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Objective: To explore the clinical or sociodemographic predictors for both successful and failed extubation among Chinese extremely and very preterm infants Methods: A retrospective cohort study was carried out among extremely and very preterm infants born at less than 32 weeks of gestational age (GA). Results: Compared with the infants who experienced extubation failure, the successful infants had higher birth weight (OR 0.997; CI 0.996–0.998), higher GA (OR 0.582; 95% CI 0.499–0.678), a caesarean section delivery (OR 0.598; 95% CI 0.380–0.939), a higher five-minute Apgar score (OR 0.501; 95% CI 0.257–0.977), and a higher pH prior to extubation (OR 0.008; 95% CI 0.001–0.058). Failed extubation was associated with older mothers (OR 1.055; 95% CI 1.013–1.099), infants intubated in the delivery room (OR 2.820; 95% CI 1.742–4.563), a higher fraction of inspired oxygen (FiO2) prior to extubation (OR 5.246; 95% CI 2.540–10.835), higher partial pressure of carbon dioxide (PCO2) prior to extubation (OR 7.820; 95% CI 3.725–16.420), and higher amounts of lactic acid (OR 1.478;95% CI 1.063–2.056). Conclusions: Higher GA, higher pre-extubation pH, lower pre-extubation FiO2 and PCO, and lower age at extubation are significant predictors of successful extubation among extremely and very preterm infants.

Abstract Currently, opinions on whether and how ride‐hailing services have impacted the use of traditional taxis are divided, and no consensus has been reached. This paper used panel data from 44 cities in China from 2010 to 2016 to estimate the impact of ride‐hailing services on the use of traditional taxis by applying the multiperiod difference‐in‐difference (multiperiod DID) method and conducting a series of robustness tests. The results show that ride‐hailing services have a large, negative impact on the use of traditional taxis, and this negative impact is more severe in eastern cities. These results suggest that in China it is necessary for traditional taxi operators to make changes and innovations to become more sustainable in response to pressure from ride‐hailing services. Additionally, it is suggested that city governments in China pay greater attention to the impact of emerging ride‐hailing services on traditional taxi services, embrace emerging modes of mobility, and create appropriate policies to coordinate the development of both new and traditional services.

Abstract Background Effective therapeutics to stop or reverse liver fibrosis have not emerged, because these potential agents cannot specifically target activated hepatic stellate cells (aHSCs) or are frequently toxic to parenchymal cells. Human umbilical cord mesenchymal stem cell (Huc-MSC)-derived exosomes show promise in nanomedicine for the treatment of liver fibrosis. However, systemic injection showed that unmodified exosomes were mainly taken up by the mononuclear phagocyte system. The discovery of ligands that selectively bind to a specific target plays a crucial role in clinically relevant diagnostics and therapeutics. Herein, we aimed to identify the targeting peptide of aHSCs by screening a phage-displayed peptide library, and modify Huc-MSC-derived exosomes with the targeting peptide. Results In this study, we screened a phage-displayed peptide library by biopanning for peptides preferentially bound to HSC-T6 cells. The identified peptide, HSTP1, also exhibited better targeting ability to aHSCs in pathological sections of fibrotic liver tissues. Then, HSTP1 was fused with exosomal enriched membrane protein (Lamp2b) and was displayed on the surface of exosomes through genetic engineering technology. The engineered exosomes (HSTP1-Exos) could be more efficiently internalized by HSC-T6 cells and outperformed both unmodified exosomes (Blank-Exos) and Lamp2b protein overexpressed exosomes (Lamp2b + Exos) in enhancing the ability of exosomes to promote HSC-T6 reversion to a quiescent phenotype. In vivo results showed HSTP1-Exos could specifically target to the aHSC region after intravenous administration, as demonstrated by coimmunofluorescence with the typical aHSCs marker α-SMA, and enhance the therapeutic effect on liver fibrosis. Conclusion These results suggest that HSTP1 is a reliable targeting peptide that can specifically bind to aHSCs and that HSTP1-modified exosomes realize the precise treatment for aHSCs in complex liver tissue. We provide a novel strategy for clinical liver fibrosis therapy. Graphical Abstract

Abstract Background Ulcerative colitis-associated colorectal cancer (UC-CRC) is an important complication of ulcerative colitis. Pou3f1 (POU class 3 homeobox 1) is a critical regulator for developmental events and cellular biological processes. However, the role of Pou3f1 in the development of UC-CRC is unclear. Methods In vivo, a UC-CRC mouse model was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS). Body weight, colon length, mucosal damage, tumor formation, and survival rate were assessed to determine the progression of UC-CRC. Western blot, quantitative real-time PCR, ELISA, immunohistochemistry, immunofluorescence and TUNEL were performed to examine the severity of inflammation and tumorigenesis. In vitro, LPS-treated mouse bone marrow-derived macrophages (BMDMs) and RAW264.7 cells were used to study the role of Pou3f1 in inflammation. ChIP and luciferase reporter assays were used to confirm the interaction between Nfatc3 and Pou3f1. Results Pou3f1 expression was increased in the colons of UC-CRC mice, and its inhibition attenuated mucosal injury, reduced colon tumorigenesis and increased survival ratio. Knockdown of Pou3f1 suppressed cell proliferation and increased cell death in colon tumors. Both the in vivo and in vitro results showed that Pou3f1 depletion reduced the production of proinflammation mediators. In addition, ChIP and luciferase reporter assays demonstrated that Nfatc3 directly bound with the Pou3f1 promoter to induce its expression. The effect of Nfatc3 on the inflammatory response in macrophages was suppressed by Pou3f1 knockdown. Conclusion Overall, it outlines that Pou3f1 mediates the role of Nfatc3 in regulating macrophage inflammation and carcinogenesis in UC-CRC development.

Genomic instability facilitates the evolution of cells, tissues, organs, and species. The progression of human malignancies can be regarded as the accumulation of genomic instability, which confers a high evolutionary potential for tumor cells to adapt to continuous changes in the tumor microenvironment. Nasopharyngeal carcinoma (NPC) is a head-and-neck squamous-cell carcinoma closely associated with Epstein–Barr virus (EBV) infection. NPC progression is driven by a combination of accumulated genomic instability and persistent EBV infection. Here, we present a review of the key characteristics of genomic instability in NPC and the profound implications of EBV infection. We further discuss the significance of profiling genomic instability for the assessment of disease progression and treatment efficacy, as well as the opportunities and challenges of targeted therapies for NPC based on its unique genomic instability.

BackgroundElderly patients with breast cancer are highly heterogeneous, and tumor load and comorbidities affect patient prognosis. Prediction models can help clinicians to implement tailored treatment plans for elderly patients with breast cancer. This study aimed to establish a prediction model for breast cancer, including comorbidities and tumor characteristics, in elderly patients with breast cancer.MethodsAll patients were ≥65 years old and admitted to the Peking Union Medical College Hospital. The clinical and pathological characteristics, recurrence, and death were observed. Overall survival (OS) was analyzed using the Kaplan–Meier curve and a prediction model was constructed using Cox proportional hazards model regression. The discriminative ability and calibration of the nomograms for predicting OS were tested using concordance (C)-statistics and calibration plots. Clinical utility was demonstrated using decision curve analysis (DCA).ResultsBased on 2,231 patients, the 5- and 10-year OS was 91.3% and 78.4%, respectively. We constructed an OS prediction nomogram for elderly patients with early breast cancer (PEEBC). The C-index for OS in PEEBC in the training and validation cohorts was 0.798 and 0.793, respectively. Calibration of the nomogram revealed a good predictive capability, as indicated by the calibration plot. DCA demonstrated that our model is clinically useful.ConclusionThe nomogram accurately predicted the 3-year, 5-year, and 10-year OS in elderly patients with early breast cancer.

