Search

Forest–grassland ecotone (FGE) has essential ecological and economic value. Unfortunately, it is impacted greatly by environmental changes and anthropogenic disturbance, and is considered one of the most severely threatened biomes in China. To protect Chinese FGE, identifying its exact boundary and exploring its landscape structure dynamic are badly needed, especially on nationwide scale at one‐year temporal resolution. Here, we mapped the annual FGE distribution of China from 1990 to 2020, investigated its changing trends of area, location and landscape patterns, and revealed the underlying driving factors. Our results showed that FGE area over the 31 years totaled 1 011 870 km2, covering about 10.54% of China's land. The FGE area first increased from 1990 and peaked in 1999, and then kept decreasing until 2020. The FGE gravity center has moved accumulatively 590.15 km over the 31 years, with the net moving distance of 228.76 km southwestward. From 1990 to 2020, forest area increased continuously while grassland and cropland area decreased, but these three landscape types had been dominating the FGE. The increase in forest area was largely converted from grassland. The decline in grassland mainly resulted from its conversion into cropland and forest. Meanwhile, the conversion of cropland to grassland supplemented grassland loss to a certain extent. At landscape level, the total area with decreased fragmentation is larger than that with increased fragmentation. Returning Farmland to Grassland Project and land reclamation were primary drivers for changes of fragmentation in the northern and middle part of the FGE, while temperature and precipitation were primary drivers in southern part. Our results will improve the understanding into the dynamic trends of distribution and pattern of FGE at nationwide scale, and thus help to optimize the designing of ecological projects and protective schemes for FGE as a unique and integral biome. [ABSTRACT FROM AUTHOR]

Basalts from the Late Carboniferous to Early Permian are extensively developed in the central Lhasa subterrane, southern Tibet. Studying the petrogenesis of these rocks may have implications for the late Paleozoic arc magmatism along the central Lhasa subterrane uncovering more of the evolution of the Sumdo Paleo‐Tethys Ocean and its dynamic mechanism. Basalt samples from the Luobadui Formation in the Leqingla area, NW of Linzhou City in the central Lhasa subterrane, southern Tibet exhibit arc‐like geochemical signatures in a subduction‐zone tectonic setting characterized by high Al2O3 and low TiO2 contents, fractionated REE patterns with low Nb/La ratios and high LREE concentrations, and negative HFSE anomalies. Based on their higher Th/Ce, Nb/Zr, and lower Ba/Th, Pb/Nd ratios, slightly negative to positive εNd(t) values, and the relatively high Sr‐Pb isotopic compositions, these samples were probably derived from partial melting of a depleted mantle source of garnet + spinel lherzolite, metasomatized by subducted sediments around 297 Ma. Modeling of the trace elements indicates that these basalts experienced fractional crystallization of olivine, clinopyroxene and minor plagioclase during magma ascent and eruption. It is proposed that these Late Carboniferous–Early Permian basalts are associated with the northward subduction of the Sumdo Paleo‐Tethys Ocean seafloor along the southern margin of the central Lhasa subterrane. [ABSTRACT FROM AUTHOR]

With the increasing consumer focus on automotive safety, Autonomous Emergency Braking (AEB) systems, recognized as effective active safety technologies for collision avoidance and the mitigation of collision-related injuries, are gaining wider application in the automotive industry. To address the issues of the insufficient working reliability of AEB systems and their unsatisfactory level of accordance with the psychological expectations of drivers, this study proposes an optimized second-order Time to Collision (TTC) safety time algorithm based on the motion state of the preceding vehicle. Additionally, the study introduces a safety distance algorithm derived from an analysis of the braking process of the main vehicle. The safety time algorithm focusing on comfort and the safety distance algorithm focusing on safety are effectively integrated in the time domain and the space domain to obtain the safety time–safety distance fusion algorithm. A MATLAB/Simulink–Carsim joint simulation platform has been established to validate the AEB control strategy in terms of safety, comfort, and system responsiveness. The simulation results show that the proposed safety time–safety distance fusion algorithm consistently achieves complete collision avoidance, indicating a higher safety level for the AEB system. Furthermore, the application of active hierarchical braking minimizes the distance error, at under 0.37 m, which meets psychological expectations of drivers and improves the comfort of the AEB system. [ABSTRACT FROM AUTHOR]

