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Background Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral‐cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke‐induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. Methods and Results In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3‐deficient mice in combination with Smart‐seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke‐induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte‐derived macrophages into the heart. Subsequently, we identified that cardiac monocyte‐derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3‐deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte‐derived macrophages and subsequent cardiac dysfunction. Conclusions Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve–monocyte‐derived macrophage axis.

Abstract Background Tobacco mosaic virus (TMV) is a harmful plant pathogen that causes a decline in the quality and yield of many economic crops. Natural products are important potential sources of biopesticides for the prevention and treatment of TMV. This study focuses on the discovery of anti-TMV active compounds from Aspergillus versicolor and investigates their activities against TMV. Results In this study, four isocoumarins 7-methoxy-3-(2-oxopropy)-5-hydroxymethyl-isocoumarin (1), 7-methyl-3-(2-oxopropy)-5-hydroxymethyl-isocoumarin (2), oryzaein A (4) and oryzaein B (5), two indole alkaloids aspergilline F (6) and aspergilline G (7), and one indole alkaloid and isocoumarin hybrid aspergillactone A (3) were isolated from Nicotiana tabacum-derived A. versicolor YNCA0363. Among them, compounds 1–3 are new isolates, compound 3 represents the first example of indole alkaloid and isocoumarin connected by C(12)-N(1′) bond. The inactivation efficacies for compounds 1, 2 and 3 were 58.9, 43.8 and 52.6% at the concentration of 50 μg/mL, respectively, which were significantly higher than that of positive control, ningnanmycin. The protective effects of these three compounds ranged from 48.6 to 62.3%, which were significantly higher than that of positive control. At the same time, the content of TMV-CP was also significantly lower than that of positive control, and compound 1 was the lowest. The curative efficacy for compound 1 was also much better than that of positive control. Transmission electron microscopy (TEM) showed that compound 1 could directly destroy viral particles into small fragments. The results of molecular docking showed that the binding ability of compounds 1, 3, 2 to TMV-CP protein decreased in turn, which was consistent with the results of activities assays. Conclusion Compounds 1–3 from A. versicolor showed potent antiviral activities against TMV including inactivation, protective and curative effects. Compound 1 can directly destroy the virus particles to achieve the effect of anti-TMV. In addition, compounds 1–3 can bind to TMV-CP protein in molecular docking experiments. The above experimental results show that TMV-CP was an important target for active indole alkaloid and isocoumarin derivatives to fracture TMV particle. The results provided evidence that indole alkaloid and isocoumarin derivatives from A. versicolor have the potential to control TMV. Graphical Abstract

Abstract Background Since Nicotiana tabacum (tobacco) has important significance to humans for their medicinal uses, to find antivirus activities inhibitors from tobacco, increase its medicinal value, and comprehensive utilization of its by-products, our group had investigated the chemical constituents of the stems of Y-202, a cultivar of tobacco which high resistance to tobacco mosaic virus (TMV). Results Four new isoindolinone-type alkaloids, nicoisoindoles A–D (1–4), along with four known isoindole derivatives (5–8) were isolated. Compounds 1–4 represent a new subclass of isoindolinone alkaloids with rare cyclopenta[f]isoindole-1-one frameworks. Among them, nicoisoindole C (3) possesses an unusual N-2-(5-methoxy-6-methylpyridin-2-yl) ethyl moiety, while nicoisoindole D (4) has a novel a N-(3-methyl-6-oxo-1,6-dihydropyridin-2-yl)methyl substituent. Interestingly, compounds 1, 3, and 4 showed high anti-TMV activities with inhibition rates of 43.8%, 58.8%, and 67.8% at the concentration of 20 μM, and IC50 values of 23.6, 19.5 and 15.4 μM, respectively, even more potent than that of positive control. Conclusions The successful isolation and structure identification of new oxocyclopenta[f]isoindole-1-ones provide materials for the screening of antivirus activities inhibitors, and contribute to the development and utilization of the waste from tobacco cultivation. Graphical Abstract

Abstract Background There has been increased development of robotic technologies for the accuracy of percutaneous pedicle screw placement. However, it remains unclear whether the robot really optimize the selection of screw sizes and enhance screw stability. The purpose of this study is to compare the sizes (diameter and length), placement accuracy and the loosening rate of pedicle screws using robotic-assisted versus conventional fluoroscopy approaches for thoracolumbar fractures. Methods A retrospective cohort study was conducted to evaluate 70 consecutive patients [34 cases of robot-assisted percutaneous pedicle screw fixation (RAF) and 36 of conventional fluoroscopy-guided percutaneous pedicle screw fixation (FGF)]. Demographics, clinical characteristics, and radiological features were recorded. Pedicle screw length, diameter, and pedicle screw placement accuracy were assessed. The patients’ sagittal kyphosis Cobb angles (KCA), anterior vertebral height ratios (VHA), and screw loosening rate were evaluated by radiographic data 1 year after surgery. Results There was no significant difference in the mean computed tomography (CT) Hounsfield unit (HU) values, operation duration, or length of hospital stay between the groups. Compared with the FGF group, the RAF group had a lower fluoroscopy frequency [14 (12–18) vs. 21 (16–25), P 0.05). Conclusion Compared with the fluoroscopy-guided technique, robotic-assisted spine surgery decreased radiation exposure and optimizes screw trajectories and dimensions intraoperatively. Although not statistically significant, the loosening rate of the RAF group was lower that of than the FGT group.