Background Psoriasis is an autoimmune skin disease characterized by immunocyte activation, excessive proliferation, and abnormal differentiation of keratinocytes. Signal transducers and activators of transcription 3 (STAT3) play a crucial role in linking activated keratinocytes and immunocytes during psoriasis development. T helper (Th) 17 cells and secreted interleukin (IL)-17A contribute to its pathogenesis. IL-17A treated STAT3 overexpressing mouse model might serve as an animal model for psoriasis. Methods In this study, we established a mouse model of psoriasiform dermatitis by intradermal IL-17A injection in STAT3 overexpressing mice. Transcriptome analyses were performed on the skin of wild type (WT), STAT3, and IL-17A treated STAT3 mice. Bioinformatics-based functional enrichment analysis was conducted to predict biological pathways. Meanwhile, the morphological and pathological features of skin lesions were observed, and the DEGs were verified by qPCR. Results IL-17A treated STAT3 mice skin lesions displayed the pathological features of hyperkeratosis and parakeratosis. The DEGs between IL-17A treated STAT3 mice and WT mice were highly consistent with those observed in psoriasis patients, including S100A8, S100A9, Sprr2, and LCE. Gene ontology (GO) analysis of the core DEGs revealed a robust immune response, chemotaxis, and cornified envelope, et al. The major KEGG enrichment pathways included IL-17 and Toll-like receptor signaling pathways. Conclusion IL-17A exacerbates psoriasis dermatitis in a STAT3 overexpressing mouse.

Objective Evidence of therapy for dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) is limited. This study was performed to compare the effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation. Methods This retrospective study enrolled 597 consecutive patients with STEMI who underwent pPCI in 3 centers from June 2016 to December 2019. Dysfunctional coronary circulation was defined by the thrombolysis in myocardial infarction (TIMI) grade and the TIMI myocardial perfusion grade (TMPG). Logistic regression analysis was used to evaluate the impact of different statin types on dysfunctional coronary circulation. Results The incidence of TIMI no/slow reflow did not differ between the two groups, but the incidence of TMPG no/slow reflow was significantly lower in the atorvastatin than rosuvastatin group (44.58% vs. 57.69%, respectively). After multivariate adjustment, the odds ratio with 95% confidence interval of rosuvastatin was 1.72 (1.17–2.52) for after pretreatment TMPG no/slow reflow and 1.73 (1.16–2.58) for after stenting TMPG no/slow reflow. Atorvastatin and rosuvastatin showed no significant differences in clinical outcomes during hospitalization. Conclusions Compared with rosuvastatin, atorvastatin was associated with better coronary microcirculatory perfusion in patients with STEMI who underwent pPCI.

Solving the risk of zombification of enterprises and relieving their business difficulties, as a key element of supply-side structural reform, is the pain point of the conversion of old and new dynamic energy and the difficulty of economic transformation and upgrading. In the Internet era, the impact on business operations is also expanding with the widening of investor attention channels. This paper selects Chinese listed companies from 2011–2020 as a research sample, and the empirical results show that, first, investor attention can effectively reduce the risk of transforming enterprises into zombie enterprises, i.e., the risk of corporate zombification decreases as the level of investor attention increases; second, there is heterogeneity in the role of investor attention in resolving the risk of corporate zombification; third, further mechanism tests find that along with Third, further mechanistic tests reveal that as the level of investor attention increases, the level of environmental uncertainty decreases and the annual market value of individual stocks increases, thereby reducing the risk of corporate zombification. The findings of this paper provide theoretical support and empirical evidence for further improving the risk mitigation of corporate zombification, promoting the “de-emphasis” of enterprises, and leading the high-quality and healthy development of enterprises.

To investigate the effects of different levels of fermented antarctic krill shell (FAKS) on the growth performance, hemolymph biochemistry, hepatopancreatic antioxidant capacity, and digestive enzyme activities of Macrobrachium nipponense, five isonitrogenous and isoenergetic experimental diets containing different proportions of FAKS (0 %, 0.25 %, 0.5 %, 1.0 %, 2.0 %) were fed to M. nipponense for 8 weeks. The results showed the weight gain rate (WGR), specific growth rate (SGR), head-to-body ratio (H/S), and head-to-tail ratio (H/T) increased first and then decreased with higher proportions of FAKS. The FAKS1.0 group exhibited the highest values, and significantly higher than that of the FAKS0 group (P

IntroductionPiglets are more susceptible to weaning stress syndrome when fed high levels of plant-based proteins that contain abundant food antigens and anti-nutritional factors. Xylo-oligosaccharides (XOS) are a potential prebiotic that may improve the tolerance of weaned piglets to plant-based proteins. The aim of this study was to investigate the effects of XOS supplementation in high and low plant-based protein diets on growth performance, gut morphology, short-chain fatty acid (SCFA) production, and gut microbiota of weaned piglets.MethodsA total of 128 weanling piglets with an average body weight (BW) of 7.63 ± 0.45 kg were randomly allocated to one of the four dietary treatments in a 2 × 2 factorial arrangement, with two levels of plant-based proteins (d 1–14: 68.3 or 81.33%, d 15–28: 81.27 or 100%) and XOS complex (0 or 0.43%) over a 28-day trial.ResultsThe growth performance of piglets did not differ significantly among groups (P > 0.05). However, the diarrhea index of weaned piglets fed a high plant-based protein diet (HP) was significantly higher than that of those fed a low plant-based protein diet (LP) at days 1–14 and throughout the experimental period (P < 0.05). XOS treatment tended to reduce the diarrhea index at days 1–14 (P = 0.062) and during the whole experiment period (P = 0.083). However, it significantly increased the digestibility of organic matter at days 15–28 (P < 0.05). Moreover, dietary XOS supplementation increased ileal mucosa mRNA expression of occludin and ZO-1 (P < 0.05). Furthermore, the concentration of butyric acid (BA) in the cecal contents and in the concentrations of BA and valeric acid (VA) in colon contents were significantly elevated in the XOS groups (P < 0.05). Additionally, XOS optimized the gut flora by lowering the number of pathogenic bacteria such as p_Campylobacterota, thereby stabilizing the gut ecosystem.DiscussionIn conclusion, the HP diet aggravated diarrhea in weaned piglets while the XOS diet alleviated it by improving nutrient digestibility, protecting intestinal morphology, and optimizing the gut flora.

Promoters are the basic functional cis-elements to which RNA polymerase binds to initiate the process of gene transcription. Comprehensive understanding gene expression and regulation depends on the precise identification of promoters, as they are the most important component of gene expression. This study aimed to develop a machine learning-based model to predict promoters in Klebsiella aerogenes (K. aerogenes). In the prediction model, the promoter sequences in K. aerogenes genome were encoded by pseudo k-tuple nucleotide composition (PseKNC) and position-correlation scoring function (PCSF). Numerical features were obtained and then optimized using mRMR by combining with support vector machine (SVM) and 5-fold cross-validation (CV). Subsequently, these optimized features were inputted into SVM-based classifier to discriminate promoter sequences from non-promoter sequences in K. aerogenes. Results of 10-fold CV showed that the model could yield the overall accuracy of 96.0% and the area under the ROC curve (AUC) of 0.990. We hope that this model will provide help for the study of promoter and gene regulation in K. aerogenes.

The purpose of this study is to investigate the effects of supplementing Yeast−derived postbiotics (Y−dP) to the diet of sows during late pregnancy and lactation on fecal microbiota and short−chain fatty acids (SCFA) in sows and their offspring weaned piglets, as well as the relationship between gut microbiota and SCFA, serum cytokines, and sow reproductive performance. A total of 150 sows were divided into three groups: control diet (CON), CON + Y−dP 1.25 g/kg, and CON + Y−dP 2 g/kg. The results showed that supplementing 0.125% Y−dP to the diet of sows can increase the content of isobutyric acid (IBA) in the feces of pregnant sows and reduce the content of butyric acid (BA) in the feces of weaned piglets (p < 0.05). The fecal microbiota of pregnant sows β diversity reduced and piglet fecal microbiota β diversity increased (p < 0.05). Y−dP significantly increased the abundance of Actinobacteria and Limosilactobacilli in the feces of pregnant sows (p < 0.05), as well as the abundance of Verrucomicrobiota, Bacteroidota, and Fusobacteriota in the feces of piglets (p < 0.05). The abundance of Bacteroidota in the feces of pregnant sows is positively correlated with propionic acid (PA) (r > 0.5, p < 0.05). The abundance of Prevotellaceae_NK3B31_group was positively correlated with Acetic acid (AA), PA, Valerate acid (VA), and total volatile fatty acid (TVFA) in the feces of pregnant sows (r > 0.5, p < 0.05), and Bacteroidota and Prevotellaceae_NK3B31_group were negatively correlated with the number of stillbirths (r < −0.5, p < 0.05). The abundance of Lactobacillus and Holdemanella in piglet feces was positively correlated with TVFA in feces and negatively correlated with IgA in serum (r > 0.5, p < 0.05). In conclusion, supplementing Y−dP to the diet of sows from late gestation to lactation can increase the chao1 index and α diversity of fecal microorganisms in sows during lactation, increase the abundance of Actinobacteria and Limosilactobacilli in the feces of sows during pregnancy, and increase the abundance of beneficial bacteria such as Bacteroidetes in piglet feces, thereby improving intestinal health. These findings provide a reference for the application of Y−dP in sow production and a theoretical basis for Y−dP to improve sow production performance.

