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To study the modulatory mechanism of let-7c-5p on the biological characteristics of lung adenocarcinoma (LUAD) cells by targeting AURKB. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. CCK-8, colony formation, scratch healing, Transwell, and flow cytometry assays were employed to test biological functions of LUAD cells. Western Blot was undertaken to assay the protein level of AURKB, and qRT-PCR was undertaken to test AURKB mRNA and let-7c-5p expression. Dual-luciferase reporter gene method was applied to detect the interaction between AURKB and let-7c-5p. Let-7c-5p was much likely to target AURKB expression. Let-7c-5p was poorly expressed in LUAD cells and suppressed AURKB. Silencing AURKB or overexpressing let-7c-5p both could suppress proliferation, migration, and invasion and stimulate apoptosis, while overexpressing the two simultaneously could reverse such effect. Forced expression of let-7c-5p inhibited proliferation, migration, and invasion and accelerated apoptosis of LUAD cells by inhibiting AURKB, which may provide a new way to understand the malignant progression of LUAD.

Severe tetanus is characterized by muscle spasm and cardiovascular system disturbance. The pathophysiology of muscle spasm is relatively well understood and involves inhibition of central inhibitory synapses by tetanus toxin. That of cardiovascular disturbance is less clear, but is believed to relate to disinhibition of the autonomic nervous system. The clinical syndrome of autonomic nervous system dysfunction (ANSD) seen in severe tetanus is characterized principally by changes in heart rate and blood pressure which have been linked to increased circulating catecholamines. Previous studies have described varying relationships between catecholamines and signs of ANSD in tetanus, but are limited by confounders and assays used. In this study, we aimed to perform detailed characterization of the relationship between catecholamines (adrenaline and noradrenaline), cardiovascular parameters (heart rate and blood pressure) and clinical outcomes (ANSD, mechanical ventilation required, and length of intensive care unit stay) in adults with tetanus, as well as examine whether intrathecal antitoxin administration affected subsequent catecholamine excretion. Noradrenaline and adrenaline were measured by ELISA from 24-h urine collections taken on day 5 of hospitalization in 272 patients enrolled in a 2 × 2 factorial-blinded randomized controlled trial in a Vietnamese hospital. Catecholamine results measured from 263 patients were available for analysis. After adjustment for potential confounders (i.e., age, sex, intervention treatment, and medications), there were indications of non-linear relationships between urinary catecholamines and heart rate. Adrenaline and noradrenaline were associated with subsequent development of ANSD, and length of ICU stay.

Phaeodactylum tricornutum (Pt) is a critical microbial cell factory to produce a wide spectrum of marketable products including recombinant biopharmaceutical N-glycoproteins. N-glycosylation modification of proteins is important for their activity, stability, and half-life, especially some special modifications, such as fucose-modification by fucosyltransferase (FucT). Three PtFucTs were annotated in the genome of P. tricornutum, PtFucT1 was located on the medial/trans-Golgi apparatus and PtFucT2-3 in the plastid stroma. Algal growth, biomass and photosynthesis efficiency were significantly inhibited in a knockout mutant of PtFucT1 (PtFucT1-KO). PtFucT1 played a role in non-core fucose modification of N-glycans. The knockout of PtFucT1 might affect the activity of PtGnTI in the complex and change the complex N-glycan to mannose type N-glycan. The study provided critical information for understanding the mechanism of protein N-glycosylation modification and using microalgae as an alternative ecofriendly cell factory to produce biopharmaceuticals.

Background To explore the efficacy of observation, laser photocoagulation, and anti-VEGF in the management of retinal arterial macroaneurysm (RAM). Methods We retrospectively included patients diagnosed with RAM at the Peking Union Medical College Hospital (PUMCH) from 2003 to 2021, and comprehensively reviewed cases documented in the literature from multiple databases (PROSPERO protocol CRD42022310417). Patients were categorized into 3 groups: the observation group, anti-VEGF group, and laser photocoagulation group. LogMAR visual acuity (VA) and central retinal thickness (CMT) at the end of the follow-up were analyzed. Results A total of 14 patients from the PUMCH and 210 patients from the literature review were included. VA and CMT in patients who underwent observation, laser photocoagulation, and anti-VEGF therapies were significantly improved from baseline (p p = 0.010), but achieved better improvement in VA than the laser photocoagulation group (p = 0.049). Patients treated with anti-VEGF also had thicker CMT than the observation group (p = 0.013), and experienced better changes in CMT than the observation, as well as laser photocoagulation groups (p = 0.005; p = 0.047). Conclusion Observation, anti-VEGF, and laser photocoagulation are effective therapeutic methods for the management of RAM, and anti-VEGF therapy is intended to better improve patients with severe VA and CMT.

Tunicamycin inhibits the first step of protein N-glycosylation modification. However, the physiological, transcriptomic, and N-glycomic effects of tunicamycin on important marine diatom Phaeodactylum tricornutum are still unknown. In this study, comprehensive approaches were used to study the effects of tunicamycin stress. The results showed that cell growth and photosynthesis were significantly inhibited in P. tricornutum under the tunicamycin stress. The soluble protein content was significantly decreased, while the soluble sugar and neutral lipid were dramatically increased to orchestrate the balance of carbon and nitrogen metabolisms. The stress of 0.3 μg ml−1 tunicamycin resulted in the differential expression of ERQC and ERAD related genes. The upregulation of genes involved in ERQC pathway, the activation of anti-oxidases and the differential expression of genes related with ERAD mechanism might be important for maintaining homeostasis in cell. The identification of N-glycans, especially complex-type N-glycan structures enriched the N-glycan database of diatom P. tricornutum and provided important information for studying the function of N-glycosylation modification on proteins. As a whole, our study proposed working models of ERQC and ERAD will provide a solid foundation for further in-depth study of the related mechanism and the diatom expression system.

