Three-Dimensional Printed Poly (Lactic-co-Glycolic Acid)-Magnesium Composite Scaffolds for the Promotion of Osteogenesis Through Immunoregulation.

Scaffolds play an important role in bone tissue engineering. The ideal engineered scaffold needs to be biocompatible, bioactive, and able to regulate immune cells to enhance bone regeneration. In this study, magnesium (Mg)-contained poly(lactic-co-glycolic acid) (PLGA) scaffolds (hereinafter, referred to as PLGA-2Mg) were fabricated by 3-dimensional printing using a mixture of PLGA and MgSO 4 powder. Poly(lactic-co-glycolic acid) scaffolds (hereinafter, referred to as PLGA) were also fabricated by 3-dimensional printing and were used as control. The biocompatibility, immunoregulatory ability, and osteogenic properties of PLGA-2Mg were analyzed and compared with those of PLGA. The results indicate that the incorporation of Mg increased the Young modulus and surface roughness of the scaffold, but did not affect its degradation. The PLGA-2Mg further promoted the adhesion and proliferation of MC3T3-E1 cells compared with PLGA, which indicates its improved biocompatibility and bioactivity. In addition, PLGA-2Mg inhibited the polarization of RAW 264.7 cells toward the M1 phenotype by down-regulating the IL-1ß , IL-6 , and iNOs gene expression when challenged with lipopolysaccharide stimulation. In contrast, it promoted the polarization of RAW 264.7 cells toward the M2 phenotype by up-regulating the TGF-ß , IL-10 , and Arg-1 gene expression without lipopolysaccharide stimulation. Finally, MC3T3-E1 cells were cocultured with RAW 264.7 cells and scaffolds using a transwell system. It was found that the expression level of osteogenic-related genes ( ALP , COL-1 , BMP2 , and BSP ) was significantly upregulated in the PLGA-2Mg group compared with that in the PLGA group. Consequently, PLGA-2Mg with increased biocompatibility and bioactivity can promote osteogenesis through immunoregulation and has the potential to be used as a novel scaffold in bone tissue engineering.

Tumor Cell Targeting and Responsive Nanoplatform for Multimodal-Imaging Guided Chemodynamic/Photodynamic/Photothermal Therapy toward Triple Negative Breast Cancer.

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with ineffective treatment and poor prognosis. It is in great demand to develop a novel theranostic strategy for accurate diagnosis and targeted treatment of TNBC. In the present study, one nanoplatform (HA-ICG-Fe-PDA), endowed with multimodal imaging-guided chemodynamic/photodynamic/photothermal (CDT/PDT/PTT) synergistic therapy capacity toward TNBC, was innovatively constructed. The nanoplatform was prepared by covalently conjugating ICG-decorated hyaluronic acid (HA) on Fe3+-chelated polydopamine (PDA). HA facilitated the targeting and accumulating of the nanoplatform in tumor tissue and cells of TNBC, thus producing enhanced magnetic resonance signal. Upon entering into TNBC cells, the intracellular hyaluronidase-catalyzed cleavage of HA-ICG-Fe-PDA activated the prequenched near-infrared (NIR) fluorescence signal, allowing for the activatable NIR fluorescence imaging. On the other hand, Fe3+ in the nanoplatform could be reduced to reactive Fe2+ in tumor microenvironment, guaranteeing efficient Fenton reaction-mediated CDT. The combination of ICG with Fe-PDA enhanced the NIR absorption of the nanoplatform so that considerable PTT/PDT and photothermal imaging were achieved under 808 nm laser irradiation. In vitro and in vivo experiments have verified that the proposed nanoplatform integrates the potential of TNBC-targeting, precise NIR fluorescence/magnetic resonance/photothermal trimodal imaging, efficient treatment via synergistic CDT/PDT/PTT, as well as excellent biocompatibility. Therefore, this multifunctional nanoplatform provides a simple and versatile strategy for imaging-guided theranostics of TNBC.

Mesoporous Silica-Encapsulated Gold Nanorods for Drug Delivery/Release and Two-Photon Excitation Fluorescence Imaging to Guide Synergistic Phototherapy and Chemotherapy.

