Research Progress in Preparation of Oxidized Cellulose

Cellulose is the most abundant natural polymer material in the world.Cellulose is diffi-cult to dissolve because it contains a large number of inter molecular hydrogen bonds.Therefore,the modification of natural cellulose by chemical oxidation can expand its application field.The oxidation process of cellulose is focused on,the oxidation methods and research progress of cellulose are introduced,and further development direction of oxidized cellulose is prospected.

Non-selective beta-blockers in cirrhosis:Current concepts and controversies

Non-selective beta-blockers(NSBBs) have been at the forefront in the management of portal hypertension in liver cirrhosis for the last three decades, a trusty component in the armamentarium of the Hepatologist. The role of beta-blockers has been cemented for years in cardiac disease including angina, hypertension and in heart failure, however NSBBs with their non-selective effects on β1 and β2 receptors have led to them fondly being termed "the hepatologist's aspirin". NSBBs' role in reduction of portal pressure in the setting of primary and secondary prophylaxis for variceal haemorrhage has been well established. NSBBs include propranolol, nadolol and carvedilol- with the latter having been shown to be effective in patients who often fail to demonstrate a haemodynamic response to propranolol. Recent observational studies however have served for the Hepatology community to question the beneficial role of NSBBs in portal hypertension, especially in advanced cases with refractory ascites. The deleterious effect in patients with refractory ascites in a few studies led to a U-turn in clinical practice, with some in the Hepatology community withdrawing their usage in patients with advanced cirrhosis. This also led to the "window hypothesis" suggesting there may be only be a finite time frame when NSBBs have a beneficial effect in portal hypertension. The window hypothesis proposed the window for the benefits of NSBBs is closed in early portal hypertension, opening as portal hypertension progresses with it closing in advanced liver disease. The window was proposed to close in conditions such as refractory ascites or spontaneous bacterial peritonitis when patients may not necessarily mount a compensatory haemodynamic response when on NSBBs. Some centres however have continued the practice of NSBBs in advanced cirrhosis with published data challenging the scepticisms of other groups who stop NSBBs. Thus the debate, like the window hypothesis has opened, with more questions to be answered about NSBB's mechanism of action not only in reducing portal hypertension but also their effects on systemic haemodynamics and on the pro-inflammatory pathways often activated in cirrhosis especially in advanced disease. This article serves to review the role of NSBBs in the management of portal hypertension/cirrhosis and concentrate on current concepts and controversies in this field.

Minimising non-selective defects in ultrathin reduced graphene oxide membranes with graphene quantum dots for enhanced water and NaCl separation

Reduced graphene oxide(rGO)membranes have been intensively evaluated for desalination and ionic sieving applications,benefiting from their stable and well-confined interlayer channels.However,rGO membranes generally suffer from low permeability due to the high transport resistance resulting from the narrowed two-dimensional(2D)channels.Although high permeability can be realized by reducing membrane thickness,membrane selectivity normally declines because of the formation of nonselective defects,in particular pinholes.In this study,we demonstrate that the non-selective defects in ultrathin rGO membranes can be effectively minimised by a facile posttreatment via surfacedeposition of graphene quantum dots(GQDs).The resultant GQDs/rGO membranes obtained a good trade-off between water permeance(14 L·m^(-2)·h^(-1).MPa^(-1))and NaCl rejection(91%).This work provides new insights into the design of high quality ultrathin 2D laminar membranes for desalination,molecular/ionic sieving and other separation applications.

Non-Selective SiGe Graphic Epitaxial by MBE

To handle the thermal budget in SiGe BiCMOS process, a non-selective graphic epitaxial technology using molecular beam epitaxial （MBE） has been developed. SEM, AFM, XRD, and dislocation density measurements are carried out. The SiGe film＇s RMS roughness is 0.45nm, and dislocation density is 0.3×10^3cm^-2-1.2×10^3cm^-2. No dislocation accumulation exists on the boundary of the windows; this indicates the high quality of the SiGe film. The experiment results show that the technology presented in this paper meets the fabrication requirements of SiGe BiCMOS.

Cirrhotic portal hypertension: From pathophysiology to novel therapeutics

Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pathogenesis of portal hypertension and attempts to provide an update on currently available therapeutic approaches in the management of portal hypertension with special emphasis on how the alternate RAS could be manipulated in our search for development of safe, specific and effective novel therapies to treat portal hypertension in cirrhosis.

Is it time to replace propranolol with carvedilol for portal hypertension?

