Protective Effect of Vitamin K2 (MK-7) on Acute Lung Injury Induced by Lipopolysaccharide in Mice.

Vitamin K2 (MK-7) has been shown to cause significant changes in different physiological processes and diseases, but its role in acute lung injury (ALI) is unclear. Therefore, in this study, we aimed to evaluate the protective effects of VK2 against LPS-induced ALI in mice. The male C57BL/6J mice were randomly divided into six groups (n = 7): the control group, LPS group, negative control group (LPS + Oil), positive control group (LPS + DEX), LPS + VK2 (L) group (VK2, 1.5 mg/kg), and LPS + VK2 (H) group (VK2, 15 mg/kg). Hematoxylin-eosin (HE) staining of lung tissue was performed. Antioxidant superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities, and the Ca2+ level in the lung tissue were measured. The effects of VK2 on inflammation, apoptosis, tight junction (TJ) injury, mitochondrial dysfunction, and autophagy were quantitatively assessed using Western blot analysis. Compared with the LPS group, VK2 improved histopathological changes; alleviated inflammation, apoptosis, and TJ injury; increased antioxidant enzyme activity; reduced Ca2+ overload; regulated mitochondrial function; and inhibited lung autophagy. These results indicate that VK2 could improve tight junction protein loss, inflammation, and cell apoptosis in LPS-induced ALI by inhibiting the mitochondrial dysfunction and excessive autophagy, indicating that VK2 plays a beneficial role in ALI and might be a potential therapeutic strategy.

Response of bacterial and micro-eukaryotic communities to spatio-temporal fluctuations of wastewater in full scale constructed wetlands.

How microbial communities respond to wastewater fluctuations is poorly understood. Full-scale surface flow constructed wetlands (SFCWs) were constructed for investigating microbial communities. Results showed that influent wastewater changed sediment bacterial community composition seasonally, indicating that a single bacterial taxonomic group had low resistance (especially, Actinobacteriota and Gammaproteobacteria). However, copy numbers of 16S rRNA, ammonia oxidizing archaea, ammonia oxidizing bacteria, nirS and nirK in the first stage SFCWs were 2.49 × 1010, 3.48 × 109, 5.76 × 106, 8.77 × 108 and 9.06 × 108 g-1 dry sediment, respectively, which remained stable between seasons. Moreover, decreases in the nitrogen concentration in wastewater, changed microbial system state from heterotrophic to autotrophic. Micro-eukaryotic communities were more sensitive to wastewater fluctuations than bacterial communities. Overall, results revealed that microbial communities responded to spatio-temporal fluctuations in wastewater through state changes and species asynchrony. This highlighted complex processes of wastewater treatment by microbial components in SFCWs.

Core fucosylation of maternal milk N-glycans imparts early-life immune tolerance through gut microbiota-dependent regulation in RORγt+ Treg cells.

Milk glycans play key roles in shaping and maintaining a healthy infant gut microbiota. Core fucosylation catalyzed by fucosyltransferase (Fut8) is the major glycosylation pattern on human milk N-glycan, which was crucial for promoting the colonization and dominant growth of Bifidobacterium and Lactobacillus spp. in neonates. However, the influence of core-fucose in breast milk on the establishment of early-life immune tolerance remains poorly characterized. In this study, we found that the deficiency of core-fucose in the milk of maternal mice caused by Fut8 gene heterozygosity (Fut8+/-) resulted in poor immune tolerance towards the ovalbumin (OVA) challenge, accompanied by a reduced proportion of intestinal RORγt+ Treg cells and the abundance of Lactobacillus spp., especially L. reuteri and L. johnsonii, in their breast-fed neonates. The administration of the L. reuteri and L. johnsonii mixture to neonatal mice compromised the OVA-induced allergy and up-regulated the intestinal RORγt+ Treg cell proportions. However, Lactobacillus mixture supplementation did not alleviate allergic responses in RORγt+ Treg cell-deficient mice caused by Rorc gene heterozygosity (Rorc+/-) post OVA challenge, indicating that the intervention effects depend on the RORγt+ Treg cells. Interestingly, instead of L. reuteri and L. johnsonii, we found that the relative abundance of another Lactobacillus spp., L. murinus, in the gut of the offspring mice was significantly promoted by intervention, which showed enhancing effects on the proliferation of splenic and intestinal RORγt+ Treg cells in in vitro studies. The above results indicate that core fucosylation of breast milk N-glycans is beneficial for the establishment of RORγt+ Treg cell mediated early-life immune tolerance through the manipulation of symbiotic bacteria in mice.