Abstract Purpose The current study aimed to optimize the culture and production parameters of industrial production of lincomycin A by Streptomyces lincolnensis using a statistical approach that could also reduce unwanted by-products. Methods The Plackett-Burman design, steepest ascent method, and response surface design were used to evaluate different factors that affect lincomycin A production. Results Using an optimized S. lincolnensis fermentation medium, lincomycin A production was increased up to 4600 mg/L in shaking flasks, which indicated a 28.3% improvement over previous production in an un-optimized medium (3585 mg/L). Additionally, the concentration of lincomycin B by-product was reduced to 0.8%, which was 82.2% lower than that in the un-optimized medium. Further, quantitative real-time PCR analysis revealed the optimized medium improved lincomycin A production by stimulating key genes in the lincomycin A biosynthesis pathway, as well as an osmotic stress gene. Conclusions Based on the results, the sequential optimization strategy in this study provides powerful means for the enhancement of lincomycin A with less by-product. We found that osmotic stress reduced the concentration of lincomycin B, which could also help reduce fermentation by-product yields in other actinobacteria.

Abstract The nuclear modification factors ( $$R_{AA}$$ R AA ) of d and $$\bar{d}$$ d ¯ have been studied using the parton and hadron cascade model plus the dynamically constrained phase space coalescence model in peripheral (40–60%) and central (0–5%) Pb–Pb collisions at $$\sqrt{s_{NN}}=2.76\,\hbox {TeV}$$ s NN = 2.76 TeV with $$|y|

Abstract The electronic structure near the Fermi surface determines the electrical properties of the materials, which can be effectively tuned by external pressure. Bi0.5Sb1.5Te3 is a p‐type thermoelectric material which holds the record high figure of merit at room temperature. Here it is examined whether the figure of merit of this model system can be further enhanced through some external parameter. With the application of pressure, it is surprisingly found that the power factor of this material exhibits λ behavior with a high value of 4.8 mW m−1 K−2 at pressure of 1.8 GPa. Such an enhancement is found to be driven by pressure‐induced electronic topological transition, which is revealed by multiple techniques. Together with a low thermal conductivity of about 0.89 W m−1 K−1 at the same pressure, a figure of merit of 1.6 is achieved at room temperature. The results and findings highlight the electronic topological transition as a new route for improving the thermoelectric properties.

AIM: To analyze the anatomical characteristics of nasolacrimal duct development in children with congenital nasolacrimal duct obstruction by nasolacrimal duct CT scan combined with three-dimensional reconstruction technology.METHODS: Prospective case control study. Totally 84 children(84 eyes)with unilateral congenital nasolacrimal duct obstruction were treated in the Department of Ophthalmology of Baoding Children's Hospital from September 2018 to September 2020. The nasolacrimal duct CT scan combined with three-dimensional reconstruction was performed. The transverse diameter and anterior posterior diameter of bilateral nasolacrimal duct were measured, and the anatomical characteristics of nasolacrimal duct development were observed and analyzed. Paired t-test was performed on the transverse diameter and anteroposterior diameter of bilateral nasolacrimal duct.RESULTS: Nasolacrimal duct CT scan combined with three-dimensional reconstruction can clearly show the anatomical characteristics of nasolacrimal duct development in children with congenital nasolacrimal duct obstruction. The transverse diameter of bony nasolacrimal duct was 4.63±0.92mm, anterior posterior diameter was 6.03±1.08mm, the transverse diameter of middle bony nasolacrimal duct was 4.02±0.88mm, anterior posterior diameter was 5.42±1.10mm, the transverse diameter of final bony nasolacrimal duct was 4.26±0.93mm, anterior posterior diameter was 5.66±1.02mm. The transverse diameter of the bony nasolacrimal duct in the initial segment of the contralateral side was 4.12±0.78mm, the anteroposterior diameter was 5.60±1.02mm, the transverse diameter of the bony nasolacrimal duct in the middle segment was 3.92±0.86mm, the anteroposterior diameter was 5.24±1.04mm, the transverse diameter of the bony nasolacrimal duct in the final segment was 4.30±0.98mm, the anteroposterior diameter was 5.52±1.04mm. The transverse diameter and anteroposterior diameter of the affected side were larger than those of the healthy side and enlarged(P0.05).CONCLUSION:The development of bony nasolacrimal duct in the affected side of congenital nasolacrimal duct obstruction is different from that in the healthy side. The initial segment of the affected side expanded obviously.

