-) chains. The total energy of Al-HA increased and the stability decreased. Consequently, Al-HA might be readily degraded by osteoclasts and bone resorption could be accelerated. The destruction and over-resorption of bones caused by excessive Al could result in abnormal bone metabolism. The present findings not only provide the first crystallographic information on the disruptive effects of Al doping in HA but also complement the present understanding of the mechanisms underlying Al-induced bone diseases.

Human Fetal Testicular Tissue Xenotransplantation: A Platform to Study the Effect of Gonadotropins on Human Germ Cell Development In Utero.

PURPOSE: We examined the effects of long-term hCG stimulation on germ cell maturation, and Sertoli and Leydig cell function in a xenotransplantation model of the human fetal testis. MATERIALS AND METHODS: A total of 20 human fetal testes were ectopically xenografted on 20 castrated NCr male nude mice. Grafts were collected for analysis 24 weeks later. Mice were treated with saline as the control or with hCG beginning 4 weeks after the grafts were transplanted. RESULTS: Of the grafts 65% survived at 24 weeks. In contrast to untreated pregrafted samples, hCG stimulated xenografts showed significantly increased density of seminiferous tubule formation with Sertoli cell migration to the basement membrane. Germ cell proliferation and differentiation from gonocytes (M2A(+)) to prespermatogonia (MAGE-4A(+)) were observed in graft samples recovered from the hCG and nonhCG treated groups at 24 weeks of treatment. Leydig cells in hCG treated grafts produced significantly more testosterone than nonhCG treated grafts. Although further studies are required to investigate the potential for further differentiation and maturation of xenografted human fetal testes, normal in utero testicular development was reproduced under long-term hCG stimulation. CONCLUSIONS: This model represents a means to study long-term effects of gonadotoxins or hormonal stimulation on the maturation of human fetal testes.

Inhibition of thioredoxin reductase and upregulation of apoptosis genes for effective anti-tumor sono-chemotherapy using a meso-organosilica nanomedicine.

The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment. In this study, an ultrasound-activatable meso-organosilica nanomedicine was prepared by integrating chloroquine (CQ) into hollow mesoporous organosilica (CQ@MOS). The meso-organosilica nanomedicine can inhibit the activity of thioredoxin reductase, elevate cellular reactive oxygen species (ROS) levels, upregulate the pro-apoptotic factors in the c-Jun N-terminal kinase (JNK) apoptosis pathway and induce autophagy inhibition, further resulting in mitochondrial membrane potential (MMP) depolarization and cellular ATP content decrease, ultimately causing significant damage to tumor cells. Moreover, CQ@MOS can efficiently deliver chloroquine into cancer cells and promote an enhanced sonodynamic effect for effective anti-tumor chemotherapy and sonodynamic therapy. This study may enlighten us on a new anti-tumor strategy and suggest its promising applications in cancer treatments.

Integrated organosilica nanomedicine enables sonoimaging, sonochemistry and antitumor sonodynamic therapy.

Sonography with its non-invasive and deep tissue-penetrating characteristics, not only contributes to promising developments in clinical disease diagnosis but also obtains acknowledgments as a prospective therapeutic approach in the field of tumor treatment. However, it remains a challenge for sonography simultaneously to achieve efficient imaging and therapeutic functionality. Here, we present an innovative integrated diagnosis and treatment paradigm by developing the nanomedicine of percarbamide-bromide-mesoporous organosilica spheres (MOS) with RGD peptide modification (PBMR) by loading percarbamide and bromide in MOS which were prepared by a one-step O/W microemulsion method. The PBMR nanomedicine effectively modifies the tumor acoustic environment to improve sonoimaging efficacy and induces sonochemical reactions to enhance the production of reactive oxygen species (ROS) for tumor treatment efficiency under sonography. The combination of PBMR nanomedicine and SDT achieved multiple ROS generation through the controlled sonochemical reactions and significantly boosted the potency of sonodynamic therapy and induced significant tumor regression with non-invasive tissue penetrability and minimizing damage to healthy tissues. Simultaneously, the generation of oxygen gas in the sonochemical process augments ultrasound reflection, resulting in a 4.9-fold increase in imaging grayscale. Our research establishes an effective platform for the synergistic integration of sonoimaging and sonodynamic antitumor therapy, offering a novel approach for precise antitumor treatment in the potential clinical applications.

MiR-29b Alleviates High Glucose-induced Inflammation and Apoptosis in Podocytes by Down-regulating PRKAB2.