Vitamin K: Infection, Inflammation, and Auto-Immunity.

Vitamin K (VK) comprises a group of substances with chlorophyll quinone bioactivity and exists in nature in the form of VK1 and VK2. As its initial recognition originated from the ability to promote blood coagulation, it is known as the coagulation vitamin. However, based on extensive research, VK has shown potential for the prevention and treatment of various diseases. Studies demonstrating the beneficial effects of VK on immunity, antioxidant capacity, intestinal microbiota regulation, epithelial development, and bone protection have drawn growing interest in recent years. This review article focuses on the mechanism of action of VK and its potential preventive and therapeutic effects on infections (eg, asthma, COVID-19), inflammation (eg, in type 2 diabetes mellitus, Alzheimer's disease, Parkinson's disease, cancer, aging, atherosclerosis) and autoimmune disorders (eg, inflammatory bowel disease, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis). In addition, VK-dependent proteins (VKDPs) are another crucial mechanism by which VK exerts anti-inflammatory and immunomodulatory effects. This review explores the potential role of VK in preventing aging, combating neurological abnormalities, and treating diseases such as cancer and diabetes. Although current research appoints VK as a therapeutic tool for practical clinical applications in infections, inflammation, and autoimmune diseases, future research is necessary to elucidate the mechanism of action in more detail and overcome current limitations.

Vitamin K2 (MK-7) attenuates LPS-induced acute lung injury via inhibiting inflammation, apoptosis, and ferroptosis.

Acute lung injury (ALI) is a life-threatening disease that has received considerable critical attention in the field of intensive care. This study aimed to explore the role and mechanism of vitamin K2 (VK2) in ALI. Intraperitoneal injection of 7 mg/kg LPS was used to induce ALI in mice, and VK2 injection was intragastrically administered with the dose of 0.2 and 15 mg/kg. We found that VK2 improved the pulmonary pathology, reduced myeloperoxidase (MPO) activity and levels of TNF-α and IL-6, and boosted the level of IL-10 of mice with ALI. Moreover, VK2 played a significant part in apoptosis by downregulating and upregulating Caspase-3 and Bcl-2 expressions, respectively. As for further mechanism exploration, we found that VK2 inhibited P38 MAPK signaling. Our results also showed that VK2 inhibited ferroptosis, which manifested by reducing malondialdehyde (MDA) and iron levels, increasing glutathione (GSH) level, and upregulated and downregulated glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) expressions, respectively. In addition, VK2 also inhibited elastin degradation by reducing levels of uncarboxylated matrix Gla protein (uc-MGP) and desmosine (DES). Overall, VK2 robustly alleviated ALI by inhibiting LPS-induced inflammation, apoptosis, ferroptosis, and elastin degradation, making it a potential novel therapeutic candidate for ALI.

[Application of Modified DTT Methods to Reduce the Interference of Daratumumab on Serological Detection].

OBJECTIVE: To modified the classic dithiothreitol (DTT) method for treating red blood cells (RBCs) in Technical Manual of American Association of Blood Banks（AABB） and evaluate its application value in pre-transfusion examination of patients treated with daratumumab. METHODS: The classic 0.2 mol/L DTT method was improved in terms of PBS, DTT concentration, donor RBCs concentration (suspended/packed) and sample processing time. The modified DTT methods and AABB classic DTT method were applied to the blood matching tests of 12 multiple myeloma patients treated with daratumumab. The effect of treating panel RBCs with modified DTT methods on the detection of other irregular antibodies was evaluated by using antiserum and antibody reagents with known antibody properties. RESULTS: Two modified DTT methods were established (method 1: changed the concentration of DTT to 0.01 mol/L; method 2: changed the concentration of DTT to 0.02 mol/L and replaced the packed RBCs with 3% RBCs suspension). The optimal treatment time was 35 min for the modified DTT methods. At this time, the pan-agglutination caused by daratumumab was eliminated, but the detection of antibodies such as anti-E, anti-JKa, anti-M were not affected, and the titer of anti-K antibodies was only slightly decreased. CONCLUSION: The modified DTT methods were effective, which can eliminate the interference of daratumumab while retaining the activity of the Kell blood group system, and can replace the current classic DTT method in AABB Technical Manual.

