Off-the-Shelf Synthetic Biodegradable Grafts Transform In Situ into a Living Arteriovenous Fistula in a Large Animal Model.

Current vascular access options require frequent interventions. In situ tissue engineering (TE) may overcome these limitations by combining the initial success of synthetic grafts with long-term advantages of autologous vessels by using biodegradable grafts that transform into autologous vascular tissue at the site of implantation. Scaffolds (6 mm-Ø) made of supramolecular polycarbonate-bisurea (PC-BU), with a polycaprolactone (PCL) anti-kinking-coil, are implanted between the carotid artery and jugular vein in goats. A subset is bio-functionalized using bisurea-modified-Stromal cell-derived factor-1α (SDF1α) derived peptides and ePTFE grafts as controls. Grafts are explanted after 1 and 3 months, and evaluated for material degradation, tissue formation, compliance, and patency. At 3 months, the scaffold is resorbed and replaced by vascular neo-tissue, including elastin, contractile markers, and endothelial lining. No dilations, ruptures, or aneurysms are observed and grafts are successfully cannulated at termination. SDF-1α-peptide-biofunctionalization does not influence outcomes. Patency is lower in TE grafts (50%) compared to controls (100% patency), predominantly caused by intimal hyperplasia. Rapid remodeling of a synthetic, biodegradable vascular scaffold into a living, compliant arteriovenous fistula is demonstrated in a large animal model. Despite lower patency compared to ePTFE, transformation into autologous and compliant living tissue with self-healing capacity may have long-term advantages.

Lithium chloride promotes diabetic corneal epithelial wound healing by activating the Wnt/ß­catenin signaling pathway.

Corneal epithelial abnormality is a common manifestation of diabetic keratopathy and leads to delayed epithelial wound healing. The Wnt/ß-catenin signaling pathway participates in the development, differentiation and stratification of corneal epithelial cells. The present study compared the expression of Wnt/ß-catenin signaling pathway related factors, including Wnt7a, ß-catenin, cyclin D1 and phosphorylated (p-) glycogen synthase kinase 3 ß (Gsk3b) between normal and diabetic mouse corneas, by reverse transcription-quantitative PCR, western blotting and immunofluorescence staining. It was found that the expression of the Wnt/ß-catenin signaling pathway related factors was downregulated in diabetic corneas. Upon corneal epithelium scraping, the wound healing rate was significantly increased in diabetic mice after topical treatment with lithium chloride. After further investigation, significantly upregulated levels of Wnt7a, ß-catenin, cyclin D1 and p-Gsk3b were found in the diabetic group 24 h after treatment, accompanied by ß-catenin nuclear translocation observed by immunofluorescence staining. These results suggest that active Wnt/ß-catenin pathway can promote diabetic corneal epithelial wound healing.

GPR84 potently inhibits osteoclastogenesis and alleviates osteolysis in bone metastasis of colorectal cancer.

The expression of GPR84 in bone marrow-derived monocytes/macrophages (BMMs) can inhibit osteoclast formation; however, its role in bone metastasis of colorectal cancer (CRC) is still unknown. To investigate the effects of GPR84 on bone metastasis of CRC, the murine CRC cell line MC-38 was injected into tibial bone marrow. We found that the expression of GPR84 in BMMs was gradually downregulated during bone metastasis of CRC, and the activation of GPR84 significantly prevented osteoclastogenesis in the tumor microenvironment. Mechanistically, the MAPK pathway mediated the effects of GPR84 on osteoclast formation. Moreover, we found that IL-11 at least partly inhibited the expression of GPR84 in the tumor microenvironment through the inactivation of STAT1. Additionally, activation of GPR84 could prevent osteolysis during bone metastasis of CRC. Our results suggest that CRC cells downregulate the expression of GPR84 in BMMs to promote osteoclastogenesis in an IL-11-dependent manner. Thus, GPR84 could be a potential therapeutic target to attenuate bone destruction induced by CRC metastasis.

RNF219 Promotes Nasopharyngeal Carcinoma Progression by Activating the NF-κB Pathway.