Kinesin-like calmodulin-binding protein (KCBP) is a unique kinesin with half kinesin and half myosin, with kinesin motor domain at C-terminus and myosin tail homology region 4 (MyTH4) and band 4.1, ezrin, radixin, moesin (FERM) domains at N-terminus. The special structure endows KCBP multi-intracellular functions, including cell division, trichome morphogenesis in plants, and flagellar function in algae. However, little is known about the molecular mechanism underlying these functions. Here, we identified a molecular chaperone Hsp90 as a novel binding partner with KCBP in Dunaliella salina using a yeast two-hybrid screen. Further analysis showed that Hsp90 interacted with both the N-terminal and C-terminal of DsKCBP. Since Hsp90 was involved in the stability and proteolytic turnover of numerous proteins, whether Hsp90 regulated the degradation of DsKCBP was investigated. Our results showed that both Hsp90 and DsKCBP presented in the purified proteasome, and the interaction of DsKCBP-Hsp90 was inhibited upon Hsp90 inhibitor geldanamycin treatment. The level of DsKCBP proteins was diminished remarkably indicating that the disassociation of DsKCBP from Hsp90 accelerated the degradation of the former. Furthermore, immunofluorescence results showed that the localization of DsKCBP at basal body and flagella was disappeared by Hsp90 inhibition. The increased mRNA level of DsKCBP during flagellar assembly was not obvious by geldanamycin treatment. These data provided evidence that Hsp90 protected DsKCBP from degradation by proteasome and was involved in the role of DsKCBP in flagellar assembly.

To compare the masseter muscle changes and bone regeneration between reduction mandibuloplasty along with partial masseter muscle resection and reduction mandibuloplasty alone. Forty-seven patients who complained of prominent mandibular angle and hypertrophy masseter muscles (MMH) were divided into group 1 treated with reduction mandibuloplasty along with partial masseter muscle resection, and group 2 treated with reduction mandibuloplasty alone. Pre-5 days and long-term postoperative computed tomography data were collected, and the masseter muscle volume, hemi-mandible volume, and unilateral lower face width were measured. Patient satisfaction and complication were also evaluated. At long-term follow-up, group 1 showed a greater decrease in masseter volume (p

The authors have previously demonstrated that one phage-displayed keratinocyte growth factor (KGF) model peptide that can bind to epidermal cells and facilitate cellular proliferation. In this study, the authors investigated the role of phage-displayed KGF model peptide on wound healing in diabetic rats. Full-thickness excisional dorsal wounds were created in the diabetic rats, after which the rats were randomly divided into five groups: negative control group [normal saline (NS)], two KGF control groups which were respectively treated with low-dose KGF (5 ng/mL, K-LD) and high-dose KGF (50 ng/mL, K-HD), and two KGF model-peptide-treated groups which were respectively treated with low-dose model peptide (5 ng/mL, M-LD) and high-dose model peptide (50 ng/mL, M-HD). On day 14 post-injury, wound closure was followed by digital planimetry and wound tissues were harvested for histologic assay and real-time polymerase chain reaction. Wounds treated with model peptide closed markedly faster than negative control wounds and were comparable to KGF treated wounds. Histology and immunohistology results demonstrated significantly higher levels of re-epithelization, granulation tissue formation and vascularization in the model peptide groups. Furthermore, real-time polymerase chain reaction expression of KGFR, collagen I and transforming growth factor-β1 in model peptide groups, were also generally higher than that in negative control group. Phage-displayed KGF peptide promotes wound healing through accelerating re-epithelialization, enhancing dermal regeneration, and inducing angiogenesis. Model peptide possesses the potential to be a promising therapeutic option for the treatment of diabetic ulcers.

Although numerous efforts have been made in direct syngas conversion to higher alcohols via Fischer–Tropsch synthesis, the higher alcohols distribution remains a challenge. Here, we introduce alkaline earth metal oxide as promoter into activated carbon supported cobalt catalyst to tune distribution of higher alcohols. With the addition of Mg, the distribution of C2-5 alcohols increase from 41.2 to 75.8% accompanying with distribution of C6-18 alcohols decrease from 52.8 to 14.0%. Ba-promoted Co based catalyst (CoBa/AC) presents similar alcohols distribution to un-promoted catalyst, while the alcohol selectivity over CoBa/AC is higher than Co/AC. For promoted catalysts, the distribution of C6-18 alcohols increased in the order of Mg