BackgroundAlthough the ratio of apolipoprotein B (apo B) to apolipoprotein A1 (apo A1) (apo B/apo A1) seems to be associated with mortality in hemodialysis (HD) patients, the association of apo B/apo A1 ratio with death remains not clear in peritoneal dialysis (PD) patients.AimsThe study targets to examine the relationship of apo B/apo A1 ratio with survival in patients receiving PD treatment.MethodsIn this single-center prospective observational cohort study, we enrolled 1,616 patients receiving PD treatment with a median follow-up time of 47.6 months. We used a multivariable Cox proportional hazards model to examine the relationship between apo B/apo A1 ratio and cardiovascular (CV) and all-cause mortality. The association of apo B/apo A1 ratio with atherosclerotic and non-atherosclerotic CV mortality was further evaluated by competing risk regression models.ResultsDuring the follow-up, 508 (31.4%) patients died, 249 (49.0%) died from CV events, of which 149 (59.8%) were atherosclerotic CV mortality. In multivariable models, for 1-SD increase in apo B/apo A1 ratio level, the adjusted hazard ratios for CV and all-cause mortality were 1.26 [95% confidence interval (CI), 1.07–1.47; P = 0.005] and 1.20 (95% CI, 1.07–1.35; P = 0.003), respectively. The adjusted subdistribution hazard ratios for atherosclerotic and non-atherosclerotic CV mortality were 1.43 (95% CI, 1.19–1.73; P < 0.001) and 0.85 (95% CI, 0.64–1.13; P = 0.256), respectively. For quartile analysis, patients in quartile 4 had higher CV, all-cause, and atherosclerotic CV mortality compared with those in quartile 1. Moreover, apo B/apo A1 ratio had a diabetes-related difference in CV, all-cause, and atherosclerotic CV mortality.ConclusionElevated apo B/apo A1 ratio level was significantly associated with CV, all-cause, and atherosclerotic CV mortality in patients undergoing PD. Moreover, the association was especially statistically significant in patients with diabetes.

AIM: To observe and analyze the therapeutic effect of fine training combined with virtual reality brain vision training in amblyopic children.METHODS: Case control study. 232 cases(416 eyes)of amblyopia were diagnosed in Baoding children's Hospital for the first time. They were randomly divided into two groups. Group A was treated with fine training, while group B was treated with fine training combined with visual training. Duration of treatment was 6mo. The patients were followed up for 6mo. Objective to observe the clinical efficacy of amblyopia in children of different ages and degrees.RESULTS: The total basic cure rate was 35.6%(74/208)in group A and 51.4%(107/208)in group B, which was higher than that in group A(P<0.01). The total effective rate was 80.8%(168/208)in group A, 91.3%(190/208)in group B, which was higher than that in group A(P=0.006). Therapeutic effect of each age group: the basic cure rates of group A were 55.9%(38/68), 34.9%(30/86), 11.1%(6/54)(rs=-0.76, P<0.01), respectively. The basic cure rates of group B were 70.6%(48/68), 54.6%(47/86), 22.2%(12/54)(rs=-0.78, P<0.01), respectively. The basic cure rate of group A and group B decreased with age. The effective rates of group A were 100%(68/68), 81.4%(70/86), 55.6%(30/54)(rs=-0.67, P<0.01), respectively. The effective rates of group B were 100%(68/68), 93.0%(80/86), 77.8%(42/54)(rs=-0.64, P<0.01), respectively. The efficiencies of A and B groups decreased with age. Therapeutic effect of amblyopia degree groups: the basic cure rates of group A were 63.3%(50/79), 25.0%(22/88)and 4.9%(2/41)(rs=-0.93, P<0.01), respectively. The basic cure rates of group B were 81.0%(64/79), 44.3%(39/88)and 9.8%(4/41),respectively(rs=-0.89, P<0.01). The basic cure rate of groups A and B was negatively correlated with the degree of amblyopia. The effective rates of group A were 83.5%(66/79), 79.5%(70/88), 78.0%(32/41)(rs=0.00, P=12.316), respectively. The effective rates of group B were 91.1%(72/79), 89.8%(79/88), 95.1%(39/41)(rs=0.00, P=15.603), respectively. There was no significant correlation between amblyopia severity and efficiency in groups A and B.CONCLUSION: Fine training combined with virtual reality brain vision training is a safe and effective way to treat amblyopia. There is a certain correlation between the clinical efficacy and the age and the degree of amblyopia.