When facing natural disasters, power transmission and distribution towers are prone to tilting, collapsing, and other situations, which can easily lead to line faults and subsequently cause power outage incidents. In order to quickly and accurately locate abnormal towers and restore power supply promptly, the power maintenance department typically employs unmanned aerial vehicles (UAVs) for post-disaster inspections of power line towers. Traditional methods for UAV ground target localization mainly rely on the UAV’s own position, attitude, and onboard sensor information to indirectly calculate the target’s position. This method is influenced by the Global Positioning System (GPS) and Inertial Navigation System (INS), relying on high-precision sensors. To achieve precise positioning of power line towers with simplified equipment on UAVs, this paper proposes a visual passive localization method based on ground control points. Addressing the sparse distribution of ground control points, a solution based on image stitching is introduced to overcome difficulties in localization caused by insufficient ground control points.

The present study assessed the protective effects and underlying mechanisms of mulberry leaf polysaccharides (MLPs) against hydrogen peroxide (H2O2)-induced oxidative stress injury in the peripheral blood leukocytes (PBLs) of Megalobrama amblycephala. Five treatment groups were established in vitro: the NC group (PBLs incubated in an RPMI-1640 complete medium for 4 h), the HP group (PBLs incubated in an RPMI-1640 complete medium for 3 h, and then stimulated with 100 μM of H2O2 for 1 h), and the 50/100/200-MLP pre-treatment groups (PBLs were pre-treated with MLPs (50, 100, and 200 μg/mL) for 3 h, and then stimulated with 100 μM of H2O2 for 1 h). The results showed that MLP pre-treatment dose-dependently enhanced PBLs’ antioxidant capacities. The 200 μg/mL MLP pre-treatment effectively protected the antioxidant system of PBLs from H2O2-induced oxidative damage by reducing the malondialdehyde content and lactic dehydrogenase cytotoxicity, and increasing catalase and superoxide dismutase activities (p < 0.05). The over-production of reactive oxygen species, depletion of nicotinamide adenine dinucleotide phosphate, and collapse of the mitochondrial membrane potential were significantly inhibited in the 200-MLP pre-treatment group (p < 0.05). The expressions of endoplasmic reticulum stress-related genes (forkhead box O1α (foxO1α), binding immunoglobulin protein (bip), activating transcription factor 6 (atf6), and C/EBP-homologous protein (chop)), Ca2+ transport-related genes (voltage-dependent anion-selective channel 1 (vdac1), mitofusin 2 (mfn2), and mitochondrial Ca2+ uniporter (mcu)), and interleukin 6 (il-6) and bcl2-associated x (bax) were significantly lower in the 200-MLP pre-treatment group than in the HP group (p < 0.05), which rebounded to normal levels in the NC group (p > 0.05). These results indicated that MLP pre-treatment attenuated H2O2-induced PBL oxidative damage in the M. amblycephala by inhibiting endoplasmic reticulum stress and maintaining mitochondrial function. These findings also support the possibility that MLPs can be exploited as a natural dietary supplement for M. amblycephala, as they protect against oxidative damage.

Phosphorus, as a key nutrient, plays an essential role in both algal growth in surface waters and crop development on land. Its presence in inorganic fertilizers is crucial for maximizing crop yields. However, an excessive accumulation of phosphorus in soils can lead to its loss and exacerbate eutrophication in water bodies. This study highlights the complex interplay among phosphorus management, agricultural productivity, and environmental health, particularly in the context of climate change’s influence on sediment transport and water pollution. We focus on the Poyang Lake Basin (PLB) and use a sophisticated process-based phosphorus model to forecast phosphorus load trends from 2020 to 2049. Our predictions indicate a significant increase in the total phosphorus load of the PLB due to the impact of climate change. To address these challenges, we explore a novel strategy combining organic and inorganic phosphorus fertilizers. This approach aims to improve crop yields while reducing non-point source phosphorus pollution through adjusted anthropogenic inputs. Our findings reveal that a synergistic application of these fertilizers, coupled with a controlled use of inorganic phosphate, can reduce its usage by more than 2.5% annually. This method not only contributes to a 2.2% average annual increase in livestock and poultry production but also promotes a 0.6% yearly growth in grain output. Consequently, it effectively diminishes non-point source phosphorus pollution, offering a sustainable solution to the dual challenge of enhancing agricultural productivity and protecting environmental health.

Plastic environmental pollution is threatening water resources, aquatic ecosystems, and human wellbeing but is still highly uncertain with global fluxes to sea of 0.4–13 Mt\yr, and up to 517 Mt of mismanaged plastics on land. Catchment modelling tools are required to challenge current knowledge, simulate impacts of management initiatives, and complement global and observation-based studies. Here we present the first spatiotemporally explicit model for mismanaged plastic mobilization and transport from land to sea from the INtegrated CAtchment (INCA) family. INCA-Macroplastics encompasses all components of the catchment, is driven by available data (weather, population, solid waste) and enables calibration and validation against diverse observations (river monitoring, household surveys). INCA-Macroplastics was applied to the Imus River, Philippines, one of World’s most polluted rivers. Given large uncertainties on catchment plastic retention, two calibrations and two emission scenarios were developed to describe catchment plastic fluxes, residence time and stocks over 1990–2020. Plastic fluxes to the sea are highly variable over years and seasons (55–75% exported during the wet season) and have increased exponentially over 1990–2020 from 5–100 to 2000–15000 tons\yr. INCA-Macroplastics is the first model handling plastic accumulation on land and highlights the importance of extreme flooding events in mobilizing and transporting legacy plastics. Model outputs explicitly show that current land plastic pollution can impact fluxes to the ocean for up to 30 years into the future. INCA-Macroplastics is useful to provide tailored recommendations for local monitoring, testing waste management scenarios and pointing towards future research avenues.

The Agulhas Return Current (ARC), as a primary component of the Agulhas system, contributes to water exchange and mass transport between the southern portions of the Indian and Atlantic Ocean basins. In this study, satellite altimeter data and reanalysis datasets, and a new set of criteria for the piecewise definition of the jet axis are used to explore the long-term change of the ARC’s axis position in recent three decades. It is found that the ARC axis exhibits a significant slanting trend with its western part (35–48°E) migrating northward and the eastern part (48–70°E) migrating southward. The meridional movement of the ARC path could be attributed to large-scale wind forcing. The anomalous surface wind stress curl, by Ekman pumping mechanism, leads to positive–negative–positive sea surface height anomalies in the western section and negative–positive–negative anomalies in the eastern section, thus the ARC axis tilts accordingly, in a northwest–southeast direction. Further analysis suggests that this ARC slanting trend is more dependent on the southward shift of the downstream axis and less on the topographic steering upstream. The downstream axis is more likely to interact with the ACC fronts and its migration could dominate the local EKE pattern by changing the background circulation and energy cascade direction. For the headstream west of 35°E, the ARC axis is more subject to topography, thus the EKE change is more dominated by eddy activity processes, including shedding, propagation and merging. This study provides some new insights into the long-term change of ARC and its interaction with the local EKE variability.

