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Abstract Adaptive deep brain stimulation (aDBS) is an emerging advancement in DBS technology; however, local field potential (LFP) signal rate detection sufficient for aDBS algorithms and the methods to set-up aDBS have yet to be defined. Here we summarize sensing data and aDBS programming steps associated with the ongoing Adaptive DBS Algorithm for Personalized Therapy in Parkinson’s Disease (ADAPT-PD) pivotal trial (NCT04547712). Sixty-eight patients were enrolled with either subthalamic nucleus or globus pallidus internus DBS leads connected to a Medtronic PerceptTM PC neurostimulator. During the enrollment and screening procedures, a LFP (8–30 Hz, ≥1.2 µVp) control signal was identified by clinicians in 84.8% of patients on medication (65% bilateral signal), and in 92% of patients off medication (78% bilateral signal). The ADAPT-PD trial sensing data indicate a high LFP signal presence in both on and off medication states of these patients, with bilateral signal in the majority, regardless of PD phenotype.

Introduction: Lyme borreliosis (LB), an infection caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. To further characterize the LB burden in the Czech Republic, we conducted a seroprevalence study and estimated the incidence of symptomatic Bbsl infections. Methods: Anti-Bbsl IgM and IgG antibodies were detected in sera collected from the adult population in 2011 −2012 by enzyme-linked immunosorbent assay and immunoblot tests at the National Reference Laboratory. The incidence of symptomatic Bbsl infections was estimated from the seroprevalence results and the symptomatic proportion and duration of persistence of anti-Bbsl IgG antibodies in Bbsl-infected individuals. Surveillance under-detection of symptomatic Bbsl infections was estimated by comparing surveillance-reported and seroprevalence-based incidence. Results: Samples from 1996 adults were tested; the median age (range) was 45 (18 −87) years; 1037 (52.0 %) were female. The prevalence (with 95 % confidence interval) of anti-Bbsl IgG, and IgM and/or IgG (IgM/IgG) antibodies was 6.3 % (5.3 −7.5 %), and 9.5 % (8.3 −10.9 %), respectively. The IgM/IgG prevalence was 7.8 % (6.5 −9.2 %) in Bohemia and 15.3 % (12.2 −19.0 %) in Moravia. There were an estimated 30,563 (26,550 −34,962) symptomatic incident Bbsl infections in adults in the Czech Republic in 2012, for an incidence of 352.2 (306.0 −402.9) symptomatic Bbsl infections per 100,000 adults per year. There were an estimated 11 (10 −13) symptomatic Bbsl infections for each surveillance-reported LB case in the Czech Republic in 2012. Conclusions: There is high incidence of symptomatic Bbsl infections in the Czech Republic, particularly in Moravia. Interventions are needed to address the substantial burden of LB in the Czech Republic.

IntroductionMitochondrial dysfunction and oxidative stress play important roles in diabetic retinal vascular injuries. Honokiol (HKL) is a small-molecule polyphenol that exhibits antioxidant effects and has a beneficial effect in diabetes. This study aimed to explore the potential ability of HKL to ameliorate vascular injury in diabetic retinopathy (DR) and its possible mechanisms of action.MethodsThe effect of HKL was evaluated in vascular injury in an in vivo type 2 diabetic (db/db) mouse model. In vitro, retinal microvascular endothelial cells were treated with high glucose (HG) to simulate the pathological diabetic environment. Cell viability, expression of apoptosis-related proteins, cellular reactive oxygen species, mitochondrial membrane potential, and morphological changes in the mitochondria were examined.ResultsThe diabetic mice exhibited severe retinal vascular damage, including vascular leakage in vivo and capillary endothelial cell apoptosis in vitro. HKL reversed the retinal vascular leakage in the diabetic mice. In vitro, HKL improved retinal capillary endothelial cell viability, decreased apoptosis, and reversed the HG-induced increased cellular oxidative stress and mitochondrial fragmentation. The sirtuin 3 (SIRT3) inhibitor 3-TYP blocked all the in vivo and in vitro protective effects of HKL against diabetic retinal vascular leakage and capillary endothelium and eliminated the decrease in oxidative stress levels and reduction of mitochondrial fragmentation.DiscussionIn conclusion, these findings suggest that HKL inhibits vascular injury in DR, which was likely achieved through SIRT3-mediated mitochondrial fusion. This study provides a potential new strategy for the treatment of DR.