The awareness and treatment of lacrimal gland prolapse (LGP) have been primarily improved with a further understanding of lateral eyelid bulging over the decades. However, for Asian single-eyelid females with LGP, a tailor-made procedure applicable to their comparatively young puffy eyes is needed. This is a retrospective study. From Jan. 2009 to Jan. 2019, two hundred and three Asian single-eyelid females with LGP, who met the inclusion criteria, underwent double-eyelid surgeries and adjunctive lacrimal gland repositions with preaponeurotic fat transposition. Pertinent demographics, complications, pre-and post-operative photography were collected. A total of 167 patients completed the 4–24 months’ follow-up (average: 16.3 months). One hundred and thirty-two cases (79.0%) were diagnosed as LGP preoperatively, and the rest (35/167, 21.0%) were diagnosed intraoperatively. All patients (average: 28.4 years old) received modified blepharoplasty. Postoperative symptoms involving local mild pain (2.9%, 5/167), upper eyelid tightness (3.6%, 6/167), and moderate epiphora (9.0%, 15/167) were all recovered spontaneously within one month. Prolapse recurrence and severe complications such as dry eye syndrome were not observed. We proposed a modified procedure to enhance the diagnosis and treatment of LGP during Asian blepharoplasty. The lacrimal gland suspension and fat transposition assured the cosmetic outcome for selected young, puffy Asian eyes. The supratarsal creases were satisfactory, and the complication rate was low. Furthermore, the rearrangement of preaponeurotic fat smoothed the contour transition and preserved the orbital volume. Therefore, this is a safe and effective technique worth recommending.

To evaluate the effect of phage-displayed TGF-β1 model peptide on cutaneous wound healing in streptozotocin-induced diabetic rats. Full-thickness excisional wounds were made on the dorsums of 50 rats which were then randomly divided into five groups: negative control group (normal saline (NS)), two TGF-β1 control groups which were respectively treated with low-dose TGF-β1 ( 5 ng/ml) and high-dose TGF-β1 (50 ng/ml), and two model-peptide-treated groups which were respectively treated with low-dose model peptide ( 5 ng/ml,) and high-dose model peptide (50 ng/ml). At day 14 post-injury, rats were euthanised and wounds were assessed by gross, histopathology, immunohistochemistry, immunofluorescence and quantificational real-time polymerase chain reaction. A significant increase in rate of wound closure was observed in model peptide groups in comparison to negative control group. The results of histopathological staining revealed that re-epithelization and collagen deposition in model-peptide-treated groups were significantly higher than those in negative control group. The results of immunohistochemistry and immunofluorescence tests showed that Ki67-positive, VEGFA-positive, CD31-positive, α-SMA-positive, CD206-positive cells in model peptide and TGF-β1 control groups were more than those in negative control group. Furthermore, comparing with the mRNA expression profile in negative control groups, mRNA expression profile in model peptide group showed a decrease in proinflammatory cytokine and an increase in anti-inflammatory cytokine and collagen. Phage-displayed TGF-β1 peptide facilitates wound healing through accelerating re-epithelialization, enhancing collagen deposition, promoting neo-vascularization, and inhibiting inflammatory response. Model peptide possesses the potential to be a promising treatment strategy for enhancing diabetic wound repair.

Oral delivery of protein drugs is considered a life-changing solution for patients who require regular needle injections. However, clinical translation of oral protein formulations has been hampered by inefficient penetration of drugs through the intestinal mucus and epithelial cell layer, leading to low absorption and bioavailability, and safety concerns owing to tight junction openings. Here we report a zwitterionic micelle platform featuring a virus-mimetic zwitterionic surface, a betaine side chain and an ultralow critical micelle concentration, enabling drug penetration through the mucus and efficient transporter-mediated epithelial absorption without the need for tight junction opening. This micelle platform was used to fabricate a prototype oral insulin formulation by encapsulating a freeze-dried powder of zwitterionic micelle insulin into an enteric-coated capsule. The biocompatible oral insulin formulation shows a high oral bioavailability of >40%, offers the possibility to fine tune insulin acting profiles and provides long-term safety, enabling the oral delivery of protein drugs. A zwitterionic micelle platform enables the oral delivery and high bioavailability of insulin by transporting the protein across mucus and epithelial barriers in the gut without opening tight junctions.

Mandibular angle ostectomy is a common plastic surgery for facial contouring in East Asians. However, rarely we could find reports on differences between East Asian males and females undergoing this surgery. To describe the differences between East Asian males and females before and after mandibular angle ostectomy. A total of 22 Asian males and 52 Asian females who underwent mandibular angle ostectomy from April 2015 to November 2018 were enrolled. Three-dimensional computed tomography was used to evaluate the preoperative and postoperative data of the mandible. Thirteen clinical data were measured on reconstructed mandibular models. The differences in data between males and females were analyzed to identify the causes of the differences before and after surgery. The follow-up was 6–12 months, and patient satisfaction was also evaluated. The ostectomy volume was positively correlated with the distance from the intersection of the occlusal plane and the anterior margin of the mandibular ramus to gonion (MR-Go; female, p

The instability of slope has already threatened life and property safety of the people, and improving the monitoring method of slope stability has important theoretical and practical significance for disaster prevention and reduction. According to the idea of “Newton force sudden drop and catastrophic occurrence” proposed by M.C. He in the landslide monitoring, a numerical model with constant resistance bolt has been established. Through numerical simulation research, it is found that the maximum principal stress, minimum principal stress and shear stress of the intersection point P of landslide surface and constant resistance bolt are sudden growth and sudden decrease, the vertical displacement and lateral displacement of this point P appear rise and fall before three kinds of stress. When loading to the next step of the step where three stress have reduced to a minimum value the slope is unstable and destroyed. At this time, the constant resistance bolt has undergone larger plastic deformation and damaged. Finally, comparing the stress curves and the acoustic emission (AE) curves, it can be seen that stress decreases from the maximum value and the AE curves begin to show a significant rise, the two curves display opposite law. It can be seen from the AE diagram that the failure mode of the slope is a combined tension and shear failure. The numerical test results provide a new idea for real-time monitoring and forecasting of slope.