Introduction: Studies have shown inconsistent results regarding the association between osteoprotegerin (OPG) concentration and cardiovascular mortality in patients with chronic kidney disease (CKD). This systematic review and meta-analysis aims to investigate the association between OPG concentration and cardiovascular mortality in patients with CKD. Methods: Between January 1970 and February 2020, the PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies investigating the association between OPG concentration and cardiovascular mortality in patients with CKD. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated using random effects models. Results: In total, 10 studies comprising 2,120 patients (including 1,723 receiving dialysis) with CKD were included. The included studies were considered to be of fair to high quality. Patients in the highest OPG concentration group had a significantly higher risk of cardiovascular mortality (4 studies; adjusted HR, 2.05; 95% CI, 1.39–3.00) than patients in the low OPG concentration group. An increase of 1 pmol/L in OPG concentration was associated with a 4% increased risk of cardiovascular mortality (6 studies; adjusted HR, 1.04; 95% CI, 1.02–1.07). Conclusion: Elevated OPG concentrations are associated with an increased risk of cardiovascular death in patients with CKD.

Abstract In this Commentary, we would like to comment on the article titled “A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)” as a featured article in Military Medical Research. In the guideline, except for “confirmed cases”, “suspected cases”, “close contact” and “suspicious exposure” were defined by clinical perspective based on epidemiological risk, clinical symptoms and auxiliary examination. Combined with our experience, we introduced a simple scoring proposal additionally based on not only CT imaging as strongly recommended by the guideline but also blood routine test, especially for primary screening of such patients in the out-patient department.

Inspired by the traditional Czochralski method of growing single crystal from liquid, the authors demonstrated that at nanoscale, metallic nanowires including Al, Ag, Cu and Sn can be controllably grown from the surface of a hot solid, by simply drawing a cold tip back after touching.

Abstract Objective To provide the cobweb classification system (CCS) for the precise digital location and description of the neurological compression in cervical degenerative disease (CDD), and the reliability and the clinical subgroup analysis of the system were tested and analyzed. Methods The CCS consisted of three parts: compression zones (1‐12), degrees (a, b) and ossification (s, m, h). Computerized tomography (CT) and magnetic resonance imaging (MRI) images from 238 CDD patients were reviewed. All compression cases were classified by five independent reviewers with varied clinical experience in spine surgery. The reliability of the CCS was tested by calculating the kappa (κ) statistics value. Finally, 74 patients with anterior cervical surgery treatment were enrolled for the clinical subgroup analysis. Results For the small compression, including single and double compression zones, there was a good interobserver reliability between the reviewers (κ coefficient = .855, P

Cerebral-cardiac syndrome (CCS) refers to cardiac dysfunction following varying brain injuries. Ischemic stroke is strongly evidenced to induce CCS characterizing as arrhythmia, myocardial damage, and heart failure. CCS is attributed to be the second leading cause of death in the post-stroke stage; however, the responsible mechanisms are obscure. Studies indicated the possible mechanisms including insular cortex injury, autonomic imbalance, catecholamine surge, immune response, and systemic inflammation. Of note, the characteristics of the stroke population reveal a common comorbidity with diabetes. The close and causative correlation of diabetes and stroke directs the involvement of diabetes in CCS. Nevertheless, the role of diabetes and its corresponding molecular mechanisms in CCS have not been clarified. Here we conclude the features of CCS and the potential role of diabetes in CCS. Diabetes drives establish a “primed” inflammatory microenvironment and further induces severe systemic inflammation after stroke. The boosted inflammation is suspected to provoke cardiac pathological changes and hence exacerbate CCS. Importantly, as the key element of inflammation, NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is indicated to play an important role in diabetes, stroke, and the sequential CCS. Overall, we characterize the corresponding role of diabetes in CCS and speculate a link of NLRP3 inflammasome between them.

Ischemic stroke remains a devastating disease which is the leading cause of death worldwide. Visual impairment after stroke is a common complication which may lead to vision loss, greatly impacting life quality of patients. While ischemic stroke is traditionally characterized by a blockage of blood flow to the brain, this may coincide with reduced blood flow to the eye, resulting in retinal ischemia and leading to visual impairment. Diabetes increases the risk of ischemic stroke and induces diabetic retinopathy; the latter may be more sensitive to the ischemic retinal injury. In diabetic status, the underlying mechanism in stroke-induced retinal injury has not been fully clarified. The NLR pyrin domain containing 3 (NLRP3) inflammasome is an important activator of inflammation, which may play a critical role in catalyzing and forming certain pro-inflammatory cytokines in both cerebral and retinal ischemia. Isoflurane has been demonstrated to inhibit the activation of the NLRP3 inflammasome and show neuroprotective effects. In this study, we established a diabetic mouse model and performed the middle cerebral artery occlusion procedure to induce ischemic stroke. Our results revealed that cerebral ischemia-induced retinal injury in the diabetic model. Isoflurane pretreatment alleviated the cerebral and retinal injury after ischemic stroke. Of note, isoflurane pretreatment inhibited the NLRP3 inflammasome activation in the retina, indicating that isoflurane pretreatment may provide substantial retinal protection in stroke-induced retinal injury in diabetes.

