Using heart rate variability to develop a predictive model for post-operative cardiovascular complications following major abdominal surgery: A pilot study.

BACKGROUND: Heart Rate Variability (HRV) is a dynamic reflection of heart rhythm regulation by various physiological inputs. HRV deviations have been found to correlate with clinical outcomes in patients under physiological stresses. Perioperative cardiovascular complications occur in up to 5% of adult patients undergoing abdominal surgery and are associated with significantly increased mortality. This pilot study aimed to develop a predictive model for post-operative cardiovascular complications using HRV parameters for early risk stratification and aid post-operative clinical decision-making. METHODS: Adult patients admitted to High Dependency Units after elective major abdominal surgery were recruited. The primary composite outcome was defined as cardiovascular complications within 7 days post-operatively. ECG monitoring for HRV parameters was conducted at three time points (pre-operative, immediately post-operative, and post-operative day 1) and analyzed based on outcome group and time interactions. Candidate HRV predictors were included in a multivariable logistic regression analysis incorporating a stepwise selection algorithm. RESULTS: 89 patients were included in the analysis, with 8 experiencing cardiovascular complications. Three HRV parameters, when measured immediately post-operatively and composited with patient age, provided the basis for a predictive model with AUC of 0.980 (95% CI: 0.953, 1.00). The negative predictive value was 1.00 at a statistically optimal predicted probability cut-off point of 0.16. CONCLUSION: Our model holds potential for accelerating clinical decision-making and aiding in patient triaging post-operatively, using easily acquired HRV parameters. Risk stratification with our model may enable safe early step-down care in patients assessed to have a low risk profile of post-operative cardiovascular complications.

Associations of vegetable and fruit intake, physical activity, and school bullying with depressive symptoms in secondary school students: the mediating role of internet addiction.

BACKGROUND: Few studies have simultaneously focused on the associations of vegetable and fruit intake, physical activity, school bullying, and Internet addiction (IA) with depressive symptoms. This study aimed to explore the direct and indirect effects of the above factors on depressive symptoms in adolescents by constructing a structural equation model (SEM). METHODS: This study was conducted in Qingdao from September to November 2021. A total of 6195 secondary school students aged 10-19 years were included in the analysis. Information on all variables was assessed using a self-administered questionnaire. An SEM was constructed with depressive symptoms as the endogenous latent variable, IA as the mediating variable, and vegetable and fruit intake, physical activity, and school bullying as the exogenous latent variables. The standardized path coefficients (ß) were the direct effects between the latent variables, and the indirect effects were obtained by the product of direct effects between relevant latent variables. RESULTS: The median value with the interquartile range of depressive symptom scores was 7 (3,12). Vegetable and fruit intake (ß=-0.100, P<0.001) and physical activity (ß=-0.140, P<0.001) were directly negatively related to depressive symptoms. While school bullying (ß=0.138, P<0.001) and IA (ß=0.452, P<0.001) were directly positively related to depressive symptoms. IA had the greatest impact on depressive symptoms. Vegetable and fruit intake, physical activity, and school bullying could not only directly affect depressive symptoms, but also indirectly affect depressive symptoms through the mediating effect of IA, the indirect effects and 95% confidence intervals (CIs) were -0.028 (-0.051, -0.007), -0.114 (-0.148, -0.089) and 0.095 (0.060, 0.157), respectively. The results of the multi-group analysis showed that the SEM we constructed still fit in boy and girl groups. CONCLUSIONS: The results indicated that vegetable and fruit intake, physical activity, school bullying, and IA had a significant direct impact on depressive symptoms, among which IA had the greatest impact. In addition, both vegetable and fruit intake, school bullying, and physical activity indirectly affected depressive symptoms through the mediating effect of IA. The impact of IA on depressive symptoms should be given extra attention by schools and parents. This study provides a scientific and effective basis for the prevention and control of adolescent depressive symptoms.

Pyridazine-Promoted Construction of Vinylene-Linked Covalent Organic Frameworks with Exceptional Capability of Stepwise Water Harvesting.