To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP). A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events. Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P

Tigecycline is one of the last-resort antibiotics to treat complicated infections caused by both multidrug-resistant Gram-negative and Gram-positive bacteria1. Tigecycline resistance has sporadically occurred in recent years, primarily due to chromosome-encoding mechanisms, such as overexpression of efflux pumps and ribosome protection2,3. Here, we report the emergence of the plasmid-mediated mobile tigecycline resistance mechanism Tet(X4) in Escherichia coli isolates from China, which is capable of degrading all tetracyclines, including tigecycline and the US FDA newly approved eravacycline. The tet(X4)-harbouring IncQ1 plasmid is highly transferable, and can be successfully mobilized and stabilized in recipient clinical and laboratory strains of Enterobacteriaceae bacteria. It is noteworthy that tet(X4)-positive E. coli strains, including isolates co-harbouring mcr-1, have been widely detected in pigs, chickens, soil and dust samples in China. In vivo murine models demonstrated that the presence of Tet(X4) led to tigecycline treatment failure. Consequently, the emergence of plasmid-mediated Tet(X4) challenges the clinical efficacy of the entire family of tetracycline antibiotics. Importantly, our study raises concern that the plasmid-mediated tigecycline resistance may further spread into various ecological niches and into clinical high-risk pathogens. Collective efforts are in urgent need to preserve the potency of these essential antibiotics. Plasmid-encoded tet(X) genes from Escherichia coli in China confer high-level tigecycline resistance.

To study the tensile mechanical properties of constant resistance bolts, the RFPA (Rock Failure Process Analysis) statics software is used to perform a uniaxial tensile test on a constant resistance bolt. The numerical test results show that the plastic strain value is 12 times the magnitude of the elastic strain. During plastic deformation, the fluctuation in the stress magnitude is relatively stable, indicating that the bolt has good constant resistance characteristics. The numerical test results are in good agreement with the laboratory test results of M.C. He, and the accuracy and reliability of the numerical test method are verified. Therefore, the RFPA software with coupled static-dynamic loading is further adopted to study the supporting effects of traditional bolts and constant resistance bolts under coupled static-dynamic loading. The numerical comparison of the test results show that the constant resistance bolts can effectively control the deformation amount and rate of the laneway surrounding rock, reduce the total and rate of increase in the accumulated acoustic emissions, decrease the stress on the units in the model and protect the stability of the laneway. This paper verifies that a constant resistance bolt has better impact resistance mechanical properties than those of a traditional bolt and provides an effective way to control rock burst and soft rock that is prone to large deformation damage.

The effect of nitrogen deficiency and subsequent recovery on photosynthetic performance of the red macroalga Gracilariopsis lemaneiformis was measured in terms of algal growth rate, accumulation of photosynthetic pigments (i.e., phycoerythrin and chlorophyll-a), maximum effective quantum yield of photosystem II (Fv/Fm), and the transcript levels of genes related to photosynthesis and photorespiration. Nitrogen deficiency and then recovery notably promoted the growth of G. lemaneiformis, significantly inhibited the accumulation of phycoerythrin and chlorophyll-a, but had no significant influence on Fv/Fm. In addition to physiological performance of algae under nitrogen stress, the key genes encoding photorespiratory and photosynthetic enzymes (i.e., gdct, gdcp, hpr, shmt, sgat, sbp, and rub) were up-regulated which might have led to more increased in growth rate than that of control after the recovery of nitrogen. While the down-regulation of gdct, gdcp, and shmt genes at the 4th day of nitrogen deficiency might be linked to the reduced accumulation of phycoerythrin and chlorophyll-a, the up-regulation of gdct and gdcp at the beginning of nitrogen deficiency and nitrogen recovery might associate with Fv/Fm that did not change significantly. Briefly, the up- and down-regulation of these genes at different times might be due to an algal complex regulatory mechanism. Thus, the combined action of these genes allows the algae to display higher photosynthetic efficiency and better growth, eventually acclimate to the varying environmental stresses. The data provided here represent a rich source for exploring the function of genes related to photorespiration and photosynthesis as well as the mechanism of algal acclimation under environmental stress.

In this paper, a new reproducing kernel Chebyshev wavelets method of solving a fractional telegraph equation is proposed. For solving the equation, reproducing kernel Chebyshev wavelets bases is constructed based on Chebyshev polynomials with a parameter. We choose an improved differential quadrature method with fourth-order truncation error to approximate second-order derivative term of the equation. Subsequently, the fractional telegraph equation is transformed into integral equation and the best approximate solution is obtained by searching the minimum of $$\varepsilon $$ -approximate solutions. It is satisfied that the accuracy of errors provided by examples is very high.

In the paper, an improved collocation method is proposed for solving a linear fractional integro-differential equation. The method is proposed by improving the residual to vanish and require the residual to the minimum in sense of $$\Vert \cdot \Vert _C$$ . It can avoid efficiently ill-conditioned of higher degree polynomials. Convergence order is superconvergence and stability analysis is also provided.