Abstract Serological detection of syphilis‐specific antibodies is the most widely used clinical method for diagnosing syphilis. However, the current methods in clinical practice are too diverse, complicating result interpretation and wasting medical resources. To meet the resultant demand for a simple fast naked‐eye detection method, we employed the bacterial cell‐binding domain (CBD) of bacteriophage lysin to functionalize bio‐microparticles (engineered non‐culturable red‐colored Staphylococcus aureus bacteria), forming a bioprobe that can detect the syphilis‐specific antibodies from human serum in 5 min with naked eyes. Specifically, CBD is bioengineered by fusion with one of three antigens of the syphilis‐causing bacteria Treponema pallidum separately. The three resulting fusion proteins bind to the bacteria surface through the CBD motif, generating a bioprobe with the antigens exposed. When the bioprobe is added to the serum samples collected from the syphilis patients, the syphilis‐specific antibodies bind the antigens on the bioprobes and cross‐link them, forming eye‐visible red aggregates for the naked‐eye antibody detection. The bioprobe was validated on 209 clinical samples, revealing its high clinical sensitivity and specificity. Exploiting the natural biorecognition between the bacteria‐specific phage‐derived species and the phage host bacteria represents a promising strategy for producing facile probes for rapid point‐of‐care testing of infectious diseases.

BackgroundHead and neck cancers are a heterogeneous, aggressive, and genetically complex collection of malignancies of the oral cavity, nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinuses and salivary glands, which are difficult to treat. Regional lymph nodes metastasis is a significant poor prognosis factor for head and neck squamous cell carcinoma. Metastasis to the regional lymph nodes reduces the 5-year survival rate by 50% compared with that of patients with early-stage disease. Accurate evaluation of cervical lymph node is a vital component in the overall treatment plan for patients with squamous cell carcinoma of the head and neck. However, current models are struggle to accurately to predict cervical lymph node metastasis. Here, we analyzed the clinical, imaging, and pathological data of 272 patients with HNSCC confirmed by postoperative pathology and sought to develop and validate a nomogram for prediction of lymph node metastasis in patients with head and neck squamous cell carcinoma.MethodsWe retrospectively analyzed the clinical, imaging, and pathological data of 272 patients with head and neck squamous cell carcinoma (HNSCC) confirmed by postoperative pathology at the Affiliated Hospital of Qingdao University from June 2017 to June 2021. Patients were randomly divided into the training and validation cohorts in a 3:1 ratio, and after screening risk factors by logistic regression, nomogram was developed for predicting lymph nodes metastasis, then the prediction model was verified by C-index, area under curve (AUC), and calibration curve.ResultsOf the 272 patients, seven variables were screened to establish the predictive model, including the differentiation degree of the tumor [95% confidence interval(CI):1.224~6.735, P=0.015], long-to-short axis ratio of the lymph nodes (95%CI: 0.019~0.217, P

Abstract Background Radiation therapy is the cornerstone of treatment for adult-type diffuse gliomas, but recurrences are inevitable. Our study assessed the prognosis and recurrence pattern of different radiotherapy volumes after temozolomide-based chemoradiation in our institution. Methods The treatment plans were classified into two groups, the plan 1 intentionally involved the entire edema area while plan 2 did not. Retrospectively investigate the differences in outcomes of 118 adult-type diffuse gliomas patients between these two treatment plans. Then, patients who underwent relapse were selected to analyze their recurrence patterns. Continuous dynamic magnetic resonance images (MRI) were collected to categorized the recurrence patterns into central, in-field, marginal, distant, and cerebrospinal fluid dissemination (CSF-d) recurrence. Finally, the clinical and molecular characteristics which influenced progression were analyzed. Results Plan 1 (n = 63) showed a median progression-free survival (PFS) and overall survival (OS) of 9.5 and 26.4 months while plan 2 (n = 55) showed a median PFS and OS of 9.4 and 36.5 months (p = 0.418; p = 0.388). Treatment target volume had no effect on the outcome in patients with adult-type diffuse gliomas. And there was no difference in radiation toxicity (p = 0.388). Among the 90 relapsed patients, a total of 58 (64.4%) patients had central recurrence, 10 (11.1%) patients had in-field recurrence, 3 (3.3%) patients had marginal recurrence, 11 (12.2.%) patients had distant recurrence, and 8 (8.9%) patients had CSF-d recurrence. By treatment plans, the recurrence patterns were similar and there was no significant difference in survival. Reclassifying the progression pattern into local and non-local groups, we observed that oligodendroglioma (n = 10) all relapsed in local and no difference in PFS and OS between the two groups (p > 0.05). Multivariable analysis showed that subventricular zone (SVZ) involvement was the independent risk factor for non-local recurrence in patients with GBM (p