Abstract The NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome is a member of the NLR family of innate immune cell sensors. These are crucial regulators of cytokine secretions, which promote ischemic cell death and insulin resistance. This review summarizes recent progress regarding the NLRP3 inflammasome as a potential treatment for ischemic stroke in patients with diabetes, two complicated diseases that often occur together. Stroke worsens glucose metabolism abnormalities, and the outcomes after stroke are more serious for diabetic patients compared with those without diabetes. Inflammation contributes to organ injury after ischemic stroke and diabetes. Recent research has focused on inhibiting the activation of inflammasomes and thus reducing the maturation of proinflammatory cytokines such as interleukin (IL)-1β and IL-18. Studies suggest that inhibition of NLRP3 prevents or alleviates both ischemic stroke and diabetes. Targeting against the assembly and activity of the NLRP3 inflammasome is a potential and novel therapy for inflammasome-associated diseases, including ischemic stroke concomitant with diabetes.

The Cassia (Leguminosae) genus has attracted a lot of attention as a prolific source of alkaloids and chromones with diverse structures and biological properties. The aim of this study is to screen the antiviral compounds from Cassia alata. The extract of the stem bark of this plant was separated using silica gel, MCI, ODS C18, and Sephadex LH-20 column chromatography, as well as semi-preparative HPLC. As a result, three new indole alkaloids, alataindoleins A–C (1–3); one new chromone, alatachromone A (4); and a new dimeric chromone-indole alkaloid, alataindolein D (5) were isolated. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Interestingly, alataindolein D (5) represents a new type of dimeric alkaloid with an unusual N-2−C-16’ linkage, which is biogenetically derived from a chromone and an indole alkaloid via an intermolecular nucleophilic substitution reaction. Compounds 1–5 were tested for their anti-tobacco mosaic virus (TMV) and anti-rotavirus activities, and the results showed that compounds 2–4 showed high anti-TMV activities with inhibition rates of 44.4%, 66.5%, and 52.3%, respectively. These rates were higher than those of the positive control (with inhibition rate of 32.8%). Compounds 1 and 5 also showed potential anti-TMV activities with inhibition rates of 26.5% and 31.8%, respectively. In addition, compounds 1–5 exhibited potential anti-rotavirus activities with therapeutic index (TI) values in the range of 9.75~15.3. The successful isolation and structure identification of the above new compounds provided materials for the screening of antivirus drugs, and contributed to the development and utilization of C. alata.

Moringa oleifera Lam. (M. oleifera) is valuable plant distributed in many tropical and subtropical countries. It has a number of medicinal uses and is highly nutritious. M. oleifera has been shown to inhibit tumor cell growth, but this effect has not been demonstrated on prostate cancer cells. In this study, we evaluated the inhibitory effect of M. oleifera alkaloids (MOA) on proliferation and migration of PC3 human prostate cancer cells in vitro and in vivo. Furthermore, we elucidated the mechanism of these effects. The results showed that MOA inhibited proliferation of PC3 cells and induced apoptosis and cell cycle arrest. Furthermore, MOA suppressed PC3 cell migration and inhibited the expression of matrix metalloproteinases (MMP)-9. In addition, MOA significantly downregulated the expression of cyclooxygenase 2 (COX-2), β-catenin, phosphorylated glycogen synthase 3β, and vascular endothelial growth factor, and suppressed production of prostaglandin E2 (PGE2). Furthermore, FH535 (β-catenin inhibitor) and MOA reversed PGE2-induced PC3 cell proliferation and migration, and the effects of MOA and FH535 were not additive. In vivo experiments showed that MOA (150 mg/kg) significantly inhibited growth of xenograft tumors in mice, and significantly reduced the protein expression levels of COX-2 and β-catenin in tumor tissues. These results indicate that MOA inhibits the proliferation and migration, and induces apoptosis and cell cycle arrest of PC3 cells. Additionally, MOA inhibits the proliferation and migration of PC3 cells through suppression of the COX-2 mediated Wnt/β-catenin signaling pathway.

Six new pimprinine alkaloids (1–6), including four dimers, dipimprinines A–D (1–4), and two monomers, (±)-Pimprinol D (5), and pimprinone A (6), along with six known congeners (7–12), were isolated from a soil-derived actinomycete Streptomyces sp. NEAU-C99. Structures of the new compounds were elucidated by extensive spectroscopic analyses, single-crystal X-ray diffractions, and ECD calculations. Dipimprinines A–D (1–4) showed weak cytotoxic activities against five tumor cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW-480, with IC50 values ranging from 12.7 to 30.7 μM.