Photothermal therapy is a promising light-based medical treatment that relies on light absorption agents converting light irradiation into localized heat to destroy cancer cells or other diseased tissues. It is critical to enhance the therapeutic effects of cancer cell ablation for their practical applications. This study reports a high-performance combinational therapy for ablating cancer cells, including both photothermal therapy and chemotherapy to improve therapeutic efficiency. The prepared AuNR@mSiO2 loading molecular Doxorubicin (Dox) assemblies were highlighted by merits of facile acquisition, great stability, easy endocytosis, and rapid drug release in addition to improved anticancer capability upon irradiation with a femtosecond pulsed near-infrared (NIR) laser, where AuNR@mSiO2 nanoparticles afforded a high photothermal conversion efficiency of 31.7%. Two-photon excitation fluorescence imaging was introduced into confocal laser scanning microscope multichannel imaging to track the drug location and cell position in real time for monitoring the process of drug delivery in killing human cervical cancer HeLa cells and then to realize imaging-guiding cancer treatment. These nanoparticles exhibit widespread potential in photoresponsive utilizations including photothermal therapy, chemotherapy, one- and two-photon excited fluorescence imaging, and 3D fluorescence imaging and cancer treatment.

[Palliative Care for End-Stage Renal Disease:A Case Report and Literature Review].

Since end-stage renal disease leads to a variety of problems such as disability,reduced quality of life,and mental and psychological disorders,it has become a serious public health problem around the globe.Renal palliative care integrates palliative care philosophy in the care for patients with end-stage renal disease.As a planned,comprehensive,patient-centered care,renal palliative care focuses on the patient's symptoms and needs,aiming to reduce the suffering throughout the course of the disease,including but not limited to end-of-life care.This study reports the palliative care practice for a patient on maintenance dialysis in the Blood Purification Center of Peking Union Medical College Hospital and reviews the present situation of palliative care in end-stage renal disease.

Bioinformatics analysis identifies potential biomarkers involved in the metastasis of locoregionally advanced nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the malignant epithelial tumors with a high metastasis rate. This study aimed to screen potential novel biomarkers involved in NPC metastasis. Microarray data of locoregionally advanced NPC (LA-NPC; GSE103611) were obtained from the database of Gene Expression Omnibus. The differentially expressed genes (DEGs) between LA-NPC tissues with and without distant metastasis after radical treatment were screened. Functional analysis was performed and the protein-protein interaction and submodule were analyzed. The univariate Cox regression analysis was performed to identify prognostic genes in NPC in the validation microarray dataset GSE102349. The drug-gene interactions and key genes were identified. Totally, 107 DEGs were identified. The upregulated DEGs and the key nodes in the protein-protein interaction network were associated with pathways or biological processes related to the cell cycle. Four genes including CD44, B2M, PTPN11, and TRIM74 were associated with disease-free survival in NPC. The drug-gene interaction analysis revealed that upregulated genes CXCL10, CD44, B2M, XRCC5, and RPL11 might be potential druggable genes for patients with LA-NPC metastasis by regulating cell cycle, autophagy, and drug resistance. Upregulated CXCL10, CD44, B2M, XRCC5, and RPL11 might play important roles in LA-NPC metastasis by regulating cell cycle-related pathways.

Comparison of Hydrus and iStent microinvasive glaucoma surgery implants in combination with phacoemulsification for treatment of open-angle glaucoma: systematic review and network meta-analysis.

OBJECTIVES: To compare the efficacy and safety of two Schlemm's canal-based microinvasive glaucoma surgery (MIGS) devices, the Hydrus Microstent and the iStent Trabecular Bypass combined with phacoemulsification for treatment of open-angle glaucoma. DESIGN: Systematic review and network meta-analysis. METHODS: Literature searches were conducted on PubMed, Web of Science, Cochrane Library and ClinicalTrials.gov to identify randomised controlled trials (RCTs) assessing the Hydrus or the iStent implantation combined with phacoemulsification for treatment of open-angle glaucoma until September 2020. Risk of bias was assessed using a six-item modified Jadad scale. Effects were estimated using the intraocular pressure (IOP) reduction (IOPR), the percentage of IOPR and the proportion of medication-free patients at follow-up end. Safety was estimated using the proportions of adverse events. The network meta-analysis was conducted within a Bayesian framework using the Markov Chain Monte Carlo method in ADDIS software. RESULTS: Six prospective RCTs comprising 1397 patients were identified. Regarding the absolute value and the percentage of IOPR, the Hydrus and 2-iStent implantation combined with phacoemulsification were significantly more effective than phacoemulsification alone. Rank probability analysis revealed the Hydrus might be the best choice to lower IOP. There was no significant difference in the proportion of medication-free patients among groups. The Hydrus and 2-iStent implantation had a higher probability to achieve the medication-free status versus the 1-iStent implantation and phacoemulsification alone. Overall safety profiles were good for each device with the focal peripheral anterior synechiae more frequently reported in Hydrus eyes. CONCLUSIONS: The Hydrus implantation may have a slight advantage over the 1-iStent or 2-iStent implantation in combination with phacoemulsification to treat open-angle glaucoma. Our findings might be of some uncertainty due to the limited included data. Further studies are needed to investigate whether our findings are robust, including high-quality RCTs to directly compare these MIGS devices.