Fermentation of Ganoderma lucidum and Raphani Semen with a probiotic mixture attenuates cyclophosphamide-induced immunosuppression through microbiota-dependent or -independent regulation of intestinal mucosal barrier and immune responses.

BACKGROUND: Probiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system. PURPOSE: We established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms. METHODS: First, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied. RESULTS: Probiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier. CONCLUSION: This is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.

Different in root exudates and rhizosphere microorganisms effect on nitrogen removal between three emergent aquatic plants in surface flow constructed wetlands.

Swine wastewater contains high concentration of nitrogen (N), causing pollution of surrounding water bodies. Constructed wetlands (CWs) are considered as an effective ecological treatment measure to remove nitrogen. Some emergent aquatic plants could tolerate high ammonia, and play a crucial part in CWs to treat high concentration N wastewater. However, the mechanism of root exudates and rhizosphere microorganisms of emergent plants on nitrogen removal is still unclear. Effects of organic and amino acids on rhizosphere N cycle microorganisms and environmental factors across three emergent plants were investigated in this study. The highest TN removal efficiency were 81.20% in surface flow constructed wetlands (SFCWs) plant with Pontederia cordata. The root exudation rates results showed that organic and amino acids were higher in 56 d than that in 0 d in SFCWs plants with Iris pseudacorus and P. cordata. The highest ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) gene copy numbers were found in I. pseudacorus rhizosphere soil, while the highest nirS, nirK, hzsB and 16S rRNA gene copy numbers were detected in P. cordata rhizosphere soil. Regression analysis results demonstrated that organic and amino acids exudation rates were positive related to rhizosphere microorganisms. These results indicated that organic and amino acids secretion could stimulate growth of emergent plants rhizosphere microorganisms in SFCWs for swine wastewater treatment. In addition, the EC, TN, NH4+-N and NO3--N were negatively correlated with organic and amino acids exudation rates, and abundances of rhizosphere microorganisms via Pearson correlation analysis. These results imply that organic and amino acids, and rhizosphere microorganisms synergically affected on the nitrogen removal in SFCWs.

Clinical effect and safety analysis of long-round needle usage in treating cervical spondylotic radiotelegraphy and its effect on pain and functional recovery.

BACKGROUND: Long-round needle usage can treat muscular pain, but there is little research on cervical spondylotic radiculopathy (CSR). OBJECTIVE: To explore the efficacy and safety of long-round needle usage in treating CSR. METHODS: Ninety-eight patients with CSR were randomly divided into control and observation groups. They were treated with filiform needles and long-round needles, respectively. The therapeutic effect, safety, inflammatory factors and neck dysfunction index (NDI), McGill pain questionnaire (MPQ) and Generic Quality of Life Inventory-74 (GQOL-74) scores were compared between the two groups. RESULTS: After treatment, the effective rate and safety of the observation group were better than those of the control group. The NDI and MPQ scores in the observation group were significantly lower than those in the control group, and the GQOL-74 score was higher than that in the control group. The level of interleukin-8 in the observation group was significantly lower than that in the control group, and the level of interleukin-10 was significantly higher than that in the control group. CONCLUSIONS: Long-round needle therapy has a good effect on patients with CSR, which can safely improve the quality of life of patients with mild local inflammatory damage.

Application of role reversal and standardized patient simulation (SPS) in the training of new nurses.

