polysaccharide inhibits retinal neovascularization and inflammation and .

Aim: To explore the effect and mechanism of polysaccharide (LBP) inhibiting retinal neovascularization.

Methods: tests were performed on human retinal microvascular endothelial cells (HRECs) from three groups, including control group (normal oxygen), hypoxic group (hypoxia at 37°C, 1% O, 5% CO, and 94% N), and LBP group (hypoxic group with LBP 100 µg/mL). experiments, C57 mice were divided into three groups: control group (normal rearing group), the oxygen-induced ischemic retinopathy (OIR) group, and the OIR with 50 mg/kg LBP group.

Development of a Cationic Polymeric Micellar Structure with Endosomal Escape Capability Enables Enhanced Intramuscular Transfection of mRNA-LNPs.

The endosomal escape of lipid nanoparticles (LNPs) is crucial for efficient mRNA-based therapeutics. Here, we present a cationic polymeric micelle (cPM) as a safe and potent co-delivery system with enhanced endosomal escape capabilities. We synthesized a cationic and ampholytic di-block copolymer, poly (poly (ethylene glycol) methacrylate--hexyl methacrylate)--poly(butyl methacrylate--dimethylaminoethyl methacrylate--propyl acrylate) (p(PEGMA--HMA)--p(BMA--DMAEMA--PAA)), via reversible addition-fragmentation chain transfer polymerization.

Clinical outcomes and safety of polymyxin B versus tigecycline combination therapy for pneumonia of carbapenem-resistant : a retrospective cohort study.

Purpose: Infection by carbapenem-resistant (CRKP) has high mortality. There is no clear optimal therapeutic choice for pneumonia caused by CRKP. The aim of this study was to compare the clinical outcomes and safety of the standard doses of polymyxin B-based regimens vs tigecycline-based regimens and to identify risk factors for mortality.

Genome-wide Cas9-mediated screening of essential non-coding regulatory elements via libraries of paired single-guide RNAs.

The functions of non-coding regulatory elements (NCREs), which constitute a major fraction of the human genome, have not been systematically studied. Here we report a method involving libraries of paired single-guide RNAs targeting both ends of an NCRE as a screening system for the Cas9-mediated deletion of thousands of NCREs genome-wide to study their functions in distinct biological contexts. By using K562 and 293T cell lines and human embryonic stem cells, we show that NCREs can have redundant functions, and that many ultra-conserved elements have silencer activity and play essential roles in cell growth and in cellular responses to drugs (notably, the ultra-conserved element PAX6_Tarzan may be critical for heart development, as removing it from human embryonic stem cells led to defects in cardiomyocyte differentiation).

Effect of the ratios of estradiol increase on the outcome of in vitro fertilization-embryo transfer with antagonist regimens: a single center retrospective cohort study.

Background: The outcome of in vitro fertilization-embryo transfer (IVF) is often determined according to follicle and estradiol levels following gonadotropin stimulation. In previous studies, although most of them analyzed the estrogen level from ovaries or the average estrogen level of a single follicle, there was no study on the ratio of estrogen increase, which was also correlated with pregnancy outcomes in the clinic. This study aimed to make timely adjustments to follow-up medication to improve clinical outcomes based on the potential value of estradiol growth rate.

Identification of an ALK-2 inhibitor as an agonist for intercellular exchange and tumor delivery of nanomaterial.

Inefficient extravasation and penetration in solid tissues hinder the clinical outcome of nanoparticles (NPs). Recent studies have shown that the extravasation and penetration of NPs in solid tumor was mostly achieved via an active transcellular route. For this transport process, numerous efforts have been devoted to elucidate the endocytosis and subcellular trafficking of NPs.

Peptide-guided delivery improves the therapeutic efficacy and safety of glucocorticoid drugs for treating acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening conditions with excessive inflammation in the lung. Glucocorticoids had been widely used for ALI/ARDS, but their clinical benefit remains unclear. Here, we tackled the problem by conjugating prednisolone (PSL) with a targeting peptide termed CRV.

Effect of Transumbilical Single-Port Laparoscopic-Assisted Duhamel Operation on Serum CRP and IL-6 Levels in Children with Hirschsprung's Disease.

Objective: To explore the clinical intervention effect of transumbilical single-port laparoscopic-assisted Duhamel operation on children with Hirschsprung's disease (HD) and to analyze the effect of treatment on children with serum C-reactive protein (CRP) and interleukin-6 (IL-6) effects.