The natural color of biological specimens plays a crucial role in body protection, signaling, physiological adaptations, etc. Full-color optical sectioning structured illumination microscopy (OS-SIM) color is a promising approach that can reconstruct biological specimens in three-dimension meanwhile maintaining their natural color. Full-color OS-SIM takes the advantages of rapid imaging speed, compatibility with fluorescence and non-fluorescence samples, compact configuration, and low cost. However, the commonly used HSV-RMS reconstruction algorithm for full-color OS-SIM faces two issues to be improved. One is the RMS (root-mean-square) OS reconstruction algorithm is prone to background noise, and the other is the reconstruction is bound in RGB and HSV color spaces, consuming more reconstructing time. In this paper, we propose a full-color Fourier-OS-SIM method that allows for the OS reconstruction using the high-frequency spectrum of the sample and thus is immune to the low-frequency background noise. The full-color Fourier-OS-SIM directly runs in the RGB color space, providing an easy way to restore the color information. Simulation and experiments with various samples (pollen grains and tiny animals) demonstrate that the full-color Fourier-OS-SIM method is superior to the HSV-RMS method regarding background noise suppression. Moreover, benefiting from the background noise suppression merit, the quantitative morphological height map analysis with the full-color Fourier-OS-SIM method is more accurate. The proposed full-color Fourier-OS-SIM method is expected to find broad applications in biological and industrial fields where the 3D morphology and the color information of objects both need to be recovered. [ABSTRACT FROM AUTHOR]

Background: Microsatellite instability‐high (MSI‐H) colorectal cancer (CRC) is known for its heightened responsiveness to immunotherapy. However, establishing robust predictive markers for immunotherapy efficacy remains imperative. This retrospective study aimed to elucidate the genetic landscape of MSI‐H CRC and correlate these genetic alterations with immunotherapy outcomes in a cohort of 121 patients. Methods: We analyzed clinical and molecular data from 121 patients with MSI‐H CRC. We conducted a thorough genetic analysis of MSI‐H CRC patients, with a specific emphasis on the APC, TP53, RAS, and MMR genes. We further analyzed the relationship between gene mutations and immunotherapy efficacy. The primary endpoints analyzed were objective response rate (ORR) and progression‐free survival (PFS). All statistical analysis was conducted using SPSS26.0 and R 4.2.0 software. Results: Our findings underscored the complexity of the genetic landscape in MSI‐H CRC, shedding light on the intricate interplay of these genes in CRC development. Notably, mutations in MMR genes exhibited a distinctive pattern, providing insights into the underlying mechanisms of MSI‐H. Furthermore, our results revealed correlations between specific genetic alterations and immunotherapy outcomes, with a particular focus on treatment response rates and progression‐free survival. Conclusion: This study represents a significant step toward unraveling the genetic nuances of MSI‐H CRC. The distinctive pattern of MMR gene mutations not only adds depth to our understanding of MSI‐H CRC but also hints at potential avenues for targeted therapies. This research sets the stage for future investigations aimed at refining therapeutic strategies and improving outcomes for patients with MSI‐H CRC. [ABSTRACT FROM AUTHOR]

To cope with global warming and increasing carbon emissions, the chemical looping process has attracted attention due to its excellent ability to convert fossil fuel and capture CO2. In this case, chemical looping partial oxidation technology has become the focus of attention due to its advantages in the production of syngas and hydrogen, especially with respect to the design and selection of oxygen carriers, which directly affect the efficiency of the production of syngas and hydrogen. In particular, the conversion of methane can reach 95% in the chemical looping partial oxidation of methane, and the selectivity of syngas, in the range of 700 °C to 900 °C at atmospheric pressure, can reach 99% for twenty or more cycles. In this review, from the perspective of metal oxide selection and structure regarding the chemical looping partial oxidation process, we discuss the role of oxygen carriers in the chemical looping partial oxidation cycle, in which the specific surface area, the lattice oxygen mobility, and the thermal stability are understood as the important factors affecting reactivity. We hope to summarize the design and development of efficient oxygen carriers with high oxygen-carrying capacity and syngas selectivity, as well as contribute to the selection, design, optimization, and redox reaction mechanism of redox catalysts. [ABSTRACT FROM AUTHOR]