Long-term irrigation promotes the infiltration of water in the thick, stratified loess layer, significantly raising the groundwater table and triggering a series of landslides in loess platform areas. The soil–water characteristic curve (SWCC) of loess buried at different depths affects the unsaturated infiltration process and is intricately connected to the soil’s microstructure. The SWCCs, scanning electron microscope (SEMs), and pore size distributions (PSDs) for five sets of undisturbed loess samples at depths ranging from 3.4 to 51.9 m are shown in this paper. The results indicate that the fitting parameter air entry value (AEV) of the SWCC rises from 13.67 kPa to 40.19 kPa as the depth increases from 3.4 to 51.9 m. And the saturated volumetric water content drops by 10.9%, with a notable SWCC shape difference between the transition and residual zones observed. Additionally, the total porosity of undisturbed loess falls by 12% when the depth increases from 3.4 to 51.9 m, while the macropores and mesopores reduce by 3.6% and 12.1%, respectively. These findings highlight the control of the pore structure on the SWCC and emphasize the correspondence between the SWCC and PSD. The conclusions also illustrate that the compaction effect changes the microstructure characteristics of loess, thereby affecting the soil’s water retention behavior.

In this paper, five phenolic acids in the rhizosphere soil of Pinellia ternate were determined to have strong allelopathy to Pinellia ternate. The phenolic acids in rhizosphere soil and non continuous cropping soil of Pinellia ternate for two years were extracted and detected by GC-MS, 5 phenolic acids were found to have different content changes. By comparing the contents of phenolic acids in the rhizosphere soil before, during and after planting, and combining with the literatures, it was determined that protocatechuic acid, vanillic acid, vanillin, syringate and syringaldehyde had strong allelopathy on the growth and development of Pinellia ternate. Furthermore, the effects of the above five phenolic acids on the growth of Pinellia ternate, the growth of seedlings and the comparison of tuber size were investigated. The results showed that the five phenolic acids had inhibitory effects on the growth of Pinellia ternate.

BackgroundGastric cancer (GC) ranks as the fifth most prevalent malignancy and the second leading cause of oncologic mortality globally. Despite staging guidelines and standard treatment protocols, significant heterogeneity exists in patient survival and response to therapy for GC. Thus, an increasing number of research have examined prognostic models recently for screening high-risk GC patients.MethodsWe studied DEGs between GC tissues and adjacent non-tumor tissues in GEO and TCGA datasets. Then the candidate DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of DEGs. We used the ROC curve, Kaplan-Meier curve, and risk score plot to evaluate the signature’s performance and prognostic power. ESTIMATE, xCell, and TIDE algorithm were used to explore the relationship between the risk score and immune landscape relationship. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model.ResultsThere were 3211 DEGs in TCGA, 2371 DEGs in GSE54129, 627 DEGs in GSE66229, and 329 DEGs in GSE64951 selected as candidate genes and intersected with to obtain DEGs. In total, the 208 DEGs were further screened in TCGA cohort through univariate Cox regression analyses. Following this, LASSO regression was utilized to generate prognostic model of 6 DEGs. External validation showed favorable predictive efficacy. We studied interaction between risk models, immunoscores, and immune cell infiltrate based on six-gene signature. The high-risk group exhibited significantly elevated ESTIMATE score, immunescore, and stromal score relative to low-risk group. The proportions of CD4+ memory T cells, CD8+ naive T cells, common lymphoid progenitor, plasmacytoid dentritic cell, gamma delta T cell, and B cell plasma were significantly enriched in low-risk group. According to TIDE, the TIDE scores, exclusion scores and dysfunction scores for low-risk group were lower than those for high-risk group. As a final step, nomogram was developed in this study, utilizing both clinical characteristics and a prognostic model.ConclusionIn conclusion, we discovered a 6 gene signature to forecast GC patients’ OS. This risk signature proves to be a valuable clinical predictive tool for guiding clinical practice.

Giant visceral artery aneurysms are uncommon. Branch vessel aneurysms, particularly of the pancreaticoduodenal territory are challenging to treat due to their location, anatomy, and access to an aneurysm. While open surgical resection is associated with significant morbidity, endovascular treatment is becoming increasingly mainstream. The utilization of coil embolization, particularly in the setting of rupture has been well described. Access and platform in these settings often involve the celiac axis. We describe unusual care of a large inferior pancreaticoduodenal aneurysm and associated retroperitoneal bleed, being fed through an ectatic superior mesenteric artery. This was associated with an occluded celiac axis. Due to the unusually large proximal and distal landing zones, a covered balloon-expandable stent was deployable with the successful exclusion of the aneurysm. This is the first reported case report of successful management of retroperitoneal rupture and associated pancreaticoduodenal aneurysm treated with a covered stent graft. This technique allowed for rapid access and exclusion of the aneurysm. In addition, it allowed the preservation of foregut flow through the collateral pathway and successfully excluded the large aneurysm.