Interstitial nephritis without glomerulonephritis in ANCA-associated vasculitis: a case series and literature review.

The typical nephrological presentation of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is rapidly progressive glomerulonephritis. AAV-associated interstitial nephritis without apparent glomerular lesions was rare. We reported three local cases of AAV-associated interstitial nephritis without glomerulonephritis confirmed by renal biopsy. Then, a literature search was conducted in PubMed using free text words and MeSH terms related to "AAV and interstitial nephritis". Fifteen cases were included, and their demographics, clinical manifestations, laboratory data, renal pathological features, and treatment response were summarized. AAV-associated interstitial nephritis usually affects elderly patients. The common symptoms include fever, arthralgias, and edema. These patients were mostly MPO-ANCA positive. Pathological lesions in the kidney showed diffuse infiltration of inflammatory cells, edema, tubulitis, and fibrosis in the interstitial area. Various immunosuppressive treatments, including glucocorticoids, immunosuppressants, and rituximab, were used, and most of the patients achieved clinical remission. AAV-associated interstitial nephritis is rare but shows a characteristic clinical phenotype, serological results, and pathogenic lesions. Immunosuppressive therapy showed good efficacy in these patients.

Anti-neutrophil cytoplasmic antibody associated vasculitis in patients with rheumatoid arthritis.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may coexist with rheumatoid arthritis (RA). However, it is unclear whether the manifestations of AAV with and without coexisting RA are similar. This observational study aimed to investigate the clinicopathological manifestations of AAV with coexisting RA and to explore potential predictors for identifying AAV superimposed on RA. METHODS: Patients with both AAV and RA were identified by searching our hospital database and the literature. Data including age, sex, clinical manifestation, laboratory tests, renal pathology, and therapeutic regimens were retrieved. To assess the difference in clinical features and renal pathology between AAV patients with and without RA, we conducted 1:4 matched case-control studies. RESULTS: A total of 47 patients were identified, 15 from our hospital and 32 from the literature, and 33 (70.2%) were women. AAV was diagnosed later than RA in 83.0% of the patients and manifested as microscopic polyangiitis (MPA) in 78.7% of the patients. The kidney was the most frequently involved extra-articular organ (74.5%), followed by the lung (51.1%), and skin (8.5%). Patients with both AAV and RA were more likely to be asymptomatic (26.7% vs 3.3%, p = 0.013) than those with isolated AAV. However, they did not differ in other clinicopathological features. In RA patients, those with ANCA associated glomerulonephritis, were more likely to have decreased renal function at renal biopsy as opposed to those with primary glomerulonephritis. CONCLUSIONS: AAV can coexist with RA. In this coexistence, AAV usually develops after RA, is more likely to be asymptomatic, and manifests predominately as MPA with renal involvement. Thus, we should remain vigilant to superimposed AAV on RA.

Invention of a non-invasive intracranial pressure (ICP) monitoring system - an enlightenment from a hydrocephalus study.