Background: Eicosapentaenoic acid (EPA) is widely used in the functional food and nutraceutical industries due to its important benefits to human health. Oleaginous microorganisms are considered a promising alternative resource for the production of EPA lipids. However, the storage of EPA in triglyceride (TG) becomes a key factor limiting its level. Results: This study aimed to incorporate more EPA into TG storage through metabolic engineering. Firstly, key enzymes for TG synthesis, the diacylglycerol acyltransferase (DGAT) and glycerol-3-phosphate acyltransferase (GPAT) genes from Schizochytrium sp. HX-308 were expressed in Yarrowia lipolytica to enhance lipid and EPA accumulation. In addition, engineering the enzyme activity of DGATs through protein engineering was found to be effective in enhancing lipid synthesis by replacing the conserved motifs "HFS" in ScDGAT2A and "FFG" in ScDGAT2B with the motif "YFP". Notably, combined with lipidomic analysis, the expression of ScDGAT2C and GPAT2 enhanced the storage of EPA in TG. Finally, the accumulation of lipid and EPA was further promoted by identifying and continuing to introduce the ScACC, ScACS, ScPDC, and ScG6PD genes from Schizochytrium sp., and the lipid and EPA titer of the final engineered strain reached 2.25 ± 0.03 g/L and 266.44 ± 5.74 mg/L, respectively, which increased by 174.39% (0.82 ± 0.02 g/L) and 282.27% (69.70 ± 0.80 mg/L) compared to the initial strain, respectively. Conclusion: This study shows that the expression of lipid synthesis genes from Schizochytrium sp. in Y. lipolytica effectively improves the synthesis of lipids and EPA, which provided a promising target for EPA-enriched microbial oil production. [ABSTRACT FROM AUTHOR]

Accurate prediction of TCR-pMHC binding is important for the development of cancer immunotherapies, especially TCR-based agents. Existing algorithms often experience diminished performance when dealing with unseen epitopes, primarily due to the complexity in TCR-pMHC recognition patterns and the scarcity of available data for training. We have developed a novel deep learning model, 'TCR Antigen Binding Recognition' based on BERT, named as TABR-BERT. Leveraging BERT's potent representation learning capabilities, TABR-BERT effectively captures essential information regarding TCR-pMHC interactions from TCR sequences, antigen epitope sequences and epitope-MHC binding. By transferring this knowledge to predict TCR-pMHC recognition, TABR-BERT demonstrated better results in benchmark tests than existing methods, particularly for unseen epitopes. [ABSTRACT FROM AUTHOR]

We retrospectively analyzed the outcomes of 136 consecutive patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center. Among them, 76 cases used hypomethylating agents (decitabine, n = 40; azacitidine, n = 36) as post-transplant maintenance therapy, whereas 60 contemporaneous patients did not adopt maintenance therapy. The 3-year incidences of relapse in two groups were 16.6% and 39.2% (p =.001). The 3-year OS and DFS in maintenance group were 84.0% and 78.6%, which were remarkably improved than in control group (60.0% and 58.0%) (p =.004, p =.011). Moreover, the 3-year relapse rates for patients receiving decitabine and azacitidine therapy were 8.5% and 25.0%, respectively (p =.019). Patients utilizing decitabine had more common possibility of grade 3–4 neutropenia than azacitidine (20.0% vs. 2.8%, p =.031). These results indicate that maintenance therapies using hypomethylating agents could reduce the risk of post-transplant recurrence, resulting into remarkable superior survival. Decitabine might lower relapse after allo-HSCT with somewhat more severe myelosuppression when being compared to azacitidine. [ABSTRACT FROM AUTHOR]

The arc suppression device based on ground fault transfer (GFT) has been preliminarily applied in the medium voltage distribution network (MVDN). An accurate travelling wave (TW) fault location method is proposed to extend the use of the ground fault transfer device. D-PMU is used as a travelling wave detection tool to record the transient voltage travelling waves of fault grounding and bus active grounding during arc suppression. Then, the faulty section is identified through the time difference of travelling wave arrival at the upstream and downstream measurement points. On this basis, the fault location equations of the arrival time and distance of the upstream travelling wave are established, and an accurate fault location method based on the arrival time difference of the travelling wave is proposed. The simulation model is established by PSCAD/EMTDC, and the results show that the method has high location accuracy, and the absolute error is less than 30 m. It is not affected by the TW velocity, the fault conditions, or the distributed power sources. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) poses a significant social and economic burden worldwide. Identifying exposures, risk factors, and biological mechanisms that are causally connected to MDD can help build a scientific basis for disease prevention and development of novel therapeutic approaches. Methods: In this systematic review, we assessed the evidence for causal relationships between putative causal risk factors and MDD from Mendelian randomization (MR) studies, following PRISMA. We assessed methodological quality based on key elements of the MR design: use of a full instrumental variable analysis and validation of the three key MR assumptions. Results: We included methodological details and results from 52 articles. A causal link between lifestyle, metabolic, inflammatory biomarkers, particular pathological states and MDD is supported by MR investigations, although results for each category varied substantially. Conclusions: While this review shows how MR can offer useful information for examining prospective treatment targets and better understanding the pathophysiology of MDD, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry. [ABSTRACT FROM AUTHOR]