AIM:To investigate the changes of corneal endothelial cells and tear film in diabetic cataract patients after operation. METHODS: Totally 88 patients(88 eyes)with diabetic cataract(study group)treated in our hospital from June 2016 to June 2017 were retrospectively analyzed, and 100 patients(100 eyes)with senile cataract(control group)were selected. Patients of two groups underwent phacoemulsification and foldable intraocular lens implantation and followed up for 3mo. The corneal endothelial cell density, endothelial cell coefficient of variation and hexagonal cell proportion were measured by TOPCON SP - 3000P non-contact corneal endothelial tester before and after operation in two groups. The tear break-up time(BUT), basal tear secretion test(SⅠt)and corneal fluorescein test(FL)in two groups were observed. RESULTS: There was no difference in corneal endothelial cell density between the two groups before treatment and 7d after treatment(P>0.05). The corneal endothelial cell density in the study group was significantly lower than that in the control group(3mo after treatment)(PPPPPPP>0.05). BUT and FL between the two groups at 7d after treatment had no significant difference(P>0.05), while the SⅠt of the study group was significantly lower than that of the control group(PPP>0.05). After treatment, BUT, SⅠt and FL were improved in the two groups(PCONCLUSION: Phacoemulsification has some damage to corneal endothelial cells and destroys the stability of tear film, corneal endothelial cells are damaged more severely and recover slowly after operation especially in diabetic cataract patients.

Abstract We study the magnetic properties of an epitaxial growth bilayer composed of ferromagnetic La0.7Sr0.3MnO3 (LSMO) and paramagnetic LaNiO3 (LNO) on SrTiO3 (STO) substrates. We find that the stack order of the bilayer heterostructure plays a key role in the interfacial coupling strength, and the coupling at the LSMO(top)/LNO(bottom) interface is much stronger than that at the LNO(top)/LSMO(bottom). Moreover, a strong spin glass state has been observed at the LSMO/LNO interface, which is further confirmed by two facts: first, that the dependence of the irreversible temperature on the cooling magnetic field follows the Almeida-Thouless line and, second, that the relaxation of the thermal remnant magnetization can be fitted by a stretched exponential function. Interestingly, we also find an exchange bias effect at the LSMO/LNO bilayer below the spin glass freezing temperature, indicating that the exchange bias is strongly correlated with the spin glass state at its interface.

Objective. Portal hypertension is a major complication of decompensated cirrhosis. In China, modified Hassab’s and Sugiura procedure are the two major methods of nonshunting surgery. This study aims to compare the efficacy and safety of the two procedures for portal hypertension. Method. Between January 1994 and December 2009, 172 elective patients diagnosed with decompensated cirrhosis with significant hypersplenism adopted elective splenectomy for hypersplenism, and also modified Hassab’s (n = 91) or Sugiura (n = 81) procedure was additionally performed to reduce the risk of variceal bleeding. Postoperative mortality and morbidity data were collected, and a retrospectively comparative analysis was conducted. Results. All of the patients were treated successfully without death during operation, and no variceal bleeding occurred during hospitalization. There were 4 (4.4%) deaths in Hassab’s group and 3 (3.7%) deaths in Sugiura group postoperatively (P > 0.05). During follow-up, the survival rate was 90.2%, 82.42%, and 71.43% in Hassab’s group and 96.29%, 81.48%, and 75.31% in Sugiura group in 1, 3, and 5 years (P > 0.05). There were 22/71 and 12/63 patients in each groups who suffered no deadly variceal bleeding (P = 0.11). Bleeding related death and no bleeding related death occurred in 7/23 and 3/13 patients in each group (P = 0.26 and 0.14, respectively). Conclusion. Elective splenectomy combined with modified Sugiura procedure seemed to be associated with a reduced trend of no deadly variceal bleeding compared with Hassab’s procedure. As statistical significance was not found, further large scale and prospective study was warranted.

Long non-coding RNAs (lncRNAs) play important roles in plant growth and stress responses. As a dominant abiotic stress factor in soil, boron (B) deficiency stress has impacted the growth and development of citrus in the red soil region of southern China. In the present work, we performed a genome-wide identification and characterization of lncRNAs in response to B deficiency stress in the leaves of trifoliate orange (Poncirus trifoliata), an important rootstock of citrus. A total of 2101 unique lncRNAs and 24,534 mRNAs were predicted. Quantitative real-time polymerase chain reaction (qRT-PCR) experiments were performed for a total of 16 random mRNAs and lncRNAs to validate their existence and expression patterns. Expression profiling of the leaves of trifoliate orange under B deficiency stress identified 729 up-regulated and 721 down-regulated lncRNAs, and 8419 up-regulated and 8395 down-regulated mRNAs. Further analysis showed that a total of 84 differentially expressed lncRNAs (DELs) were up-regulated and 31 were down-regulated, where the number of up-regulated DELs was 2.71-fold that of down-regulated. A similar trend was also observed in differentially expressed mRNAs (DEMs, 4.21-fold). Functional annotation of these DEMs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and the results demonstrated an enrichment of the categories of the biosynthesis of secondary metabolites (including phenylpropanoid biosynthesis/lignin biosynthesis), plant hormone signal transduction and the calcium signaling pathway. LncRNA target gene enrichment identified several target genes that were involved in plant hormones, and the expression of lncRNAs and their target genes was significantly influenced. Therefore, our results suggest that lncRNAs can regulate the metabolism and signal transduction of plant hormones, which play an important role in the responses of citrus plants to B deficiency stress. Co-expression network analysis indicated that 468 significantly differentially expressed genes may be potential targets of 90 lncRNAs, and a total of 838 matched lncRNA-mRNA pairs were identified. In summary, our data provides a rich resource of candidate lncRNAs and mRNAs, as well as their related pathways, thereby improving our understanding of the role of lncRNAs in response to B deficiency stress, and in symptom formation caused by B deficiency in the leaves of trifoliate orange.

Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1β, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.

Objectives. To evaluate the efficacy and safety of endoscopic intralesional triamcinolone injection (ITI) for benign esophageal strictures combined with endoscopic dilation (ED). Methods. Online databases including MEDLINE, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for prospective randomized control trials (RCTs) between 1966 and March 2018. A meta-analysis was conducted according to the methods recommended by the Cochrane Collaboration. Results. Six RCTs consisting of 176 patients were selected. Meta-analysis results showed that additional ITI had a significant advantage in terms of stricture rate and required ED sessions. Surgery-related and non-surgery-related strictures showed similar results. Additional ITI was not associated with significantly increased risk of complications. Conclusions. Our meta-analysis showed that additional ITI therapy was supposed to be effective and safe for benign esophageal strictures as it reduced the stricture rate and required ED sessions. However, more RCTs are necessary to support these findings.

AIM: To investigate the relative factors of the incidence and development of diabetic retinopathy(DR).METHODS: The retinopathy of the 631 patients with type 2 diabetes mellitus(T2DM)was examined by ophthalmoscopy and fundus fluorescein angiography(FFA), and the relative factors which possibly associate with the incidence and development of DR were collected.RESULTS: There were 205 patients with DR, the morbidity rate of DR was 32.5%(95%CI:28.82%-36.15%), the nonproliferative diabetic retinopathy(NPDR)and proliferative diabetic retinopathy(PDR)were 134 cases occupying 21.2%(95%CI: 18.04%-24.44%)and 71 cases occupying 11.3%(95%CI: 8.78%-13.72%)of the patients with DR, respectively. Univariate analysis showed that income, living environment, whether treatment by insulin, combined with diabetic nephropathy(DN), combined with diabetic peripheral neuropathy(DPN), hold on exercise, course of diabetes, fasting plasma glucose(FPG), 2 hours' postprandial plasma glucose(2hPG), glycosylated hemoglobin A1c(HbA1c), systolic blood pressure(SBP), total cholesterol(TC), urinary albumin excretion rate(UAER), serum creatinine(SCr), and blood urea nitrogen(BUN)were significant different among the patients without DR, the patients with NPDR and the patients with PDR(PPPP<0.01).CONCLUSION: There was a high morbidity rate of DR in patients with patients with type 2 diabetes. The longer course of diabetes, high HbA1c, and without exercise were the independent development factors of DR, whether combined with DN, combined with DPN and UAER were indices for the incidence and development of DR.

An accurate and reliable method of high-performance liquid chromatographic fingerprint combining with multi-ingredient determination was developed and validated to evaluate the influence of sulfur-fumigated Paeoniae Radix Alba on the quality and chemical constituents of Si Wu Tang. Multivariate data analysis including hierarchical cluster analysis and principal component analysis, which integrated with high-performance liquid chromatographic fingerprint and multi-ingredient determination, was employed to evaluate Si Wu Tang in a more objective and scientific way. Interestingly, in this paper, a total of 37 and 36 peaks were marked as common peaks in ten batches of Si Wu Tang containing sun-dried Paeoniae Radix Alba and ten batches of Si Wu Tang containing sulfur-fumigated Paeoniae Radix Alba, respectively, which indicated the changed fingerprint profile of Si Wu Tang when containing sulfur-fumigated herb. Furthermore, the results of simultaneous determination for multiple ingredients showed that the contents of albiflorin and paeoniflorin decreased significantly (P

This study uses a MRI technique, three-dimension pulse continuous arterial spin labeling (3D-PCASL), to measure the patient's cerebral blood flow (CBF) at the subacute stage of mild traumatic brain injury (MTBI) in order to analyze the relationship between cerebral blood flow and neurocognitive deficits.To provide the relationship between cortical CBF and neuropsychological dysfunction for the subacute MTBI patients.After MTBI, perfusion MR imaging technique (3D-PCASL) measures the CBF of MTBI patients (n = 23) within 1 month and that of normal controls (n = 22) to determine the quantity and location of perfusion defect. The correlation between CBF abnormalities and cognitive deficits was elucidated by combining the results of the neuropsychological tests of the patients.We observed a substantial reduction in CBF in the bilateral frontal and left occipital cortex as compared with the normal persons. In addition, there were correlation between post concussive symptoms (including dizziness and simulator sickness) and CBF in the hypoperfused areas. The more severe symptom was correlated with higher CBF in bilateral frontal and left occipital lobes.First, this study determined that despite no significant abnormality detected on conventional CT and MRI studies, hypoperfusion was observed in MTBI group using 3D-PCASL technique in subacute stage, which suggested that this approach may increase sensitivity to MTBI. Second, the correlation between CBF and the severity of post concussive symptoms suggested that changes in cerebral hemodynamics may play a role in pathophysiology underlies the symptoms.