In this study, we successfully developed two novel vinylene-linked covalent organic frameworks (COFs) using 2-connected 3,6-dimethylpyridazine through Knoevenagel condensation. These COFs featured finely tailored micro-/nano-scale pore sizes, high surface areas and stable non-polar vinylene linkages. Finely resolved powder X-ray diffraction patterns demonstrated highly crystalline structures with a hexagonal lattice in the AA layer stacking. The resulting one-dimensional channels possess strong hydrogen-bond accepting sites arising from the decorated cis-azo/azine units with two pairs of fully exposed lone pair electrons, endowing the as-prepared COFs with exceptional water absorption properties. The g-DZPH-COF exhibited successive steep water uptake steps starting from low relative pressures (P/PSTA = 0.1), with the remarkable water uptake capacity of 0.26 g/g at P/PSTA = 0.2 (25°C), which is the optimal value recorded among the reported COFs. Dynamic vapour sorption measurements revealed the fast kinetics of these COFs, even in the cluster formation process. Water uptake and release cycling tests demonstrated their outstanding hydrolytic stability, durability, and adsorption-desorption retention ability.

Spinal infection caused by Coxiella burnetii.

BACKGROUND: Spinal infection caused by Coxiella burnetii is rare and difficult to diagnose. Here we reported a case of spinal infection from Coxiella burnetii detected by the metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 66-year-old male farmer with no medical history reported severe sharp low back pain, numbness and lower limb weakness for three years. Magnetic resonance imaging (MRI) revealed bone destruction and spinal cord compression within L1 and L2. mNGS testing showed that the inspected specimen collected from spinal lesion was detected positively for Coxiella burnetii. After receiving the combined treatment of antibiotic therapy and surgical intervention, the patient recovered well, and the sagittal MRI showed that vertebral edema signals disappeared and the graft of bone fused 16 months after surgery. CONCLUSION: The mNGS may be benefit for early diagnosis and intervention of non-specific spinal infection, and future studies should validate its effectiveness for clinical use in spinal infections. Additionally, antibiotic therapy combined with surgical intervention plays an important role on the treatment of spinal infection caused by Coxiella burnetii.

The study on the feasibility of dietary supplementation with dimethyl silicone oil to prevent frothy rumen bloat in goats fed with high concentrate diets.

The current study was conducted to investigate the feasibility of high concentration diet (HCD) supplementation with Dimethyl Silicone Oil (DSO) to prevent frothy rumen bloat in goats. The treatments were control group (group C, feeding HCD) and test group (group T, feeding HCD supplemented with 0.1%DSO). The results showed that compared with the group C, the ruminal pH value, Microbial Crude Protein content of group T was extremely significantly higher (p < 0.01), the levels of acetic acid and propionic acid were significantly (p < 0.05) and extremely significantly (p < 0.01) lower in group T, respectively. The foam production and foam strength of the rumen fluid in the group T was extremely significantly lower (p < 0.01), the viscosity was extremely significantly (p < 0.01) higher than those of group C. The total gastrointestinal apparent digestibility of various nutrients, the rumen microbial relative abundance at the phylum level and genus level were not significantly different (p > 0.05). The results indicated that the supplementation of 0.1% DSO in HCD can significantly eliminate foam of the rumen fluid, and didn't disturb the ruminal microorganisms, no negatively affect on digestibility of nutrients in goats, thereby has the application prospect of preventing frothy rumen bloat.

The gas produced by rumen fermentation is wrapped in foam and cannot be discharged is the root cause of frothy bloat induced by a high concentration diet. In the present study, the feasibility of dietary supplementation with Dimethyl Silicone Oil (DSO) to prevent frothy bloat was preliminarily evaluated. The results indicated that DSO can significantly eliminate foam of the rumen fluid, and has not negatively effect on the ruminal microorganisms and the digestibility of nutrients in goats, thereby has the application prospect of preventing frothy bloat.

Effect of dietary concentrate level on digestibility of nutrients in each region of the gastrointestinal tract and rumen fermentation in goats.

