Search

Doxorubicin (Dox) is widely used to the treatment of cancer, however, it could cause damage to gastric mucosa. To investigate the protective effects and related mechanisms of coenzyme Q10 (CoQ10) and vitamin C (VC) on Dox-induced gastric mucosal injury, we presented the survey of the 4 groups of the rats with different conditions. The results showed Dox treatment significantly induced GES-1 apoptosis, but preconditioning in GES-1 cells with VC or CoQ10 significantly inhibited the Dox-induced decrease and other harm effects, including the expression and of IκKβ, IκBα, NF-κB/p65 and tumor necrosis factor (TNF-α) in GES-1 cells. Moreover, high-throughput sequencing results showed Dox treatment increased the number of harmful gut microbes, and CoQ10 and VC treatment inhibited this effect. CoQ10 and VC treatment inhibits Dox-induced gastric mucosal injury by inhibiting the activation of the IkKB/IκBα/NF-κB/p65/TNF-α pathway, promoting anti-inflammatory effects of gastric tissue and regulating the composition of the intestinal flora. [ABSTRACT FROM AUTHOR]

Abstract The tunability of reaction pathways is required for exploring efficient and low cost catalysts for ammonia synthesis. There is an obstacle by the limitations arising from scaling relation for this purpose. Here, we demonstrate that the alkali earth imides (AeNH) combined with transition metal (TM = Fe, Co and Ni) catalysts can overcome this difficulty by utilizing functionalities arising from concerted role of active defects on the support surface and loaded transition metals. These catalysts enable ammonia production through multiple reaction pathways. The reaction rate of Co/SrNH is as high as 1686.7 mmol·gCo −1·h−1 and the TOFs reaches above 500 h−1 at 400 °C and 0.9 MPa, outperforming other reported Co-based catalysts as well as the benchmark Cs-Ru/MgO catalyst and industrial wüstite-based Fe catalyst under the same reaction conditions. Experimental and theoretical results show that the synergistic effect of nitrogen affinity of 3d TMs and in-situ formed NH2− vacancy of alkali earth imides regulate the reaction pathways of the ammonia production, resulting in distinct catalytic performance different from 3d TMs. It was thus demonstrated that the appropriate combination of metal and support is essential for controlling the reaction pathway and realizing highly active and low cost catalysts for ammonia synthesis.

Soft materials with mechanical adaptability have substantial potential for various applications in tissue engineering. Gaining a deep understanding of the structural evolution and adaptation dynamics of soft materials subjected to cyclic stretching gives insight into developing mechanically adaptive materials. Here, we investigate the effect of hierarchy structure on the mechanical adaptation of self-healing hydrogels under cyclic stretching training. A polyampholyte hydrogel, composed of hierarchical structures including ionic bonds, transient and permanent polymer networks, and bicontinuous hard/soft-phase networks, is adopted as a model. Conditions for effective training, mild overtraining, and fatal overtraining are demonstrated in soft materials. We further reveal that mesoscale hard/soft-phase networks dominate the long-term memory effect of training and play a crucial role in the asymmetric dynamics of compliance changes and the symmetric dynamics of hydrogel shape evolution. Our findings provide insights into the design of hierarchical structures for adaptive soft materials. [ABSTRACT FROM AUTHOR]