Nucleophosmin (NPM1) is an abundant and ubiquitously expressed phosphoprotein that is known to influence solid tumors progression. However, little is known about the role of NPM1 in leukemia. Here, we knocked down the NPM1 expression by RNA interference to investigate the role of NPM1 in leukemic cells proliferation and apoptosis. The interference vector pNPM1-shRNA was constructed and transfected into the human leukemic K562 cell line. The expression levels of NPM1 mRNA and protein were detected by quantitative real-time PCR and Western blot, respectively. Cells proliferation potential in vitro was assessed by methyl thiazolyl tetrazolium (MTT) and colony formation assays. Flow cytometry was used to detect the distribution of cell cycle. Cellular apoptosis was reflected by the relative activities of caspase-3 and caspase-8. The results showed that the expression levels of NPM1 mRNA and protein in K562 cells were significantly reduced after pNPM1-shRNA transfection. The cells growth was significantly inhibited in a time-dependent manner and the number of colonies was significantly reduced in the pNPM1-shRNA transfected cells. Meanwhile, the percentage of cells in G1 phase in the K562/pNPM1-shRNA cells was significantly increased. In addition, there were higher relative activities of caspase-3/8 in the pNPM1-shRNA transfected cells. These results indicate that down-regulation of NPM1 expression inhibits leukemic cells proliferation, blocks cell cycle progression and induces cellular apoptosis. It may implicate a potential target for leukemia gene therapy.

Surveys were carried out in 2003–2006 to better understand the epidemiology of hantaviruses in the Inner Mongolia Autonomous Region of China (Inner Mongolia). Hemorrhagic fever with renal syndrome (HFRS) was first reported in this region in 1955 and has been an important public health problem here since then. During 1955–2006, 8,309 persons with HFRS were reported in Inner Mongolia (average incidence rate 0.89/100,000), and 261 (3.14%) died. Before the 1990s, all HFRS cases occurred in northeastern Inner Mongolia. Subsequently, HFRS cases were registered in central (1995) and western (1999) Inner Mongolia. In this study, hantaviral antigens were identified in striped field mice (Apodemus agrarius) from northeastern Inner Mongolia and in Norway rats (Rattus norvegicus) from middle and western Inner Mongolia. Phylogenetic analysis of hantaviral genome sequences suggests that HFRS has been caused mainly by Hantaan virus in northeastern Inner Mongolia and by Seoul virus in central and western Inner Mongolia.

The apolipoprotein E-ε4 allele is a well-known genetic risk factor for late-onset Alzheimer's disease, which also impacts the cognitive functions and brain network connectivity in healthy middle-aged adults without dementia. Previous studies mainly focused on the effects of apolipoprotein E-ε4 allele on single index using task or resting-state fMRI. However, how these evoked and spontaneous BOLD indices interact with each other remains largely unknown. Therefore, we evaluated the 'rest-stimulus interaction' between working-memory activation and resting-state connectivity in middle-aged apolipoprotein E-ε4 carriers (n=9) and non-carriers (n=8). Four n-back task scans (n = 0, 1, 2, 3) and one resting-state scan were acquired at a 3T clinical MRI scanner. The working-memory beta maps of low-, moderate-, and high-memory loads and resting-state connectivity maps of default mode, executive control, and hippocampal networks were derived and compared between groups. Apolipoprotein E-ε4 carriers presented declined working-memory activation in the high-memory load across whole brain regions and reduced hippocampal connectivity compared with non-carriers. In addition, disrupted rest-stimulus interactions were found in the right anterior insula and bilateral parahippocampal regions for middle-aged adults with apolipoprotein E-ε4 allele. The rest-stimulus interaction improved the detectability of network integrity changes in apolipoprotein E-ε4 carriers, demonstrating the disrupted intrinsic connectivity within the executive-functional regions and the modulated memory-encoding capability within hippocampus-related regions.

β-amyloid hypothesis is the predominant hypothesis in the study of pathogenesis of Alzheimer's disease. This hypothesis claims that aggregation and neurotoxic effects of amyloid β (Aβ) is the common pathway in a variety of etiological factors for Alzheimer's disease. Aβ peptide derives from amyloid precursor protein (APP). β-sheet breaker peptides can directly prevent and reverse protein misfolding and aggregation in conformational disorders. Based on the stereochemical structure of Aβ1-42 and aggregation character, we had designed a series of β-sheet breaker peptides in our previous work and screened out a 10-residue peptide β-sheet breaker peptide, H102. We evaluated the effects of H102 on expression of P-tau, several associated proteins, inflammatory factors and apoptosis factors, and examined the cognitive ability of APP transgenic mice by behavioral test. This study aims to validate the β-amyloid hypothesis and provide an experimental evidence for the feasibility of H102 treatment for Alzheimer's disease.