Discovery of NO Donor-Aurovertin Hybrids as Dual Ferroptosis and Apoptosis Inducers for Treating Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure-activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.

Minimally invasive delivery of human umbilical cord-derived mesenchymal stem cells by an injectable hydrogel via Diels-Alder click reaction for the treatment of intrauterine adhesions.

Intrauterine adhesions (IUA) are the most common cause of uterine infertility, and conventional treatments have not consistently achieved satisfactory pregnancy rates. Stem cell therapy shows promising potential for the clinical treatment of IUA. Although various advanced biomaterials have been designed for delivering stem cells to the uterine cavity, there remain significant challenges, particularly in devising therapeutic strategies for clinical application that minimize surgical incisions and conform to the intricate structure of uterine cavity. Herein, an injectable hydrogel loaded with human umbilical cord-derived mesenchymal stem cells (UCMSCs) was synthesized via the Diels-Alder click reaction for endometrial regeneration and fertility restoration, exhibiting suitable mechanical properties, good biocompatibility, and desirable degradation properties. Notably, this hydrogel permitted minimally invasive administration and integrated seamlessly with surrounding tissue. Our study revealed that the UCMSCs-laden injectable hydrogel enhanced cell proliferation, migration, angiogenesis, and exhibited anti-fibrotic effects in vitro. The implantation of this hydrogel significantly facilitated endometrium regeneration and restored fertility in a rat endometrial damage model. Mechanistically, in vivo results indicated that the UCMSCs-laden injectable hydrogel effectively promoted macrophage recruitment and facilitated M2 phenotype polarization. Collectively, this hydrogel demonstrated efficacy in regenerating damaged endometrium, leading to the restoration of fertility. Consequently, it holds promise as a potential therapeutic strategy for endometrial damage and fertility decline arising from intrauterine adhesions. STATEMENT OF SIGNIFICANCE: Severe endometrial traumas frequently lead to intrauterine adhesions and subsequent infertility. Stem cell therapy shows promising potential for the clinical treatment of IUA; however, challenges remain, including low delivery efficiency and compromised stem cell activity during the delivery process. In this study, we fabricated an injectable hydrogel loaded with UCMSCs via the Diels-Alder click reaction, which exhibited unique bioorthogonality. The in situ-gelling hydrogels could be introduced through a minimally invasive procedure and adapt to the intricate anatomy of the uterus. The UCMSCs-laden injectable hydrogel promoted endometrial regeneration and fertility restoration in a rat endometrial damage model, efficaciously augmenting macrophage recruitment and promoting their polarization to the M2 phenotype. The administration of UCMSCs-laden injectable hydrogel presents a promising therapeutic strategy for patients with severe intrauterine adhesion.

Inhibition of EZH2 alleviates SAHA-induced senescence-associated secretion phenotype in small cell lung cancer cells.

Chemotherapy has been widely used in small cell lung cancer (SCLC) treatment in the past decades. However, SCLC is easy to recur after chemotherapy. The senescence of cancer cells during chemotherapy is one of the effective therapeutic strategies to inhibit the progression of cancer. Nevertheless, the senescence-associated secretion phenotype (SASP) promotes chronic inflammation of the cancer microenvironment and further accelerates the progression of tumors. Therefore, inducing the senescence of cancer cells and inhibiting the production of SASP factors during anticancer treatment have become effective therapeutic strategies to improve the anticancer effect of drugs. Here we reported that SCLC cells treated with an FDA-approved HDAC inhibitor SAHA underwent senescence and displayed remarkable SASP. In particular, SAHA promoted the formation of cytoplasmic chromatin fragments (CCFs) in SCLC cells. The increased CCFs in SAHA-treated SCLC cells were related to nuclear porin Tpr, which activated the cGAS-STING pathway, and promoted the secretion of SASP in cancer cells. Inhibition of EZH2 suppressed the increase of CCFs in SAHA-treated SCLC cells, weakened the production of SASP, and increased the antiproliferative effect of SAHA. Overall, our work affords new insight into the secretion of SASP in SCLC and establishes a foundation for constructing a new therapeutic strategy for SCLC patients.