The MnFe2O4/g-C3N4/diatomite composites (Mn/G/D) were prepared via a facile precipitation-calcination method in this study. The Mn/G/D possessed higher specific surface area, lower electron-hole pairs’ recombination rate, as well as wider and stronger visible light absorption capacity. Since the synergistic effect between g-C3N4 and MnFe2O4, the photogenerated electron could transfer from g-C3N4 to MnFe2O4, which could promote the migration of electrons as well as enhance the photocatalytic activity and peroxymonosulfate (PMS) activation efficiency. Mn/G/D-5% composite displayed the excellent degradation performance of bisphenol A (BPA) with the removal efficiency of 99.9% under PMS/Vis system, which was approximately 2.47 and 63.8 times as high as that of the Mn/G/D-5%/PMS and Mn/G/D-5%/Vis system, respectively. Moreover, negative electricity derived from diatomite surface also promoted the photogenerated carriers’ migration, and the degradation rate constant was around 2.4 times higher than that of MnFe2O4/g-C3N4 (Mn/G). In addition, quenching experiments showed that both radical pathway (h+, ·OH, ·O2− and SO4·−) and non-radical pathway (1O2) were responsible for the degradation of BPA.

BackgroundLung squamous cell carcinoma (LUSC) represents 30% of all non-small cell lung carcinoma. Targeted therapy is not sufficient for LUSC patients because of the low frequency of targeted-effective mutation in LUSC whereas immunotherapy offers more options for patients with LUSC. We explored a ferroptosis-related prognostic signature that can potentially assess the prognosis and immunotherapy efficacy of LUSC patients.MethodsA total of 502 LUSC patients were downloaded from The Cancer Genome Atlas (TCGA). The external validation data were obtained from the Gene Expression Omnibus (GEO): GSE73403. Then, we identified the candidate genes and constructed the prognostic signature through the Cox survival regression analyses and least absolute shrinkage and selection operator (LASSO). Risk score plot, Kaplan–Meier curve, and ROC curve were used to assess the prognostic power and performance of the model. The CIBERSORT algorithm estimated the fraction of immune cell types. TIDE was utilized to predict the response to immunotherapy. IMvigor210 was used to explore the association between the risk scores and immunotherapy outcomes. A nomogram combined selected clinical characteristics, and the risk scores were constructed.ResultsWe screened 132 differentially expressed ferroptosis-related genes. According to KEGG and GO pathway analyses, these genes were mainly engaged in the positive regulation of cytokine production, cytokine metabolic process, and oxidoreductase activity. We then constructed a prognostic model via LASSO regression. The proportions of CD8+ T cells, CD4+ activated T cells, and follicular helper T cells were significantly different between low-risk and high-risk groups. TIDE algorithm indicated that low-risk LUSC patients might profit more from immune checkpoint inhibitors. The predictive value of the ferroptosis gene model in immunotherapy response was further confirmed in IMvigor210. Finally, we combined the clinical characteristics with a LASSO regression model to construct a nomogram that could be easily applied in clinical practice.ConclusionWe identified a prognostic model that provides an accurate and objective basis for guiding individualized treatment decisions for LUSC.

Abstract Background Fucoidan, a water-soluble polysaccharide, exerts anticoagulant and antiviral functions. It was recently reported that fucoidan also exerts an antitumor function. Lung cancer is one of the most common cancers in the world. The aim of this study was to investigate anti-tumor,apoptosis and anti-metastasis effects of fucoidan in both cell-based assays and mouse xenograft model, as well as to clarify possible role of m-TOR pathway in the protection. Methods In vitro: Different concentrations of fucoidan were given to act on non-small cell lung cancer (NSCLC) cell lines A549 and H1650. The effects of fucoidan on cell proliferation were observed by detecting cyclin expression levels, CCK8 and EDU experiments and cloning experiments. The apoptotic level was detected by flow cytometry and the apoptotic protein level was detected by Westernblot. By detecting the expression of adhesion molecules, the expression of matrix metalloproteinase (MMP) family, and Transwell cell invasion and migration experiment, the effect of fucoidan on cell adhesion, invasion and migration was observed. Meanwhile the effect of fucoidan on angiogenesis was observed by detecting the expression of vascular endothelial growth factor (VEGF). In vivo experiment: An animal model of NSCLC cell mouse subcutaneous xenograft tumor was established to analyze the correlation between the consumption of fucoidan and the size and volume of xenograft tumor through gross observation. Through immunohistochemical staining and immunofluorescence double staining, ki67 and cell adhesion molecules (E-cadherin, N-cadherin and CD31) and VEGF-A in the tumor were detected, and the correlation between the amount of fucoidan and the above indexes was analyzed. Results Fucoidan inhibited the proliferation and angiogenesis of NSCLC cells via the mTOR pathway and promoted their apoptosis by increasing the Bax/Bcl-2 ratio. Not only that, fucoidan inhibited NSCLC cell invasion via epithelial–mesenchymal transformation (EMT). The mice fed fucoidan exhibited significant reductions in tumor volumes and weights. These indicators (Ki67, VEGF-A,N-cadherin) were decreased and E-cadherin expression was up-regulated in A549 mice that treated with fucoidan. The results showed that fucoidan inhibited tumor proliferation in vivo by affecting the expression of related proteins. Conclusion Fucoidan conveys antitumor effects and our results represent an ideal therapeutic agent for NSCLC.