In Southeast Asia, the prevalence of nasopharyngeal carcinoma (NPC) is high; however, the molecular mechanism governing the progression of NPC is unclear. The results of the present study revealed upregulation of ring finger protein 219 (RNF219) expression in NPC tissues and cells. Overexpression of RNF219 enhanced NPC cell invasion, migration, and proliferation; whereas knockdown of RNF219 had the opposite effects. Mechanistically, RNF219 activated the nuclear factor kappa B (NF-κB) pathway, mainly reflected by increased p65 nuclear translocation, and increased NF-κB pathway target gene expression. NF-κB pathway inhibition in cells overexpressing RNF219 resulted in reduced invasion, migration, and proliferation, confirming that progression of NPC was promoted by RNF219-mediated NF-κB pathway activation. In addition, the expression of RNF219 correlated positively with the activity of the NF-κB pathway, verifying that RNF219 regulates the activity of the NF-κB pathway in the clinical setting. Our results identified a novel therapeutic target that could promote the development of novel treatments for NPC.

Safety and efficacy of unilateral and bilateral pedicle screw fixation for lumbar degenerative diseases by transforaminal lumbar interbody fusion: An updated systematic review and meta-analysis.

Background: The purpose of this study was to compare the safety and efficacy of unilateral vs. bilateral pedicle screw fixation (BPSF) for lumbar degenerative diseases. Methods: Electronic databases including PubMed, Web of science, the Cochrane Library, Scopus, MEDLINE, EMBASE, EBSCO were searched by computer. The deadline was set for June 1, 2022. This study included all high-quality randomized controlled trials (RCTs), prospective clinical controlled studies (PRO), and retrospective studies (Retro) that compared unilateral and bilateral pedicle screw fixation in the treatment of lumbar degenerative diseases. Revman5.3 software was used for meta-analysis after two researchers independently screened the literature, extracted data, and assessed the risk of bias in the study. Results: Fourteen studies with a total of 1,086 patients were included. Compared with BPSF, unilateral pedicle screw fixation (UPSF) has shorter operation time and hospital time, and less blood loss and operation cost, operation time [SMD = -1.75, 95% CI (-2.46 to -1.03), P < 0.00001], hospital time [SMD = -1.10, 95% CI (-1.97 to -0.22), P = 0.01], Blood loss [SMD = -1.62, 95% CI (-2.42 to -0.82), P < 0.0001], operation cost [SMD = -14.03, 95% CI (-20.08 to -7.98), P < 0.00001], the ODI after bilateral pedicle screw fixation was lower, and the degree of lumbar dysfunction was lighter, [SMD = 0.19, 95% CI (0.05-0.33), P = 0.007], better fusion effect, fusion rate [RR=0.95, 95% CI (0.91-1.00), P = 0.04]. VAS-Low back pain [SMD = 0.07, 95% CI (-0.07-0.20), P = 0.35], VAS-Leg pain [SMD = 0.18, 95% CI (-0.00-0.36), P = 0.05], SF-36 [SMD = 0.00, 95% CI (-0.30-0.30), P = 1.00], complications rate [RR = 0.94, 95% CI (0.9154-1.63), P = 0.82], the overall difference was not statistically significant. Conclusions: Currently limited evidence suggests that UPSF significantly reduces blood loss, significantly shortens the operative time and hospital stay, and reduces blood loss and costs. After BPSF, the ODI was lower, the degree of lumbar spine dysfunction was lower, and the fusion rate was significantly higher. The VAS, SF-36, and complications scores of the two groups were comparable, and there was no significant clinical difference.

Engineering the Dynamics of Cell Adhesion Cues in Supramolecular Hydrogels for Facile Control over Cell Encapsulation and Behavior.