Abstract Background E1A-associated 300-kDa protein (P300), an endogenous histone acetyltransferase, contributes to modifications of the chromatin landscape of genes involved in multiple cardiovascular diseases. Ferroptosis of vascular smooth muscle cells (VSMCs) is a novel pathological mechanism of aortic dissection. However, whether P300 regulates VSMC ferroptosis remains unknown. Methods Cystine deprivation (CD) and imidazole ketone erastin (IKE) were used to induce VSMC ferroptosis. Two different knockdown plasmids targeting P300 and A-485 (a specific inhibitor of P300) were used to investigate the function of P300 in the ferroptosis of human aortic smooth muscle cells (HASMCs). Cell counting kit-8, lactate dehydrogenase and flow cytometry with propidium iodide staining were performed to assess the cell viability and death under the treatment of CD and IKE. BODIPY-C11 assay, immunofluorescence staining of 4-hydroxynonenal and malondialdehyde assay were conducted to detect the level of lipid peroxidation. Furthermore, co-immunoprecipitation was utilized to explore the interaction between P300 and HIF-1α, HIF-1α and P53. Results Compared with normal control, the protein level of P300 was significantly decreased in HASMCs treated with CD and IKE, which was largely nullified by the ferroptosis inhibitor ferrostatin-1 but not by the autophagy inhibitor or apoptosis inhibitor. Knockdown of P300 by short-hairpin RNA or inhibition of P300 activity by A-485 promoted CD- and IKE-induced HASMC ferroptosis, as evidenced by a reduction in cell viability and aggravation of lipid peroxidation of HASMCs. Furthermore, we found that hypoxia-inducible factor-1α (HIF-1α)/heme oxygenase 1 (HMOX1) pathway was responsible for the impacts of P300 on ferroptosis of HASMCs. The results of co-immunoprecipitation demonstrated that P300 and P53 competitively bound HIF-1α to regulate the expression of HMOX1. Under normal conditions, P300 interacted with HIF-1α to inhibit HMOX1 expression, while reduced expression of P300 induced by ferroptosis inducers would favor HIF-1α binding to P53 to trigger HMOX1 overexpression. Furthermore, the aggravated effects of P300 knockdown on HASMC ferroptosis were largely nullified by HIF-1α knockdown or the HIF-1α inhibitor BAY87-2243. Conclusion Thus, our results revealed that P300 deficiency or inactivation facilitated CD- and IKE-induced VSMC ferroptosis by activating the HIF-1α/HMOX1 axis, which may contribute to the development of diseases related to VSMC ferroptosis.

A monocular-vision-based coordinate measuring system (MVB-CMS) obtains the 3D coordinates of the probe tip center of a light pen by analyzing the monocular image of the target points on the light pen. The light pen calibration, including the target point calibration and the probe tip center calibration, is critical to guarantee the accuracy of the MVB-CMS. The currently used method resorts to special equipment to calibrate the feature points on the light pen in a separate offsite procedure and uses the system camera to calibrate the probe tip center onsite. Instead, a complete onsite light pen calibration method is proposed in this paper. It needs only several auxiliary target points with the same visual features of the light pen targets and two or more cone holes with known distance(s). The target point calibration and the probe tip center calibration are jointly implemented by simply taking two groups of images of the light pen with the camera of the system. The proposed method requires no extra equipment other than the system camera for the calibration, so it is easier to implement and flexible for use. It has been incorporated in a large field-of-view MVB-CMS, which uses active luminous infrared LEDs as the target points. Experimental results demonstrate the accuracy and effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Nephrotoxicity is a major side effect of cisplatin treatment of solid tumors in the clinical setting. Long-term low-dose cisplatin administration causes renal fibrosis and inflammation. However, few specific medicines with clinical application value have been developed to reduce or treat the nephrotoxic side effects of cisplatin without affecting its tumor-killing effect. The present study analyzed the potential reno-protective effect and mechanism of asiatic acid (AA) in long-term cisplatin-treated nude mice suffering from tumors. AA treatment significantly attenuated renal injury, inflammation, and fibrosis induced by long-term cisplatin injection in tumor-bearing mice. AA administration notably suppressed tubular necroptosis and improved the autophagy-lysosome pathway disruption caused by chronic cisplatin treatment in tumor-transplanted nude mice and HK-2 cells. AA promoted transcription factor EB (TFEB)-mediated lysosome biogenesis and reduced the accumulation of damaged lysosomes, resulting in enhanced autophagy flux. Mechanistically, AA increased TFEB expression by rebalancing Smad7/Smad3, whereas siRNA inhibition of Smad7 or TFEB abolished the effect of AA on autophagy flux in HK-2 cells. In addition, AA treatment did not weaken, but actually enhanced the anti-tumor effect of cisplatin, as evidenced by the promoted tumor apoptosis and inhibited proliferation in nude mice. In summary, AA alleviates cisplatin-induced renal fibrosis in tumor-bearing mice by improving the TFEB-mediated autophagy-lysosome pathway.