A novel Ag/g-C3N4/kaolinite composite photocatalyst was fabricated for the first time through a two-step assembly strategy by employing in situ calcination and a photodeposition process. The synthesized Ag/g-C3N4/kaolinite composite reached a higher degradation rate of ibuprofen (IBP) with a reaction rate constant of 0.0113 min−1 at an Ag content of 7% under visible-light irradiation, which was approximately 1.87 times that of the Ag/g-C3N4 composite. Based on the physicochemical properties, the enhanced photocatalytic activity was attributed to the stronger adsorption property, wider photoresponse range and more efficient separation and transfer of electron-hole pairs. Furthermore, the incorporation of monodispersed Ag nanoparticles onto the g-C3N4/kaolinite sheets provided more reactive sites for the IBP degradation. In addition, according to the EPR study and trapping experiments, it was demonstrated that holes (h+) should be the key reactive species. A possible pathway of IBP degradation was also proposed based on the detected intermediates. Overall, the results of this work may facilitate the design of a novel visible-light-driven photocatalyst with a high efficiency that is derived from a natural mineral for environmental remediation.

Dysregulation of tumor-relevant proteins may contribute to human hepatocellular carcinoma (HCC) tumorigenesis. FBXO45 is an E3 ubiquitin ligase that is frequently elevated expression in human HCC. However, it remains unknown whether FBXO45 is associated with hepatocarcinogenesis and how to treat HCC patients with high FBXO45 expression. Here, IHC and qPCR analysis revealed that FBXO45 protein and mRNA were highly expressed in 54.3% (57 of 105) and 52.2% (132 of 253) of the HCC tissue samples, respectively. Highly expressed FBXO45 promoted liver tumorigenesis in transgenic mice. Mechanistically, FBXO45 promoted IGF2BP1 ubiquitination at the Lys190 and Lys450 sites and subsequent activation, leading to the upregulation of PLK1 expression and the induction of cell proliferation and liver tumorigenesis in vitro and in vivo. PLK1 inhibition or IGF2BP1 knockdown significantly blocked FBXO45-driven liver tumorigenesis in FBXO45 transgenic mice, primary cells, and HCCs. Furthermore, IHC analysis on HCC tissue samples revealed a positive association between the hyperexpression of FBXO45 and PLK1/IGF2BP1, and both had positive relationship with poor survival in HCC patients. Thus, FBXO45 plays an important role in promoting liver tumorigenesis through IGF2BP1 ubiquitination and activation, and subsequent PLK1 upregulation, suggesting a new strategy for treating HCC by targeting FBXO45/IGF2BP1/PLK1 axis.

Abstract Background To assess bioactive transforming growth factor-β2 (TGFβ2) and secreted frizzled-related protein-1 (SFRP1) levels in aqueous humor (AH) of different types of glaucoma. Methods AH samples were obtained immediately before ophthalmic surgery with a 27-gauge needle attached to a microsyringe from 126 eyes (105 patients) divided into five groups: cataract (control), primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), primary angle-closure suspects (PACS), and acute angle-closure glaucoma (AACG). Bioactive TGFβ2 and SFRP1 levels were assayed by ELISA. Results The concentration of TGFβ2 in AH of POAG patients, but not CACG, PACS, or AACG patients, was significantly higher than control eyes. However, within the AACG group, although the TGFβ2 levels in AH did not differ significantly from the control level when all AACG patients were grouped together, there were differences when the AACG patients were divided into high and normal intraocular pressure (IOP); TGFβ2 of AACG patients with high IOP (> 21 mmHg) was significantly higher than those with normal IOP. AH levels of SFRP1 were not significantly different among the groups. However, a statistical significant, negative correlation between SFRP1 and IOP existed in the POAG group. POAG patients with high IOP had lower levels of SFRP1 than those with normal IOP. In contrast, a significant, positive correlation between SFRP1 level and IOP was detected in the AACG group. AACG patients with high IOP had a higher level of SFRP1 than those with normal IOP. Concentrations of TGFβ2 and SFRP1 did not correlate significantly with each other, or with age. Conclusions These results indicate that AH levels of TGFβ2 and SFRP1 showed different profiles in different types of glaucomas.