The extracellular matrix (ECM) forms through hierarchical assembly of small and larger polymeric molecules into a transient, hydrogel-like fibrous network that provides mechanical support and biochemical cues to cells. Synthetic, fibrous supramolecular networks formed via non-covalent assembly of various molecules are therefore potential candidates as synthetic mimics of the natural ECM, provided that functionalization with biochemical cues is effective. Here, combinations of slow and fast exchanging molecules that self-assemble into supramolecular fibers are employed to form transient hydrogel networks with tunable dynamic behavior. Obtained results prove that modulating the ratio between these molecules dictates the extent of dynamic behavior of the hydrogels at both the molecular and the network level, which is proposed to enable effective incorporation of cell-adhesive functionalities in these materials. Excitingly, the dynamic nature of the supramolecular components in this system can be conveniently employed to formulate multicomponent supramolecular hydrogels for easy culturing and encapsulation of single cells, spheroids, and organoids. Importantly, these findings highlight the significance of molecular design and exchange dynamics for the application of supramolecular hydrogels as synthetic ECM mimics.

Adjuvant Radiotherapy After Minimally Invasive Surgery in Patients With Stage IA1-IIA1 Cervical Cancer.

To estimate whether adjuvant radiotherapy is necessary for patients with stage IA1-IIA1 cervical cancer after laparoscopic hysterectomy, 221 patients were retrospectively analyzed. Sixty-two of them were treated with laparoscopic hysterectomy and adjuvant radiotherapy (group A), 115 underwent open surgery (group B) and 44 received laparoscopic hysterectomy alone (group C). Results showed that the 3-year local recurrence-free survival (LRFS) rates of group A, B and C were 98.4%, 97.4% and 86.4%, respectively. The LRFS rates of group A and B surpassed C (A vs. B, p=0.634; A vs. C, p=0.011; B vs. C, p=0.006). The inter-group differences of 3-year overall survival (OS) and distant metastasis free survival (DMFS) were not statistically significant. In subgroup analysis of stage IB disease, the 3-year LRFS rates of group A, B and C were 100%, 98.8% and 83.1%, the 3-year OS rates of group A, B and C were 100%, 98.9% and 91.5%, respectively. The 3-year LRFS and OS rates of group A and B were significantly superior to group C (p<0.05). Our findings suggest that adjuvant radiotherapy can reduce the risk of recurrence for women with early-stage cervical cancer after laparoscopic hysterectomy and bring survival benefits for patients with stage IB disease.

Half-Brain Delineation for Prediction of Radiation-Induced Temporal Lobe Injury in Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

PURPOSE: To investigate the role of half-brain delineation in the prediction of radiation-induced temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 220 NPC cases treated with IMRT and concurrent platinum-based chemotherapy were retrospectively analyzed. Dosimetric parameters of temporal lobes, half-brains, and brains included maximum dose (Dmax), doses covering certain volume (DV) from 0.03 to 20 cc and absolute volumes receiving specific dose (VD) from 40 to 80 Gy. Inter-structure variability was assessed by coefficients of variation (CV) and paired samples t-tests. Receiver operating characteristic curve (ROC) and Youden index were used for screening dosimetric parameters to predict TLI. Dose/volume response curve was calculated using the logistic dose/volume response model. RESULTS: CVs of brains, left/right half-brains, and left/right temporal lobes were 9.72%, 9.96%, 9.77%, 27.85%, and 28.34%, respectively. Each DV in temporal lobe was significantly smaller than that in half-brain (P < 0.001), and the reduction ranged from 3.10% to 45.98%. The area under the curve (AUC) of DV and VD showed an "increase-maximum-decline" behavior with a peak as the volume or dose increased. The maximal AUCs of DVs in brain, half-brain and temporal lobe were 0.808 (D2cc), 0.828 (D1.2cc) and 0.806 (D0.6cc), respectively, and the maximal AUCs of VDs were 0.818 (D75Gy), 0.834 (V72Gy) and 0.814 (V70Gy), respectively. The cutoffs of V70Gy (0.86 cc), V71Gy (0.72 cc), V72Gy (0.60 cc), and V73Gy (0.45 cc) in half-brain had better Youden index. TD5/5 and TD50/5 of D1.2cc were 58.7 and 80.0 Gy, respectively. The probability of TLI was higher than >13% when V72Gy>0 cc, and equal to 50% when V72Gy = 7.66 cc. CONCLUSION: Half-brain delineation is a convenient and stable method which could reduce contouring variation and could be used in NPC patients. D1.2cc and V72Gy of half-brain are feasible for TLI prediction model. The dose below 70 Gy may be relatively safe for half-brain. The cutoff points of V70-73Gy could be considered when the high dose is inevitable.