This study evaluated the effects of high concentrate diets (HCD) on the rumen fermentation and the digestibility of nutrients in different sites of the gastrointestinal tract (GIT) in goats. Four goats were used in a crossover design. The goats were fitted with a ruminal cannula and flexible T-cannulae proximal duodenum and terminal ileum. Treatments were as follows: low concentrate group (LCG) and high concentrate group (HCG). Duodenal flow and forestomach digestibility of starch were significantly higher in the HCG than those in the LCG (p < 0.05); There was no significant difference in ileum flow and digestibility of starch in the small intestine, large intestine and total GIT (p > 0.05). The digestibility of crude protein (CP) in the forestomach was significantly higher in the HCG than in the LCG (p < 0.05); the flow of the duodenum and ileum of CP, and the CP digestibility of the small intestine, large intestine and total GIT were not significantly different between groups (p > 0.05). The duodenal and ileal flow of neutral detergent fiber (NDF), the NDF digestibility of the different segments and total GIT were not significantly different between groups (p > 0.05). Compared to the LCG, the ruminal pH of the HCG was significantly lower (p < 0.05). The HCG concentrations of microbial crude protein, ammonia nitrogen and isovaleric acid were significantly higher (p < 0.05) than the LCG. The foam strength, foam production and viscosity of the rumen fluid in the HCG were higher than the LCG (p < 0.01). These results showed that when the goats were fed with HCD, the digestibility of nutrients was not significantly impaired, but the risk of frothy rumen bloat increased. ImplicationsDue to a serious shortage of high-quality roughage in China, producers commonly used a high-concentrate diet in ruminants, which can improve animal production performance.Gastrointestinal digestive function plays a vital role in the absorption of nutrients and the healthy growth of animals.Therefore, this research evaluated the digestibility of various nutrients in different segments of the gastrointestinal tract (GIT) under HCD feeding by using three-site cannula goats as experimental animals.The results indicated that the GIT of goats could fully digest nutrients such as starch and protein under HCD feeding conditions.

Effects of uni and bilateral castration on growth performance and lipid metabolism in yellow cattle.

This study was conducted to examine the influence of uni and bilateral castration on growth performance and lipid metabolism in yellow cattle. Eighteen 9-month-old healthy yellow cattle (average body weight 184.03 ± 4.09 kg) were selected and divided into three groups: The uncastrated cattle (C), half castrated cattle (HC) and full castrated cattle (FC). The results showed that the growth rate of FC group was significantly reduced as compared to HC and C group, while the feed to gain ratio exhibited an opposite trend. The concentrations of triglycerides (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein (HDL) were increased significantly in FC group from day 60 to the end of the trial compared to HC and control groups. Serum testosterone concentration of FC group cattle was decreased from day 60 to 120 d of the trial compared to HC and control groups. The concentration of the lauric acid in FC cattle was significantly increased from the HC and control groups. In the FC group, the acetyl-CoA carboxylase alpha (ACACA), ACC and fatty acid synthase (FAS) gene expression levels were significantly higher compared to control and HC groups. Our results of this study suggest that bilateral castration increased the lipid metabolism and fatty acid composition compared to unilateral castrated and un-castrated cattle.HighlightsBilateral castration alters the growth performance in yellow cattle.Bilateral castration alters hormones levels and lipid metabolites levels in serum.Bilateral castration improves the lipid metabolism and fatty acid profile.

circ_0000337 Promotes the Progression of Cervical Cancer by miR-155-5p/RAB3B Axis.