BACKGROUND: Mechanical obstruction is the most common cause of shunt failure for hydrocephalic patients. However, the diagnosis is extremely challenging and often requires invasive testing methods. Thus, a simple and non-invasive technique is in urgent need to predict the intracranial pressure (ICP) of hydrocephalic patients during their post-surgical follow-up, which could help neurosurgeons to determine the conditions of the shunt system. MATERIALS AND METHODS: Two groups of patients were enrolled in the current study. In group I, patients were enrolled as they were diagnosed with high ICP hydrocephalus and received shunt surgery. The shunt valve pressures were taken for their post-surgical ICP. Meanwhile, the participants of group II exhibited abnormally increased lumbar puncture opening pressure (LPOP; from 180 to 400 mmH2O). Both the ICP and LPOP were used to match with their corresponding tympanic membrane temperature (TMT). RESULTS: When patients' ICP were in the normal range (group I, from 50 to 180 mmH2O), the TMT correlated with ICP in a linear regression model (R2 = 0.59, p < 0.001). Interestingly, when patients exhibited above-normal ICP (LPOP was from 180 to 400 mmH2O), their TMT fit well with the ICP in a third-order polynomial regression (R2 = 0.88). When the ICP was 287.98 mmH2O, the TMT approached the vertex, which was 38.54 °C. Based on this TMT-ICP algorithm, we invented a non-invasive ICP monitor system. Interestingly, a tight linear correlation was detected between the ICP data drawn from the non-invasive device and Codman ICP monitoring system (R2 = 0.93, p < 0.01). CONCLUSIONS: We believe the TMT-ICP algorithm (the Y-Jiang model) could be used for preliminary prediction of shunt malfunction as well as monitoring ICP changes.

Endocarditis-associated rapidly progressive glomerulonephritis mimicking vasculitis: a diagnostic and treatment challenge.

BACKGROUND: Infective endocarditis (IE)-associated rapidly progressive glomerulonephritis (RPGN) is rarely reported. Sporadic case reports have noted the diagnostic and therapeutic challenge in IE-associated glomerulonephritis because it may masquerade as idiopathic vasculitis. METHODS: Patients with clinical diagnosis of IE-related RPGN in a tertiary hospital in China between January 2004 and May 2021 were identified and retrospectively reviewed. RESULTS: Twenty-four patients with IE-associated RPGN were identified. All patients presented with fever and multiorgan system involvement on top of heart and kidneys, spleen (79%, 19/24), skin (63%, 15/24), lung (33%, 8/24) and nervous system (17%, 4/24). Six of the 24 patients (25%) were initially suspected to have ANCA-associated or IgA vasculitis. Forty-five percent of patients are seropositive for ANCA. Renal histology showed mesangial and/or endocapillary hypercellularity with extensive crescents in most patients. C3-dominant deposition was the predominant pattern on immunofluorescence and pauci-immune necrotising crescentic glomerulonephritis was observed in one case. All patients received antibiotics with or without surgery. Six patients received immunosuppressive therapy before antibiotics due to misdiagnosis and seven patients received immunosuppressive therapy after antibiotics due to persistence of renal failure. Three of the 24 patients died due to severe infection. All the surviving patients had partial or complete recovery of renal function. CONCLUSION: IE-associated RPGN is rare and the differential diagnosis from idiopathic vasculitis can be challenging due to overlaps in clinical manifestations, ANCA positivity and absence of typical presentations of IE. The prognosis is generally good if antibiotics and surgery are not delayed. The decision on introducing immunoruppressive treatment should be made carefully on a case by case basis when kidney function does not improve appropriately after proper anti-infective therapy.Key messagesInfective endocarditis associated RPGN is rare and differentiating it from idiopathic vasculitis can be challenging due to overlap in clinical manifestations, ANCA positivity and occasional absence of typical manifestations of infective endocarditis.Kidney function usually responds to antibiotic therapy alone.Immunosuppressive therapy may be beneficial in carefully selected patients whose kidney function does not improve with antibiotics alone.

Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats.

BACKGROUND: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons leading to brain dysfunction. Recurrent seizures can lead to cognitive and behavioral deficits, and irreversible brain damage. While the PI3K/Akt/mTOR pathway regulates various physiological processes of neurons and glia, it may also lead to abnormal neuronal signal transduction under pathological conditions, including that of epilepsy. Everolimus (Eve), an mTOR inhibitor, may modulate neuronal excitability and therefore exert protection against epilepsy. Therefore, this study aimed to investigate the neuroprotective effect of Everolimus on seizure-induced brain injury and its regulation of the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway. Kainic acid (KA) 15 mg/kg was used to induce seizures and Everolimus (1, 2, 5 mg/kg) was administered as a pretreatment. Hippocampal tissue was extracted 24 h post-seizure. RESULTS: The protein and mRNA expression levels of PI3K、p-AKt、p-mTOR、NF-kB and IL-6 as well as neuronal apoptosis and microglia activation, significantly increased after KA-induced seizures, however, these effects were inhibited by Everolimus treatment. Furthermore, pretreatment with Everolimus decreased seizure scores and increased seizure latency. CONCLUSIONS: Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce neuronal apoptosis and microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on seizure-induced brain damage.