Currently, studies of ancient faunal community networks have been based mostly on uniformitarian and functional morphological evidence. As an important source of data, taphonomic evidence offers the opportunity to provide a broader scope for understanding palaeoecology. However, palaeoecological research methods based on taphonomic evidence are relatively rare, especially for body fossils in lacustrine sediments. Such fossil communities are not only affected by complex transportation and selective destruction in the sedimentation process, they also are strongly affected by time averaging. Historically, it has been believed that it is difficult to study lacustrine entombed fauna by a small-scale quadrat survey. Herein, we developed a software, the TaphonomeAnalyst, to study the associational network of lacustrine entombed fauna, or taphocoenosis. TaphonomeAnalyst allows researchers to easily perform exploratory analyses on common abundance profiles from taphocoenosis data. The dataset for these investigations resulted from fieldwork of the latest Middle Jurassic Jiulongshan Formation near Daohugou Village, in Ningcheng County of Inner Mongolia, China, spotlighting the core assemblage of the Yanliao Fauna. Our data included 27,000 fossil specimens of animals from this deposit, the Yanliao Fauna, whose analyses reveal sedimentary environments, taphonomic conditions, and co-occurrence networks of this highly studied assemblage, providing empirically robust and statistically significant evidence for multiple Yanliao habitats. A new method and its companion software to study the associational network of lacustrine entombed fauna, or taphocoenosis. The application allows researchers to easily perform exploratory analyses on common abundance profiles from taphocoenosis data. [ABSTRACT FROM AUTHOR]

Background: Nitrogen- and water-use efficiency (NUE and WUE) reflect the capacity of plants to take up and utilize resources in the environments. Although N deposition and drought are known to affect plant growth and persistence, it remains elusive how plants adjust NUE, WUE and their relationship to adapt to the concurrent N deposition and drought under the context of global change. We conducted a field experiment in a temperate grassland in Inner Mongolia, in which N addition (10 g m–2 yr−1), drought (reduced 66% precipitation during growing season) and their combination were manipulated, and we explored the responses of both instantaneous (NUEINST and WUEINST) and long-term (NUELT and WUELT) WUE and NUE for six common plant species (Leymus chinensis, Stipa baicalensis, Thermopsis lanceolata, Potentilla bifurca, Thalictrum squarrosum, Klasea centauroide). Results: Across all the six species, NUEINST decreased and WUEINST increased with both N addition and drought; NUELT decreased with both N addition and drought, while WUELT decreased with N addition and increased with drought. A significant interactive effect between N addition and drought was detected, in that, drought weakened the negative effect of N addition on WUELT and NUELT, and N addition weakened the negative effect of drought on NUELT, but enhanced the positive effect of drought on WUELT. As a consequence, drought caused a trade-off between NUE and WUE, and N addition brought forth positive correlation between NUE and WUE. Meanwhile, the relationship between NUE and WUE varied among the species of different functional groups. Conclusions: Our study demonstrated that NUE, WUE and their relationship play an important role in determining their responses and adaptability to changes in soil nitrogen and water availability induced by N deposition and drought. Our results shed light on the antagonistic, synergetic and neutral effects between nitrogen deposition and drought on resource use efficiency, and further clarified the different adaptability among species of different functional groups, which will conduce to a comprehensive understanding on the role of NUE and WUE in plant persistence and coexistence in grassland ecosystems. [ABSTRACT FROM AUTHOR]