Abstract Background Human mesenchymal stem cell (hMSC) differentiation into osteoblasts has important clinical significance in treating bone injury, and the stiffness of the extracellular matrix (ECM) has been shown to be an important regulatory factor for hMSC differentiation. The aim of this study was to further delineate how matrix stiffness affects intracellular signaling through integrin α5/β1, FAK, and Wnt signaling, subsequently regulating the osteogenic phenotype of hMSCs. Methods hMSCs were cultured on tunable polyacrylamide hydrogels coated with fibronectin with stiffness corresponding to a Young’s modulus of 13–16 kPa and 62–68 kPa. After hMSCs were cultured on gels for 1 week, gene expression of alpha -1 type I collagen, BGLAP, and RUNX2 were evaluated by real-time PCR. After hMSCs were cultured on gels for 24 h, signaling molecules relating to integrin α5 (FAK, ERK, p-ERK, Akt, p-Akt, GSK-3β, p-GSK-3β, and β-catenin) were evaluated by western blot analysis. Results Osteogenic differentiation was increased on 62–68 kPa ECM, as evidenced by alpha-1 type I collagen, BGLAP, and RUNX2 gene expression, calcium deposition, and ALP staining. In the process of differentiation, gene and protein expression of integrin α5/β1 increased, together with protein expression of the downstream signaling molecules FAK, p-ERK, p-Akt, GSK-3β, p-GSK-3β, and β-catenin, indicating that these molecules can affect the osteogenic differentiation of hMSCs. An antibody blocking integrin α5 suppressed the stiffness-induced expression of all osteoblast markers examined. In particular, alpha-1 type I collagen, RUNX2, and BGLAP were significantly downregulated, indicating that integrin α5 regulates hMSC osteogenic differentiation. Downstream expression of FAK, ERK, p-ERK, and β-catenin protein was unchanged, whereas Akt, p-Akt, GSK-3β, and p-GSK-3β were upregulated. Moreover, expression of Akt and p-Akt was upregulated with anti-integrin α5 antibody, but no difference was observed for FAK, ERK, and p-ERK between the with or without anti-integrin α5 antibody groups. At the same time, expression of GSK-3β and p-GSK-3β was upregulated and β-catenin levels showed no difference between the groups with or without anti-integrin α5 antibody. Since Akt, p-Akt, GSK-3β, and p-GSK-3β displayed the same changes between the groups with or without anti-integrin α5 antibody, we then detected the links among them. Expression of p-Akt and p-GSK-3β was reduced effectively in the presence of the Akt inhibitor Triciribine. However, Akt, GSK-3β, and β-catenin were unchanged. These results suggested that expression of p-GSK-3β was regulated by p-Akt on 62–68 kPa ECM. Conclusions Taken together, our results provide evidence that matrix stiffness (62–68 kPa) affects the osteogenic outcome of hMSCs through mechanotransduction events that are mediated by integrin α5.

Purpose. To study the efficacy of a modified four-point fixation technique for the repositioning of a dislocated intraocular lens (IOL) with four eyelets in the absence of capsule support. Methods. Four patients with dislocated four-eyelet hydrophilic acrylic IOLs (Akreos AO60) were enrolled. The modified technique combined four-point fixation with intrascleral sutures and suture burying. The technique minimized the limbus incision to 1 mm with no externalization of the IOL or its haptics. Follow-ups included routine ophthalmic examinations, corneal endothelial cell counts, and measurement of IOL tilt and decentration (measured using Pentacam® HR images). Results. The IOLs were successfully repositioned in all cases. After a mean follow-up period of 19.75 ± 7.85 months (range: 8 to 24 months), the patients’ best-corrected vision acuity (BCVA (LogMAR), before: 0.63 ± 0.36, after: 0.58 ± 0.43, P=0.604) and intraocular pressure (pre 13.35 ± 0.85 mmHg, post 14.80 ± 2.03 mmHg, P=0.150) remained unchanged. Corneal endothelium density decreased about 6.84 ± 2.97%. In all cases, the IOL was well positioned during the follow-up. At the final visit, the average IOL tilt was 1.36 ± 0.35° horizontally and 1.31 ± 0.14° vertically. The average IOL decentration was 0.23 ± 0.12 mm horizontally and 0.18 ± 0.13 mm vertically. Conclusions. With this modified technique, dislocated IOLs with four-eyelets could be treated safely with favorable outcomes.