BackgroundPeripheral Retinal neovascularization is well-described as a complication of X-linked retinoschisis, but less often observed in myopic and primary retinoschisis. We present a case of a myopic female who developed retinal microvascular abnormalities due to retinoschisis and subsequent vitreous hemorrhage which would cause severe visual damage without timely and proper treatment.Case presentationA 38-year-old highly myopic Chinese female complained of blurred vision in her right eye. Her best corrected visual acuitiy was 20/20 OU, and her refraction was − 9.00S OU. Dilated fundus examination revealed mild vitreous hemorrhage and abnormal vascular network nasal to the optic disc in her right eye. Optical Coherence Tomography (OCT)- angiography (OCTA) B-Scan showed superficial retinoschisis and well-depicted abnormal retinal microvascular network in inner retinal layer. Sectoral scatter laser photocoagulation was administered. Regression of most abnormal vessels was achieved in 1 month, but the patient experienced an unexpected episode of vitreous hemorrhage 3 months after the initial treatment, which was absorbed spontaneously in 2 weeks. Supplemental laser photocoagulation was applied and regular follow-up visit was suggested.ConclusionSuperficial retinoschisis in pathological myopia can be a driver of retinal microvascular abnormalities, possibly neovascularization, an extremely rare but severe complication which can be vision-threatening without timely and proper intervention.

To establish the clinical value of endoscopic papillectomy for duodenal papillary tumor based on endoscopic and clinical characteristics. This single-center, retrospective study included 110 patients with duodenal papillary tumor who underwent endoscopic papillectomy between January 2006 and April 2017 at the gastrointestinal endoscopic center of the Chinese PLA General Hospital. Clinical data, postoperative pathology, procedure-related complications, and therapeutic outcomes were analyzed. Endoscopic papillectomy was technically feasible in all patients, and was mainly performed by four experienced endoscopists. The primary success rate of endoscopic papillectomy for ampullary neoplasms was 78.2%. A total of 13 patients experienced recurrence during a mean follow-up period of 16.28 months (range 6–132 months), the predictive factors that were related to recurrence were complete resection (53.8% vs. 94.2%; P = 0.001), and final pathology findings (P = 0.001). Delayed hemorrhage, the most common procedure-related complication, occurred in 20% (22/110) of patients and was significantly related to intraoperative bleeding (P = 0.042). Pancreatitis was the second most common complication, which was closely related to intraoperative bleeding requiring intervention (P = 0.040) and larger tumor size (P = 0.044). Histology, type of resection, stent placement, sphincterotomy, and duration of procedure were not related to post-procedure hemorrhage or pancreatitis. Older age (63.7 ± 13.5 vs. 57.4 ± 12.2; P = 0.033), jaundice (47.8% vs. 13.8%; P = 0.001), endoscopic forceps biopsy diagnosis of high-grade intraepithelial neoplasia (82.6% vs. 14.9%; P = 0.001), tumor size ≥ 2 cm (60.9% vs. 34.5%; P = 0.022), and dilation of the bile duct (34.8% vs. 9.2%; P = 0.006) were clinical features for ampullary carcinoma. The rate of complete resection (52.2% vs. 92.0%; P = 0.001) and recurrence (34.8% vs. 6.8%; P = 0.001) were also related to the diagnosis of ampullary carcinoma at final pathology. Endoscopic papillectomy is a feasible and reasonable option for both diagnosis and treatment of tumors of the duodenal papilla in properly selected patients.

We analyzed the secondary structure of the small subunit (SSU) rRNA genes of Mobilida (Ciliophora, Peritrichia) and found that the secondary structures of some regions within the SSU-rRNA gene are distinct between the families Trichodinidae and Urceolariidae. Therefore, some of these important regions including H10, H11, H17, H47, H29, H30, H37, E10-1, H45-H46, and V4 (E23-4, E23-7) could be used as the barcodes for classification of these two families. In contrast, V4 (E23-1, E23-2) belongs to a hypervariable region and is not a good barcode at the genus level because of its great inter-specific variation. Our results indicated that the comprehensive analysis of the secondary structure of SSU-rRNA genes is a reliable auxiliary approach for phylogenic study of mobilid ciliates. It was further found that the coevolution between hosts or habitats and the Mobilida ciliates was existent, because the host types and their habitats were critical ecological factors that influenced the evolution of Mobilida ciliates.

Ru supported on the porous vinyl-functional triphenylphosphine organic polymer (Ru–PPh3@POP) as a heterogeneous catalyst for the selective hydrogenation of cinnamaldehyde (CAL) was synthesized. This catalyst, which combines the advantages of heterogeneous and homogeneous catalyst, showed much higher catalytic activity of continuous trickle bed hydrogenation of CAL than traditional inorganic material supported heterogeneous catalysts. The high efficiency of the Ru–PPh3@POP catalyst was attributed to the formation of the strong coordination bonds between the Ru species and the exposure phosphorus atoms on the surface of PPh3@POP support according to the results of EDS-mapping, 31P NMR, XPS analysis and HRTEM. Importantly, Ru species maintained their nanoparticles without further aggregation during the long-term reaction, and thus the catalyst exhibited a high conversion of CAL of 55% and selectivity towards cinnamyl alcohol (COL) of 63% even over 312 h of time on stream of hydrogenation of CAL. The ICP results of the reaction solution revealed that there was no Ru leaching from the PPh3@POP support during the continuous reaction process. This excellent catalytic activity and stability make it very attractive. Our approaches provide a methodology to expand the heterogenized homogeneous catalysts widely spread in exploitation in fine chemical industries.