Biodiversity is threatened by global changes, but related research has focused primarily on species or functional group diversity, neglecting their interaction networks. The latter are particularly sensitive to global changes and essential for biodiversity maintenance. Furthermore, multiple global change factors are typically examined separately, rather than in concert which is more realistic in nature.To explore the responses of arthropod networks to multiple global changes, we conducted a field experiment in temperate grassland in northeast China, in which nitrogen (N) deposition, drought, snowmelt timing and their interactions were manipulated. We constructed and assessed networks of arthropod functional groups, and explored their responses to changes in plant communities and the abiotic environments.Nitrogen addition decreased arthropod network complexity because increased foliar N and simplified plant community strengthened trophic chains along a single pathway, weakening the net effect of other pathways. However, experimental drought decreased network complexity by filtering out plant species and changing micro‐habitats. While delayed snowmelt significantly increased arthropod abundance only in early spring, its interaction with N addition or with drought had various impacts on arthropod functional groups. Our results suggest that the interaction of arthropod consumers with plant species richness and with plant nutrients finally reduced the robustness, connectedness and function of entire species/functional group networks in response to global change factors.In conclusion, species loss and increasing plant nutrient concentrations are key factors simplifying networks under multiple global changes, and such simplification is likely to be strengthened if coupled with changes in micro‐habitats. Our study highlighted that the effects of multiple global change factors should be studied in concert, even though they occur in different seasons, so that their effects on ecological networks can be perceived as a panorama. Read the free Plain Language Summary for this article on the Journal blog. [ABSTRACT FROM AUTHOR]

The classic BCR-ABL1-negative myeloproliferative neoplasm (MPN) is a highly heterogeneous hematologic tumor that includes three subtypes, namely polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). Despite having the same JAK2V617F mutation, the clinical manifestations of these three subtypes of MPN differ significantly, which suggests that the bone marrow (BM) immune microenvironment may also play an important role. In recent years, several studies have shown that peripheral blood monocytes play an important role in promoting MPN. However, to date, the role of BM monocytes/macrophages in MPN and their transcriptomic alterations remain incompletely understood. The purpose of this study was to clarify the role of BM monocytes/macrophages in MPN patients with the JAK2V617F mutation. MPN patients with the JAK2V617F mutation were enrolled in this study. We investigated the roles of monocytes/macrophages in the BM of MPN patients, using flow cytometry, monocyte/macrophage enrichment sorting, cytospins and Giemsa-Wright staining, and RNA-seq. Pearson correlation coefficient analysis was also used to detect the correlation between BM monocytes/macrophages and the MPN phenotype. In the present study, the proportion of CD163+ monocytes/macrophages increased significantly in all three subtypes of MPN. Interestingly, the percentages of CD163+ monocytes/macrophages are positively correlated with HGB in PV patients and PLT in ET patients. In contrast, the percentages of CD163+ monocytes/macrophages are negatively correlated with HGB and PLT in PMF patients. It was also found that CD14+CD16+ monocytes/macrophages increased and correlated with MPN clinical phenotypes. RNA-seq analyses demonstrated that the transcriptional expressions of monocytes/macrophages in MPN patients are relatively distinct. Gene expression profiles of BM monocytes/macrophages suggest a specialized function in support of megakaryopoiesis in ET patients. In contrast, BM monocytes/macrophages yielded a heterogeneous status in the support or inhibition of erythropoiesis. Significantly, BM monocytes/macrophages shaped an inflammatory microenvironment, which, in turn, promotes myelofibrosis. Thus, we characterized the roles of increased monocytes/macrophages in the occurrence and progression of MPNs. Our findings of the comprehensive transcriptomic characterization of BM monocytes/macrophages provide important resources to serve as a basis for future studies and future targets for the treatment of MPN patients. [ABSTRACT FROM AUTHOR]

The mammalian cochlear epithelium undergoes substantial remodeling and maturation before the onset of hearing. However, very little is known about the transcriptional network governing cochlear late-stage maturation and particularly the differentiation of its lateral nonsensory region. Here, we establish ZBTB20 as an essential transcription factor required for cochlear terminal differentiation and maturation and hearing. ZBTB20 is abundantly expressed in the developing and mature cochlear nonsensory epithelial cells, with transient expression in immature hair cells and spiral ganglion neurons. Otocyst-specific deletion of Zbtb20 causes profound deafness with reduced endolymph potential in mice. The subtypes of cochlear epithelial cells are normally generated, but their postnatal development is arrested in the absence of ZBTB20, as manifested by an immature appearance of the organ of Corti, malformation of tectorial membrane (TM), a flattened spiral prominence (SP), and a lack of identifiable Boettcher cells. Furthermore, these defects are related with a failure in the terminal differentiation of the nonsensory epithelium covering the outer border Claudius cells, outer sulcus root cells, and SP epithelial cells. Transcriptome analysis shows that ZBTB20 regulates genes encoding for TM proteins in the greater epithelial ridge, and those preferentially expressed in root cells and SP epithelium. Our results point to ZBTB20 as an essential regulator for postnatal cochlear maturation and particularly for the terminal differentiation of cochlear lateral nonsensory domain. [ABSTRACT FROM AUTHOR]