Beta-adrenergic receptor antagonists(β-blockers) have been well established for use in portal hypertension for more than three decades. Different Non-selective β-blockers like propranolol, nadolol, timolol, atenolol, metoprolol and carvedilol have been in clinical practice in patients with cirrhosis. Carvedilol has proven 2-4 times more potent than propranolol as a beta-receptor blocker in trials conducted testing its efficacy for heart failure. Whether the same effect extends to its potency in the reduction of portal venous pressures is a topic of on-going debate. The aim of this review is to compare the hemodynamic and clinical effects of carvedilol with propranolol, and attempt assess whether carvedilol can be used instead of propranolol in patients with cirrhosis. Carvedilol is a promising agent among the beta blockers of recent time that has shown significant effects in portal hypertension hemodynamics. It has also demonstrated an effective profile in its clinical application specifically for the prevention of variceal bleeding. Carvedilol has more potent desired physiological effects when compared to Propranolol. However, it is uncertain at the present juncture whether the improvement in hemodynamics also translates into a decreased rate of disease progression and complications when compared to propranolol. Currently Carvedilol shows promise as a therapy for portal hypertension but more clinical trials need to be carried out before we can consider it as a superior option and a replacement for propranolol.

Nonselective β-blockers may induce development of portal vein thrombosis in cirrhosis

Currently, nonselective β-blockers (NSBBs) are commonly used for the prevention of variceal bleeding in liver cirrhosis. The beneficial effects of NSBBs are primarily attributed to the reduction in cardiac output by blockade of β1 receptors and vasoconstriction of the splanchnic circulation by the blockade of β2 receptors. The prognostic value of occlusive portal vein thrombosis (PVT) in cirrhotic patients has been increasingly recognized. The most important risk factor for the development of PVT in liver cirrhosis is the decreased portal vein inflow velocity. Collectively, we propose that the use of NSBBs potentially increases the development of portal vein thrombosis by reducing portal vein inflow velocity. The hypothesis should be confirmed by prospective cohort studies, in which cirrhotic patients without prior PVT treated with and without NSBBs are enrolled, and the development of PVT during follow-up is compared between the two groups. Additionally, subgroup analyses should be performed according to the dosage of NSBBs and the reduction of portal inflow velocity after use of NSBBs.

Clinical algorithms for the prevention of variceal bleeding and rebleeding in patients with liver cirrhosis

Portal hypertension(PH),a common complication of liver cirrhosis,results in development of esophageal varices.When esophageal varices rupture,they cause significant upper gastrointestinal bleeding with mortality rates up to 20%despite state-of-the-art treatment.Thus,prophylactic measures are of utmost importance to improve outcomes of patients with PH.Several high-quality studies have demonstrated that non-selective beta blockers(NSBBs)or endoscopic band ligation(EBL)are effective for primary prophylaxis of variceal bleeding.In secondary prophylaxis,a combination of NSBB+EBL should be routinely used.Once esophageal varices develop and variceal bleeding occurs,standardized treatment algorithms should be followed to minimize bleeding-associated mortality.Special attention should be paid to avoidance of overtransfusion,early initiation of vasoconstrictive therapy,prophylactic antibiotics and early endoscopic therapy.Pre-emptive transjugular intrahepatic portosystemic shunt should be used in all Child C10-C13 patients experiencing variceal bleeding,and potentially in Child B patients with active bleeding at endoscopy.The use of carvedilol,safety of NSBBs in advanced cirrhosis(i.e.with refractory ascites)and assessment of hepatic venous pressure gradient response to NSBB is discussed.In the present review,we give an overview on the rationale behind the latest guidelines and summarize key papers that have led to significant advances in the field.

Primary prophylaxis of variceal bleeding in patients with cirrhosis:A comparison of different strategies

Patients with cirrhosis and esophageal varices bleed at a yearly rate of 5%-15%,and,when variceal hemorrhage develops,mortality reaches 20%.Patients are deemed at high risk of bleeding when they present with medium or large-sized varices,when they have red signs on varices of any size and when they are classified as Child-Pugh C and have varices of any size.In order to avoid variceal bleeding and death,individuals with cirrhosis at high risk of bleeding must undergo primary prophylaxis,for which currently recommended strategies are the use of traditional non-selective beta-blockers(NSBBs)(i.e.,propranolol or nadolol),carvedilol(a NSBB with additional alpha-adrenergic blocking effect)or endoscopic variceal ligation(EVL).The superiority of one of these alternatives over the others is controversial.While EVL might be superior to pharmacological therapy regarding the prevention of the first bleeding episode,either traditional NSBBs or carvedilol seem to play a more prominent role in mortality reduction,probably due to their capacity of preventing other complications of cirrhosis through the decrease in portal hypertension.A sequential strategy,in which patients unresponsive to pharmacological therapy would be submitted to endoscopic treatment,or the combination of pharmacological and endoscopic strategies might be beneficial and deserve further investigation.