PURPOSE: To explore the effect of role reversal and standardized patient simulation on the training of new nurses. METHOD: This study was conducted in a territory hospital in China between August 2021 and August 2022. The selected staff were all newly recruited and trained nurses, with a total of 58 cases. This study is a randomised controlled trial. The selected nurses were randomly divided into two groups. One group of 29 nurses (the control group) received routine training and assessment; the other group (the experimental group) was given role reversal combined with a standardized vertebral patient training examination. The implementation effects of different training and assessment methods were compared and analysed. RESULTS: Before the training, the core competence scores of nurses in the two groups were lower, and there was no significant data difference (P > 0.05). After training, the core competence scores of nurses were improved, and the score of nurses in the experimental group was 165.49 ± 22.34. The difference was statistically significant when compared with the score of nurses in the control group (P < 0.05), indicating that nurses in the experimental group had better abilities. At the same time, the satisfaction of the two groups of nurses with the training was 96.55% (experimental group) and 75.86% (control group), and the difference in data was significant (P < 0.05). The satisfaction of the experimental group of nurses was higher, and the training effect was better. CONCLUSION: In the training of new nurses, the combined application of role interchange and standardized patient training and assessment methods has significant effects, which can improve the core competency of nurses and improve the training satisfaction of nurses, which is significant.

Long-term storage protocol of reagent red blood cells treated with 0.01M dithiothreitol (DTT) for pre-transfusion testing of patients receiving anti-CD38 therapy, daratumumab.

OBJECTIVE: Use red blood cell stabilizer to store the antibody screening and antibody identification reagent red blood cells (RBCs) treated with 0.01 mol/L DTT and investigate its value in the pre-transfusion examinations of patients treated with daratumumab. METHOD: Determined the optimal incubation time for the 0.01 mol/L DTT-treated RBCs method by evaluating the effect of treatment at different time points. Added ID-CellStab to store DTT-treated RBCs, determined the maximum shelf life of reagent RBCs by monitoring the hemolysis index, and assessed changes in the antigenicity of blood group antigens on the surface of RBCs during storage with antibody reagents. RESULT: A protocol for long-term storage of reagent red blood cells treated with the 0.01 mol/L DTT method was established. The optimal incubation time was 40-50 min. RBCs could be stored stably for 18 days after adding ID-CellStab. The protocol was able to eliminate pan-agglutination caused by daratumumab, with no significant changes in the antigens of most blood group systems, except for some attenuation of K antigen and Duffy blood group system antigens during the storage period. CONCLUSION: The storage protocol of reagent RBCs based on the 0.01 mol/L DTT method does not affect the detection of most blood group antibodies and retains a certain degree of detection ability for anti-K antibodies, allowing patients treated with daratumumab to quickly perform pre-transfusion examinations, making up for the shortcomings of currently commercial reagent RBCs.

Characteristics of gut microbiota in patients with primary Sjögren's syndrome in Northern China.

This study analyzes and compares the structure and diversity of gut microbiota in patients with primary Sjögren's syndrome (pSS) in Northern China to healthy individuals to identify clinical features associated with dysbiosis. We included 60 Chinese pSS patients and 50 age- and gender-matched healthy controls. DNA was extracted from stool samples and subjected to 16S ribosomal RNA gene analysis (V3-V4) for intestinal dysbiosis. In addition, patients were examined for laboratory and serological pSS features. A Spearman's correlation analysis was performed to assess correlations between individual bacteria taxa and clinical characteristics. The alpha-diversity (Chao1 and Shannon Index) and beta-diversity (unweighted UniFrac distances) of the gut microbiota differed significantly between pSS patients and healthy controls. Further analysis showed that several gut opportunistic pathogens (Bacteroides, Megamonas, and Veillonella) were significantly more abundant in pSS patients and positively correlated with their clinical indicators. In contrast, some probiotic genera (Collinsella, unidentified_Ruminococcaceae, Romboutsia, and Dorea) were significantly decreased in pSS patients and negatively correlated with their clinical indicators. Therefore, pSS patients in Northern China showed a dysbiotic intestinal microbiome enriched for potentially pathogenic genera that might be associated with autoimmune disease.