Background Translocation-associated renal cell carcinoma involving ALK (ALK-tRCC) is a rare subtype of adult renal cell carcinoma (RCC) reported in recent years. It was recognized as a group of emerging /provisional RCC in the latest World Health Organization’s classification (2016). Case presentation A new Chinese case of ALK-tRCC was reported. The patient was a 58-year-old man with a tumor in kidney. The tumor was composed of sheets of large cells with abundant eosinophilic cytoplasm and indistinct cell borders but conspicuous intracytoplasmic vacuoles. The nuclei were enlarged with a nucleolar of grade 4. Immunohistochemically, tumor cells were diffusely positive for PAX8, keratin (AE1/AE3), epithelial membrane antigen (EMA) and CK7. Fluorescent in situ hybridization (FISH) showed a rearrangement of ALK in tumor cells. Conclusion ALK-tRCC is a rare subtype of adult RCC. Its diagnosis is very difficult because the histological spectrum is very wide. We suggested that RCCs should be screened for ALK expression by immunohistochemistry (IHC) for the patient might benefit from ALK inhibitors therapy.

Background Chlorotoxin (Cltx) isolated from scorpion venom is an established tumor targeting and antiangiogenic peptide. Radiolabeled Cltx therapeutic (131I-TM601) yielded promising results in human glioma clinical studies, and the imaging agent tozuleristide, is under investigation in CNS cancer studies. Several binding targets have previously been proposed for Cltx but none effectively explain its pleiotropic effects; its true target remains ambiguous and is the focus of this study. Methods A peptide-drug conjugate (ER-472) composed of Cltx linked to cryptophycin as warhead was developed as a tool to probe the molecular target and mechanism of action of Cltx, using multiple xenograft models. Results Neuropilin-1 (NRP1), an endocytic receptor on tumor and endothelial cells, was identified as a novel Cltx target, and NRP1 binding by Cltx increased drug uptake into tumor. Metabolism of Cltx to peptide bearing free C-terminal arginine, a prerequisite for NRP1 binding, took place in the tumor microenvironment, while native scorpion Cltx with amidated C-terminal arginine did not bind NRP1, and instead acts as a cryptic peptide. Antitumor activity of ER-472 in xenografts correlated to tumor NRP1 expression. Potency was significantly reduced by treatment with NRP1 blocking antibodies or knockout in tumor cells, confirming a role for NRP1-binding in ER-472 activity. Higher cryptophycin metabolite levels were measured in NRP1-expressing tumors, evidence of NRP1-mediated enhanced drug uptake and presumably responsible for the superior antitumor efficacy. Conclusions NRP1 was identified as a novel Cltx target which enhances tumor drug uptake. This finding should facilitate tumor selection for chlorotoxin-based therapeutics and diagnostics. Electronic supplementary material The online version of this article (10.1186/s12964-019-0368-9) contains supplementary material, which is available to authorized users.

Background Abnormal aggregation of brain α-synuclein is a central step in the pathogenesis of Parkinson’s disease (PD), thus, it is reliable to promote the clearance of α-synuclein to prevent and treat PD. Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels in the clearance of brain macromolecules, however, their pathophysiological aspects remain elusive. Method Meningeal lymphatic drainage of 18-week-old A53T mice was blocked via ligating the deep cervical lymph nodes. Six weeks later, glymphatic functions and PD-like phenotypes were systemically analyzed. Results Glymphatic influx of cerebrospinal fluid tracer was reduced in A53T mice, accompanied with perivascular aggregation of α-synuclein and impaired polarization of aquaporin 4 expression in substantia nigra. Cervical lymphatic ligation aggravated glymphatic dysfunction of A53T mice, causing more severe accumulation of α-synuclein, glial activation, inflammation, dopaminergic neuronal loss and motor deficits. Conclusion The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology. Electronic supplementary material The online version of this article (10.1186/s40035-019-0147-y) contains supplementary material, which is available to authorized users.

Spin-dependent electron temperature effect on the spin pump in a single quantum dot connected to Normal and/or Ferromagnetic leads are investigated with the help of master equation method. Results show that spin heat accumulation breaks the tunneling rates balance at the thermal equilibrium state thus the charge current and the spin current are affected to some extent. Pure spin current can be obtained by adjusting pumping intensity or chemical potential of the lead. Spin heat accumulation of certain material can be detected by measuring the charge current strength in symmetric leads architectures. In practical devices, spin-dependent electron temperature effect is quite significant and our results should be useful in quantum information processing and spin Caloritronics.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an ideal apoptosis inducer and believed to have promise in cancer therapy, yet part of cancer cells exhibit resistance to TRAIL-mediated apoptosis. This necessitates the exploration of agents that resensitizes cancer cells to TRAIL. In our study, we found that Trichostatin A (TSA), an histone deacetylase (HDAC) inhibitor, augmented TRAIL-induced apoptosis in gastric cancer cells in a caspase-dependent manner. Besides, upregulation of DR5 and downregulation of anti-apoptotic proteins including XIAP, Mcl-1, Bcl-2 and Survivin also contributed to this synergism. Noticeably, TSA treatment inhibited Forkhead boxM1 (FOXM1), which expression level showed negative correlation with TRAIL sensitivity. Similarly, silencing of FOXM1 by small interfering RNA (siRNA) resensitized cancer cells to TRAIL and strengthened the TRAIL-augmenting effect of TSA. In addition, we demonstrated the depletion of FOXM1 was a consequence of the inactivation of ERK mediated by TSA. Collectively, it was first shown that TSA potentiated TRAIL sensitivity via ERK/FOXM1 pathway in gastric cancer cells. FOXM1 might serve as a biomarker for predicting sensitivity to TRAIL.