Ex-PRESS shunt implantation for intractable glaucoma with posterior chamber phakic intraocular lens: a case report.

BACKGROUND: Implantation of the posterior chamber phakic intraocular lens has been widely performed to correct high and extreme myopia. Chronic intraocular pressure (IOP) elevation may occur in its late postoperative period. For medically uncontrolled cases, surgical treatment is necessary, and benefits should be weighed against risks when determining whether to remove the lens. CASE PRESENTATION: A 32-year-old man with extremely high myopia presented with progressive blurred vision and medically uncontrolled IOP in the right eye. His past ocular history was significant for bilateral implantable collamer lens (ICL) implantation ten years ago. On ophthalmic examination, the ICL was well placed with a vault height of 456 µm in the right eye. The anterior chamber angles were open but narrow, and mild to moderate trabecular pigmentation was noted. Ex-PRESS glaucoma filtration surgery without ICL removal was performed to control IOP. During surgery, an Ex-PRESS P50 shunt was inserted into the anterior chamber via the front edge of the blue-grey transition zone between the sclera and cornea. Transient hypotony and shallow anterior chamber occurred in the first week after surgery, along with an ICL tilt towards the cornea with reduced vault height. No other complications related to either the ICL or the Ex-PRESS shunt were noted. IOP remained stable at 12 ~ 14 mmHg at the first 3-month follow-up. CONCLUSIONS: Ex-PRESS glaucoma filtration surgery might be a safe and effective alternative treatment for intractable glaucoma with high myopia and ICL implantation. Careful assessment of the ICL position and anterior chamber angle is necessary to plan the appropriate surgical procedure. A postoperative shallow anterior chamber may result in ICL dislocation.

Catalyst-Free Four-Component Polymerization of Propiolic Acids, Benzylamines, Organoboronic Acids, and Formaldehyde toward Functional Poly(propargylamine)s.

Multicomponent polymerizations (MCPs) are a group of fascinating polymer synthesis approaches that are developed rapidly in the recent decade. As a popular alkyne-based MCP, the A3 -polycouplings of alkynes, aldehydes, and amines are developed for the synthesis of poly(propargylamine)s under the catalysis of metal catalysts. In this work, through the design of carboxylic acid group-activated alkyne monomers, a catalyst-free, four-component polymerization of propiolic acids, benzylamines, organoboronic acids, and formaldehyde is reported under mild condition at 45 °C in dichloroethane. This four-component polymerization is applicable to different monomer structures, which can afford seven poly(propargylamine)s with up to 94% yields and molecular weights of up to 13 900 g mol-1 . Moreover, the poly(propargylamine)s demonstrate good solubility and processibility, high thermal stability and light refractivity, unique photophysical property, and so on. The simple monomers, mild condition, low cost, high efficiency, and procedure simplicity of this catalyst-free four-component polymerization demonstrates an elegant example of functional polymer synthesis.

Renal immune-related adverse events of immune checkpoint inhibitor.

The status of immune checkpoint inhibitors (ICPIs) is raising in the treatment of malignancy for their effectiveness. The ICPIs therapy takes the risk of off-target toxicity because of immune system overactivation, including renal toxicity. It was declared that the renal toxicity was rare. However, with the increasing experience of ICPIs therapy, the renal immune-relate adverse events of ICPIs were reported more and their management was launching an enthusiastic discussion nowadays. In this review, we focused on the mechanism of ICPIs related renal irAEs (immune-related adverse events), the clinical and pathological manifestation of different forms of renal injury, and management strategies when the renal irAEs happened. Good management of irAEs might need help from Multi-Disciplinary Treatment and could promote a better clinical practice on ICPIs.

Optic disk hemorrhage and vitreous hemorrhage after phacoemulsification in a normal tension glaucoma patient: A case report.