Mitochondrial-Targeted Delivery of Polyphenol-Mediated Antioxidases Complexes against Pyroptosis and Inflammatory Diseases.

Excess accumulation of mitochondrial reactive oxygen species (mtROS) is a key target for inhibiting pyroptosis-induced inflammation and tissue damage. However, targeted delivery of drugs to mitochondria and efficient clearance of mtROS remain challenging. In current study, it is discovered that polyphenols such as tannic acid (TA) can mediate the targeting of polyphenol/antioxidases complexes to mitochondria. This affinity does not depend on mitochondrial membrane potential but stems from the strong binding of TA to mitochondrial outer membrane proteins. Taking advantage of the feasibility of self-assembly between TA and proteins, superoxide dismutase, catalase, and TA are assembled into complexes (referred to as TSC) for efficient enzymatic activity maintenance. In vitro fluorescence confocal imaging shows that TSC not only promoted the uptake of biological enzymes in hepatocytes but also highly overlapped with mitochondria after lysosomal escape. The results from an in vitro model of hepatocyte oxidative stress demonstrate that TSC efficiently scavenges excess mtROS and reverses mitochondrial depolarization, thereby inhibiting inflammasome-mediated pyroptosis. More interestingly, TSC maintain superior efficacy compared with the clinical gold standard drug N-acetylcysteine in both acetaminophen- and D-galactosamine/lipopolysaccharide-induced pyroptosis-related hepatitis mouse models. In conclusion, this study opens a new paradigm for targeting mitochondrial oxidative stress to inhibit pyroptosis and treat inflammatory diseases.

The Diagnosis of Early Gastric Cancer Based on Medical Imaging Technology and Mathematical Modeling.

The key to reducing the mortality of gastric cancer is early detection, early diagnosis, and early treatment of gastric cancer. Early diagnosis of gastric cancer is the key to early detection and diagnosis of gastric cancer. Early diagnosis and treatment of gastric cancer is of great significance for improving the curative effect and reducing mortality of gastric cancer. The purpose of this paper is to study the diagnosis of early gastric cancer based on medical imaging techniques and mathematical modeling. The effect of W-DeepLab network-assisted diagnosis of images under white light was analyzed, and the value of Narrow Band Imaging and Blue Laser Imaging in the diagnosis of early gastric cancer was compared. Because Blue Laser Imaging endoscopy can clearly observe the demarcation line and microvascular morphology; but when using Narrow Band Imaging observation, part of the demarcation line and microvascular morphology is not observed. The results show that Blue Laser Imaging is brighter than Narrow Band Imaging's endoscopic images, and it is easier to observe the microstructure of lesions under endoscopy, so as to accurately determine the nature of lesions.

Inflammatory environment-adaptive patterned surface for spatiotemporal immunomodulation of macrophages.

Designing biomaterials with precise immunomodulation can help to decipher the dynamic interactions between macrophages and biomaterials to match the tissue healing process. Although some advanced stimuli-responsive immunomodulatory biomaterials were reported for cell dynamic modulation, while most triggers need external stimuli by manual intervention, there would be the inevitable errors and uncertainties. Thus, developing immunomodulatory biomaterials with adaptive abilities, which can recognize the inflammation signals, change their properties spatiotemporally under the microenvironment triggers, and provide feedback to realize macrophages modulation in different healing stages, has become a promising strategy. In this work, we developed an inflammation-adaptive Arg-Gly-Asp (RGD) -patterned surface for spatiotemporal immunomodulation of macrophage. We fabricated a methacrylated hyaluronic acid (MA-HA) hydrogel with thiol-functionalized RGD-patterned surface by employing photolithography technology. Then, thiol-functionalized RGD contained ROS-cleavable linker was filled the remaining sites and consequently, a dynamic surface with temporary homogeneous RGD was obtained. Under the overproduction of ROS by the inflammation-activated macrophages, the linker was cleaved, and the homogeneous RGD surface was transformed to the RGD patterned surface, which triggered elongation of macrophages and consequently the upregulated expressions of arginase-1, IL-10 and TNF-ß1, indicating the polarization toward to anti-inflammatory phenotype. Developing inflammatory environment-adaptive surface for spatiotemporal modulation of macrophages polarization provides a precise and smart strategy for the healing-matched immunomodulation to facilitate healing outcomes. STATEMENT OF SIGNIFICANCE: Designing biomaterials with precise immunomodulation can help to decipher the dynamic interactions between macrophages and biomaterials to match tissue repair process. Some immunomodulatory biomaterials were reported for cell dynamic modulation, while most triggers need external manual intervention. Thus, we developed an immunomodulatory biomaterial with inflammation-adaptive patterned surface, which can recognize abnormal signals and change its properties spatiotemporally under the microenvironment triggers, and provide feedback to realize macrophages modulation in different stages. The dynamic surface can adapt to the changes of microenvironment and dynamically to match the cell behavior and tissue healing process on demand without external manual intervention. Additionally, the surface achieves the balance of macrophages with pro- and anti-inflammatory phenotypes in the tissue repair process.