Methods: Retrospectively select 80 children with HD who underwent surgery in our hospital from May 2017 to May 2020 as the research subjects and they are classified as group A according to the difference of the children's surgical procedures (receiving transumbilical single-port laparoscopic-assisted Duhamel surgery, 40 cases) and group B (receiving conventional laparoscopic surgery, 40 cases), compare the perioperative period (operating time, intraoperative blood loss, surgical posthospitalization, and postoperative gastrointestinal function recovery time), early postoperative complications (perianal dermatitis, urinary retention, enterocolitis, and anastomotic leakage), and late postoperative complications (anastomotic stenosis, dirty stool, recurrence of constipation, and enterocolitis), compare the differences in the levels of CRP and IL-6 between the two groups of children before and after the operation, and conduct a 1-year follow-up of the two groups of children to compare the long-term defecation status.

Results: The surgical time of children in group A, postoperative hospitalization time, and postoperative gastrointestinal function recovery time were significantly shorter than those of group B, and the differences between groups were statistically significant ( < 0.

Precise puncture combined with simplified percutaneous vertebroplasty to treat osteoporotic vertebral compression fractures: a comparative analysis with conventional percutaneous vertebroplasty.

Objective: To investigate the feasibility and clinical efficacy of precise puncture combined with simplified percutaneous vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures (OVCF).

Methods: A total of 82 patients with single-segment osteoporotic vertebral compression fractures (OVCF) treated with PVP from Dec. 2016 to Nov.

iRGD-liposomes enhance tumor delivery and therapeutic efficacy of antisense oligonucleotide drugs against primary prostate cancer and bone metastasis.

Nucleotide-based drugs, such as antisense oligonucleotides (ASOs), have unique advantages in treating human diseases as they provide virtually unlimited ability to target any gene. However, their clinical translation faces many challenges, one of which is poor delivery to the target tissue . This problem is particularly evident in solid tumors.

Effectiveness of proprotein convertase subtilisin/kexin-9 monoclonal antibody treatment on plasma lipoprotein(a) concentrations in patients with elevated lipoprotein(a) attending a clinic.

Background: Lipoprotein(a) (Lp[a]) is a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin-9 monoclonal antibodies (PCSK9mAbs) can lower Lp(a) levels in clinical trials, but their effects in patients with elevated Lp(a) in clinical practice remain unclear.

Aims: To investigate the effectiveness and safety of PCSK9mAbs in lowering plasma Lp(a) in patients with elevated Lp(a) concentrations in a lipid clinic.

Assessment of trends and clinical presentation in the emergency department of patients with renal colic during the COVID-19 pandemic era.

Introduction: We hypothesized that the recent COVID-19 pandemic may lead to a delay in renal colic patients presenting to the Emergency Department due to the fear of getting infected. This delay may lead to a more severe clinical condition at presentation with possible complications for the patients.

Material And Methods: Retrospective review of data collected from three institutions from Spain and Italy.

Human Amyloid-β Kinetics after Intravenous and Intracerebroventricular Injections and Calcitriol Treatment in Rats In Vivo.

Amyloid-β peptides of 40 and 42 amino acid lengths, which are synthesized in neurons and degraded in the brain and liver, have the potential to aggregate and form neuritic plaques in Alzheimer disease. The kinetics of human amyloid-β (hAβ) 40 were examined in the rat pursuant to intravenous and intracerebroventricular administration after pretreatment with calcitriol, the active vitamin D receptor ligand (6.4 nmol·kg in 0.

An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms of -Catecholaminergic Polymorphic Ventricular Tachycardia.

Background: Genetic variants in calsequestrin-2 () cause an autosomal recessive form of catecholaminergic polymorphic ventricular tachycardia (CPVT), although isolated reports have identified arrhythmic phenotypes among heterozygotes. Improved insight into the inheritance patterns, arrhythmic risks, and molecular mechanisms of -CPVT was sought through an international multicenter collaboration.

Methods: Genotype-phenotype segregation in -CPVT families was assessed, and the impact of genotype on arrhythmic risk was evaluated using Cox regression models.

Blockade of TIM-1 on the donor graft ameliorates graft-versus-host disease following hematopoietic cell transplantation.