Abstract SARS-CoV-2, the culprit pathogen of COVID-19, elicits prominent immune responses and cytokine storms. Intracellular Cl− is a crucial regulator of host defense, whereas the role of Cl− signaling pathway in modulating pulmonary inflammation associated with SARS-CoV-2 infection remains unclear. By using human respiratory epithelial cell lines, primary cultured human airway epithelial cells, and murine models of viral structural protein stimulation and SARS-CoV-2 direct challenge, we demonstrated that SARS-CoV-2 nucleocapsid (N) protein could interact with Smad3, which downregulated cystic fibrosis transmembrane conductance regulator (CFTR) expression via microRNA-145. The intracellular Cl− concentration ([Cl−]i) was raised, resulting in phosphorylation of serum glucocorticoid regulated kinase 1 (SGK1) and robust inflammatory responses. Inhibition or knockout of SGK1 abrogated the N protein-elicited airway inflammation. Moreover, N protein promoted a sustained elevation of [Cl−]i by depleting intracellular cAMP via upregulation of phosphodiesterase 4 (PDE4). Rolipram, a selective PDE4 inhibitor, countered airway inflammation by reducing [Cl−]i. Our findings suggested that Cl− acted as the crucial pathological second messenger mediating the inflammatory responses after SARS-CoV-2 infection. Targeting the Cl− signaling pathway might be a novel therapeutic strategy for COVID-19.

Background: Eustachian tube dysfunction (ETD) is a common disorder causing ear pressure, pain, and hearing loss. Balloon Eustachian tuboplasty (BET) is an emerging technique for dilating the Eustachian tube and treating ETD. Whether adding myringotomy improves BET efficacy is controversial. Methods: This retrospective study included 95 ETD patients undergoing BET alone (n = 44) or BET with myringotomy (BET + M; n = 51) between June 2020 and August 2021 at a single medical center. The primary outcome was the change in ETDQ-7 symptom scores from baseline to 6 months after treatment. Secondary outcomes included audiometry, endoscopy, Valsalva maneuver, and complications. Results: The ETDQ-7 scores improved significantly after treatment in both groups (p < 0.001), without significant between-group differences (p = 0.417). No significant differences occurred in the audiometry, endoscopy, and Valsalva results or in most complications between groups. One BET + M patient had a persistent tympanic membrane perforation. Conclusions: Both BET alone and BET + M effectively and safely improved the subjective and objective ETD outcomes. However, adding myringotomy did not further improve the outcomes over BET alone, while it incurred risks such as persistent perforation. BET alone may sufficiently treat ETD without requiring myringotomy in this cohort. Further randomized controlled trials should identify optimal candidates for BET alone versus combined approaches.

BackgroundMost previous studies on acupuncture in the treatment of knee osteoarthritis (KOA) have focused on improving functional efficacy and safety, while related mechanisms have not been systematically reviewed. Acupuncture modulates cytokines to attenuate cartilage extracellular matrix degradation and apoptosis, key to the pathogenesis of KOA, but the mechanisms are complex.ObjectivesThe purpose of this study is to assess the efficacy of acupuncture quantitatively and summarily in animal studies of KOA.MethodsNine databases including PubMed, Embase, Web of Science (including Medline), Cochrane library, Scopus, CNKI, Wan Fang, and VIP were searched to retrieve animal studies on acupuncture interventions in KOA published since the inception of the journal. Relevant literature was screened, and information extracted. Meta-analysis was performed using Revman 5.4 and Stata 17.0 software.ResultsThe 35 included studies involved 247 animals, half of which were in acupuncture groups and half in model groups. The mean quality level was 6.7, indicating moderate quality. Meta-analysis showed that acupuncture had the following significant effects on cytokine levels in p38MAPK and mitochondrial pathways: (1) p38MAPK pathway: It significantly inhibits p38MAPK, interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNF-α), phosphorylated (p)-p38MAPK, matrix metalloproteinase-13 (MMP-13), MMP-1, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMST-5) expression, and significantly increased the expression of collagen II and aggrecan. (2) mitochondrial pathway: It significantly inhibited the expression of Bcl-2-associated X protein (Bax), cysteine protease-3 (caspase-3), caspase-9, and Cytochrome-c (Cyt-c). And significantly increased the expression of B cell lymphocytoma-2 (Bcl-2). In addition, acupuncture significantly reduced chondrocyte apoptosis, Mankin’s score (a measure of cartilage damage), and improved cartilage morphometric characteristics.ConclusionAcupuncture may inhibit cytokine expression in the p38MAPK pathway to attenuate cartilage extracellular matrix degradation, regulate cytokines in the mitochondrial pathway to inhibit chondrocyte apoptosis, and improve cartilage tissue-related phenotypes to delay cartilage degeneration. These findings provide possible explanations for the therapeutic mechanisms and clinical benefits of acupuncture for KOA.Systematic review registrationhttps://inplasy.com, identifier INPLASY20 2290125.