Current study aims to investigate the biological function of circular RNA (circRNA, circ_0000337) in cervical cancer (CC). Bioinformatic analyses were used to predict targets for circ_0000337 and miR-155-5p, and analyze the gene expression differences between cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tissues and normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to assess mRNA and protein expressions of circ_0000337, microRNA-155-5p (miR-155-5p) and member RAS oncogene family (RAB3B), respectively. Following the establishment of gain/loss-of-function models, CCK-8 was performed to evaluate cell proliferation. Bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to identify the interaction in circ_0000337, miR-155-5p, and RAB3B. Circ_0000337 and RAB3B were upregulated, while miR-155-5p was downregulated in CC tissues and cell lines. circ_0000337 overexpression promoted cell proliferation, circ_0000337 knock down inhibited cell proliferation by sponging miR-155-5p. RAB3B was a target of miR-155-5p which was positively regulated by circ_0000337. In the collected CC tissues, there was a negative correlation between miR-155-5p and circ_0000337 or RAB3B, and a positive correlation between circ_0000337 and RAB3B. miR-155-5p was positively, while RAB3B was negatively correlated with OS in patients with CC, and they were negatively correlated. In conclusion, circ_0000337 upregulates RAB3B by sponging miR-155-5p to promote CC cell proliferation.

Collaborative Assessment of Molecular Geometries and Energies from the Open Force Field.

Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein-ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field. In this report, industry members of the consortium worked together to objectively evaluate the performance of the force fields (referred to here as OpenFF) produced by the initiative on a combined public and proprietary dataset of 19,653 relevant molecules selected from their internal research and compound collections. This evaluation was important because it was completely blind; at most partners, none of the molecules or data were used in force field development or testing prior to this work. We compare the Open Force Field "Sage" version 2.0.0 and "Parsley" version 1.3.0 with GAFF-2.11-AM1BCC, OPLS4, and SMIRNOFF99Frosst. We analyzed force-field-optimized geometries and conformer energies compared to reference quantum mechanical data. We show that OPLS4 performs best, and the latest Open Force Field release shows a clear improvement compared to its predecessors. The performance of established force fields such as GAFF-2.11 was generally worse. While OpenFF researchers were involved in building the benchmarking infrastructure used in this work, benchmarking was done entirely in-house within industrial organizations and the resulting assessment is reported here. This work assesses the force field performance using separate benchmarking steps, external datasets, and involving external research groups. This effort may also be unique in terms of the number of different industrial partners involved, with 10 different companies participating in the benchmark efforts.

Effects of dry yeast supplementation on growth performance, rumen fermentation characteristics, slaughter performance and microbial communities in beef cattle.

This study aimed to investigate the effects of active dry yeast (ADY) on growth performance, rumen microbial composition and carcass performance of beef cattle. Thirty-two finishing beef cattle (yak ♂ × cattle-yaks ♀), with an average body weight of 110 ± 12.85 kg, were randomly assigned to one of four treatments: the low plane of nutrition group (control), low plane of nutrition group + ADY 2 g/head daily (ADY2), low plane of nutrition group + ADY 4 g/head daily (ADY4) and the high plane of nutrition group (HPN). Supplementation of ADY increased average daily gain compared to the control group. The neutral detergent fiber and acid detergent fiber apparent digestibility in HPN group was greater than that in control group. The propionic acid concentration in the rumen in ADY2, ADY4, and HPN groups was greater than that in control group. The Simpson and Shannon indexes in control and HPN groups were higher than that in ADY4 group. At the phylum level, the relative abundance of Firmicutes in the HPN group was higher than that in ADY4 group. The relative abundance of Ruminococcaceae UCG-002 in ADY4 group was higher than that in control and HPN groups. In conclusion, supplementation ADY 4 g/head daily shift the rumen microbial composition of beef cattle fed low plane of nutrition to a more similar composition with cattle fed with HPN diet and produce the similar carcass weight with HPN diet.HighlightsThe ADY can improve the utilization of nitrogen and decrease the negative impact on the environment in beef cattle.Cattle fed low plane of nutrition diet supplemented with ADY 4 g/head daily increased growth performance.Supplementation ADY 4 g/head daily in low plane of nutrition diet might be produced comparable carcass weight to HPN diet.

Bioinformatics analysis of mRNA and miRNA microarray to identify the key miRNA-mRNA pairs in cisplatin-resistant ovarian cancer.