Aging is a biological process with a gradual decline in functional capacity, and this process often enhances the risk of chronic disease morbidity and mortality. With advanced age, the immune system undergoes a process of remodeling that can lead to a chronic inflammatory state, termed immunosenescence and inflammaging, respectively. Immunosenescence is accompanied by changes in the number, proportion, and functional capacity of the innate immune cells. The accumulation of dysfunctional immune cells and the presence of low-grade inflammation can lead to organ damage and expedite the aging process. The liver, crucial in regulating the body’s metabolism and immune function, is not exempt from these effects. Age-related modifications affect its immune function and regenerative abilities, potentially increasing the prevalence of age-related liver diseases. While aging’s impact on the liver is relatively less severe compared to other organ systems, it still experiences an infiltration of innate immune cells and heightened inflammation levels. This review will elaborate on how aging affects the liver’s innate immune cells, such as neutrophils, macrophages, dendritic cells, mast cells, and innate lymphoid cells. It will also explore potential strategies for delaying immunosenescence to alleviate these age-related changes.

The liver is the primary organ accountable for complex physiological functions, including lipid metabolism, toxic chemical degradation, bile acid synthesis, and glucose metabolism. Liver function homeostasis is essential for the stability of bodily functions and is involved in the complex regulation of the balance between cell proliferation and cell death. Cell proliferation-halting mechanisms, including autophagy and senescence, are implicated in the development of several liver diseases, such as cholestasis, viral hepatitis, nonalcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Among various cell death mechanisms, autophagy is a highly conserved and self-degradative cellular process that recycles damaged organelles, cellular debris, and proteins. This process also provides the substrate for further metabolism. A defect in the autophagy machinery can lead to premature diseases, accelerated aging, inflammatory state, tumorigenesis, and cellular senescence. Senescence, another cell death type, is an active player in eliminating premalignant cells. At the same time, senescent cells can affect the function of neighboring cells by secreting the senescence-associated secretory phenotype and induce paracrine senescence. Autophagy can promote and delay cellular senescence under different contexts. This review decodes the roles of autophagy and senescence in multiple liver diseases to achieve a better understanding of the regulatory mechanisms and implications of autophagy and senescence in various liver diseases.

To investigate the mechanisms through which ferrous ion (Fe2+) addition improves the utilization of a cottonseed meal (CSM) diet, two experimental diets with equal nitrogen and energy content (low-cottonseed meal (LCM) and high-cottonseed meal (HCM) diets, respectively) containing 16.31% and 38.46% CSM were prepared. Additionally, the HCM diet was supplemented with graded levels of FeSO4·7H2O to establish two different Fe2+ supplementation groups (HCM + 0.2%Fe2+ and HCM + 0.4%Fe2+). Juvenile Ctenopharyngodon idellus (grass carps) (5.0 ± 0.5 g) were fed one of these four diets (HCM, LCM, HCM + 0.2%Fe2+ and HCM + 0.4%Fe2+ diets) for eight weeks. Our findings revealed that the HCM diet significantly increased lipid peroxide (LPO) concentration and the expression of lipogenic genes, e.g., sterol regulatory element binding transcription factor 1 (srebp1) and stearoyl-CoA desaturase (scd), leading to excessive lipid droplet deposition in the liver (p < 0.05). However, these effects were significantly reduced in the HCM + 0.2%Fe2+ and HCM + 0.4%Fe2+ groups (p < 0.05). Plasma high-density lipoprotein (HDL) concentration was also significantly lower in the HCM and HCM + 0.2%Fe2+ groups compared to the LCM group (p < 0.05), whereas low-density lipoprotein (LDL) concentration was significantly higher in the HCM + 0.2%Fe2+ and HCM + 0.4%Fe2+ groups than in the LCM group (p < 0.05). Furthermore, the plasma levels of liver functional indices, including alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose (GLU), were significantly lower in the HCM + 0.4%Fe2+ group (p < 0.05). Regarding the expression of genes related to iron transport regulation, transferrin 2 (tfr2) expression in the HCM group and Fe2+ supplementation groups were significantly suppressed compared to the LCM group (p < 0.05). The addition of 0.4% Fe2+ in the HCM diet activated hepcidin expression and suppressed ferroportin-1 (fpn1) expression (p < 0.05). Compared to the LCM group, the expression of genes associated with ferroptosis and inflammation, including acyl-CoA synthetase long-chain family member 4b (acsl4b), lysophosphatidylcholine acyltransferase 3 (lpcat3), cyclooxygenase (cox), interleukin 1β (il-1β), and nuclear factor kappa b (nfκb), were significantly increased in the HCM group (p < 0.05), whereas Fe2+ supplementation in the HCM diet significantly inhibited their expression (p < 0.05) and significantly suppressed lipoxygenase (lox) expression (p < 0.05). Compared with the HCM group without Fe2+ supplementation, Fe2+ supplementation in the HCM diet significantly upregulated the expression of genes associated with ferroptosis, such as heat shock protein beta-associated protein1 (hspbap1), glutamate cysteine ligase (gcl), and glutathione peroxidase 4a (gpx4a) (p < 0.05), and significantly decreased the expression of the inflammation-related genes interleukin 15/10 (il-15/il-10) (p < 0.05). In conclusion, FeSO4·7H2O supplementation in the HCM diet maintained iron transport and homeostasis in the liver of juvenile grass carps, thus reducing the occurrence of ferroptosis and alleviating hepatic lipid deposition and inflammatory responses caused by high dietary CSM contents.

Whether amino acids act on cellular insulin signaling remains unclear. Here, the authors find that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake and positively correlated with T2D onset.

Gibellula penicillioides sp. nov. and G. longispora sp. nov., two new species parasitising spiders collected in China, are illustrated and described, based on morphological features and multiloci phylogenetic analysis. The G. penicillioides sp. nov. group is sister to the G. scorpioides group, but form long penicilloid conidiophore producing enlarged fusiform conidia ((7–) 7.5–9 (–10) × 2.5–3.5 μm). G. longispora sp. nov. is sister to G. pigmentosinum, but has slender long conidia (5–7 × 1–2 μm); teleomorph and Granulomanus-synanamorphic conidiogenous cells are absent in these two species. Type specimens of G. penicillioides sp. nov. and G. longispora sp. nov. were deposited in the Anhui Agricultural University (RCEF). In addition, a key to all known species of Gibellula is illustrated.

Abstract Background Abnormal proliferation and migration of cells are hallmarks of cancer initiation and malignancy. Asparagine endopeptidase (AEP) has specific substrate cleavage ability and plays a pro-cancer role in a variety of cancers. However, the underlying mechanism of AEP in cancer proliferation and migration still remains unclear. Methods Co-immunoprecipitation and following mass spectrometry were used to identify the substrate of AEP. Western blotting was applied to measure the expression of proteins. Single cell/nuclear-sequences were done to detect the heterogeneous expression of Tmod3 in tumor tissues. CCK-8 assay, flow cytometry assays, colony formation assay, Transwell assay and scratch wound-healing assay were performed as cellular functional experiments. Mouse intracranial xenograft tumors were studied in in vivo experiments. Results Here we showed that AEP cleaved a ubiquitous cytoskeleton regulatory protein, tropomodulin-3 (Tmod3) at asparagine 157 (N157) and produced two functional truncations (tTmod3-N and tTmod3-C). Truncated Tmod3 was detected in diverse tumors and was found to be associated with poor prognosis of high-grade glioma. Functional studies showed that tTmod3-N and tTmod3-C enhanced cancer cell migration and proliferation, respectively. Animal models further revealed the tumor-promoting effects of AEP truncated Tmod3 in vivo. Mechanistically, tTmod3-N was enriched in the cell cortex and competitively inhibited the pointed-end capping effect of wild-type Tmod3 on filamentous actin (F-actin), leading to actin remodeling. tTmod3-C translocated to the nucleus, where it interacted with Staphylococcal Nuclease And Tudor Domain Containing 1 (SND1), facilitating the transcription of Ras Homolog Family Member A/Cyclin Dependent Kinases (RhoA/CDKs). Conclusion The newly identified AEP-Tmod3 protease signaling axis is a novel “dual-regulation” mechanism of tumor cell proliferation and migration. Our work provides new clues to the underlying mechanisms of cancer proliferation and invasive progression and evidence for targeting AEP or Tmod3 for therapy.