Species diversity has been shown to be influenced by environmental factors, but the mechanism underlying their relationship remains unclear across spatial scales. Based on field investigation data collected from 3077 sample plots in temperate forest ecosystems, we compared tree species richness, evenness and dominance at 10 km × 10 km, 30 km × 30 km and 90 km × 90 km spatial scales. Then, we detected the scale dependence of changes in tree species composition on climate, topography and forest structure using variation partitioning and quantified their contribution to tree diversity with gradient–boosted models (GBMs) and fitted their relationships. The magnitude of tree richness, evenness and dominance significantly increased with spatial scale. Ecological factors jointly accounted for 24.3%, 26.5% and 38.5% of the variation in tree species composition at the three spatial scales, respectively. The annual mean temperature had a strong impact on tree richness, evenness and dominance and peaked at an intermediate scale. Tree evenness and dominance increased with the variation of temperature but had upper and lower limits. Tree richness obviously increased with annual precipitation on multiple scales and decreased with annual sunshine duration at large spatial scales. Tree richness, evenness and dominance obviously increased with the variation in elevation and diameter at breast height at large scales and small scales, respectively. Tree dominance decreased with tree height at a small scale. The dependence of tree diversity on ecological factors increased with spatial scales. Furthermore, different factors exert various controls on tree diversity at different spatial scales, representing a comprehensive mechanism regulating tree diversity. [ABSTRACT FROM AUTHOR]

As a branch of 3D microscopy, optical sectioning structured illumination microscopy (OS-SIM) has the advantages of fast imaging speed, weak photobleaching and phototoxicity, and flexible and compatible configuration. Although the method of using the one-dimensional periodic fringe pattern projected on the sample can remove the out-of-focus background from the in-focus signal, the axial resolution of the final reconstructed 3D image is not improved. Here, we propose a three-beam interference OS-SIM, namely TBOS, instead of the common-used dual-beam interference OS-SIM (DBOS). The three-beam interference scheme has been adopted in 3D super-resolution SIM (3D-SR-SIM), where the fringe phase shifting needs to be along each of the three orientations. In contrast, TBOS applies phase shifting only in one arbitrary direction. We built a TBOS SIM microscope and performed the 3D imaging experiments with 46 nm diameter fluorescent microspheres and a mouse kidney section. The axial resolution of the 3D image obtained with TBOS was enhanced by a factor of 1.36 compared to the DBOS method, consistent with the theoretical analysis and simulation. The OS-SIM with enhanced axial resolution for 3D imaging may find a wide range of applications in the biomedical field. [ABSTRACT FROM AUTHOR]

Grasslands are expected to experience droughts of unprecedented frequency and magnitude in the future. Characterizing grassland responses and recovery from drought is therefore critical to predict the vulnerability of grassland ecosystems to climate change. Most previous studies have focused on ecosystem responses during drought while investigations of post‐drought recovery are rare. Few studies have used functional traits, and in particular bud or clonal traits, to explore the mechanisms underlying grassland responses to and recovery from drought.To address this issue, we experimentally imposed a four‐year drought in a C3‐dominated grassland in northeastern China and monitored recovery for 3 years post‐drought. We investigated the immediate and legacy effects of drought on total above‐ground net primary productivity (ANPP), ANPP of functional groups (rhizomatous grasses, bunch grasses and forbs), and how the legacy effects were driven by plant species diversity, clonal traits and vegetative traits.We found that drought progressively reduced total ANPP over the 4‐year period. The reductions in total ANPP in the first and third drought years were caused by the decrease in ANPP of bunch grasses only, while that of the second year was caused by declines in ANPP of bunch grasses and forbs, and the fourth year decline was linked to all three functional groups. The post‐drought recovery of ANPP, which occurred despite the continued loss of plant species diversity, was mainly driven by rapid recovery of rhizomatous and bunch grasses, which compensated for the slow response by forbs. The rapid post‐drought recovery of these grasses can be attributed to their relatively large, intact bud and shoot densities post‐drought, as well as the recovery of plant height and specific leaf area. The rapid recovery of grasses possibly restricted the growth and distribution of forbs, resulting in reduced forb ANPP and, consequently, lower species diversity during the recovery period.Synthesis. These results highlight the potential for positive legacy effects of drought on ANPP as well as the important and complementary roles of plant reproductive and vegetative traits in mediating ecosystem recovery from drought in a C3‐dominated grassland. [ABSTRACT FROM AUTHOR]