Purpose. To compare the efficacy of passive drainage (PD) and repeated fluid-air (FA) exchange for removing emulsified silicone oil (SO) droplets. Methods. Twenty rhegmatogenous retinal detachment (RRD) patients who underwent primary pars plana vitrectomy (PPV) with SO tamponade were randomly and evenly divided into two groups for PD and FA exchange. Once the bulk of SO was removed, the first 2 mL of the washout fluid was collected, and then, another 2 mL of the washout fluid was collected after PD or FA exchange. The size and number of SO droplets in the washout fluid were measured using a Coulter counter (Multisizer 3, Beckman Coulter, Indianapolis, IN, USA). The efficiencies of FA exchange and PD for removing emulsified SO were compared. Results. The number of SO droplets decreased significantly after FA exchange and PD. The decrease in the number of droplets was statistically significant for larger droplets (>4 µm) with PD and for all droplet sizes with FA exchange. The decrease in the number of SO droplets of

Summary: FBXW7 is a tumor suppressive E3 ligase, whereas RAS-ERK and mechanistic target of rapamycin kinase (mTORC1) are two major oncogenic pathways. Whether and how FBXW7 regulates these two oncogenic pathways are unknown. Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation. FBXW7-mediated SHOC2 degradation terminates the RAS-MAPK signals and inhibits proliferation. Furthermore, SHOC2 selectively binds to Raptor to competitively inhibit the Raptor-mTOR binding to inactivate mTORC1 and induce autophagy, whereas Raptor binding of SHOC2 inhibits the SHOC2-RAS binding to block the MAPK pathway and proliferation. Finally, SHOC2 is overexpressed in pancreatic cancer, which correlated with poor patient survival. SHOC2 mutations were found in lung cancer tissues with gain-of-function activity. Collectively, the SHOC2-Raptor interaction triggers negative cross-talk between RAS-ERK and mTORC1 pathways, whereas FBXW7 regulates both pathways by targeting SHOC2 for ubiquitylation and degradation. : In this study, Xie et al. show upon growth stimulation that RAS-MAPK is activated to phosphorylate SHOC2 on T507 to facilitate its binding with FBXW7β for ubiquitylation and degradation, thus establishing a negative feedback loop. Furthermore, the SHOC2-RAPTOR interaction can inactivate either pathway to keep proliferation and autophagy under precise control. Keywords: autophagy, cell proliferation, FBXW7, MAPK, mTOR, Raptor, RAS-RAF-ERK, SCF E3 ligase, SHOC2, ubiquitylation and degradation

Dynamic compression experiments of bismuth (Bi) in a shock pressure range of 38-100 GPa were conducted using an explosive drive. The time-resolved particle velocity profiles at the Bi/LiF (lithium fluoride) interface and the impact velocities were recorded with a displacement interferometer system for any reflector (DISAR). Shock velocities of Bi were measured based on the shorted-pin technique. Sound velocities of Bi were obtained from the peak state time duration measurements with the overtake method. Uncertainties in the measured Hugoniots and sound velocities were analyzed carefully. The new Hugoniot relation, Us = (1.666 ± 0.057) km/s + (1.596 ± 0.037)Up (1.13 km/s ≤Up≤2.05 km/s), was determined by fitting the measured shock velocity and particle velocity to a line. The relation between the Grüneisen coefficient and the density, γρ=const., is found to be a good approximation to describe the sound velocities of Bi above the shock-induced melting pressure, by carefully analysis of the sound velocity data.

This study examines how second/foreign language (L2) word difficulty estimates derived from item response theory (IRT) and classical test theory (CTT) frameworks are virtually identical in the context of vocabulary testing. This conclusion is reached via a two-stage process: (a) psychometric assessments of both approaches and (b) L2 word difficulty modelling with lexical sophistication. Using data collected from first/native language (L1) Japanese EFL learners, both approaches led to similar conclusions in terms of the psychometric properties of the construct. Furthermore, CTT- and IRT/Rasch-derived estimates for word difficulty yielded nearly identical results in the predictive models. Although the "CTT-vs-IRT" debates in the past few decades have concluded with a middle ground agreed upon in most educational settings, this study acts as a useful demonstration to L2 vocabulary researchers who appear to rely heavily on Rasch/IRT analysis. The findings have practical applications to the area of L2 word difficulty research. Namely, that Rasch (an IRT procedure) alone might not be sufficient for validation, although it could be preferable when conducting inferential testing because of its potential utility for reducing chances of Type II errors.