New Jatrophane-Type Diterpenoids from Euphorbia kansui as Potential MDR Reversal Agents.

A serial jatrophane-type diterpenoids, comprised with three undescribed compounds kanesulones C-E (1-3) and four known ones (4-7), were obtained from the roots of Euphorbia kansui. The structures of compounds 1-3 were elucidated by detailed interpretation of their spectroscopic data, especially 2D-NMR and HR-ESI-MS, the absolute configuration of 1 was revealed by single crystal X-ray diffraction. These isolates were assayed for their multidrug resistance reversing activities on human breast adenocarcinoma cell line MCF-7/ADR. Compound 1 possessed potential as low toxic MDR modulator that could promote the efficacy of anticancer drug adriamycin ca. 85-fold at 5 µM, as 12 times stronger than the positive drug verapamil.

An Acellular Scaffold Facilitates Endometrial Regeneration and Fertility Restoration via Recruiting Endogenous Mesenchymal Stem Cells.

Severe intrauterine adhesions (IUAs), characterized by inadequate endometrial repair and fibrosis, can lead to infertility. Stem cell-based therapies, which deliver mesenchymal stem cells (MSCs) to the wound site, hold a considerable promise for endometrium regeneration. However, some notable hurdles, such as stemness loss, immunogenicity, low retention and survival rate, limit their clinical application. Evidence shows a strategy of mobilizing endogenous MSCs recruitment can overcome the traditional limitations of exogenous stem cell-based therapies. Here, an acellular biomaterial named stromal derived factor-1 alpha (SDF-1α)/E7-modified collagen scaffold (CES) is explored. CES based on harnessing the innate regenerative potential of the body enables near-complete endometrium regeneration and fertility restoration both in a rat endometrium acute damage model and a rat IUA model. Mechanistically, the CES implantation promotes endogenous MSCs recruitment via a macrophage-coordinated strategy; then the homing MSCs exert the function of immunomodulation and altered local microenvironments toward regeneration. To conclude, CES, which can harness endogenous MSCs and overcome the traditional limitations of cell-based therapies, can serve as a clinically feasible and cell-free strategy with high therapeutic efficiency for IUA treatment.

Clinical Outcomes of BCMA CAR-T Cells in a Multiple Myeloma Patient With Central Nervous System Invasion.