AIM: To study the effect of miR-26b on lens epithelial cells induced by transforming growth factor beta (TGF-β) 2 and the underlying signaling pathways. METHODS: Human lens epithelial cell line B-3 (HLE-B3) was incubated with TGF-β2 (5 ng/mL) and then transfected with miR-26b mimics. The expression of miR-26b was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), while 5'-bromodeoxyuridine (BrdU) and wound-healing assays were used to measure the growth and migration of HLE-B3 cells, respectively. The expression of epithelial-mesenchymal transition (EMT) markers and the activity of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway were measured by Western blotting assay and immunofluorescence staining. Electron microscopy was also used to observe cellular morphology. RESULTS: The expression levels of miR-26b were significantly reduced in human posterior capsular opacification-attached lens tissue and TGF-β2-stimulated HLE-B3 cells. In the presence of TGF-β2, the growth, migration, and EMT of HLE-B3 cells were distinctly enhanced; these effects were attenuated by the administration of miR-26b mimics. Furthermore, the overexpression of miR-26b significantly reduced upregulation of the PI3K/Akt pathway when stimulated by TGF-β2 in HLE-B3 cells. Moreover, the addition of an activator (740 Y-P) led to the upregulation of the PI3K/Akt pathway and abolished the protective effect of miR-26b on the HLE-B3 cells that was mediated by TGF-β2. CONCLUSION: The miR-26b suppresses TGF-β2-induced growth, migration, and EMT in HLE-B3 cells by regulating the PI3K/Akt signaling pathway.

On the basis of the inhibition effects of pymetrozine on the reproductive behavior of N. lugens, we established a bioassay method to accurately evaluate the toxicity of pymetrozine in N. lugens and clarified the level of pymetrozine resistance of N. lugens in the field. In this study, pymetrozine’s effects on the fecundity of N. lugens were evaluated using the topical application method and rice-seedling-dipping method. Moreover, the resistance of N. lugens to pymetrozine in a pymetrozine-resistant strain (Pym-R) and two field populations (YZ21 and QS21) was determined using the rice-seedling-dipping method and fecundity assay methods. The results showed that treatment of N. lugens third-instar nymphs with LC15, LC50, and LC85 doses of pymetrozine resulted in a significantly reduced fecundity of N. lugens. In addition, N. lugens adults treated with pymetrozine, using the rice-seedling-dipping and topical application method, also exhibited a significantly inhibited fecundity. Using the rice-stem-dipping method, pymetrozine resistance levels were shown to be high in Pym-R (194.6-fold), YZ21 (205.9-fold), and QS21 (212.8-fold), with LC50 values of 522.520 mg/L (Pym-R), 552.962 mg/L (YZ21), and 571.315 (QS21) mg/L. However, when using the rice-seedling-dipping or topical application fecundity assay method, Pym-R (EC50: 14.370 mg/L, RR = 12.4-fold; ED50: 0.560 ng/adult, RR = 10.8-fold), YZ21 (EC50: 12.890 mg/L, RR = 11.2-fold; ED50: 0.280 ng/adult; RR = 5.4-fold), and QS21 (EC50: 13.700 mg/L, RR = 11.9-fold) exhibited moderate or low levels of resistance to pymetrozine. Our studies show that pymetrozine can significantly inhibit the fecundity of N. lugens. The fecundity assay results showed that N. lugens only developed low to moderate levels of resistance to pymetrozine, indicating that pymetrozine can still achieve effective control on the next generation of N. lugens populations.