Abstract Background α-1-syntrophin (SNTA1), a protein encoded by SNTA1, is highly expressed in human cardiomyocytes. Mutations in SNTA1 are associated with arrhythmia and cardiomyopathy. Previous research on SNTA1 has been based on non-human cardiomyocytes. This study was designed to identify the phenotype of SNTA1-deficiency using human cardiomyocytes. Methods SNTA1 was knocked out in the H9 embryonic stem cell line using the CRISPR-Cas9 system. H9SNTA1KO cells were then induced to differentiate into cardiomyocytes using small molecule inhibitors. The phenotypic discrepancies associated with SNTA1-deficient cardiomyocytes were investigated. Results SNTA1 was truncated at the 149th amino acid position of PH1 domain by a stop codon (TGA) using the CRISPR-Cas9 system. SNTA1-deficiency did not affect the pluripotency of H9SNTA1KO, and they retain their in vitro ability to differentiate into cardiomyocytes. However, H9SNTA1KO derived cardiomyocytes exhibited hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower level of calcium in the sarcoplasmic reticulum. Early treatment of SNTA1-deficient cardiomyocytes with ranolazine improved the calcium transient intensity and cardiac contractility. Conclusion SNTA1-deficient cardiomyocytes can be used to research the etiology, pathogenesis, and potential therapies for myocardial diseases. The SNTA1-deficient cardiomyocyte model suggests that the maintenance of cardiac calcium homeostasis is a key target in the treatment of myocardial-related diseases.

This experiment evaluated the impacts of essential oils (EO) and protease (PRO), independently or in combination, on growth performance, antioxidation, inflammation and intestinal function of weaned pigs. One hundred and sixty weaned pigs (21 d of age, BW of 6.74 ± 0.20 kg) were randomly divided into 4 treatments with 8 replicate pens of 5 pigs per pen. Dietary treatments included the following: 1) control diet (CON), 2) CON with 300 mg/kg essential oils (EO), 3) CON with 500 mg/kg protease (PRO), 4) CON with 300 mg/kg essential oil and 500 mg/kg protease (EO + PRO). On d 8, one pig from each pen was selected for sampling. The remaining pigs were fed for an additional week and growth performance was monitored during this period. Dietary treatments had no marked effects (P > 0.05) on the growth performance of pigs. However, pigs receiving EO diet had higher (P

Background: Breast cancer is the most common malignancy in women. Clinical models such as Oncotype DX recurrence score (RS) and Clinical Treatment Score post–5 years (CTS5) model for survival prediction are crucial for clinical practice. However, it remains unclear whether CTS5 or RS would be a more powerful clinical model for recurrence risk evaluation. Therefore, we conducted the present study to compare the performance of CTS5 risk model and RS on different recurrence evaluation. And we further integrated the two models into a novel nomogram to improve the power for prognosis prediction. Methods: Female patients with invasive hormone receptor positive breast cancer in the Surveillance, Epidemiology, and End Results Program (SEER) database with RS data available were included. The clinicopathological data were directly extracted from SEER database. Participants were divided into three subsets according to recurrence timing (60 months) for model evaluation. Survival receiver operating characteristic curve and C-index were calculated to evaluate discrimination. Calibration curve were used to visual inspection for calibration. Model comparison was assessed by net reclassification index (NRI) method. Nomogram prognostic model was developed with the combination of CTS5 score and RS and also included other critical clinicopathological parameters. Results: In total, 64044 breast cancer patients were enrolled for analysis. The number of patients with survival 60 months (late recurrence subset) were 64044, 36878 and 15926, respectively. For model discrimination, CTS5 model was superior to RS for overall survival (OS) prediction (likelihood ratio test P

Objective: In order to provide scientific basis for further clarifying the species and characteristics of dominant pathogens causing guava black spot. Method: A dominant pathogen, named S1, was isolated and purified from the guava fruit infected with black spot disease, and subjected to morphology observation, pathogenicity determination, growth characteristics study and polymerase chain reaction (PCR) sequencing comparison analysis were conducted for comprehensive identification of the dominant pathogen S1. Results: According to the morphological observation, the aerial hyphae of the S1 colony were fluffy and dense, and the color was dark green or black. The spore morphology was monospore and transparent, and the size was uniform, about (6~10) μm×(6~7) μm, round or elliptical, compared with the "Fungus Identification Manual", it was preliminarily determined to belong to Phyllanthus spp., and once again inoculated to healthy guava fruits for pathogenicity determination. The results showed that S1 was the dominant pathogen causing guava black spot disease. Research on growth characteristics showed that S1 was more suitable for growth under alkaline, dark and normal temperature conditions. Moreover, S1 was identified as Phyllosticta capitalensis by the comparison of the PCR sequencing results. Conclusion: The dominant pathogen causing guava black spot disease was Phyllosticta capitalensis.

IntroductionBurn injury has been shown to lead to changes in the composition of the gut microbiome and cause other damage in patients. However, little is known about how the gut microbial community evolves in individuals who have recovered from burn injury.MethodsIn this study, we established a model of deep partial-thickness burn in mice and collected fecal samples at eight time points (pre-burn, 1, 3, 5, 7, 14, 21, and 28 days post-burn) for 16S rRNA amplification and high-throughput sequencing.ResultsThe results of the sequencing were analyzed using measures of alpha diversity, and beta diversity and taxonomy. We observed that the richness of the gut microbiome declined from day 7 post-burn and that the principal component and microbial community structure varied over time. On day 28 after the burn, the microbiome composition largely returned to the pre-burn level, although day 5 was a turning point for change. Some probiotics, such as the Lachnospiraceae_NK4A136_group, decreased in composition after the burn but were restored in the later recovery period. In contrast, Proteobacteria showed an opposite trend, which is known to include potential pathogenic bacteria.ConclusionThese findings demonstrate gut microbial dysbiosis after burn injury and provide new insights into the burn-related dysbiosis of the gut microbiome and strategies for improving the treatment of burn injury from the perspective of the microbiota.

Summary: Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.

IntroductionSeveral studies have evaluated the effects of tributyrin on sow reproductive performance; however, none of these studies have investigated the effects of tributyrin on sow gut microbiota and its potential interactions with immune systems and milk composition. Therefore, we speculated that tributyrin, the combination of butyrate and mono-butyrin without odor, would reach the hindgut and affect the intestinal microbiota composition and play a better role in regulating sow reproductive performance, gut flora, and health.MethodsThirty sows (Landrace × Yorkshire) were randomly divided into two groups: the control group (CON) and the tributyrin group (TB), which received basal diet supplemented with 0.05% tributyrin. The experimental period lasted for 35 days from late pregnancy to lactation.ResultsThe results showed that TB supplementation significantly shortened the total parturition time and reduced the diarrhea rate in suckling piglets. On day 20 of lactation, the milk fat and protein levels increased by 9 and 4%, respectively. TB supplementation significantly improved the digestibility of dry material, gross energy, and crude fat in the sow diet, but had no significant effect on crude protein digestibility. Furthermore, TB supplementation increased the levels of IL-10, IL-6, and IgA in the blood of weaned piglets, but had no effect on maternal immunity. Analysis of the fecal microbial composition revealed that the addition of TB during late gestation and lactation increased the microbiota diversity in sows and piglets. At the phylum level, sows in the TB group had a slight increase in the relative abundance of Bacteroidota and Spirochaetota and a decrease in Firmicutes. At the order level, the relative abundance of Lactobacillales was increased in piglets and sows, and the TB group showed increased relative abundance of Enterobacterales and significantly decreased relative abundance of Oscillospirales in piglets. At family level, the relative abundance of Lactobacillaceae, Oscillospiraceae, and Christensenellaceae increased in sows, and the relative abundance of Enterobacteriaceae and Lactobacillaceae increased in piglets. At genus level, the relative abundance of Lactobacillus increased in sows and piglets, but the relative abundance of Subdoligranulum and Eubacterium_fissicatena_group decreased in piglets in the TB group.DiscussionIn conclusion, tributyrin supplementation shortened the farrowing duration and reduced the diarrhea rate of piglets by improving the inflammatory response and composition of gut microbiota in piglets and sows.