Background: Multiple myeloma (MM) is the second most common hematological malignancy that still lacks effective clinical treatments. In particular, MM with central nervous system (CNS) invasion occurs rarely. Although B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor-T (CAR-T) cell therapy has shown great promise for the treatment of relapsed/refractory MM, few studies have reported whether BCMA CAR-T could inhibit MM with CNS invasion. Case Presentation: In this study, we report a special case of a 63-year-old male patient who suffered MM with CNS invasion and presented rapid extramedullary disease (EMD) progression into multiple organs. Before CAR-T cell infusion, this patient received five cycles of bortezomib, Adriamycin, and dexamethasone (PAD) and an autologous transplant as the front-line treatment, followed by two cycles of bortezomib, lenalidomide, and dexamethasone (VRD) as the second-line regimen, and daratumumab, bortezomib, dexamethasone (DVD) as the third-line regimen. Since the patient still showed rapid progressive disease (PD), BCMA CAR-T cells were infused, and 1 month later, a stringent complete response (sCR) was achieved, and the response lasted for 4 months. Meanwhile, only grade 1 cytokine release syndrome (CRS) was observed. Conclusion: This case report demonstrated that BCMA CAR-T could effectively eradicate CNS-involved MM with low adverse events, suggesting that CAR-T cell therapy could be a feasible therapeutic option for this kind of refractory disease. Clinical Trial Registration: https://ClinicalTrials.gov, identifier: NCT04537442.a.

Clinicopathological study of the polypoidal lesions of polypoidal choroidal vasculopathy.

PURPOSE: To investigate the pathogenic features of the polypoidal lesions from the specimens of polypoidal choroidal vasculopathy extracted from human subjects. METHODS: Seven specimens of polypoidal lesions extracted from five eyes of six patients (mean age, 60.16 ± 10.41 years) of polypoidal choroidal vasculopathy were examined. The polypoidal lesions were obtained by surgical excision. Thereafter, a histopathological analysis of the specimens was performed. RESULTS: The polypoidal lesions were oval nodules located underneath the retinal pigment epithelium. A pathological study of the lesions revealed that Bruch's membrane schisis was observed in all specimens and they were all located in the Bruch's membrane. The Bruch's membrane schisis and serosanguineous materials constituted the main structure of the lesions in five of the seven specimens, with small vessels being observed in two specimens. One specimen was composed of two polypoidal lesions of different characteristics, and one specimen had a neovessel membrane complex with several polypoidal lesions. Inflammatory cells and blood vessels were observed in the polypoidal lesion of the specimen with neovessel membrane complex. CONCLUSION: Polypoidal lesions of polypoidal choroidal vasculopathy are abnormalities of the Bruch's membrane. The lesions are characterized by the Bruch's membrane schisis, which is filled with serosanguineous materials. The lesions are progressive and may contain inflammatory cells and blood vessels.

Lignans and sesquiterpenes from Schisandra tomentella A. C. Smith.

This is the first phytochemical investigation of Schisandra tomentella A. C. Smith. 11 lignans and 8 sesquiterpenoids, were isolated from the stems of S. tomentella, including two undescribed lignans, tomentaschinins A-B (1-2), and two new sesquiterpenoids, tomentaschinnes A-B (3-4). Their structures were elucidated based on the interpretation of their spectroscopic data. Cytotoxicity and MDR reversal effect of these compounds were screened on multidrug resistance cancer cell line MCF-7/ADR, and results showed gomisin M2 (7) could promote the efficacy of adriamycin against MCF-7/ADR.

Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor.

Genome editing through adeno-associated viral (AAV) vectors is a promising gene therapy strategy for various diseases, especially genetic disorders. However, homologous recombination (HR) efficiency is extremely low in adult animal models. We assumed that increasing AAV transduction efficiency could increase genome editing activity, especially HR efficiency, for in vivo gene therapy. Firstly, a mouse phenylketonuria (PKU) model carrying a pathogenic R408W mutation in phenylalanine hydroxylase (Pah) was generated. Through co-delivery of the general AAV receptor (AAVR), we found that AAVR could dramatically increase AAV transduction efficiency in vitro and in vivo. Furthermore, co-delivery of SaCas9/sgRNA/donor templates with AAVR via AAV8 vectors increased indel rate over 2-fold and HR rate over 15-fold for the correction of the single mutation in PahR408W mice. Moreover, AAVR co-injection successfully increased the site-specific insertion rate of a 1.4 kb Pah cDNA by 11-fold, bringing the HR rate up to 7.3% without detectable global off-target effects. Insertion of Pah cDNA significantly decreased the Phe level and ameliorated PKU symptoms. This study demonstrates a novel strategy to dramatically increase AAV transduction which substantially enhanced in vivo genome editing efficiency in adult animal models, showing clinical potential for both conventional and genome editing-based gene therapy.