Potential Defects and Improvements of Equivalent Uniform Dose Prediction Model Based on the Analysis of Radiation-Induced Brain Injury.

PURPOSE: To study the impact of dose distribution on volume-effect parameter and predictive ability of equivalent uniform dose (EUD) model, and to explore the improvements. METHODS AND MATERIALS: The brains of 103 nasopharyngeal carcinoma patients treated with IMRT were segmented according to dose distribution (brain and left/right half-brain for similar distributions but different sizes; V D with different D for different distributions). Predictive ability of EUDV D (EUD of V D ) for radiation-induced brain injury was assessed by receiver operating characteristics curve (ROC) and area under the curve (AUC). The optimal volume-effect parameter a of EUD was selected when AUC was maximal (mAUC). Correlations between mAUC, a and D were analyzed by Pearson correlation analysis. Both mAUC and a in brain and half-brain were compared by using paired samples t-tests. The optimal D V and V D points were selected for a simple comparison. RESULTS: The mAUC of brain/half-brain EUD was 0.819/0.821 and the optimal a value was 21.5/22. When D increased, mAUC of EUDV D increased, while a decreased. The mAUC reached the maximum value when D was 50-55 Gy, and a was always 1 when D ≥55 Gy. The difference of mAUC/a between brain and half-brain was not significant. If a was in range of 1 to 22, AUC of brain/half-brain EUDV55 Gy (0.857-0.830/0.845-0.830) was always larger than that of brain/half-brain EUD (0.681-0.819/0.691-0.821). The AUCs of optimal dose/volume points were 0.801 (brain D2.5 cc), 0.823 (brain V70 Gy), 0.818 (half-brain D1 cc), and 0.827 (half-brain V69 Gy), respectively. Mean dose (equal to EUDV D with a = 1) of high-dose volume (V50 Gy-V60 Gy) was superior to traditional EUD and dose/volume points. CONCLUSION: Volume-effect parameter of EUD is variable and related to dose distribution. EUD with large low-dose volume may not be better than simple dose/volume points. Critical-dose-volume EUD could improve the predictive ability and has an invariant volume-effect parameter. Mean dose may be the case in which critical-dose-volume EUD has the best predictive ability.

Long Non-coding RNA MALAT1 Alleviates the Elevated Intraocular Pressure (Eiop)-induced Glaucoma Progression via Sponging miR-149-5p.

Background: Glaucoma is an optic neuropathic disease and contributed to the irreversible blindness caused by the slow death of retinal ganglion cells (RGCs). Long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be aberrantly expressed in diverse diseases, including glaucoma. However, the mechanism of MALAT1 in glaucoma was still undefined.Methods: The levels of MALAT1, microRNA-149-5p (miR-149-5p) in RGCs cultured under elevated pressure were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The putative target of MALAT1 was predicted by starBase v2.0 online database, and dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay were performed to verify this interaction. The cell viability of RGCs was measured by Cell Counting Kit-8 (CCK-8) assay. The apoptotic rate was evaluated via flow cytometry. The protein levels of apoptosis-related proteins (Bax, B-cell lymphoma 2 (Bcl-2)) and Cleaved caspase 3 were assessed by Western blot.Results: The level of MALAT1 was significantly down-regulated, and the level of miR-149-5p was distinctly up-regulated in RGCs under pressure in a dose-dependent manner. Functionally, MALAT1 overexpression or miR-149-5p inhibitor alleviated the inhibitory effect on cell viability and the promoted effect on apoptotic rate of RGCs in EIOP. The interaction between MALAT1 and miR-149-5p was predicted by starBase v2.0 online database, and dual luciferase reporter assay, RIP assay and RNA pull-down assay validated the interaction. Combined with the loss and gain experiment results, miR-149-5p was negatively interacted with MALAT1. Furthermore, miR-149-5p mimics mitigated the promoted impact on cell viability and the suppressive impact on apoptotic rate by targeting MALAT1.Conclusion: MALAT1 promoted cell proliferation and inhibited cell apoptosis of RGCs via targeting miR-149-5p in glaucoma in vitro, which might shed light on the mechanism of glaucoma pathogenesis.