Therapeutic potential of targeting the renin angiotensin system in portal hypertension

Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis.Drug therapy to reduce portal pressure involves targeting two vascular beds.The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells.The second approach is to reduce mesenteric and portal blood flow.Non-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis.However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients.Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding.This review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this condition.It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered "alternate axis" of the RAS.

Diuretic window hypothesis in cirrhosis: Changing the point of view

Since the 1970s,non-selective beta-blockers(NSBB)have been used to prevent variceal upper bleeding in advanced cirrhotic patients.However,several recent studies have raised the doubt about the benefit of NSBB in end-stage cirrhotic patients.In fact,they suggested a detrimental effect in these patients that even reduced survival.All of these studies have been assembled to compose the“window therapy hypothesis”,in which NSBB would have traditional indication to be initiated to prevent variceal upper bleeding;however,treatment should be stopped(or not be initiated)in patients with end-stage cirrhosis.NSBB would reduce the cardiac reserve of these patients,worsening systemic perfusion and prognosis.However,it should be emphasized that these studies present important bias issues,and their results also suggested that diuretic treatment may also be behind the effects observed.In this opinion review,we changed the point of view from NSBB to diuretic treatment,based on a physiopathogenic approach of circulatory parameters of cirrhotic patients studied,and based on diuretic effect in blood pressure lowering and in other hypervolemic disease,as heart failure.We suggest a“diuretic window hypothesis”,composed by an open window in hypervolemic phase,an attention window when patient present in a normal plasma volume phase,and a closed window during the plasma hypovolemic phase.

Research progress on the correlation between ion channel and excitability of striatum neurons in Parkinson's disease

Parkinson's disease(PD)is a neurodegenerative disorder due to gradual loss of dopaminergic neurons in the substantia nigra in the midbrain,however the pathogenesis is unclear.There is a correlation between the excitability of striatal neurons and PD.Ion channels are important to maintain membrane potential and regulate excitability of neurons,while ionic mechanisms for modulation of neurons excitability are not fully understood.This article reviews the relationship between ion channels and excitability of striatal neurons in PD and ion channel changes in the pathogenesis of PD.In order to find new targets to treatment PD by intervening ion channels.

Characteristics of the Nonselective Cation Current (NSCCs) in Rabbit Left Ventricular Epicardial, Midmyocardial and Endocardial Myocytes

Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventric- ular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current （INa-Ca） and late INa in M region （ deep subepicardial to midmyocardial）. Studies from our laboratory have found a new repolarization current-nonselective cation current （NSCCs） existing in rabbit fight ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp tech- niques. The permeability to Na^＋ , K^＋ , Li^＋ , Cs^＋ but not to Cl^- indicating that it was a nonselective cation current. Gd^＋3 （0. 1 mmol/1） and La^3＋ （0. 1 retool/1 ） can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to - 80 mV, INa current density was （ -0. 44 ±0. 05） PA/PF in endocardial cells, （ -0. 12 ±0. 05） PA/PF in M cells and （ - 0. 28 ±0. 07） PA/PF in epicardial cells ; and with repolarization to ＋ 30 mV, INa, current density was （ 1.09 ± 0. 29） PA/PF in endocardial cells, （0. 38±0. 09） PA/PF in M cells and （0. 91 ± 0. 32） PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias.

A COMMENSAL SYMBIOSIS MODEL WITH HOLLING TYPE FUNCTIONAL RESPONSE AND NON-SELECTIVE HARVESTING IN A PARTIAL CLOSURE

A two species commensal symbiosis model with Holling type functional response and non-selective harvesting in a partial closure is considered. Local and global stability property of the equilibria are investigated. Depending on the the area available for capture, we show that the system maybe extinct or one of the species will be driven to extinction, while the rest one is permanent, or both of the species coexist in a stable state. The dynamic behaviors of the system is complicated and sensitive to the fraction of the harvesting area.

Development status and trend of agricultural robot technology

In the face of the contradiction between the increasing demand for agricultural products and the sharp reduction of agricultural resources and labor force,agricultural robot technology is developing explosively on the basis of decades of technical and industrial exploration.In view of the complexity and particularity of the development of agricultural robot technology,it is of great value to summarize its development characteristics and make reasonable judgments on its development trend.In this paper,the type of agricultural robot systems was first discussed.From the classification of agricultural robot systems,the development of main types of monitoring robots,non-selective and selective working robots for crop farming,livestock and poultry farming and aquaculture were introduced in detail.Then the scientific research,core technology,and commercialization of different types of agricultural robots were summarized.It is believed that navigation in complex agricultural environments,damage-free robot-crop interaction,and agronomy-robot fusion have high scientific value and significance to promote the revolutionary advances in agricultural robot technology.The characteristics of inter-discipline between agricultural robot technology and new materials,artificial intelligence,bionics,agronomy are research focus.The fast damage-free operation,autonomous navigation for complex environments,target detection for complex backgrounds,and special design for agricultural robots are considered to be the key technology of agricultural robot development,and the development path is given.Finally,robot-crop interaction simulation,big data support,and artificial intelligence are regarded as paths to realize the breakthrough of key agricultural robot technologies.The summary and prospect of this paper are of positive significance to promote the overall development of agricultural robot technology.