Zwitterionic hydrogel-coated heart valves with improved endothelialization and anti-calcification properties.

Valve replacement surgery is the golden standard for end-stage valvular disease due to the lack of self-repair ability. Currently, bioprosthetic heart valves (BHVs) crosslinked by glutaraldehyde (GA) have been the most popular choice in clinic, especially after the emerge of transcatheter aortic valve replacement (TAVR). Nevertheless, the lifespan of BHVs is limited due to severe calcification and deterioration. In this study, to improve the anti-calcification property of BHVs, decellularized heart valves were modified by methacrylic anhydride to introduce double bonds (MADHVs), and a hybrid hydrogel made of sulfobetaine methacrylate (SBMA) and methacrylated hyaluronic acid (MAHA) was then coated onto the surface of MADHVs. Followed by grafting of Arg-Glu-Asp-Val (REDV), an endothelial cell-affinity peptide, the BHVs with improved affinity to endothelial cell (SMHVs-REDV) was obtained. SMHVs-REDV exhibited excellent collagen stability, reliable mechanical property and superior hemocompatibility. Moreover, enhanced biocompatibility and endothelialization potential compared with GA-crosslinked BHVs were achieved. After subcutaneous implantation for 30 days, SMHVs-REDV showed significantly reduced immune response and calcification compared with GA-crosslinked BHVs. Overall, simultaneous endothelialization and anti-calcification can be realized by this strategy, which was supposed to be benefit for improving the main drawbacks for available commercial BHVs products.

A novel detergent-based decellularization combined with carbodiimide crosslinking for improving anti-calcification of bioprosthetic heart valve.

Currently, valve replacement surgery is the only therapy for the end-stage valvular diseases because of the inability of regeneration for diseased heart valves. Bioprosthetic heart valves (BHVs), which are mainly derived from glutaraldehyde (GA) crosslinked porcine aortic heart valves or bovine pericardium, have been widely used in the last decades. However, it is inevitable that calcification and deterioration may occur within 10-15 years, which are still the main challenges for the BHVs in clinic. In this study, N-Lauroylsarcosine sodium salt (SLS) combined with N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) were utilized to decellularize and crosslink the heart valves instead of GA treatment. The obtained BHVs exhibited excellent extracellular matrix stability and mechanical properties, which were similar with GA treatment. Moreover, the obtained BHVs exhibited betterin vitrobiocompatibilities than GA treatment. After subcutaneous implantation for 30 d, the obtained BHVs showed mitigated immune response and reduced calcification compare with GA treatment. Therefore, all the above results indicated that the treatment of SLS-based decellularization combined with EDC/NHS crosslink should be a promising method to fabricate BHVs which can be used in clinic in future.

Short-term changes in and preoperative factors affecting vaulting after posterior chamber phakic Implantable Collamer Lens implantation.

BACKGROUND: To describe the very early vault changes in the first month after Implantable Collamer Lens (ICL) implantation and to evaluate the effect of preoperative biometric factors on vault. METHODS: Eighty-three eyes from eighty-three subjects with complete data who met follow-up requirements were recruited in this retrospective study between May 2019 and March 2020. We quantitatively assessed the postoperative vault at 2 h, 1 day, 1 week, and 1 month following implantation. Associations between the postoperative vault and age, ICL size, spherical equivalent (SE), axial length (AL), central corneal thickness (CCT), flat keratometry (K), steep K, mean K, anterior chamber depth (ACD), crystalline lens thickness (LT), white-to-white (WTW) diameter obtained by three devices, horizontal and vertical sulcus-to-sulcus (STS) diameter, bright and dark pupil sizes (BPS and DPS) and DPS-BPS were investigated using Spearman's correlation analysis and stepwise multiple regression analysis. RESULTS: The mean vault values at 2 h, 1 day, 1 week, and 1 month after ICL implantation were 672.05 ± 30.72, 389.15 ± 28.33, 517.23 ± 30.76 and 530.12 ± 30.22 µm, respectively. Significant differences were found in the vault values at 2 h, 1 day and 1 week after the operation. The ICL size (ß = 0.942; p < 0.001), followed by horizontal STS (ß = -0.517; p < 0.001), crystalline LT (ß = -0.376; p < 0.001) and vertical STS (ß = -0.257; p = 0.017), significantly influenced the vault at 1 month after the operation. The multiple regression equation was expressed as follows: central vault (µm) = -1369.05 + 657.121 × ICL size- 287.408 × horizontal STS - 432.497 × crystalline LT - 137.33 × vertical STS (adjusted R2 = 0.643). CONCLUSIONS: After ICL implantation, the vault decreased and then increased, but it did not return to the vault value 2 h after surgery. The ICL size, horizontal and vertical STS and crystalline LT are key factors for predicting postoperative vaulting.