Transcription factors can affect autophagy activity by promoting or inhibiting the expression of autophagic and lysosomal genes. As a member of the zinc finger family DNA-binding proteins, ZKSCAN3 has been reported to function as a transcriptional repressor of autophagy, silencing of which can induce autophagy and promote lysosomal biogenesis in cancer cells. However, studies in Zkscan3 knockout mice showed that the deficiency of ZKSCAN3 did not induce autophagy or increase lysosomal biogenesis. In order to further explore the role of ZKSCAN3 in the transcriptional regulation of autophagic genes in human cancer and non-cancer cells, we generated ZKSCAN3 knockout HK-2 (non-cancer) and Hela (cancer) cells via the CRISPR/Cas9 system and analyzed the differences in gene expression between ZKSCAN3 deleted cells and non-deleted cells through fluorescence quantitative PCR, western blot and transcriptome sequencing, with special attention to the differences in expression of autophagic and lysosomal genes. We found that ZKSCAN3 may be a cancer-related gene involved in cancer progression, but not an essential transcriptional repressor of autophagic or lysosomal genes, as the lacking of ZKSCAN3 cannot significantly promote the expression of autophagic and lysosomal genes.

Convolutional neural networks in the field of artificial intelligence show great potential in image recognition. It assisted endoscopy to improve the detection rate of early gastric cancer. The 5-year survival rate for advanced gastric cancer is less than 30%, while the 5-year survival rate for early gastric cancer is more than 90%. Therefore, earlier screening for gastric cancer can lead to a better prognosis. However, the detection rate of early gastric cancer in China has been extremely low due to many factors, such as the presence of gastric cancer without obvious symptoms, difficulty identifying lesions by the naked eye, and a lack of experience among endoscopists. The introduction of artificial intelligence can help mitigate these shortcomings and greatly improve the accuracy of screening. According to relevant reports, the sensitivity and accuracy of artificial intelligence trained on deep cirrocumulus neural networks are better than those of endoscopists, and evaluations also take less time, which can greatly reduce the burden on endoscopists. In addition, artificial intelligence can also perform real-time detection and feedback on the inspection process of the endoscopist to standardize the operation of the endoscopist. AI has also shown great potential in training novice endoscopists. With the maturity of AI technology, AI has the ability to improve the detection rate of early gastric cancer in China and reduce the death rate of gastric cancer related diseases in China.

Organ transplantation has evolved rapidly in recent years as a reliable option for patients with end-stage organ failure. However, organ shortage, surgical risks, acute and chronic rejection reactions and long-term immunosuppressive drug applications and their inevitable side effects remain extremely challenging problems. The application of nanotechnology in medicine has proven highly successful and has unique advantages for diagnosing and treating diseases compared to conventional methods. The combination of nanotechnology and transplantation brings a new direction of thinking to transplantation medicine. In this article, we provide an overview of the application and progress of nanotechnology in kidney and islet transplantation, including nanotechnology for renal pre-transplantation preservation, artificial biological islets, organ imaging and drug delivery.

Nail gun injuries usually occur at the extremities due to working accidents. Intracranial or intrathoracic injuries are relatively rare, and cases combined with both injuries are even rarer. Such situations pose challenges for surgeons due to their uniqueness during operation. Radiologic imaging findings in our case were significant in indicating surgical findings. Herein, we report a patient who shot himself using a nail gun, damaging his brain and heart. Keywords: Nail gun injury, Computed tomography, Trauma

Stabilize the active metal single atoms under harsh conditions is critical for the development of single atom catalysts. Here the authors report a nanoporous crystal, 12CaO·7Al2O3, that can firmly stabilize Pt single atoms in its surface cavities for efficient catalytic hydrogenation of nitroarenes.

In Suzuki coupling reactions, excellent catalytic performance require negatively charged Pd species and the avoidance of metal leaching or clustering. Here the authors implanted Pd sites into an intermetallic electride, Y3Pd2, which serves as an efficient and stable catalyst for Suzuki coupling reactions.

Objective This study was performed to analyze the risk factors associated with flexor pollicis longus (FPL) attrition or rupture after volar plating of distal radius fractures. Methods Three hundred thirty-eight patients with distal radius fractures were included in this retrospective study. Univariate analysis and multivariate logistic regression analysis were performed to predict risk factors. Results Univariate analysis showed that sex, volar tilt, the Soong grade, the plate-to-critical line distance (PCLD), the plate-to-volar rim distance (PVRD), and the time of plate removal were significantly associated with FPL attrition or rupture. Multivariate logistic regression analysis demonstrated that decreased volar tilt, Soong grade 2, PCLD of >2 mm, PVRD of 2 mm, and PVRD of 2 mm, the PVRD is