BACKGROUND: Podocyte injury and inflammatory response are the core contributors to the pathogenesis of diabetic nephropathy. This study aims to identify novel regulatory miRNAs and elucidate their underlying mechanisms, which will help us understand the pathogenesis of diabetic nephropathy more comprehensively. MATERIALS AND METHODS: Different glucose concentrations were used to treat podocytes to mimic the pathology of diabetic nephropathy in vitro. Flow cytometry was used to determine cell apoptosis. Inflammatory cytokines released by podocytes were measured by using an enzymelinked immunosorbent assay (ELISA). Western Blot was used to detect the expression of PRKAB2 protein in podocytes. RESULTS: Genecard and g: profiler results revealed that miR-29b might be involved in regulating HG-induced cell injury. QRT-PCR indicated that HG-induced downregulation of miR-29b in podocytes. MiR-29b knockdown promoted cell apoptosis and inflammatory response in podocytes. MiR-29b overexpression repressed cell apoptosis and inflammatory response induced by high glucose treatment in podocytes. Luciferase reporter assay and Western Blot showed that miR-29b targeted PRKAB2 to negatively regulate PRKAB2 expression directly. Knockdown of PRKAB2 reversed the increased cell apoptosis and inflammation induced by miR-29b inhibitors. CONCLUSION: MiR-29b plays a role in inhibiting inflammation and apoptosis in high glucose (HG) treated podocytes by negatively regulating PRKAB2 expression. This study provides new potential targets and ideas for the treatment of diabetic nephropathy.

Impact of Flammulina velutipes polysaccharide on properties and structural changes of pork myofibrillar protein during the gel process in the absence or presence of oxidation.

The present study aimed to investigate the impact of Flammulina velutipes polysaccharide (FVSP) on the rheological properties and structural alterations of myofibrillar protein (MP) and oxidized MP (OMP), utilizing techniques such as rhehometer, fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In the unoxidized system, the addition of 5.00% FVSP significantly improved (p < 0.05) the storage and loss moduli of the composite gel and promoted the α-helix to ß-sheet transformation. These effects enhanced the protein's gel strength and water-holding capacity (WHC). In the oxidation system, 5.00% FVSP had significant effects (p < 0.05) on repair and improvement of the oxidized MP. These effects inhibited the cross-linking aggregation and degradation of the protein. In addition, the addition of FVSP significantly improved the gel properties of MPs after oxidation (p < 0.05), hindered fracture of the protein gel network structure. In summary, polysaccharides have a substantial effect on the functional characteristics of MP, and FVSP could potentially be applied in meat products.

The Protection of Quinoa Protein on the Quality of Pork Patties during Freeze-Thaw Cycles: Physicochemical Properties, Sensory Quality and Protein Oxidative.

The present study investigated the impact of quinoa protein (QP) on the physicochemical properties, sensory quality, and oxidative stability of myofibrillar protein (MP) in pork patties during five freeze-thaw (F-T) cycles. It was observed that repeated F-T cycles resulted in a deterioration of pork patty quality; however, the incorporation of QP effectively mitigated these changes. Throughout the F-T cycles, the sensory quality of the QP-treated group consistently surpassed that of the control group. After five F-T cycles, the thiobarbituric acid reactive substance (TBARS) content in the control group was measured at 0.423 mg/kg, whereas it significantly decreased to 0.347 mg/kg in the QP-treated group (p < 0.05). Furthermore, QP inclusion led to a decrease in pH and an increase in water-holding capacity (WHC) within pork patties. Following five F-T cycles, Ca2+-ATPase activity exhibited a significant increase of 11.10% in the QP-treated group compared to controls (p < 0.05). Additionally, supplementation with QP resulted in elevated total sulfhydryl content and reduced carbonyl content, Schiff base content, and dityrosine content within myofibrillar proteins (MPs), indicating its inhibitory effect on MP oxidation. In particular, after five F-T cycles, total sulfhydryl content reached 58.66 nmol/mL for the QP-treated group significantly higher than that observed for controls at 43.65 nmol/mL (p < 0.05). While carbonyl content increased from 2.37 nmol/mL to 4.63 nmol/mL between the first and fifth F-T cycle for controls; it only rose from 2.15 nmol/mL to 3.47 nmol/mL in the QP-treated group. The endogenous fluorescence levels were significantly higher (p < 0.05) in the QP-treated group compared to controls. In conclusion, the addition of QP enhanced the quality of pork patties and effectively inhibited the oxidative denaturation of MP during F-T cycles.