A "sandwich" cell culture platform with NIR-responsive dynamic stiffness to modulate macrophage phenotypes.

Considering the key roles of macrophages in tissue repair and immune therapy, designing smart biomaterials able to harness macrophage phenotypes on demand during the healing process has become a promising strategy. Here, a novel "sandwich" cell culture platform with near-infrared (NIR) responsive dynamic stiffness was fabricated to polarize bone marrow-derived macrophages (BMDMs) in situ for revealing the relationship between the macrophage phenotype and substrate stiffness dynamically. Under NIR irradiation, calcium ions (Ca2+) diffused through the middle layer of the IR780-mixed phase change material (PCM) due to the photothermal effect of IR780, resulting in an increase of hydrogel stiffness in situ by the crosslinking of the upper layer of the hyaluronic acid-sodium alginate hydrogel (MA-HA&SA). The up-regulation of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) was quantified by immunostaining and enzyme-linked immune sorbent assay (ELISA), respectively, indicating the transformation of macrophages from the anti-inflammatory to pro-inflammatory phenotype under dynamic stiffness. The nuclear Yes-associated-protein (YAP) ratio positively correlated with the shift of the macrophage phenotype. The modulation of macrophage phenotypes by stiffness-rise without the stimuli of cytokines offers an effective and noninvasive strategy to manipulate immune reactions to achieve optimized healing or therapeutic outcomes.

E7-Modified Substrates to Promote Adhesion and Maintain Stemness of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have drawn great attention in clinical applications due to the self-renewal ability, multi-differentiation potential, and low immunogenicity. However, there are challenges in the ex vivo expansion of MSCs, including low efficiency, stemness loss, and safety. Therefore, it is crucial to construct a substrate that can show an alterable affinity to MSCs, and induce efficient cell expansion with minimal stemness loss. In this study, EPLQLKM (E7)-modified substrates with tunable E7 densities are fabricated on PEGylated substrates. The PEG layer with an average thickness of 1.7 nm shows good antifouling ability. E7-modified substrates have an improving effect on adhesion and spreading of the rat bone marrow-derived mesenchymal stem cells (rBMSCs), along with the increase of E7 densities. rBMSCs on E7-modified substrates maintain the stem cell phenotypes, and shows robust proliferation and multilineage differentiation, especially on the substrates with high E7 densities. In summary, this study provides a novel strategy of E7 functionalization to promote adhesion and maintain stemness of MSCs, which holds great potentials in the functionalization of microcarriers for the expansion of MSCs.

Analysis of macular microvasculature and thickness after ICL implantation in patients with myopia using optical coherence tomography.