The increasing market demand for squalene requires novel biotechnological production platforms. Schizochytrium sp. is an industrial oleaginous host with a high potential for squalene production due to its abundant native acetyl‐CoA pool. We first found that iron starvation led to the accumulation of 1.5 g/L of squalene by Schizochytrium sp., which was 40‐fold higher than in the control. Subsequent transcriptomic and lipidomic analyses showed that the high squalene titer is due to the diversion of precursors from lipid biosynthesis and increased triglycerides (TAG) content for squalene storage. Furthermore, we constructed the engineered acetyl‐CoA C‐acetyltransferase (ACAT)‐overexpressing strain 18S::ACAT, which produced 2.79 g/L of squalene, representing an 86% increase over the original strain. Finally, a nitrogen‐rich feeding strategy was developed to further increase the squalene titer of the engineered strain, which reached 10.78 g/L in fed‐batch fermentation, a remarkable 161‐fold increase over the control. To our best knowledge, this is the highest squalene yield in thraustochytrids reported to date. [ABSTRACT FROM AUTHOR]

Recurrent droughts are an inevitable consequence of climate change, yet how grasslands respond to such events is unclear. We conducted a 6‐year rainfall manipulation experiment in a semiarid grassland that consisted of an initial 2‐year drought (2015–2016), followed by a recovery period (2017–2018) and, finally, a second 2‐year drought (2019–2020). In each year, we estimated aboveground net primary productivity (ANPP), species richness, community‐weighted mean (CWM) plant traits, and several indices of functional diversity. The initial drought led to reduced ANPP, which was primarily driven by limited growth of forbs in the first year and grasses in the second year. Total ANPP completely recovered as the rapid recovery of grass productivity compensated for the slow recovery of forb productivity. The subsequent drought led to a greater reduction in total ANPP than the initial drought due to the greater decline of both grass and forb productivity. The structural equation models revealed that soil moisture influenced ANPP responses directly during the initial drought, and indirectly during the subsequent drought by lowering functional diversity, which resulted in reduced total ANPP. Additionally, ANPP was positively influenced by CWM plant height and leaf nitrogen during the recovery period and recurrent drought, respectively. Overall, the greater impact of the second drought on ecosystem function than the initial drought, as well as the underlying differential mechanism, underscores the need for an understanding of how increased drought frequency may alter semiarid grassland functioning. [ABSTRACT FROM AUTHOR]

Presently, the supply of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) traditionally produced by marine fisheries will be insufficient to meet their market demand in food industry. Thus a sustainable alternative source is urgently required. Schizochytrium sp. is an ideal producer of DHA; however, its ability to co-produce DHA and EPA has not yet been proved. Herein, we first described a cobalamin-independent methionine synthase-like (MetE-like) complex, which contains independent acyltransferase and 3-ketoacyl synthase domains, independent of the traditional polyketide synthase (PKS) system. When the MetE-like complex was activated, the EPA content was increased from 1.26% to 7.63%, which is 6.06-folds higher than that in the inactivated condition. Through lipidomics, we find that EPA is more inclined to be stored as triglyceride. Finally, the EPA production was enhanced from 4.19 to 29.83 (mg/g cell dry weight) using mixed carbon sources, and the final yield reached 2.25 g/L EPA and 9.59 g/L DHA, which means that Schizochytrium sp. has great market potential for co-production of EPA and DHA. The MetE like complex is found to be capable of regulating the PKS system to produce EPA in Schizochytrium, with its activation regulating the expression of key enzymes, improving the efficiency of DHA and EPA production. [ABSTRACT FROM AUTHOR]