Objective: To evaluate the predictive value of the autoregressive integrated moving average (ARIMA) product seasonal model for the daily outpatient volume of paediatric internal medicine departments in hospitals. Methods: The daily outpatient volume of paediatric internal medicine recorded by the hospital information system of the Chengdu Women's and Children's Central Hospital from 1 January 2011 to 31 December 2020 was collected. Using the data from 1 January 2011 to 31 December 2019, the seasonal summation ARIMA model of the time product was established by fitting the tseries program in the R-3.6.3 software. The monthly outpatient volume from January to December 2020 was predicted, and the prediction effect was evaluated according to the mean absolute percentage error (MAPE) between the predicted value and the actual value. Results: The outpatient volume of paediatric internal medicine in the hospital from 2011 to 2019 showed an upward trend, with obvious seasonal fluctuations. The optimal model was the ARIMA model ([3,4], 1,2) × (1,1,0) 12, with an Akaike information criterion of 3116.656 and a Bayesian information criterion of 3217.412. The model's residual was a white noise sequence (x2 = 7.56, P = 0.819), and the MAPE between the predicted value and the actual value of the model was 9.56%. Within a 95% confidence interval of the predicted value, the prediction accuracy of the model was high. Conclusion: The ARIMA multiplicative seasonal model established in this study is suitable for the short-term prediction of the outpatient volume.

During an investigation of Diatrypaceae from southern China, 10 xylariales-like taxa have been collected. Morphological and multi-gene analyses confirmed that these taxa reside in Diatrypaceae and represent eight novel taxa and two new records belonging to six genera (viz., Allocryptovalsa, Diatrype, Diatrypella, Paraeutypella, Peroneutypa, and Vasilyeva gen. nov.). Vasilyeva gen. nov. was proposed to accommodate Vasilyeva cinnamomi sp. nov. Among the other collections, seven new species were introduced (viz., Diatrype camelliae-japonicae sp. nov., Diatrype rubi sp. nov., Diatrypella guiyangensis sp. nov., Diatrypella fatsiae-japonicae sp. nov., Paraeutypella subguizhouensis sp. nov., Peroneutypa hainanensis sp. nov., and Peroneutypa qianensis sp. nov.), while two were reported as new records from China (Allocryptovalsa rabenhorstii and Diatrype enteroxantha). For Diatrypaceae, the traditional taxonomic approach based on morphology may not be applicable.

The study aims to investigate the effects of dietary Astragalus membranaceus extract (AME) and Eucommia ulmoides leaf extract (ELE) supplementation on the growth performance, blood biochemistry, and antioxidant capacity of gibel carp (Carassius auratus gibelio var. CAS V, 10.01 g ± 0.24 g). Six experimental diets supplemented were marked as A0E0 (basic diet, 0% AME and 0% ELE), A0E0.1 (0% AME and 0.1% ELE), A0.02E0, A0.02E0.05, A0.02E0.1, A0.02E0.2 (0.02% AME with 0%, 0.05%, 0.1%, and 0.2% ELE). After 8 weeks, A0.02E0 diet significantly increased the final body weight (FBW), weight gain rate (WGR), specific growth rate (SGR), and decreased the glucose (GLU), triglyceride content (TG), and total cholesterol (TC) of the plasma, the malonaldehyde (MDA) content of the liver, the A0E0.1 group significantly increased the total protein (TP) and albumin (ALB) content of the plasma, decreased the alanine aminotransferase (ALT) content of the plasma when compared with A0E0 group (Independent T-test: P

Previous studies investigating the characteristics of imported cases were mostly limited to a certain province/city or a specific sub-group during a certain period with a small sample size, which may not provide an overall picture of the characteristics of imported cases. In this scoping literature review, we comprehensively synthesized the epidemiological characteristics of overseas imported COVID-19 cases into China by retrieving six literature databases, with aims to provide implications for more targeted control, prevention, and medical treatment of this disease. After dropping duplicates and reviewing titles, abstracts, and full-texts, 50 articles were included in the review finally, including 26 (52%) articles in English and 24 (48%) articles in Chinese. According to the type of data sources, the 50 studies were divided into three categories: 13 (26%) articles using data sourced from the Chinese Infectious Diseases Online Reporting System, 15 (30%) articles using data from the websites of national/local health departments, and 22 (44%) articles using hospital admission data. Most of the overseas imported COVID-19 cases were young and middle-aged Chinese students and businessmen returning from the United States, Europe, and some neighboring countries. Airport routine health screening measures could not identify COVID-cases effectively, although scheduled multiple nucleic acid tests were required before boarding. Almost all imported cases were identified during the hotel quarantine period. Although a large proportion of imported cases were asymptomatic or with mild symptoms in the published literature, they may be due to participant selection bias. The exact proportion of asymptomatic cases may need to be further investigated especially through population-based large-scale studies.

Background: Combined use of hypnotic and opioids during anesthesia inductions decreases blood pressure. Post-induction hypotension (PIHO) is the most common side effect of anesthesia induction. We aimed to compare the difference in mean arterial pressure (MAP) induced by remimazolam with that induced by etomidate in the presence of fentanyl at tracheal intubation.Methods: We assessed 138 adult patients with American Society of Anesthesiologists physical status I–II who underwent elective urological surgery. Patients were randomly allocated to receive either remimazolam or etomidate as alterative hypnotic in the presence of fentanyl during anesthesia induction. Comparable BIS values were achieved in both groups. The primary outcome was the difference in the MAP at tracheal intubation. The secondary outcomes included the characteristics of anesthesia, surgery, and adverse effects.Results: The MAP was higher in the etomidate group than in the remimazolam group at tracheal intubation (108 [22] mmHg vs. 83 [16] mmHg; mean difference, −26; 95% confidence interval [CI], −33 to −19; p < 0.0001). Heart rate was significantly higher in the etomidate group than in the remimazolam group at tracheal intubation. The patients’ condition warranted the administration of ephedrine more frequently in the remimazolam group (22%) than in the etomidate group (5%) (p = 0.0042) during anesthesia induction. The remimazolam group had a lower incidence of hypertension (0% vs. 9%, p = 0.0133), myoclonus (0% vs. 47%, p < 0.001), and tachycardia (16% vs. 35%, p = 0.0148), and a higher incidence of PIHO (42% vs. 5%, p = 0.001) than the etomidate group during anesthesia induction.Conclusion: Remimazolam was associated with lower MAP and lower heart rate compared to etomidate in the presence of fentanyl at tracheal intubation. Patients in the remimazolam group had a higher incidence of PIHO, and their condition warranted the administration of ephedrine more frequently than in the etomidate group during anesthesia induction.

IntroductionAlthough geriatric assessment (GA) has been used for a long time in the field of geriatrics and internal medicine, there are few studies on its application in the field of breast surgery. Therefore, the utility of specific GA domains for the assessment of older patients with breast cancer remains unclear. The aim of the present study was to evaluate the association between specific GA domains and the survival rate of older patients with breast cancer.MethodsWe used the database of Peking Union Medical College Hospital to identify older patients who were newly diagnosed with breast cancer between 2012 and 2018 and retrospectively analysed the data of 541 patients aged ≥65 years. Patients with metastatic cancer and those with missing vital status data were excluded. The primary outcomes were overall survival (OS) and breast cancer-specific survival. The GA domains used in this study included functional status, comorbidities, and psychological state. Multivariate regression analysis was used to estimate hazard ratios for these three domains.ResultsAfter a median follow-up of 72 months, we observed a significant relationship between functional impairment and mortality (adjusted HR: 3.06, 95% confidence interval [CI]: 1.83-5.10, P

Phosphorus (P) is one of the essential macronutrients for plant growth and development, and it is an integral part of the major organic components, including nucleic acids, proteins and phospholipids. Although total P is abundant in most soils, a large amount of P is not easily absorbed by plants. Inorganic phosphate (Pi) is the plant-available P, which is generally immobile and of low availability in soils. Hence, Pi starvation is a major constraint limiting plant growth and productivity. Enhancing plant P efficiency can be achieved by improving P acquisition efficiency (PAE) through modification of morpho-physiological and biochemical alteration in root traits that enable greater acquisition of external Pi from soils. Major advances have been made to dissect the mechanisms underlying plant adaptation to P deficiency, especially for legumes, which are considered important dietary sources for humans and livestock. This review aims to describe how legume root growth responds to Pi starvation, such as changes in the growth of primary root, lateral roots, root hairs and cluster roots. In particular, it summarizes the various strategies of legumes to confront P deficiency by regulating root traits that contribute towards improving PAE. Within these complex responses, a large number of Pi starvation-induced (PSI) genes and regulators involved in the developmental and biochemical alteration of root traits are highlighted. The involvement of key functional genes and regulators in remodeling root traits provides new opportunities for developing legume varieties with maximum PAE needed for regenerative agriculture.