[Annual Nitrogen Removal Efficiency and Change in Abundance of Nitrogen Cycling Microorganisms in Swine Wastewater Treated by Crop Straw Materials].

Based on previous research, using straw material to treat swine wastewater can effectively reduce the concentration of nitrogen (N); however, the annual N-removal efficiency and change in the abundance of N-cycling functional genes remain unclear. In this study, four treatments (wheat straw, rice straw, corn stalk, and CK) were set up, with the aim of studying the annual N-removal efficiency and change in the abundance of functional genes. Our results showed that:① the total nitrogen (TN) removal and NH4+-N removal efficiency were the best in the first six months and were significantly reduced in the following six months. In addition, the TN removal and NH4+-N efficiency in straw and wheat straw were better than those in corn straw. The TN-removal efficiency in straw and wheat straw were 32.81%±11.34% and 32.99%±9.60%, respectively. The NH4+-N removal efficiency in straw and wheat straw were 35.3%±13.23% and 34.97%±12.00%, respectively. ② The abundance of N-cycling functional genes significantly increased by the addition of straw materials, compared with that of the CK (P<0.05). The average abundances of nirK, nirS, and hzsB were 6.45×109 copies·L-1, 6.18×109 copies·L-1, and 2.31×109 copies·L-1, respectively. The average abundances of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were 6.12×1010 copies·L-1 and 4.93×109 copies·L-1, respectively. The average hzsB gene abundance was 2.31×109 copies·L-1. The average abundance of 16S rRNA in the treatment was 8.90×1010 copies·L-1. The abundances of hzsB and nirS genes in the straw and wheat straw were higher than those in the other treatment, indicating that the activities of anaerobic ammonia oxidation and denitrifying microorganisms were significantly increased by the addition of straw and wheat straw (P<0.05). In addition, the abundance of AOA and AOB genes were increased in wheat straw, suggesting that wheat straw could promote nitrification. The results provided data supporting the molecular mechanism of nitrogen removal in swine wastewater treatment with straw materials.

Multi-spatial scale effects of multidimensional landscape pattern on stream water nitrogen pollution in a subtropical agricultural watershed.

Multidimensional (coupled land use, soil properties, and topography) landscape effects on stream water nitrogen (N) are complex and scale-dependent. However, studies that identify critical buffer zones that explain large variations in riverine N, and estimate specific thresholds of multidimensional landscape patterns at the class level, result in a sudden changes in riverine N pollution, are still limited. Here, a new multidimensional landscape metric that combined land use, soil properties, and topography effects was applied to various riparian buffer zones and sub-watershed scales, and their relationships to riverine N levels were investigated. We used stream water ammonium-N, nitrate-N, and total-N concentrations datasets, from 2010 to 2017, in the nine subtropical sub-watersheds in China. The results of model selection and model averaging in ordinary least squares regressions, indicated that the riparian buffer zone with widths of 400 m, had more pronounced influence on water NH4-N and TN levels than at other scales. Within the 400 m buffer zone, the key landscape metrics for NH4-N, NO3-N and TN concentrations in stream water were different, and explained up to 43.35%-76.55% (adjusted R2) of the total variation in river N levels. When ENN_MNClass17 below 39-56 m, PDClass8 above 4.63-6.55 n/km2, PLANDClass27 above 23-29%, and CONTIG_MNClass42 below 0.35-0.37% within the 400 m buffer zone, riverine NH4-N and TN would be abruptly increased. This study provided practical ideas for regulation regarding landscape management linked to watershed structure, and identified reference thresholds for multidimensional landscape metrics, which should help reduce riverine N pollution in subtropical China.

Influence path identification of topography, soil, hydrology and landscape on phosphorus buffering capacity in typical agricultural catchments in central subtropical China.