Background: A higher compliance with clinical guidelines helps improve treatment outcomes. But the clinical practice of otolaryngologists is not always consistent with guidelines. Objective: To describe otolaryngologists’ compliance with guidelines about allergic rhinitis (AR) management and identify factors responsible for the discordance between clinical practice and guideline recommendations in China. Methods: A cross-sectional nationwide survey was designed and conducted via an online platform. Recruitment was done by emailing otolaryngologists registered in the Chinese Society of Otorhinolaryngology-Head and Neck Surgery or by inviting otolaryngologists to scan a Quick Respond (QR) code that linked to the questionnaire at various academic meetings. Results: A total of 2142 otolaryngologists were eligible and completed the survey. Of them, 64.7% had over 10 years work experience and 97.4% had a bachelor's degree or higher. About 18.3% of the participants strictly copied the guideline in clinical practice, while 73.7% used the guideline that had been adjusted according to their clinical experience. Otolaryngologists were most concerned about the efficacy, safety, and minimum age of AR medications, and least concerned about patient preferences. Regarding the use of intranasal steroids (INS), leukotriene receptor antagonists (LTRA), and H1-antihistamines, 86.8%, 55.7% and 51.2% of otolaryngologists complied with the guideline recommendations, respectively. Educational background was a factor affecting the compliance with guidelines and acceptance of INS. Conclusion: A vast majority of Chinese otolaryngologists complied with the current Chinese AR guidelines. A difference still existed between the otolaryngologists' real-world and guideline-recommended management. The otolaryngologists should pay more attention to patient preferences. A higher education could improve otolaryngologists’ adherence to the guidelines.

Two-dimensional materials are promising for electrochemical storage and conversion, but are somewhat limited in composition. Here the authors use a computational strategy to predict the existence of a layered boride material, which they synthesize and demonstrate prospective for use as an anode material.

Abstract Background Dyslipidaemia has always been regarded as the cornerstone of arteriosclerosis and is related to the pathogenesis of renal insufficiency. However, it is unclear which routinely available lipid parameter is related to urinary albumin to creatinine ratio (UACR). The purpose of this study was to examine the lipid abnormalities associated with UACR in the general population in China. Methods The present study was nested in an ongoing Risk Evaluation of cAncers in Chinese diabetic Individuals: A lONgitudinal (REACTION) study, which was designed to demonstrate the association of abnormal glucose metabolism with the risk of cancer in the Chinese population. This cross-sectional study included 34, 569 subjects (11, 390 males and 23, 179 females) from 8 different regional community cohorts, with an average age of 57.9 years. The UACR data were divided into the

Inflammatory injury and neuronal apoptosis participate in the period of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Suppression of inflammation has recently been shown to reduce neuronal death and neurobehavioral dysfunction post SAH. Biochanin A (BCA), a natural bioactive isoflavonoid, has been confirmed to emerge the anti-inflammatory pharmacological function. This original study was aimed at evaluating and identifying the neuroprotective role of BCA and the underlying molecular mechanism in an experimental Sprague-Dawley rat SAH model. Neurobehavioral function was evaluated via the modified water maze test and modified Garcia neurologic score system. Thus, we confirmed that BCA markedly decreased the activated level of TLRs/TIRAP/MyD88/NF-κB pathway and the production of cytokines. BCA also significantly ameliorated neuronal apoptosis which correlated with the improvement of neurobehavioral dysfunction post SAH. These results indicated that BCA may provide neuroprotection against EBI through the inhibition of inflammatory injury and neuronal apoptosis partially via the TLRs/TIRAP/MyD88/NF-κB signal pathway.

Background. Previous studies suggested that visual evoked potential (VEP) was impaired in patients with Parkinson’s disease (PD), but the results were inconsistent. Methods. We conducted a systematic review and meta-analysis to explore whether the VEP was significantly different between PD patients and healthy controls. Case-control studies of PD were selected through an electronic search of the databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials. We calculated the pooled weighted mean differences (WMDs) and 95% confidence intervals (CIs) between individuals with PD and controls using the random-effects model. Results. Twenty case-control studies which met our inclusion criteria were included in the final meta-analysis. We found that the P100 latency in PD was significantly higher compared with healthy controls (pooled WMD = 6.04, 95% CI: 2.73 to 9.35, P=0.0003, n=20). However, the difference in the mean amplitude of P100 was not significant between the two groups (pooled WMD = 0.64, 95% CI: −0.06 to 1.33, P=0.07) based on 10 studies with the P100 amplitude values available. Conclusions. The higher P100 latency of VEP was observed in PD patients, relative to healthy controls. Our findings suggest that electrophysiological changes and functional defect in the visual pathway of PD patients are important to our understanding of the pathophysiology of visual involvement in PD.