Three arecophila-like fungal samples were collected on dead culms of gramineous plants in China. Morphological studies of our new collections and the herbarium specimen of Arecophila gulubiicola (generic type) were conducted and the morphological affinity of our new collections with Arecophila was confirmed. Maximum likelihood and Bayesian analyses using combined ITS, LSU, rpb2 and β-tubulin data from our collections revealed the phylogeny of Cainiaceae. The monospecific genus Alishanica (type species Al. miscanthi), which had been accepted in Cainiaceae, is revisited and synonymised under Arecophila. Based on morphology and phylogeny, Arecophila australis sp. nov. and A. clypeata sp. nov. are introduced as new species, while A. miscanthi is a new record for China. All the new collections are illustrated and described.

Abstract Background Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). Methods A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. Results Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). Conclusions Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.

Objective To investigate the efficacies of Femoral Neck System (FNS) and the three cannulated screws fixation (3CS) as therapeutic options for femoral neck fractures. Method This was a retrospective study involving 69 patients (26 males and 43 females; mean age of 54.9 years (range, 28–66 years)) subjected to either FNS or 3CS for femoral neck fracture therapy. These patients were treated in our hospital from October 2019 to May 2020. Patient follow up was done at 1, 2, 3 and 6 months. During the short‐term (6 months) follow‐up period, surgical procedures for the two groups and incidences of complications were analyzed. Perioperative parameters were recorded and analyzed. Postoperative hip joint functions were measured and compared using the Harris score. The assessed perioperative parameters included surgical time, hemoglobin loss, fluoroscopy duration, hospitalization length and hospitalization cost. The main complications at last follow‐up (6 months) included varus tilting, femoral neck shortness, and implant removal. Results Differences in the number of patients, age, Garden type of fracture and time from injury to surgery between the two groups were not significant (P > 0.05). With regards to perioperative parameters, compared to 3CS, FNS treatment performed better in surgical time (60.00 ± 12.44 vs 76.81 ± 13.10 min, P = 0.000), blood loss (13.67 ± 8.02 vs 16.58 ± 4.16 g/L, P = 0.059) and fluoroscopy time (39.73 ± 9.57 vs 58.14 ± 9.15 s, P = 0.000). Differences in hospitalization length and cost between the groups were not significant (P > 0.05). During the whole follow‐up period, all patients did not exhibit dysfunction, pulmonary embolism or even death as a result of long‐term immobilization of affected limbs. Surgical incisions for all patients healed well without infections. During the 6‐month follow‐up period, the FNS group exhibited a higher Harris score (84.61 ± 3.42 vs 78.67 ± 3.72, p = 0.000). In addition, treatment‐associated complications (FNS vs 3CS) included femoral neck varus tilt (3.03% vs 11.11%), femoral neck shortness (6.06% vs 13.89%), and implant removal (0% vs. 13.89%). Implant removal rate for the FNS group was significantly less than that of the 3CS group (P = 0.026). Differences in incidences of femoral neck varus tilt (P = 0.196) and femoral neck shortness (P = 0.282) between the two groups were not significant. However, the difference in number was significant (FNS group was less). Conclusion FNS treatment is associated with a smaller surgical trauma, stronger stability, and reductions in post‐operative complication incidences, therefore, it is a potential therapeutic option for femoral neck fractures.

Abstract Background The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. Methods This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1–7, then 4 mg bid on days 8–21) or the first 2 cycles (4 mg tid on days 1–7, then 4 mg bid on days 8–42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. Discussion This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. Trial registration ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.

Nasolacrimal duct (NLD) damage is associated in the majority of type II and III naso-orbito-ethmoid (NOE) fractures.1 Our study aims to investigate the efficacy and safety of prophylactic NLD intubation in the setting of facial fractures, by comparing incidence of postoperative epiphora and wound infection. A retrospective matched control study was conducted on all patients with surgically treated facial fractures from 2008 to 2013 (n = 280) (IRB ref number: DSRB 2013/01198). Patients with the following fracture types were included: NOE (n = 16), frontal sinus (n = 2), Le Fort II/III (n = 8), and > 1 type (n = 48). All patients in this study were included with the intention to treat. The study group comprised patients who were intubated, while the control group patients were not intubated. Each group had 37 patients matched for age, gender, fracture type, and injury type. A single oculoplastic surgeon skilled in lacrimal surgery performed the procedure for all intubated patients. Patients with more severe and complex facial fractures were intubated with bicanalicular Crawford stents. Postoperative epiphora and infective complications (both facial wound and dacryocystitis) were assessed at 1, 3, 6, and 12 months. There was no significant difference in incidence of either postoperative epiphora (p = 0.152) or wound infection (p = 0.556) comparing both groups. Reduced incidence of postoperative epiphora in the study group is statistically not significant and does not support the need for prophylactic intubation. If radiographic evidence of NLD disruption or regurgitation seen on syringing on the NLD intraoperatively is present, intubation is safe and efficacious only if performed by an expert.

Abstract The gestational weight gain (GWG) range of Chinese women with gestational diabetes mellitus (GDM) remains unclear. Our objective was to identify the ranges of GWG in Chinese women with GDM and to investigate the associations between prepregnancy body mass index (BMI), GWG and maternal-infant adverse outcomes. Cases of GDM women who delivered singletons from 2013 to 2018 in a public hospital were collected. Logistic regression analysis was used to assess the joint effects of prepregnancy BMI and GWG on maternal-infant adverse outcomes. Ultimately, 14,578 women were collected. The ranges of GWG in Chinese women with GDM were different from the National Academy of Medicine’s (NAM) recommendation. The ranges of GWG of Chinese women with GDM in the underweight, normal weight, overweight and obese groups were 5.95–21.95 kg, 4.23–21.83 kg, 0.88–21.12 kg and − 1.76 to 19.95 kg, respectively. The risks of large for gestational age (LGA), macrosomia and caesarean delivery were significantly increased with the increasing prepregnancy BMI. Furthermore, the risks of LGA, macrosomia and caesarean delivery were significantly higher in the normal weight group with a GWG higher than the NAM recommendation. Similarly, in the overweight group with a GWG higher than the NAM recommendation, the risks of LGA were significantly higher, while the risks of macrosomia were significantly lower. Overall, we determined the range of GWG in different prepregnancy BMI groups. And GDM women with high prepregnancy BMI and excessive GWG were associated with the higher risks of maternal-infants adverse outcomes in China.

Abstract Background Multiple system atrophy (MSA) associated with neuroleptic malignant-like syndrome (NMLS) is rare and few cases have been described in the literature. Case presentation In the present study, three patients with MSA associated with NMLS were analyzed from January 2012 to January 2020 to characterize their clinical presentations. Data collected from the patients for analysis included general patient history, the fluctuation and severity of disease symptoms, the indicated therapies and disease progression at follow-up. All patients had histories of sudden withdrawal or reduction of levodopa prior to the onset of symptoms. Clinical presentations were characterized by hyperthermia, autonomic dysfunction, worsening of extrapyramidal symptoms, and elevated serum creatine kinase (CK) levels. During hospitalization, one patient rapidly progressed and died, while the other two patients were successfully treated. Conclusions Early diagnosis and treatment are very important for patient outcomes in NMLS. Notably, the correct dose and time of administration of dopaminergic medication may be key in treating NMLS.