The catchment phosphorus buffering capacity (PBF) determines the pressure-state-response relationship between anthropogenic P inputs and aquatic ecosystems at a catchment scale, and is affected by biogeochemical, hydrological, and ecological catchment characteristics. However, the complex relationship between these catchment characteristic factors and their impact pathways on PBF remains ambiguous, leading to large uncertainty in balancing agricultural productivity and water conservation via improving BF through management practices. In this study, the short-term buffering index, calculated from net anthropogenic P input and riverine P exports, was used to quantify the spatiotemporal variations in PBF in source agricultural catchments in the Dongting Lake basin. Partial least squares structural equation modeling was used to investigate the relationship between the PBF and the catchment characteristics. The results indicate that catchment PBF was directly determined by soil properties and hydrological conditions, while landscape patterns significantly mediated the effects of topography on soil and hydrology. Considering the pathway preferences of the model, landscape patterns could be the priority for characterizing and regulating PBF. According to a change-point analysis, the probability of PBF weakening increases dramatically when the proportion of farmland (Farm%) > 24.6%, degree of patch interspersion (Contagion index) < 64.5%, and Perimeter-Area Ratio Distribution (PARA) > 348.7. These findings provide new insights into catchment buffering mechanisms and can be used to promote the simultaneous achievement of agricultural production and environmental conservation goals.

Alterations of gut fungal microbiota in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease, in addition, gut microbiota plays an important role in the etiology of RA. However, our understanding of alterations to the gut fungal microbiota in Chinese population with RA is still limited. METHODS: Serum samples were obtained from 62 patients with RA, and 39 age- and gender-matched healthy controls (HCs). Fecal samples were obtained from 42 RA patients and 39 HCs. Fecal fungal microbiota targeting internal transcribed spacer region 2 (ITS2) rRNA genes was investigated using MiSeq sequencing, as well as their associations with some diagnostic biomarkers for RA. RESULTS: Our results showed that the fungal diversity did not alter in RA patients but taxonomic composition of the fecal fungal microbiota did. The gut mycobiota of RA patients was characterized by decreased abundance of Pholiota, Scedosporium, and Trichosporon. The linear discriminant analysis (LDA) effect size analysis (LEfSe) analysis identified several RA-enriched fungal genera, which were positively correlated with most RA biomarkers. Furthermore, since RA is an age- and gende-related disease, we classified RA patients into subgroups with age and gender and analyzed the sequencing results. Our data demonstrated that Wallemia and Irpex were the most discriminatory against RA patients over 60 years old, while Pseudeurotiaceae was the most discriminatory against female RA patients. CONCLUSIONS: The case-control study presented here confirmed the alterations of gut fungal microbiota in Chinese patients with RA, and we speculated that the fungal dysbiosis may contribute to RA development.

Clinical study on flipped classroom and mind map in newly recruited nurses' pre-job training.

BACKGROUND: Traditional pre-job training mainly provides theoretical lectures and operational skill training for new nurses. However, it has a single teaching method, lacks in comprehensiveness and flexibility, and has unsatisfactory teaching effects. The purpose of this article is to evaluate the influence of the flipped classroom and mind map in the pre-job training of newly recruited nurses. METHOD: A total of 92 nurses newly recruited in 2019 were included in the present study and randomly divided into two groups: the intervention group and the control group (n = 46, each). An ordinary training program was applied in the control group, and the flipped classroom + mind map training method was applied in the intervention group. All the new nurses were evaluated using the autonomous learning ability scale before and after pre-job training. RESULTS: The results of the present study showed that before the pre-job training, the total scores of independent learning ability, learning motivation, self-management ability, learning cooperation ability and information quality of nursing staff were similar in the control group and the intervention group; the differences were not statistically significant (P > 0.05). After the application of different training methods, the total score of independent learning ability (84.95 ± 5.146 vs. 66.73 ± 11.213), learning motivation (28.65 ± 3.198 vs. 22.78 ± 5.995), self-management ability (24.97 ± 3.586 vs. 17.89 ± 4.153), learning and cooperation ability (14.391 ± 1.584 vs. 12.17 ± 2.584) and information quality score (16.93 ± 1.306 vs. 13.89 ± 2.651) in the intervention group were significantly higher than in the control group; the differences were statistically significant (P < 0.05). CONCLUSION: The flipped classroom + mind map training method can effectively improve the autonomous learning ability of newly recruited nurses.