Acute graft-versus-host disease (GVHD) is a leading cause of mortality after allogeneic hematopoietic cell transplantation (HCT) mediated by dysregulated T-cell immune reconstitution. Given the role of the T-cell immunoglobulin and mucin 1 (TIM-1) surface protein in many immune processes, including organ transplantation tolerance, we asked if TIM-1 might drive post-transplant inflammation and acute GVHD. TIM-1 binds to phosphatidylserine (PtdSer), and agonism of TIM1 on immune cells is proinflammatory.

Oceanic mantle reflections in deep seismic profiles offshore Sumatra are faults or fakes.

In the late 90's, some faults identified within oceanic crust were demonstrated to be artifacts arising from out-of-plane scattering along linear sediment-buried fault scarps. Symmetrical mantle reflections observed southwest northern Sumatra on seismic reflection profiles have been identified as faults cutting through the upper mantle down to unprecedented depths reaching ~45 km. Seawater being conveyed along sub-vertical re-activated fracture zones (FZs) to the upper mantle, the mantle portions of FZs are serpentinized and act as mirrors for seismic rays.

Effects of Serelaxin in Patients with Acute Heart Failure.

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.

Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care.

Chlamydia muridarum infection induces CD4+ T cells apoptosis via PI3K/AKT signal pathway.

Apoptosis is essential for the homeostatic control of the lymphocytes number during the development of an immune response to an invasive microorganism. CD4+ T cells play a major role in homeostasis of the immune system and are sufficient to confer protection against Chlamydia muridarum (Cm) infection in mice. The present study demonstrated that phosphatidylinositol 3-kinase (PI3K) p110δ mRNA and phosphorylation of protein kinase B (p-AKT) level were significantly increased in lung cells and spleen cells at day 3 and day 7 post-infection, p-AKT level was inhibited when adding PI3K inhibitor LY294002.

In situ reconstruction of long-term extreme flooding magnitudes and frequencies based on geological archives.

Extreme flooding magnitudes and frequencies are essentially related to assessment of risk and reliability in hydrological design. Extreme flooding and its discharge are highly sensitive to regional climate change. Presently, its discharge can be reconstructed by a geological archive or record along the river valley.

Semen hoveniae extract ameliorates alcohol-induced chronic liver damage in rats via modulation of the abnormalities of gut-liver axis.

Background: Hovenia dulcis Thunb. is considered as a traditional herbal medicine that has been used in the treatment for ethanol-induced liver disease for centuries. Recently, substantial studies demonstrated that Semen hoveniae extract (SHE) not only suppressed the hepatic steatosis caused by chronic ethanol exposure, but also inhibited lipopolysaccharide-stimulated inflammatory responses.

Role of Kidneys in Sex Differences in Angiotensin II-Induced Hypertension.

The significance of kidneys in regulation of sodium and water balance and hemodynamics has been demonstrated both in patients and animal models. In the present study, we tested our hypothesis that kidneys play an essential role in control of sex differences in angiotensin II (Ang II)-dependent hypertension. Kidney transplantations (KTXs) were performed between male (M) and female (F) C57BL/6 mice (donor→recipient: F→F, M→M, F→M, and M→F).

Regulation of human feto-placental endothelial barrier integrity by vascular endothelial growth factors: competitive interplay between VEGF-Aa, VEGF-Ab, PIGF and VE-cadherin.

The human placenta nourishes and protects the developing foetus whilst influencing maternal physiology for fetal advantage. It expresses several members of the vascular endothelial growth factor (VEGF) family including the pro-angiogenic/pro-permeability VEGF-Aa isoform, the anti-angiogenic VEGF-Ab, placental growth factor (PIGF) and their receptors, VEGFR1 and VEGFR2. Alterations in the ratio of these factors during gestation and in complicated pregnancies have been reported; however, the impact of this on feto-placental endothelial barrier integrity is unknown.

Comment on "Outburst flood at 1920 BCE supports historicity of China's Great Flood and the Xia dynasty".

Wu (Reports, 5 August 2016, p. 579) reported an enormous flood in the upper Yellow River that destroyed the Lajia Ruins. However, published research shows that the Ruins were destroyed at 3950 years before the present (B.

Role of miR-145 in chronic constriction injury in rats.

The present study aims to investigate the effects and underlying mechanisms of miRNA-145 (miR-145) in rat models of chronic constriction injury (CCI). Rats were randomly divided into control, sham, CCI, agomiRNA (agomiR)-normal control (NC) and agomiR-145 groups (n=25 in each group); in addition, 30 rats with CCI were divided into small hairpin (sh)RNA-NC and shRNA-ras responsive element binding protein 1 (RREB1) groups. Paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT) were detected.