Deregulation of the Wnt signaling pathway leads to colorectal cancer progression. Natural dietary compounds serve as promising candidates for development as chemopreventive agents by suppressing the Wnt/β-catenin signaling pathway. Physalis peruviana-derived 4βHWE showed a significant inhibitory activity with a calculated IC50 of 0.09 μΜ in a screening of novel inhibitors of Wnt signaling with the dual-luciferase reporter assay. This study investigated the anti-tumor effect of 4βHWE and the potential Wnt signaling inhibitory mechanism. Both the western blot analysis and immunofluorescence assay showed that 4βHWE promoted the phosphorylation and degradation of β-catenin and the subsequent inhibition of its nuclear translocation to attenuate the endogenous Wnt target gene expression in colorectal cancer (CRC) cells. The cell viability assay indicated that 4βHWE preferentially inhibited the proliferation of CRC compared with CCD-841-CoN, a normal human colonic epithelial cell line. 4βHWE-mediated G0/G1 cell cycle arrest and apoptosis induction contributed to the suppression of the proliferation of CRC in the cell cycle and Annexin V-FITC/Propidium Iodide apoptosis analysis. Moreover, in vivo, 4βHWE dramatically inhibited tumor growth in HCT116 xenografts by attenuating the Wnt/β-catenin signaling pathway. In conclusion, our study suggested that 4βHWE could be of potential use in anti-tumor agent development as a novel Wnt signaling inhibitor.

The mechanical property of projectile material, especially the strength and ductility, will greatly affect the deformation and damage of a kinetic energy projectile in the process of penetration. This paper presents a comparison methodology concerning the deformation and fracture behavior of kinetic energy projectiles with three kinds of strength and ductility manufactured from 1100, 6061 and 2A12 aluminum alloy bars. In the experiments, flat-nosed projectiles were fired using a two-stage light gas gun against hard steel plates within the velocity range of 150-600 m/s. Experimental results showed that there are different deformation and fracture modes for the three kinds of projectiles within different velocity ranges. With the increasing of impact velocity, deformation and fracture modes for each kind of projectile are listed as follows, respectively: mushrooming, tensile splitting and sunflower-like petalling for 1100 projectiles with high ductility; mushrooming, shear cracking, shear petalling and petals falling off for 6061 projectiles with medium ductility; mushrooming, shearing cracking and fragmentation for 2A12 projectiles with low ductility. In order to achieve a more comprehensive understanding of the influence of strength and ductility on material fracture mechanism, microscopic observations of typical fracture surfaces were conducted by a scanning electron microscope (SEM). [ABSTRACT FROM AUTHOR]

Understanding the energy dissipation mechanism during deformation is essential for the design and application of tough soft materials. We show that, in a class of tough and self-healing polyampholyte hydrogels, a bicontinuous network structure, consisting of a hard network and a soft network, is formed, independently of the chemical details of the hydrogels. Multiscale internal rupture processes, in which the double-network effect plays an important role, are found to be responsible for the large energy dissipation of these hydrogels. [ABSTRACT FROM AUTHOR]

In the title compound, C9H10BrNO, molecules are interconnected by a framework of intermolecular N—H...O hydrogen bonds. Infinite one-dimensional hydrogen-bonded chains extend along the a direction. These chains are aggregated into layers through weak inter-chain C—H...Br contacts along c. [ABSTRACT FROM AUTHOR]