Landscape patterns of catchment and land-use regulate legacy phosphorus releases in subtropical mixed agricultural and woodland catchments.

Landscape composition and configuration determine the exchange of matter and energy among different landscape patches and may affect riverine phosphorus (P) exports derived from watershed legacy sources. However, a lack of understanding of landscape pattern effects on legacy P releases has yielded large uncertainties in mitigating watershed water quality using management practices or landscape planning. This study revealed the significance of legacy effect in the headwater catchments through the time-lag response of the long-term trend of river P exports to the change of net anthropogenic P input (NAPI). By constructing empirical statistical models that incorporated NAPI, hydroclimatic, terrain factors, soil chemical properties, and land use variables, the sources of annual riverine total phosphorus (TP) and dissolved inorganic phosphorus (DIP) exports were divided into current annual NAPI input and legacy sources inputs. The model estimations indicated that the contribution of legacy sources to riverine TP exports was 0.33-1.12 kg ha-1 yr-1 (50.7-82.8%), which was significantly higher than the contribution to DIP exports (0.18-0.49 kg ha-1 yr-1, 42.4-81.4%) in 2012-2017. Redundancy analysis (RDA) and variance partitioning analysis (VPA) methods were used to quantify the relative contribution of landscape patterns, soil P content, and terrain factors to legacy P releases. Results revealed that the relative contribution of the landscape composition and configuration to the total variations of legacy P releases was greater than that of the soil P and terrain factors. For different land use patches, a large area of woodland with a high aggregation degree and a large area of ponds with multiple net structures may significantly alleviate legacy P releases. In contrast, the legacy P releases were significantly positively associated with highly aggregated agricultural, tea plantation, and residential patches. This study provides theoretical support for strategies aiming to control legacy P from the perspective of landscape planning.

Farnesoid X receptor (FXR) inhibits coagulation process via inducing hepatic antithrombin III expression in mice.

Farnesoid X receptor (FXR) has been identified as an inhibitor of platelet function and an inducer of fibrinogen protein complex. However, the regulatory mechanism of FXR in hemostatic system remains incompletely understood. In this study, we aimed to investigate the functions of FXR in regulating antithrombin III (AT III). C57BL/6 mice and FXR knockout (FXR KO) mice were treated with or without GW4064 (30 mg/kg per day). FXR activation significantly prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT), lowered activity of activated factor X (FXa) and concentrations of thrombin-antithrombin complex (TAT) and activated factor II (FIIa), and increased level of AT III, whereas all of these effects were markedly reversed in FXR KO mice. In vivo, hepatic AT III mRNA and protein expression levels were up-regulated in wild-type mice after FXR activation, but down-regulated in FXR KO mice. In vitro study showed that FXR activation induced, while FXR knockdown inhibited, AT III expression in mouse primary hepatocytes. The luciferase assay and ChIP assay revealed that FXR can bind to the promoter region of AT III gene where FXR activation increased AT III transcription. These results suggest FXR activation inhibits coagulation process via inducing hepatic AT III expression in mice. The present study reveals a new role of FXR in hemostatic homeostasis and indicates that FXR might act as a potential therapeutic target for diseases related to hypercoagulation.

QKI-Regulated Alternative Splicing Events in Cervical Cancer: Pivotal Mechanism and Potential Therapeutic Strategy.

QKI is a vital regulator in RNA splicing and maturation, but its role in cervical cancer (CC) is little known. In this study, we found that QKI is decreased in human CC, and overexpression of QKI inhibits HeLa cell proliferation and promotes the apoptosis of cancer cells. We identified hundreds of endogenous QKI-regulated alternative splicing events (ASEs) and differentially expressed genes (DEGs) in QKI-overexpressed HeLa cells by RNA-seq and selectively validated their expression by quantitative reverse-transcription polymerase chain reaction. The gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that QKI-regulated ASEs and DEGs were closely related to cancer, apoptosis, and transcriptional regulatory functions. In short, QKI may affect the occurrence and development of CC by regulating gene expression through AS.