A series of iridium-rhenium catalysts with different impregnation sequences were prepared and the catalytic properties of these catalysts for glycerol hydrogenolysis were evaluated. The catalyst prepared by the impregnation of Ir prior to Re afforded the best selectivity to 1,3-propanediol of 49.2 % with 43.7 % glycerol conversion. These catalysts were also characterized by temperature programmed reduction (TPR), X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), NH3-temperature programmed desorption (NH3-TPD), Fourier transform infrared spectroscopy (FT-IR) and H2-chemisorption. It was found that Ir0 species played a key role on the activities of glycerol conversion, and Re species might act as an efficient promoter to improve the dispersive state of Ir species as well as the reducibility. Kinetic studies have also been conducted and it was observed that the number of Ir0 may affect the extent of consecutive hydrogenolysis of 1,3-propanediol over catalysts, and an appropriate number of Ir0 was of importance to 1,3-propanediol selectivity.

Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson’s disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6.1/K-ATP) channel switched microglia from the detrimental M1 phenotype toward the beneficial M2 phenotype. Kir6.1 knockdown inhibited M2 polarization and simultaneously exaggerated M1 microglial inflammatory responses, while Kir6.1 overexpression promoted M2 polarization and synchronously alleviated the toxic phase of M1 microglia polarization. Furthermore, we observed that the Kir6.1 deficiency dramatically exacerbated dopaminergic neuron death companied by microglia activation in mouse model of PD. Mechanistically, Kir6.1 deficiency enhanced the activation of p38 MAPK–NF-κB pathway and increased the ratio of M1/M2 markers in the substantia nigra compacta of mouse model of PD. Suppression of p38 MAPK in vivo partially rescued the deleterious effects of Kir6.1 ablation on microglia phenotype and dopaminergic neuron death. Collectively, our findings reveal that Kir6.1/K-ATP channel modulates microglia phenotypes transition via inhibition of p38 MAPK–NF-κB signaling pathway and Kir6.1/K-ATP channel may be a promising therapeutic target for PD.

Background Until now, there is non-specific treatment, and exploring early and novel biomarkers to determine the disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS) would be of importance for clinician to take systematic and timely intervention. This study observed the expression of plasma sCD138, a soluble component shedding from the glycocalyx (GCX) to the circulating blood, and evaluated its predictive value on disease severity and prognosis of HFRS. Methods One hundred and seventy-six patients with HFRS who were treated at our center between January 2011 and December 2013 were randomly enrolled in this study. The patients were divided into a mild-type group, a moderate-type group, a severe-type group and a critical-type group according to the HFRS criteria for clinical classification. Thirty-five blood samples from healthy subjects were obtained as the controls. The concentrations of sCD138 were detected using enzyme linked immunosorbent assay (ELISA). The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cells (WBC), platelets (PLT), glucose (GLU), blood urea nitrogen (BUN) and serum creatinine (Scr) in the samples were routinely tested. The levels of sCD138 among the different types were compared; the correlation among sCD138 and the laboratory parameters mentioned above were analyzed. The predictive effectiveness for prognosis of sCD138 was evaluated using the receiver operating characteristic (ROC) curve analysis. Results Except for the mild-type, the levels of sCD138 in the moderate-, severe- and critical-type patients during the acute stage were significantly higher than that of the convalescent stage and the control (P0.05). sCD138 was negatively correlated with Fib, PLT and ALB, and was positively correlated with WBC and AST (P

The rhodophyte Gracilaria lemaneiformis is an important macroalga of great economic value, and is cultured on the southeastern coast of China. In this study, two G. lemaneiformis strains, 981 and 07–2, were cultured at three temperatures (25, 30 and 35 °C) for 48 h. Analysis of the physiological parameters of the two strains under the heat treatments showed that the specific growth rates (SRGs) and photochemical efficiencies (Fv/Fm) were decreased in both strains with increasing temperatures. The decrease in the Fv/Fm in strain 07–2 was less than that in strain 981. However, the phycobiliprotein (PB) and soluble protein (SP) concentrations in strain 981 were decreased at 35 °C throughout the experiment. The PB and SP concentrations in strain 07–2 exhibited initial decreases and then recovered under the heat treatments (25, 30 and 35 °C). These findings suggest that the heat tolerance of strain 07–2, but not that of strain 981, is probably promoted by heat stress. Furthermore, proteomics analysis of the two strains at 35 °C was conducted using 2-DE. Thirteen proteins were identified and classified into eight categories, including photosynthesis, energy metabolism, protein-folding catalysis, transcription, molecular chaperoning, and unknown function. The western blotting results demonstrated that cytosolic HSP70 expression was increased at 35 °C in strain 07–2 and was stable in strain 981. These results indicate that this cytosolic heat shock protein plays an important role in ameliorating damage caused by heat stress and that strain 07–2 is more heat-resistant than strain 981.

Gastric cancer (GC) is an aggressive malignancy whose mechanisms of development and progression are poorly understood. The identification of prognosis-related genomic loci and genes may suffer from the relatively small case numbers and a lack of systematic validation in previous studies. Array-based comparative genomic hybridization (aCGH) coupled with patient clinical information was applied to identify prognosis-related loci and genes with high-frequency recurrent gains in 129 GC patients. The candidate loci and genes were then validated using an independent cohort of 384 patients through branched DNA signal amplification analysis (QuantiGene assays). In the 129 patients, a copy number gain of three chromosome regions—namely, 8q22 (including ESRP1 and CCNE2), 8q24 (including MYC and TNFRSF11B), and 20q11-q13 (including SRC, MMP9, and CSE1L)—conferred poor survival for patients. In addition, the correlation between the branched DNA signal amplification analysis results and the aCGH results was analyzed in 73 of these 129 patients, and MYC, TNFRSF11B, ESRP1, CSE1L, and MMP9 were found to be well correlated. Further validation using an independent cohort (n = 384) verified that only MYC and TNFRSF11B within 8q24 are related to survival. Patients with gains in both MYC and TNFRSF11B had poorer survival than those with no gains, particularly those with noncardia GC. Gains in both of these genes were also a significant independent prognostic indicator. Our results revealed that copy number gains in MYC and TNFRSF11B located at 8q24 are associated with survival in GC, particularly noncardia GC.