BACKGROUND: Ovarian cancer (OC) is a gynecological malignancy with the highest mortality rate. Cisplatin (DDP) based chemotherapy is a standard strategy for ovarian cancer. Despite good response rates for initial chemotherapy, almost 80% of the patients treated with DDP based chemotherapy will experience recurrence due to drug-resistant, which will ultimately result in fatality. The aim of the present study was to examine the pathogenesis and potential molecular markers of cisplatin-resistant OC by studying the differential expression of mRNAs and miRNAs between cisplatin resistant OC cell lines and normal cell lines. METHODS: Two mRNA datasets (GSE58470 and GSE45553) and two miRNA sequence datasets (GSE58469 and GSE148251) were downloaded from the Gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were screened by the NetworkAnalyst. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEGs. The protein-protein interaction network was constructed using STRING and Cytoscape software to identify the molecular mechanisms of key signaling pathways and cellular activities. FunRich and MiRNATip databases were used to identify the target genes of the DEMs. RESULTS: A total of 380 DEGs, and 5 DEMs were identified. Protein-protein interaction (PPI) network of DEGs containing 379 nodes and 1049 edges was constructed, and 4 key modules and 24 hub genes related to cisplatin-resistant OC were screened. Two hundred ninety-nine target genes of the 5 DEMs were found out. Subsequently, one of these 299 target genes (UBB) belonging to the hub genes of GSE58470 and GSE45553 was identified by MCODE and CytoHubba,which was regulated by one miRNA (mir-454). CONCLUSIONS: One miRNA-mRNA regulatory pairs (mir-454-UBB) was established. Taken together, our study provided evidence concerning the alteration genes involved in cisplatin-resistant OC, which will help to unravel the mechanisms underlying drug resistant.

A new hand-held holder optimizes the parameters of the laser-induced choroidal neovascularization model in mice.

BACKGROUND: The laser-induced choroidal neovascularization (CNV) mouse model, as the most classic animal model of age-related macular degeneration (AMD), has been widely used. We designed a hand-held mouse holder to optimize mouse fixation in the laser-induced CNV modelling process, which was inconvenient until now. This study aimed to evaluate the effectiveness of our in-house hand-held mouse holder design in the laser-induced CNV mouse modelling process. METHODS: Six ophthalmic residents were invited to perform laser-induced CNV mouse modelling by hand or using the holder. We compared the learning time of residents and their physical and mental fatigue with the two methods. In addition, we compared the parameters of CNV modelling with two methods by a skilled operator, including the time of photocoagulation, induction rate and uniformity of CNV lesions. RESULTS: In the learning phase, the average learning time to master the modelling method was significantly shortened by utilizing the holder. The fatigue in the operation process was quantified to a level from 0 to 4, and the physical fatigue by using holder (0.8 ± 0.3) was lower than by hand (2.6 ± 0.4), and the mental fatigue was relieved from 2.3 ± 0.5 to 0.4 ± 0.3. On the other hand, the skilled operator can significantly shorten the time of laser photocoagulation from 146.7 ± 36.0 s to 63.6 + 5.7 s and improve the success rate of modelling from 50.0% ± 8.3%-87.5% ± 6.7% by using a holder compared to hand. In addition, the standard error of the mean (SEM) of the distance between the CNV lesion and the optic nerve (ON) and the distance between each lesion was reduced. CONCLUSION: This hand-held mouse holder could optimize the setting and conditions of laser-induced CNV mouse modelling by improving the learning curve, reducing fatigue, shortening the time for photocoagulation, improving the success rate and consistency of laser-induced lesions.

Multiple Stimuli-Responsive Supramolecular Hydrogels Constructed by Decamethylcucurbit[5]uril-para-phenylenediamine Exclusion Complex.