RATIONALE: Optic disk hemorrhage has been closely correlated with glaucoma for its development and progression. Phacoemulsification surgery results in large intraocular pressure (IOP) fluctuation. We report a case of optic disk hemorrhage and consequently progressive vitreous hemorrhage after an unsuccessful phacoemulsification surgery in an advanced normal tension glaucoma (NTG) patient. PATIENT CONCERNS: An advanced NTG patient of 82 years old with chronic hypertension underwent an unsuccessful phacoemulsification surgery complicated by posterior capsule rupture. During the postoperative 2 weeks, recurrent episodes of fresh hyphema occurred and B ultrasonography scan revealed the progressive vitreous hemorrhage. The IOP went out of control under the maximum tolerable IOP-lowering medications. DIAGNOSIS: Vitreous hemorrhage after phacoemulsification in an advanced NTG patient. INTERVENTIONS: Vitrectomy was performed to search for the cause of the progressive vitreous hemorrhage. After removal of the thick vitreous hemorrhage, a fresh spot of optic disk hemorrhage was detected at the nasal margin of the significantly-cupping disk. OUTCOMES: Postoperatively, the hemorrhagic vitreous opacity gradually resolved and the IOP remained stable at 10 ∼13 mmHg with topical prostaglandin analogue drops. Fundus examination revealed the dilated disk vessel with localized angiomatous change at the nasal disk margin. LESSONS: Severe optic disk hemorrhage may occur after phacoemulsification in advanced glaucoma patients. Systemic vascular factors, such as chronic hypertension and old age, and surgical complications, such as posterior capsule rupture and postoperative IOP elevation, would further increase the risk. For phacoemulsification in advanced glaucoma cases, extra care should be taken to control intraoperative IOP fluctuations and monitor postoperative IOP.

The suppressive effects of miR-508-5p on the odontogenic differentiation of human dental pulp stem cells by targeting glycoprotein non-metastatic melanomal protein B.

BACKGROUND: Although the involvement of glycoprotein non-metastatic melanomal protein B (GPNMB) in regulating the odontogenic differentiation of human dental pulp stem cells (hDPCs) has been identified, the underlying mechanisms are largely unknown. The purpose of this study is to investigate the effects of miR-508-5p on the GPNMB expression and the odontogenic differentiation of hDPCs. METHODS: In this study, hDPCs were isolated and identified by flow cytometric analysis. Based on bioinformatics analysis, dual luciferase reporter assay was performed to verify GPNMB acting as a target of miR-508-5p. The regulatory roles of miR-508-5p in odontogenetic differentiation of hDPCs were investigated through its inhibition or overexpression (miRNA mimics and miRNA inhibitors). qRT-PCR and Western blot analysis were used to detect the expression of odontogenetic marker genes and proteins. The assays of alkaline phosphatase (ALP) activity and Alizarin Red S staining were performed to evaluate the odontogenetic phenotype. RESULTS: We first found that the levels of miR-508-5p expression decreased gradually during odontogenesis of hDPCs, while the expressions of GPNMB were upregulated obviously. The suppressive effects of miR-508-5p on GPNMB were determined by oligonucleotide transfection in hDPCs and dual luciferase reporter assay in 293T cells. Subsequently, the significant inhibition of hDPC odontogenesis after the overexpression of miR-508-5p was observed, which is consistent with the decreased expression levels of several odontoblast-specific genes, such as dentin matrix protein 1 (DMP-1), dentin sialophosphoprotein (DSPP), and osteocalcin (OCN), as well as the decreased activity of ALP and weakened Alizarin Red S staining. Furthermore, ectopic expression of GPNMB (lacking 3'-UTR) rescued the effects of miR-508-5p on odontogenic differentiation. CONCLUSIONS: Our study demonstrated that miR-508-5p regulated the osteogenesis of hDPCs by targeting GPNMB and provided novel insight into the critical roles of microRNAs in hDPC differentiation.

Red-emissive azabenzanthrone derivatives for photodynamic therapy irradiated with ultralow light power density and two-photon imaging.

Photodynamic therapy has proved to be an effective strategy for cancer therapy, and advanced photosensitizers for image-guided photodynamic therapy require biocompatibility, intense absorption, high ROS generation efficiency, phototoxicity, low irradiation power density and efficient emission. In this work, four red emissive azabenzanthrone derivatives have been designed and synthesized, which generally exhibit efficient aggregated state emission. Through structural optimization, 3-diphenylamino-11-azabenzanthrone was found to show satisfactory photo-induced ROS generation and high emission efficiency in the aggregated state. Under the irradiation of a white LED lamp with an ultralow power density of 1.67 mW cm-2, this compound demonstrates significant photo-induced cytotoxicity toward HeLa cells. Moreover, deep tissue penetration can be realized by two-photon imaging of mouse brain vessels with these azabenzanthrone derivatives at vertical depths of up to 280 µm, attributed to the large emission wavelength and efficient emission.

Occult lens subluxation related to laser peripheral iridotomy: A case report and literature review.