Role of HCO3- umbrella in the pathogenesis of primary biliary cholangitis / 临床肝胆病杂志

Primary biliary cholangitis (PBC) is an autoimmune disease. Although PBC has the features of autoimmune disease, it has poor response to immunosuppressants and good response to the drugs participating in bile acid metabolism, such as ursodeoxycholic acid. Studies have shown that the bicarbonate secretion of biliary epithelial cells is impaired in PBC patients, and bile acid not blocked by HCO3- umbrella enters biliary epithelial cells and mediates their damage and apoptosis, leading to the expression of autoantibodies in apoptotic cells and immunologic injury. In order to explore the role of HCO3- umbrella secreted by biliary epithelial cells in the pathogenesis of PBC, this article briefly introduces the physiological function and production mechanism of HCO3- umbrella and the influencing factors for HCO3- secretion, and it is pointed out that reduced HCO3- secretion may be a key link in the pathogenesis of PBC and a potential therapeutic target.

The role of SIRT6 in nonalcoholic steatohepatitis / 生理学报

SIRT6, a member of the silencing information regulatory protein family, is a nicotinamide adenine dinucleotide-dependent histone deacetylase and an ADP-ribose transferase enzyme. It plays an important role in fundamental physiological and pathological processes, including lipid metabolism, inflammation, oxidative stress and fibrosis, and is considered as a potential therapeutic target for metabolic syndrome. SIRT6 knockout mice displayed severe fatty liver, and the expression of SIRT6 in the liver of nonalcoholic steatohepatitis (NASH) mice was significantly lower than that of normal mice. Overexpression of SIRT6 significantly ameliorated NASH-induced liver damage. It is suggested that SIRT6 may play a key role in protecting against NASH. In this paper, we review the important regulatory functions of SIRT6 in the occurrence and development of NASH.

Insulin Promotes Corneal Nerve Repair and Wound Healing in Type 1 Diabetic Mice by Enhancing Wnt/ß-Catenin Signaling.

The insulin and Wnt signaling pathways are involved in cell proliferation, tissue homeostasis, and tumorigenesis. However, their interrelationship in the pathophysiological process of diabetic corneal injury remains unclear. In this study, the role of insulin in the diabetic cornea was investigated in vitro, using cultured TKE2 cells and trigeminal ganglion neurons, and in vivo, by assessing corneal wound-healing responses in diabetic mice. A selective Wnt antagonist (XAV-939) and activator (BML-284) were used to regulate the interactions between insulin and the Wnt pathway. The results demonstrated that insulin promoted corneal epithelial wound healing and sensation recovery, whereas the expression of molecules involved in the Wnt/ß-catenin pathway was also up-regulated in the injured corneal epithelium. However, XAV-939 limited the insulin-induced epithelial and corneal nerve repair. By contrast, BML-284 treatment promoted the healing of the corneal epithelium and corneal nerve repair in diabetic mice. These results indicate that insulin, via Wnt signaling, contributes to diabetic corneal epithelial wound healing and nerve injury recovery and is, therefore, a potential protective factor for diabetic corneal epithelial wounds and nerve injury.

An Investigation of the Organoborane/Lewis Base Pairs on the Copolymerization of Propylene Oxide with Succinic Anhydride.

The copolymerization of biorenewable succinic anhydride (SA) with propylene oxide (PO) is a promising way to synthesize biodegradable aliphatic polyesters. However, the catalytic systems for this reaction still deserve to be explored because the catalytic activity of the reported catalysts and the molecular weights of produced polyesters are unsatisfied. Herein, we investigate the copolymerization of SA with PO catalyzed by the organoborane/base pairs. The types of Lewis bases, organoboranes, and their loadings all have a large impact on the activity and selectivity of the copolymerization. High ester content of >99% was achieved when performed the PO/SA copolymerization using triethyl borane (TEB)/phosphazene base P1-t-Bu (t-BuP1) pair with a molar ratio of 1/1 at 30-80 °C. Using TEB/t-BuP1 pair with the molar ratio of 4/1 at 80 °C, the turnover of frequency (TOF) was up to 128 h-1 and clearly higher than the known TOF values (0.5-34 h-1) of the PO/SA copolymerization by previously reported catalysts. The number-average molecular weights (Mns) of the resultant polyesters reached up to 20.4 kg/mol when copolymerization was carried out using TEB/t-BuP1 (1/1, in molar ratio) at 30 °C.