The hydrogels composed of decamethylcucurbit[5]uril (Me10 Q[5]) and para-phenylenediamine (p-PDA) are first reported herein. They are the first Q[5]-based supramolecular hydrogels, the formation of which is driven by portal exclusion between Me10 Q[5] and p-PDA. The composition, structure, and properties of the Me10 Q[5]/p-PDA-based hydrogels are investigated by various techniques. Since the 1D supramolecular chain forms via portal exclusion between Me10 Q[5] and p-PDA is the key to the formation of the hydrogels, any competitive species, such as metal ions, organic molecules, and amino acids, which can affect the portal exclusion, can change the behavior of the Me10 Q[5]/p-PDA-based hydrogels. Hence, the hydrogels can be used for various applications. Importantly, the results may provide a new research direction for the preparation of Q[n]-based hydrogels via portal exclusion of Q[n]s with guests.

Comparative study of the bacterial communities throughout the gastrointestinal tract in two beef cattle breeds.

Investigation of the compositional and functional characteristics of the gastrointestinal bacterial community in beef cattle breeds can improve our understanding of the influence of gastrointestinal tract (GIT) regions and host breeds on the bacterial community. In this study, 16S ribosomal RNA (16S rRNA) gene amplicon sequencing was used to characterize the bacterial communities in the rumen, duodenum, jejunum, ileum, caecum, and colon of Xuanhan yellow cattle (XHC) and Simmental crossbred cattle (SXC). The results showed that the diversity of the bacterial population was different in GIT regions of XHC and SXC (P < 0.05). In total, ten bacterial phyla, sixteen bacterial genera, and nine metabolic pathways were identified in the core bacteria. The phyla Firmicutes, Bacteroidetes, and Proteobacteria were predominant, but their proportions were different in GIT regions (P < 0.05). The diversity, structure, and composition of the bacteria in the rumen were similar between the breeds (P > 0.05), and the indices in the intestine showed significant differences (P < 0.05). Moreover, the composition and structure of the bacterial communities in the rumen, small intestine, and large intestine were different regardless of the breed. Thus, the bacterial communities were different among the gastrointestinal regions in each breed, and the bacterial community in the rumen had more stable characteristics than that in the intestine between two breeds. Further studies may focus on the minor microbial communities and the functions of GIT bacteria to better understand gut-microbe interactions. KEY POINTS: • Differences in bacteria among gastrointestinal regions differ in cattle breeds. • Differences between the breeds in the ruminal bacteria are less pronounced than differences in the intestinal bacteria.

Single-crystal metal growth on amorphous insulating substrates.

Metal structures on insulators are essential components in advanced electronic and nanooptical systems. Their electronic and optical properties are closely tied to their crystal quality, due to the strong dependence of carrier transport and band structure on defects and grain boundaries. Here we report a method for creating patterned single-crystal metal microstructures on amorphous insulating substrates, using liquid phase epitaxy. In this process, the patterned metal microstructures are encapsulated in an insulating crucible, together with a small seed of a differing material. The system is heated to temperatures above the metal melting point, followed by cooling and metal crystallization. During the heating process, the metal and seed form a high-melting-point solid solution, which directs liquid epitaxial metal growth. High yield of single-crystal metal with different sizes is confirmed with electron backscatter diffraction images, after removing the insulating crucible. Unexpectedly, the metal microstructures crystallize with the [Formula: see text] direction normal to the plane of the film. This platform technology will enable the large-scale integration of high-performance plasmonic and electronic nanosystems.

Comparison of carcass characteristics and meat quality between Simmental crossbred cattle, cattle-yaks and Xuanhan yellow cattle.

BACKGROUND: The study compared the growth performance, carcass characteristics and meat quality of steers of Xuanhan yellow cattle, Simmental crossbreed cattle (Simmental × Xuanhan yellow cattle) and cattle-yak (Jersey × yak). All steers were feed with the same diet from 6 months until slaughter at 30 months. The longissimus dorsi muscle was used to compare the meat quality traits. RESULTS: By comparison, Simmental crossbreed cattle had higher growth performance (P < 0.05) and carcass characteristics (P < 0.05); cattle-yak had higher value of a*, b* of meat color (P < 0.05) and higher protein contents of meat (P < 0.05); Xuanhan yellow cattle had higher water holding capacity (P < 0.05) and lower shear force (P < 0.05). CONCLUSIONS: The results show that Simmental crossbred cattle had better meat performance and provided low-fat meat with a beneficial fatty acid composition, but with lower meat quality; cattle-yaks provided greater meat color and higher protein content; Xuanhan yellow cattle provided meat with preferable tenderness. © 2020 Society of Chemical Industry.