RATIONALE: Laser peripheral iridotomy (LPI) is commonly performed as a primary treatment for acute primary angle closure glaucoma after administration of anti-glaucoma medications or for prevention of this condition. Minor complications may occur following LPI and most of them do not have deleterious consequences. We report a rare case of lens subluxation that has a possible relationship with LPI treatment. PATIENT CONCERNS: A 54-year-old female patient was initially referred for surgical treatment of medication-uncontrollable angle closure glaucoma in her left eye. The patient had undergone Neodymium:YAG LPI at an outside hospital 2 months prior to the presentation due to an episode of elevated intraocular pressure (IOP). About 5 days after the LPI, she had spontaneous blurred vision, redness, and pain in the left eye. Her IOP was found to re-rise and was not controlled well even with maximum tolerated anti-glaucoma medications during the following 2 months. On slit-lamp examination, the significant shallowing of both peripheral and central anterior chamber was noted in the left eye. Ultrasound biomicroscopy examination revealed the lens tilting towards the iris and the inferior zonular dehiscence corresponding to the iridotomy site. DIAGNOSES: Lens subluxation secondary to LPI treatment in the left eye. INTERVENTIONS: Phacoemulsification combined with in-the-bag intraocular lens implantation was performed in the left eye. The zonular weakness corresponding to the iridotomy site was further confirmed during surgery. OUTCOMES: The patient's IOP remained stable in the first postoperative 3 months without additional anti-glaucoma medications. LESSONS: Laser peripheral iridotomy may cause structural zonular damage, and ophthalmologists should be aware of this potential complication and proceed with caution.

Metal-Free Multicomponent Tandem Polymerizations of Alkynes, Amines, and Formaldehyde toward Structure- and Sequence-Controlled Luminescent Polyheterocycles.

Sequence-controlled polymers, including biopolymers such as DNA, RNA, and proteins, have attracted much attention recently because of their sequence-dependent functionalities. The development of an efficient synthetic approach for non-natural sequence-controlled polymers is hence of great importance. Multicomponent polymerizations (MCPs) as a powerful and popular synthetic approach for functional polymers with great structural diversity have been demonstrated to be a promising tool for the synthesis of sequence-controlled polymers. In this work, we developed a facile metal-free one-pot multicomponent tandem polymerization (MCTP) of activated internal alkynes, aromatic diamines, and formaldehyde to successfully synthesize structural-regulated and sequence-controlled polyheterocycles with high molecular weights (up to 69 800 g/mol) in high yields (up to 99%). Through such MCTP, polymers with the in situ generated multisubstituted tetrahydropyrimidines or dihydropyrrolones in the backbone and inherent luminescence can be easily obtained with high atom economy and environmental benefit, which is inaccessible by other synthetic approaches.

MiR-34a Inhibits Breast Cancer Proliferation and Progression by Targeting Wnt1 in Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: As microRNA-34a (miR-34a) has been suggested to be associated with breast cancer (BC), this study was proposed to explore the underlying mechanism of miR-34a in suppressing BC progression. METHODS: A total of 123 pairs of tumor tissues and matched nontumor tissues were obtained from patients. Reverse transcription polymerase chain reaction and in situ hybridization were used to detect the differences in miR-34a expression in tissues and cells. Whether Wnt1 is a direct downstream target of miR-34a was confirmed by both bioinformatics target gene prediction and dual-luciferase report assay. Wnt1 and other gene expressions that are related to Wnt/ß-catenin signaling pathway were assessed by reverse transcription polymerase chain reaction and western blot when MCF-7A cells were transfected with miR-34a mimic or miR-34a inhibitor. The proliferation, invasion and migration status of MCF-7 cells after transfection were assessed by MTT assay, wound healing assay and transwell assays, respectively. Breast tumor xenograft models on mice were also constructed to determine the effect of miR-34a on breast tumor growth in vivo. RESULTS: MiR-34a expression was remarkably down-regulated in BC tissues and cell lines compared with normal tissues and cell lines. Wnt1 was a direct downstream target of miR-34a and low expression of miR-34a contributed to the Wnt/ß-catenin signaling pathway activation in MCF-7A cells. MiR-34a inhibited the proliferation, invasion and migration of BC in vitro and breast tumor growth in vivo through deactivating the Wnt/ß-catenin signaling pathway. CONCLUSION: MiR-34a may suppress the proliferation and progression of BC via mediating the Wnt/ß-catenin signaling pathway.