Clinical analysis of fungal keratitis in patients with and without diabetes.

We compared the clinical characteristics, treatments, and prognoses of fungal keratitis in patients with and without diabetes. Patients diagnosed with fungal keratitis at Shandong Eye Institute between January 2010 and December 2016 were retrospectively reviewed and classified as diabetic and nondiabetic groups. One-hundred-and-eleven patients (111 eyes) with diabetes and 740 patients (740 eyes) without diabetes were included. The diabetic patients showed significantly older (p< 0.05) and lower male:female ratio (p<0.05). Plants trauma was the primary risk factor in both groups, and there was no significant difference of pathogen type (the most common was Fusarium genus, followed by Alternaria and Aspergillus genera). Multivariate logistic regression analyses revealed that diabetes and topical glucocorticoid use were the independent risk factors for the severity of fungal keratitis. The recurrent infection rate between the diabetic and nondiabetic patients during the follow-up (6 to 24 months) after penetrating keratoplasty (PKP) was not significantly different. Although the recurrent epithelial defect, rejection, and best-corrected visual acuity were similar between the patients with matched bed/graft size (7.75/8.0 mm) in the two groups 1 year after PKP, the incidence of delayed re-epithelialization (>7 days) was significantly higher in diabetic patients (3/10 versus 2/43 in nondiabetic patients, p<0.05). More specially, the diabetic patients with the duration ≥10 years showed more significantly delayed re-epithelialization than those with the diabetic duration less than 10 years (3/5 versus 1/26, p<0.05). In conclusion, the diabetes mellitus is an independent risk factor that affect the severity of fungal keratitis. Corneal re-epithelialization was significantly delayed after PKP in the diabetic patients, especially with the duration ≥10 years.

Cholesterol Modification of an Anticancer Drug for Efficient Incorporation into a Supramolecular Hydrogel System.

Treatment of cancer in the peritoneal cavity may be improved with macroscale drug delivery systems that offer control over intraperitoneal concentration of chemotherapeutic agents. Currently, suitable drug carriers to facilitate a sustained release of small hydrophilic drugs such as mitomycin C are lacking. For this purpose, a pH-responsive supramolecular hydrogel based on ureido-pyrimidinone (UPy) chemistry is utilized here. In order to provide a sustained release profile, a lipophilicity-increasing cholesterol conjugation strategy is proposed that enhances affinity between the modified drug (mitomycin-PEG24 -cholesterol, MPC) and the hydrophobic compartments in the UPy gel. Additional advantages of cholesterol conjugation include improved chemical stability and potency of mitomycin C. In vitro the tunability of the system to obtain optimal effective concentrations over time is demonstrated with a combinatorial treatment of mitomycin C and MPC in one UPy hydrogel delivery system.

Engineering a humanized bone organ model in mice to study bone metastases.

Current in vivo models for investigating human primary bone tumors and cancer metastasis to the bone rely on the injection of human cancer cells into the mouse skeleton. This approach does not mimic species-specific mechanisms occurring in human diseases and may preclude successful clinical translation. We have developed a protocol to engineer humanized bone within immunodeficient hosts, which can be adapted to study the interactions between human cancer cells and a humanized bone microenvironment in vivo. A researcher trained in the principles of tissue engineering will be able to execute the protocol and yield study results within 4-6 months. Additive biomanufactured scaffolds seeded and cultured with human bone-forming cells are implanted ectopically in combination with osteogenic factors into mice to generate a physiological bone 'organ', which is partially humanized. The model comprises human bone cells and secreted extracellular matrix (ECM); however, other components of the engineered tissue, such as the vasculature, are of murine origin. The model can be further humanized through the engraftment of human hematopoietic stem cells (HSCs) that can lead to human hematopoiesis within the murine host. The humanized organ bone model has been well characterized and validated and allows dissection of some of the mechanisms of the bone metastatic processes in prostate and breast cancer.