Objective: The longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood., Design: This community-based, case-control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006-2016. Nested within this population, we identified 695 cases of CRC and 3475 CRC-free controls (matched 5:1 to cases for age, sex and year of colonoscopy). Two expert pathologists reviewed the tissue slides of all SPs identified on the first colonoscopy and reclassified them to sessile serrated lesions (SSLs), hyperplastic polyps (HPs) and traditional serrated adenomas. SPs with borderline characteristics of SSLs but insufficient to make a definitive diagnosis were categorised as unspecified SPs. The association with development of CRC was assessed using multivariable logistic regression., Results: Compared with individuals with no polyp, the adjusted ORs (aORs) for SSL alone or with synchronous adenoma were 2.9 (95% CI: 1.8 to 4.8) and 4.4 (95% CI: 2.7 to 7.2), respectively. The aORs for SSL with dysplasia, large proximal SSL,and small proximal SSL were 10.3 (95% CI: 2.1 to 50.3), 12.8 (95% CI: 3.5 to 46.9) and 1.9 (95% CI: 0.8 to 4.7), respectively. Proximal unspecified SP also conferred an increased risk (aOR: 5.8, 95% CI: 2.2 to 15.2). Women with SSL were associated with higher risk (aOR: 4.4; 95% CI: 2.3 to 8.2) than men (aOR: 1.7; 95% CI: 0.8 to 3.8)., Conclusion: Increased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To establish a new animal model for the research of human rotavirus (HRV) infection, its pathogenesis and immunity and evaluation of potential vaccines., Methods: 5-d, 30-d and 60-d-old Chinese mini-pigs, Guizhou and Bamma, were inoculated with a single oral dose of attenuated strain Wa, G1, G3 of HRV, and PBS (control), respectively, and fecal samples of pigs from 0 to 7 d post infection (DPI) were collected individually. Enzyme linked immunosorbent assay was used to detect HRV antigen in feces. The HRV was tested by real-time PCR (RT-PCR). The sections of the intestinal tissue were stained with hematoxylin and eosin to observe the morphologic variation by microscopy. Immunofluorescence was used to determine the HRV in intestinal tissue. HRV particles in cells of the ileum were observed by electron micrography., Results: When inoculated with HRV, mini-pigs younger than 30 d developed diarrhea in an age-dependent manner and shed HRV antigen of the same inoculum, as demonstrated by RT-PCR. Histopathological changes were observed in HRV inoculated mini-pigs including small intestinal cell tumefaction and necrosis. HRV that was distributed in the small intestine was restricted to the top part of the villi on the internal wall of the ileum, which was observed by immunofluorescence and transmission electron microscopy. Virus particles were observed in Golgi like follicles in HRV-infected neonatal mini-pigs. Guizhou mini-pigs were more sensitive to HRV than Bamma with respect to RV antigen shedding and clinical diarrhea., Conclusion: These results indicate that we have established a mini-pig model of HRV induced diarrhea. Our findings are useful for the understanding of the pathogenic mechanisms of HRV infection.

The title compound, C(12)H(16)O(5), is a derivative of β-(3,4-dihydroxy-phen-yl)-α-hydr-oxy acid. The crystal packing is stabilized by inter-molecular O-H⋯O hydrogen bonds.

In the title compound, C(12)H(13)NO(5), the azlactone of vanillin, the acrylic acid side chain has a trans extended conformation. There are inter-molecular N-H⋯O and O-H⋯O hydrogen bonds in the crystal structure.

Objective: To investigate the CYP17A1 gene mutations in Chinese patients with 17 alpha-hydroxylase/17, 20-lyase deficiency., Methods: Clinical data were retrospectively analyzed. The CYP17A1 gene mutations were detected in 5 cases with 17 alpha-hydroxylase/17, 20-lyase deficiency and their relatives. The genomic DNA of the patients was isolated from whole blood. Seven pairs of primers were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. In order to confirm the DNA sequences of different alleles, some fragments were inserted into pMD 18-T vector and then sequenced. Sequencing results were compared to the established human CYP17A1 sequence., Results: Briefly, we found 2 kinds of compound mutations, of which were: (1) 6436-6438(TAC-->AA), causing amino acid Y329K, 418X; (2) 6531-6532(GC-->A), causing amino acid L361F, 418X. Among the five cases, four were homozygous for 6436-6438(TAC-->AA), whereas one was compound heterozygous for 6436-6438(TAC-->AA)/6531-6532(GC-->A). The clinical characteristics of 5 cases were all completely combined defects of 17 alpha-hydroxylase/17, 20-lyase, and they all carried two alleles of CYP17A1 gene mutations that all shifted the reading frame and resulted in truncated protein which lack of the activity center site of P450C17, of which corresponding with their clinical feature., Conclusion: Nine alleles have the mutation of 6436-6438(TAC-->AA), accounting for 90% of total alleles (9/10). That suggests this kind of mutation may have racial specificity. More study should be done to have better understanding of the function of the truncated P450C17 enzymes.