Nei-like 1 inhibition results in motor dysfunction and promotes inflammation in Parkinson's disease mice model.

Parkinson's disease (PD) is well known as a neurodegenerative disorder with progressive loss of dopaminergic (DA) neurons. Nei-like 1 (NEIL1) is one of four mammalian DNA glycosylases involved in the progression of various diseases, including neuroinflammation. However, it is still unknown if the expression changes of NEIL1 could contribute to PD progression. In the present study, we established mouse model with PD using 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to explore the effects of NEIL1 on PD development. Here, we found that NEIL1 deletion significantly promoted the motor dysfunction in the wild type mice treated with 6-OHDA. Furthermore, DA neuronal loss was further accelerated by NEIL1 deletion in 6-OHDA-injected mice, as evidenced by the significantly reduced expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT). Furthermore, in PD mice induced by MPTP, remarkably reduced expression of NEIL1 was observed in nigra and striatum of mice. A strong positive correlation was detected in the expression of NEIL1 and the survival rate of DA neurons. Also, NEIL1 ablation further elevated the DA neuronal loss in MPTP-treated mice, accompanied with higher glial activation, as evidenced by the obvious up-regulation of glial fibrillary acidic protein (GFAP) and Ionized calcium-Binding Adapter molecule 1 (Iba1). Moreover, MPTP-triggered inflammation was highly aggravated by the loss of NEIL1 through inducing the expression of pro-inflammatory cytokines and chemokines. In contrast, promoting NEIL1 expression effectively reversedPD progression induced by MPTP in mice. Together, these results demonstrated that NEIL1 insufficiency might be a contributing factor for the progression of PD, which therefore could be considered as a novel candidate to develop effective treatments against PD progression.

Leukemia inhibitory factor promotes the regeneration of rat uterine horns with full-thickness injury.

Severe uterine injuries may lead to infertility or pregnancy complications. There is a lack of effective methods to restore the structure and function of seriously injured uteri. Leukemia inhibitory factor (LIF), which plays a crucial role in blastocyst implantation, promotes the process of regeneration after injury in several different tissues. In this study, we explored the effect of LIF on the regeneration of rat uterine horns following full-thickness injury. One hundred and twenty four female Sprague-Dawley rats were assigned to three groups, including a sham-operated group (n = 34 uterine horns), a PBS/collagen group (n = 90 uterine horns), and a LIF/collagen group (n = 124 uterine horns). The regenerated uterine horns were collected at 1, 2, 4, 8, or 12 weeks after the surgery. The results showed that LIF/collagen scaffolds increased the number of endometrial cells and neovascularization 2 weeks after uterine full-thickness defect in excision sites (p < 0.001 vs PBS/collagen). Eight weeks after the surgery, the number of endometrial glands was dramatically higher in the LIF/collagen scaffolds group (35.2 ± 4.1/field) than in the PBS/collagen scaffolds (15.1 ± 1.4/field). The percentage of a-smooth muscle actin (a-SMA)-positive areas in the LIF/collagen scaffolds (88.8% ± 9.8%) was also significantly higher than that in the PBS/collagen group (52.9% ± 3.7%). Moreover, LIF improved the pregnancy rate and fetus number. We also found that LIF inhibited the infiltration of inflammatory cells and down-regulated the pro-inflammatory cytokine IL-12 expression while up-regulating the anti-inflammatory cytokine IL-10 expression in the injured part of the uterine horns. Our results indicate that LIF promotes regeneration of the uterus after injury, and this is at least partially due to its immunomodulatory properties. In addition, it is worth to explore further the possibility for LIF/collagen to be an alternative therapeutic approach for uterine damage in the clinic in near future.