Can arbuscular mycorrhizal fungi reduce Cd uptake and alleviate Cd toxicity of Lonicera japonica grown in Cd-added soils?

A greenhouse pot experiment was conducted to study the impact of arbuscular mycorrhizal fungi--Glomus versiforme (Gv) and Rhizophagus intraradices (Ri) on the growth, Cd uptake, antioxidant indices [glutathione reductase (GR), ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT), ascorbate (ASA), glutathione (GSH) and malonaldehyde (MDA)] and phytochelatins (PCs) production of Lonicera japonica in Cd-amended soils. Gv and Ri significantly increased P acquisition, biomass of shoots and roots at all Cd treatments. Gv significantly decreased Cd concentrations in shoots and roots, and Ri also obviously reduced Cd concentrations in shoots but increased Cd concentrations in roots. Meanwhile, activities of CAT, APX and GR, and contents of ASA and PCs were remarkably higher in Gv/Ri-inoculated plants than those of uninoculated plants, but lower MDA and GSH contents in Gv/Ri-inoculated plants were found. In conclusion, Gv and Ri symbiosis alleviated Cd toxicity of L. japonica through the decline of shoot Cd concentrations and the improvement of P nutrition, PCs content and activities of GR, CAT, APX in inoculated plants, and then improved plant growth. The decrease of shoot Cd concentrations in L. japonica inoculated with Gv/Ri would provide a clue for safe production of this plant from Cd-contaminated soils.

The treatment of solvent recovery raffinate by aerobic granular sludge in a pilot-scale sequencing batch reactor.

Mature aerobic granular sludge (AGS) was inoculated for the start-up of a pilot-scale sequencing batch reactor for the treatment of high concentration solvent recovery raffinate (SRR). The proportion of simulated wastewater (SW) (w/w) in the influent gradually decreased to zero during the operation, while volume of SRR gradually increased from zero to 10.84 L. AGS was successfully domesticated after 48 days, which maintained its structure during the operation. The domesticated AGS was orange, irregular, smooth and compact. Sludge volume index (SVI), SV30/SV5, mixed liquor volatile suspended solids/mixed liquor suspended solids (MLVSS/MLSS), extracellular polymeric substances, proteins/polysaccharides, average particle size, granulation rate, specific oxygen utilization rates (SOUR)H and (SOUR)N of AGS were about 38 mL/g, 0.97, 0.52, 39.73 mg/g MLVSS, 1.17, 1.51 mm, 96.66%, 47.40 mg O2/h g volatile suspended solids (VSS) and 8.96 mg O2/h g VSS, respectively. Good removal effect was achieved by the reactor. Finally, the removal rates of chemical oxygen demand (COD), total inorganic nitrogen (TIN), NH4+-N and total phosphorus (TP) were more than 98%, 96%, 97% and 97%, respectively. The result indicated gradually increasing the proportion of real wastewater in influent was a useful domestication method, and the feasibility of AGS for treatment of high C/N ratio industrial wastewater.

Dysfunction of autophagy as the pathological mechanism of motor neuron disease based on a patient-specific disease model.

Autophagy is the main catabolic pathway in cells for the degradation of impaired proteins and organelles. Accumulating evidence supports the hypothesis that dysfunction of autophagy, leading to an imbalance of proteostasis and the accumulation of toxic proteins in neurons, is a central player in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). The clinical pathology of ALS is complex and many genes associated with autophagy and RNA processing are mutated in patients with the familial form. But a causal relationship between autophagic dysfunction and ALS has not been fully established. More importantly, studies on the pathological mechanism of ALS are mainly based on animal models that may not precisely recapitulate the disease itself in human beings. The development of human iPSC techniques allows us to address these issues directly in human cell models that may profoundly influence drug discovery for ALS.