In plants, sphingolipids, such as long-chain bases (LCBs), act as bioactive molecules in stress responses. Until now, it is still not clear if these lipids are involved in biotic stress responses to herbivore. Herein we report that a rice LCB gene, OsLCB2a1 encoding a subunit of serine palmitoyltransferase (SPT), a key enzyme responsible for the de novo biosynthesis of sphingolipids, plays a critical role in plant defense response to the brown planthopper (BPH) attack and that its up-regulation protects plants from herbivore infestation. Transcripts of OsLCB2a1 gene in rice seedlings were increased at 4 h, but decreased at 8–24 h after BPH attack. Sphingolipid measurement profiling revealed that overexpression of OsLCB2a1 in Arabidopsis thaliana increased trihydroxylated LCB phytosphingosine (t18:0) and phytoceramide by 1.7 and 1.3-fold, respectively, compared with that of wild type (WT) plants. Transgenic Arabidopsis plants also showed higher callose and wax deposition in leaves than that of WT. Overexpression of OsLCB2a1 gene in A. thaliana reduced the population size of green peach aphid (Myzus persicae). Moreover, the electrical penetration graph (EPG) results indicated that the aphids encounter resistance factors while reaching for the phloem on the transgenic plants. The defense response genes related to salicylic acid signaling pathway, remained uplgulated in the OsLCB2a1-overexpressing transgenic plants. Our data highlight the key functions of OsLCB2a1 in biotic stress response in plants.

Remote sensing end-products related to vegetation have potential applications in monitoring the health of crops. The sensitivity of a spectral index to crop stress determines its application prospect. Our aim in this study was to explore the sensitivity of a ratio vegetation index (RVI) to identify the damage caused by brown planthoppers (BPHs) on rice plants, and to evaluate the potential application of hyperspectral end-products to monitor population size of BPH. Different numbers of the second-instar nymphs were released onto potted rice at the tillering stage. The plants were exposed to BPH for two, four, six, and eight days, and reflectance from the damaged rice was measured using a hyperspectral spectroradiometer. Measurements were done again two, four, and six days after exposure (recover days), and then the spectral index RVI746/670 was compared among rice plants infested with different numbers of BPH. The relationships between RVI746/670, the number of BPH and exposure day were simulated by linear and curve models. BPH damage resulted in a decreased spectral index RVI746/670 of rice plants. RVI746/670 well indicated the damage of rice plants caused by six–eight BPH nymphs per plant in six–eight days, but the index could not identify the damage of these nymphs in two days. The RVI746/670 showed a two–four-day delay to indicate a slight BPH damage. The spectral index RVI746/670 could indicate the physiologic compensation of plants for the feeding of BPH and the post-effect of BPH damage on rice. The RVI746/670 of rice showed a quadratic curve relation with the number of BPH nymphs and a quadratic or linear relation with the exposure day. The recover day had no significant effects on RVI746/670. The RVI746/670 (Y) could be simulated by a quadratic surface model based on the number of BPH (N) and exposure day (T): Y = 3.09427 + 0.59111T + 0.44296N − 0.03683T2 − 0.03035N2 − 0.08188NT (R2 = 0.5228, p < 0.01). In summary, the spectral index RVI746/670 of rice is sensitive to damage caused by BPH.

Abstract Decomposition of submerged plants releases organic matter, nitrogen, and phosphorus into water bodies, generating an important impact on the aquatic ecosystem. This study explored the influence of growth substrate with different compositions on the decomposition process of eelgrass (Vallisneria spinulosa Yan, V. spinulosa Yan). The sediment + iron–carbon fillers system exhibited significantly lower concentrations of total nitrogen (TN) and total phosphorus (TP) in the overlying water than other systems, with the maximum values of 5.68 and 7.05 mg/L, respectively. The addition of ceramic and calcium nitrate promoted the formation of HCl-extracted phosphorus (HCl–P) in the sediment, while the addition of iron–carbon fillers increased the content of NaOH-extracted phosphorus (NaOH–P). Three-dimensional fluorescence spectroscopy of dissolved organic matter (DOM) in overlying water showed that different substrate compositions did not significantly affect the compositions of organic matter released during the decomposition of V. spinulosa Yan. The microbial community and abundance in each experimental group changed significantly before and after the decomposition of V. spinulosa Yan. The sediment + iron–carbon fillers system showed significantly higher abundance of microbial community than other systems, with the enrichment of functional bacteria related to denitrification and sulfate reduction. In contrast, the sediment + calcium nitrate system exhibited a smaller change of microbial community abundance, with the enrichment of aerobic denitrifying bacteria. In this paper, it was found that the sediment + iron–carbon group had a good adsorption effect on nitrogen and phosphorus released during the decomposition process of V. spinulosa Yan, and had a good effect on water purification as the growth substrate of submerged plants.