AIM: To investigate changes in macular vessels and thickness in myopic eyes after intraocular collamer lens (ICL) implantation using quantitative optical coherence tomography angiography (OCTA). METHODS: This retrospective included 73 myopic eyes of 73 patients (average age, 27.53±6.16y) who underwent ICL implantation (28 eyes were Toric ICL). Axial length (AL), uncorrected visual acuity (UCVA), refractive dioptre (RD), intraocular pressure (IOP) and OCTA were measured and compared with before and 1wk, 1, and 3mo after surgery. OCTA was used to image vessel density (VD) and skeleton density (SD) in both the superficial (SCP) and deep capillary plexus (DCP). Central retinal thickness (CRT) and ganglion cell-inner plexiform layer thickness (GCT) were also measured. Changes between pre- and postoperative measurements were analysed by repeated measures analysis of variance. RESULTS: Compared with preoperative data, postoperative data on UCVA revealed significant improvements in all patients (P<0.05). However, there was no significant difference in IOP. After the operation, CRT and GCT exhibited significant changes (P<0.05). Among these measures, CRT was significantly higher at one and three months postoperative (all P<0.01). GCT was significantly higher at 1wk, 1, and 3mo postoperative (all P<0.01). Changes in VD and SD were nonsignificant in both the SCP and DCP. There was no difference in postoperative changes between the ICL and Toric ICL groups. CONCLUSION: ICL and Toric ICL implantation both have good efficacy and safety for myopic eyes, but macular area changes that occur after surgery need attention.

Bioprosthetic heart valves with reduced immunogenic residuals using vacuum-assisted decellularization treatment.

Despite the good hemodynamic characteristics of bioprosthetic heart valves, it is inevitable that they will suffer from calcification and tissue deterioration. Decellularization has been utilized to reduce the immunogenicity and calcification of bioprosthetic heart valves. However, it can take several days or even weeks to obtain the decellularized tissues or organs. Therefore, time-frame should be taken into consideration during the decellularization process. A detergent-enzymatic-method, combined with vacuum, has been proposed as a method of obtaining desirable decellularized heart valves. In this study, heart valves treated under vacuum and normal atmosphere are investigated via histological, biochemical and mechanical analysis. The results show that the decellularization efficiency of heart valves treated under vacuum is enhanced, based on histological staining, DNA contents and α-Gal quantification. The decellularization procedures decrease the contents of the extracellular matrix. However, the mechanical properties, including elastic modulus, fracture tensile strength and fracture strain, show no significant difference between the samples. In vitro cell cytotoxicity experiments indicate the feasibility of further in vivo experiments. Therefore, we conclude that vacuum-assisted decellularization procedures can significantly enhance decellularization efficiency by reducing the decellularization time, without compromising the properties of the heart valves, which is also beneficial in terms of reducing clinical costs. To the best of our knowledge, vacuum is a novel parameter which can be designed into decellularization procedures for heart valves.

Preventive Effect of Small Molecular Fraction of Irpex lacteus (Agaricomycetes) Fruiting Body against Chronic Nephritis in Mice and Identification of Active Compounds.

Previous study found that the fruit body of Irpex lacteus has an effect on the prevention and treatment of chronic nephritis. In this study, we systematically investigated the preventive effect of small molecular fraction (SMF) of the fungal fruit body against chronic nephritis. In addition, we analyzed, isolated, and identified the chemical constituents of SMF, and screened the activity of three small peptides isolated in vitro. The results showed SMF significantly reduced amounts of urine protein (UP), the content of urea (BUN), creatinine (Cr), tumor necrosis factor-α (TNF-α), and maleic dialdehyde (MDA) in serum, and significantly increased superoxide dismutase (SOD) level in renal tissue homogenate (P < 0.05). Moreover, the results of hematoxylin and eosin (H&E) and Masson staining of renal tissues indicated that SMF has protective effects on renal tissues and prevents renal interstitial from fibrosis. The peptide sequences isolated from SMF were identified as WSMGPAPDSVH (SP1), QCTGNASCSPPC (SP2), and HYCCTAKYA (SP3), which were active compounds for the prevention of nephritis, and these new peptides were isolated for the first time. The cell proliferation assay showed that 10 µg/L transforming growth factor-ß1 (TGF-ß1) significantly induced the proliferation of human renal tubular epithelial cells (HK-2), compared with the control group, and the difference was statistically significant (P < 0.01). However, when combined with three small peptides, respectively, the cell proliferation was significantly inhibited (P < 0.05). These results suggest that isolated peptides can maintain the morphological stability of HK-2 cells, inhibit cell proliferation induced by TGF-ß1 to some extent, and prevent cell fibrosis.