This study sought to investigate and evaluate a modified axial translaminar screw fixation for treating odontoid fractures. We performed a retrospective study at Wenzhou Medical University Affiliated Second Hospital between March 2016 and June 2018. We retrospectively collected and analyzed the medical records of 23 cases with odontoid fractures. All patients were identified as type II odontoid fractures without neurological deficiency and serious diseases following the classification of Anderson. The average age, gender ratio, and body mass index (BMI) were 54.3 ± 11.1 years, 12 men to 11 women, and 22.6 ± 2.4 kg/m2, respectively. Patients in this study accepted screw fixation using our modified axial translaminar screw fixation combined with atlas pedicle or lateral mass screw fixation. Within the technique, a small cortical “window” was dug in the middle of the axial contralateral lamina, such that the screws in the lamina were visualized to prevent incorrectly implanting the posterior spinal canal through the visualized “window.” A total of 46 bone screws were accurately inserted into the axial lamina without using fluoroscopy. The length of all translaminar screws ranged between 26 and 30 mm, while the diameter was 3.5 mm. During the follow‐up survey, the visual analog scale (VAS) and neck disability index (NDI) were measured. We provide a simple modification of Wright's elegant technique with the addition of “visualized windows” at the middle of the axial lamina. In all patients, screws were inserted accurately without bony breach and the screw angle was 56.1 ± 3.0°. Mean operative time was 102 ± 28 min with an average blood loss of 50 ± 25 mL. Postoperative hemoglobin and mean length of hospital stay were 12.0 ± 1.4 g/dL and 10.4 ± 3.4 days, respectively. The average follow‐up time of all cases was 14.7 months and no internal fixation displacement, loosening, or breakage was found. All patients with odontoid fractures reported being satisfied with the treatment during the recheck period and good clinical outcomes were observed. At 1, 6, and 12 months, NDI and VAS showed that the symptoms of neck pain and limitations of functional disability improved significantly during follow‐up. Our results suggest that the modified translaminar screw fixation technique can efficiently treat Anderson type II odontoid fracture, followed by the benefits of less soft tissue dissection, simple operation, no fluoroscopy, and accurate placement of screws.

Drug-induced liver injury (DILI) is a widespread and harmful disease, and is closely linked to acute endoplasmic reticulum (ER) stress. Previous reports have shown that acute ER stress can suppress hepatic gluconeogenesis and even leads to hypoglycemia. However, the mechanism is still unclear. MAPK phosphatase 3 (MKP-3) is a positive regulator for gluconeogenesis. Thus, this study was conducted to investigate the role of MKP-3 in the suppression of gluconeogenesis by acute ER stress, as well as the regulatory role of acute ER stress on the expression of MKP-3. Results showed that acute ER stress induced by tunicamycin significantly suppressed gluconeogenesis in both hepatocytes and mouse liver, reduced glucose production level in hepatocytes, and decreased fasting blood glucose level in mice. Additionally, the protein level of MKP-3 was reduced by acute ER stress in both hepatocytes and mouse liver. Mkp-3 deficiency eliminated the inhibitory effect of acute ER stress on gluconeogenesis in hepatocytes. Moreover, the reduction effect of acute ER stress on blood glucose level and hepatic glucose 6-phosphatase (G6pc) expression was not observed in the liver-specific Mkp-3 knockout mice. Furthermore, activation of protein kinase R-like ER kinase (PERK) decreased the MKP-3 protein level, while inactivation of PERK abolished the reduction effect of acute ER stress on the MKP-3 protein level in hepatocytes. Taken together, our study suggested that acute ER stress could suppress hepatic gluconeogenesis by stimulating MKP-3 degradation via PERK, at least partially. Thus, MKP-3 might be a therapeutic target for DILI-related hypoglycemia.

Appropriate protein sources are vital for the growth, development and health of neonates. Twenty–four 2–day–old piglets were randomly divided into three groups and fed isoenergetic and isonitrogenous diets. The experimental diets included a milk replacer with 17.70% whey protein concentrate (WPC group), a milk replacer with 6% spray–dried porcine plasma isonitrogenously substituting WPC (SDPP group), and a milk replacer with 5.13% soy protein isolate isonitrogenously substituting WPC (SPI group). Neonatal piglets were fed milk replacer from postnatal day 2 (PND 2) to day 20 (PND 20). The growth performance, intestinal morphology, activities of digestive enzymes, plasma biochemical parameters, immunity–related genes, short–chain fatty acids (SCFA) and intestinal microbiota in the colonic chyme were determined. The results showed that SDPP–fed piglets had higher final BW (p = 0.05), ADG (p = 0.05) and F/G (p = 0.07) compared with WPC– and SPI–fed piglets, and SDPP–fed piglets had a lower diarrhea index (p < 0.01) from PND 2 to PND 8. SDPP–fed piglets had an increased ileal villus height (p = 0.04) and ratio of villus height to crypt depth (VCR) (p = 0.02), and increased activities of sucrase (p < 0.01), lactase (p = 0.02) and trypsin (p = 0.08) in the jejunum, compared with WPC– and SPI–fed piglets. Furthermore, SPI–fed piglets had an increased mRNA expression of IL-6 (p < 0.01) and concentration of plasma urea (p = 0.08). The results from LEfSe analysis showed that SDPP–fed piglets had a higher abundance of beneficial Butyricicoccus compared with WPC– and SPI–fed piglets, in which higher abundances of pathogenic bacteria such as Marinifilaceae, Fusobacterium and Enterococcus were observed. Moreover, SDPP–fed piglets had an increased concentration of butyric acid (p = 0.08) in the colonic chyme compared with WPC– and SPI–fed piglets. These results suggest that neonatal piglets fed milk replacer with SDPP partially substituting WPC had improved growth performance and intestinal morphology and function, associated with higher digestive enzyme activity and fewer pathogenic bacteria.

In this study, nine as-cast Ni-Al-Cr-Os alloys were prepared, and their constituent phases and microstructure were examined using X-ray diffraction and electron probe microanalysis techniques. The solidification paths of all the alloys in a Ni-rich corner were revealed based on a detailed analysis of the as-cast microstructure. The liquidus cube of the quaternary Ni-Al-Cr-Os system in a Ni-rich corner was established accordingly. A eutectic-type invariant reaction on the liquidus surface was explicitly identified, and its reaction can be expressed as L → α + β + γ. No quaternary invariant reaction was found in the alloys following the addition of Os. The Ni-Al-Cr-Os alloy points were then vertically mapped onto the Ni-Al-Cr liquid phase projection to better observe the effect of Os addition on the solidification path of the Ni-Al-Cr system. It was found that the addition of a small amount of Os has no significant effect on the solidification path of the Ni-Al-Cr system. Furthermore, the microhardness of each alloy, which was determined to be in the range of 207 HV to 565 HV, was found to be closely related to the phase constitution and phase fraction of the alloy.

C2+ hydrocarbons, especially C2+ olefins, as important basic chemical raw materials, mainly come from petroleum cracking. With the increasing scarcity of petroleum resources, the search for new olefins production routes has become the focus of research, and the production of olefins by the oxidative coupling of methane (OCM) process has attracted extensive attention. The OCM route is an important alternative to the production of olefins from petroleum resources and is also an important direction for the development of efficient and clean utilization of natural gas. In this paper, the mechanism, catalysts, and other key factors for the production of olefins by methane oxidative coupling are reviewed. The mechanism of OCM, including the reaction pathway and the formation of intermediate products, is introduced. Then, commonly used catalysts, such as alkali metal/alkaline earth metal oxides, rare earth metal oxides, composite metal oxides with special structures, and classical catalysts Mn/Na2WO4/SiO2, and their mechanisms of action in the reaction are discussed. In addition, the application of chemical looping oxidative coupling of methane (CLOCM) in olefin production is also investigated, which is a promising alternative way due to the high selectivity of olefins and the low cost of catalysts owing to the excellent performance of the catalyst recycling. These studies will help to further understand the mechanism of OCM for olefin production and provide guidance and support for applications in related fields.