Recent advances in the management of variceal bleeding

Acute haemorrhage from ruptured gastroesophageal varices is perhaps the most serious consequence of uncontrolled portal hypertension in cirrhotic patients.It represents a medical emergency and is associated with a high morbidity and mortality.In those who survive the initial bleeding event,the risks of further bleeding and other decompensated events remain high.The past 30 years have seen a slow evolution of management strategies that have greatly improved the chances of surviving a variceal haemorrhage.Liver cirrhosis is a multi-staged pathological process and we are moving away from a one-size-fits-all therapeutic approach.Instead there is an increasing recognition that a more nuanced approach will yield optimal survival for patients.This approach seeks to risk stratify patients according to their disease stage.The exact type and timing of treatment offered can then be varied to suit individual patients.At the same time,the toolbox of available therapy is expanding and there is a continual stream of emerging evidence to support the use of endoscopic and pharmacological therapies.In this review,we present a summary of the treatment options for a variety of different clinical scenarios and for when there is failure to control bleeding.We have conducted a detailed literature review and presented up-to-date evidence from either primary randomized-controlled trials or meta-analyses that support current treatment algorithms.

Canonical transient receptor potential 4 and its small molecule modulators

Canonical transient receptor potential 4(TRPC4) forms non-selective cation channels that contribute to phospholipase C-dependent Ca2+ entry into cells following stimulation of G protein coupled receptors and receptor tyrosine kinases.Moreover,the channels are regulated by pertussis toxin-sensitive Gi/o proteins,lipids,and various other signaling mechanisms.TRPC4-containing channels participate in the regulation of a variety of physiological functions,including excitability of both gastrointestinal smooth muscles and brain neurons.This review is to present recent advances in the understanding of physiology and development of small molecular modulators of TRPC4 channels.

Novel treatment options for portal hypertension

Portal hypertension is most frequently associated with cirrhosis and is a major driver for associated complications,such as variceal bleeding,ascites or hepatic encephalopathy.As such,clinically significant portal hypertension forms the prelude to decompensation and impacts significantly on the prognosis of patients with liver cirrhosis.At present,non-selective bblockers,vasopressin analogues and somatostatin analogues are the mainstay of treatment but these strategies are far from satisfactory and only target splanchnic hyperemia.In contrast,safe and reliable strategies to reduce the increased intrahepatic resistance in cirrhotic patients still represent a pending issue.In recent years,several preclinical and clinical trials have focused on this latter component and other therapeutic avenues.In this review,we highlight novel data in this context and address potentially interesting therapeutic options for the future.

A 150%enhancement of PMOSFET mobility using hybrid orientation

A high-performance PMOSFET based on silicon material of hybrid orientation is obtained.Hybrid orientation wafers,integrated by（100） and（110） crystal orientation,are fabricated using silicon-silicon bonding, chemical mechanical polishing,etching silicon and non-selective expitaxy.A PMOSFET with W/L = 50μm/8μm is also processed,and the measured results show that the drain-source current and peak mobility of the PMOSFET are enhanced by up to 50.7%and 150%at V_（gs） =-15 V and V_（ds） =-0.5 V,respectively.The mobility values are higher than that reported in the literature.

Variceal bleeding in cirrhotic patients

Variceal bleeding is one of the major causes of death in cirrhotic patients.The management during the acute phase and the secondary prophylaxis is well defined.Recent recommendations(2015 Baveno VI expert consensus)are available and should be followed for an optimal management,which must be performed as an emergency in a liver or general intensive-care unit.It is based on the early administration of a vasoactive drug(before endoscopy),an antibiotic prophylaxis and a restrictive transfusion strategy(hemoglobin target of 7 g/dL).The endoscopic treatment is based on band ligations.Sclerotherapy should be abandoned.In the most severe patients(Child Pugh C or B with active bleeding during initial endoscopy),transjugular intrahepatic portosystemic shunt(TIPS)should be performed within 72 hours after admission to minimize the risk of rebleeding.Secondary prophylaxis is based on the association of non-selective beta-blockers(NSBBs)and repeated band ligations.TIPS should be considered when bleeding reoccurs in spite of a well-conducted secondary prophylaxis or when NSBBs are poorly tolerated.It should also be considered when bleeding is refractory.Liver transplantation should be discussed when bleeding is not controlled after TIPS insertion and in all cases when liver function is deteriorated.