An algorithm for optimizing data clustering in feature space is studied in this work. Using graph Laplacian and extreme learning machine (ELM) mapping technique, we develop an optimal weight matrix W for feature mapping. This work explicitly performs a mapping of the original data for clustering into an optimal feature space, which can further increase the separability of original data in the feature space, and the patterns points in same cluster are still closely clustered. Our method, which can be easily implemented, gets better clustering results than some popular clustering algorithms, like k-means on the original data, kernel clustering method, spectral clustering method, and ELM k-means on data include three UCI real data benchmarks (IRIS data, Wisconsin breast cancer database, and Wine database).

In order to improve the gelling properties of agarose, we modified it by methylation. The agarose was prepared from Gracilaria asiatica, G. bailinae, and G. lemaneiformis with alkaline, treated with diatomaceous earth and activated carbon, and anhydrous alcohol precipitation. The methylation reaction process of agarose was performed with dimethyl sulfate while the chemical structure of low-gelling temperature of agarose was also studied by 13C-NMR and FT-IR spectra. Results showed that the quality of agarose from G. asiatica is optimal. Its electroendosmosis is 0.116, sulfate content is 0.128%, and its gel strength (1.5%, w/v) is 1024 g cm−2, like those of the Sigma product (A9539). The gelling temperature, melting temperature, and gel strength of the low-gelling temperature agarose is 28.3, 67.0 °C, and 272.5 g cm−2, respectively. FT-IR Spectra and 13C-NMR spectra also showed that agarose was successfully methylated. Overall, this work suggests that low-gelling temperature agarose may have potential uses as an agar embedding material in various applications such as biomedicine, food, microbiology, and pharmaceutical.

The invasion and metastasis of tumors are triggered by an epithelial to mesenchymal transition (EMT), which is regulated by microRNAs (miRNAs). EMT also promotes malignant tumor progression and the maintenance of the stem cell property, which endows cancer cells with the capabilities of self-renewal and immortalized proliferation. The transcriptional repressor zinc-finger E-box binding homeobox 2 (ZEB2), as an EMT activator, might be an important promoter of metastasis in some tumors. Here, we report that ZEB2 directly represses the transcription of miR-145, which is a strong repressor of EMT. In turn, ZEB2 is also a direct target of miR-145. Further, our findings show that the downregulation of ZEB2 not only represses invasion, migration, EMT, and the stemness of prostate cancer (PCa) cells, but also suppresses the capability of PC-3 cells to invade bone in vivo. Importantly, the expression level of ZEB2 as revealed by immunohistochemical analysis is positively correlated to bone metastasis, the serum free PSA level, the total PSA level, and the Gleason score in PCa patients and is negatively correlated with miR-145 expression in primary PCa specimens. Thus, our findings demonstrate a double-negative feedback loop between ZEB2 and miR-145 and indicate that the ZEB2/miR-145 double-negative feedback loop plays a significant role in the control of EMT and stem cell properties during the bone metastasis of PCa cells. These results suggest that the double-negative feedback loop between ZEB2 and miR-145 contributes to PCa progression and metastasis and might have therapeutic relevance for the bone metastasis of PCa.

Nanosheet AlOOH and silica spheres composite thin film was deposited onto glass by sol–gel dip-coating method through hydrolysis of boiling water immersion. A silica sol and an alumina sol are employed in dipping process for the preparation of hierarchical nanostructures thin film. The morphology and structure of the films were characterized using field emission scanning electron microscopy and X-ray diffraction. The super-hydrophobicity with high adhesion forces can be attributed to both the rough multi-scale structural coating and surface enrichment of low surface energy with the chemical vapor deposition of 1H,1H,2H,2H-perfluorodecyltriethoxysilane.

Recent evidence has suggested that microglial activation plays an important role in the pathogenesis of depression. Activated microglia can secrete various pro-inflammatory cytokines, which may contribute to the development and maintenance of depression. Thus, inhibition of microglial activation may have a therapeutic benefit in the treatment of depression. In the present study, we found that fluoxetine significantly inhibited lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6) and nitric oxide (NO) and reduced the phosphorylation of transforming growth factor-beta-activated kinase 1 (TAK1) and nuclear factor-kappa B (NF-κB) p65 nuclear translocation in microglia. We further found that fluoxetine increased the expression of β-arrestin 2 and enhanced the association of β-arrestin 2 with TAK1-binding protein 1 (TAB1) and disrupted TAK1-TAB1 interaction. Moreover, β-arrestin 2 knock-down abolished the anti-inflammatory effects of fluoxetine in lipopolysaccharide-stimulated microglial cells. Collectively, our findings suggest that β-arrestin 2 is necessary for the anti-inflammatory effects of fluoxetine and offers novel drug targets in the convergent fluoxetine/β-arrestin 2 and inflammatory pathways for treating microglial inflammatory neuropathologies like depression.