Malignant melanoma (MM) is a neoplasm that develops from human melanocytes. It was reported that eukaryotic translation initiation factor 3 subunit B (EIF3B) is associated with multiple types of cancers, but its role in MM has not been reported. In the present study, we found that EIF3B was abundantly expressed in MM and was strongly related to lymphatic metastasis and pathological stage of MM patients. In addition, EIF3B depletion could block the progression of MM in vitro and in vivo. In contrast, EIF3B overexpression increased cell proliferation and migration in melanoma cells. More importantly, we identified that EIF3B's driver role in MM was mediated by PTGS2. In detail, we found that EIF3B stabilized PTGS2 expression by inhibiting PTGS2 ubiquitination, which is mediated by the E3 ligase MDM2. Moreover, like EIF3B, silencing PTGS2 could suppress MM development, and more interestingly, it could reverse the situation caused by overexpression of EIF3B in vitro and in vivo. Furthermore, the proliferation and migration inhibited by silencing of EIF3B were also partially recovered by overexpression of PTGS2. Overall, our findings revealed the potential of EIF3B as a therapeutic target for MM. Identification of EIF3B's function in MM may pave the way for future development of more specific and more effective targeted therapy strategies against MM. [ABSTRACT FROM AUTHOR]

Copyright of Functional Ecology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Given the increasing environmental pollution around the world, air pollutants such as particulate matters (PM) have been becoming typical carcinogenic factors to cause lung cancer. The PM with aerodynamic diameter less than or equal to 2.5 μm (PM2.5) plays an important role in lung cancer mortality. However, effects of PM2.5 on the mortality of lung cancer patients have not been investigated well. The purpose of this study is to assess the associations between PM2.5 exposure and lung cancer-related mortality, by regions and races. This systematic review was developed and conducted according to PRISMA protocol. A comprehensive literature search for peer-reviewed studies published up to October 2021 was conducted using the electronic databases PubMed, EMBASE, and Cochrane Library. The identified records were carefully evaluated following the PICOS criteria. Relative risks (RRs) and 95% confidence interval (CI) of lung cancer mortality associated with PM2.5 were extracted and meta-analyzed. The Chi-squared test, Begg's test, and Eggerr analysis were performed to assess the heterogeneity and publication bias. Sensitivity analysis and subgroup analysis were also conducted to make sure the authenticity and stability of the present study. In total, 16 studies met the inclusion criteria. For the overall effects of PM2.5 on lung cancer-related mortality, there was heterogeneity among the included studies (I2 = 62.30%, P < 0.01); thus, the random effects model was chosen to conduct related analysis. The pooled adjusted RR of lung cancer mortality associated with PM2.5 was 1.12 (95% CI: 1.09–1.15) for per 10 µg/m3 increase in PM2.5 concentrations. For different continents, the RRs of subgroup analysis in North-America, Asia, and Europe were 1.16 (1.09–1.22), 1.08 (CI: 1.07–1.09), and 1.14 (CI: 1.04–1.23), respectively. Subgroup analysis by race showed that for Mongoloid RR = 1.08 (1.07–1.09), and for Caucasoid RR = 1.13 (CI: 1.11–1.15). With per 10 µg/m3 increase in PM2.5, the mortality rate of Caucasoid lung cancer patients increased by 1.13 times, greater than that of the Mongoloid. Increase in PM2.5 concentrations is associated positively with the mortality of lung cancer patients. For different regions and races, the adverse effects of PM2.5 are discrepant. Our Findings can provide necessary evidence to protect public health further from air pollution. [ABSTRACT FROM AUTHOR]

Dynamic reconfiguration is an effective method to improve the unbalanced distribution of load demand. The traditional global dynamic reconfiguration based on the centralized cloud service system may lead to large-scale power flow regulation and increase the computational burden in large-scale distribution networks. In this letter, a time-segmented multi-level method preferring local reconfiguration is proposed to minimize the photovoltaic power generation curtailment and load shedding. Furthermore, a novel cloud-edge collaboration framework is devised to alleviate the huge pressure bought by excessive concentration of computational tasks. Numerical results on a 445-node system are presented to demonstrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Summary: Climate extremes pose enormous threats to natural ecosystems. Arbuscular mycorrhizal (AM) fungi are key plant symbionts that can affect plant community dynamics and ecosystem stability. However, knowledge about how AM fungal communities respond to climate extremes in natural ecosystems remains elusive.Based on a grassland extreme drought experiment in Inner Mongolia, we investigated the response of AM fungal communities to extreme drought in association with plant communities. The experiment simulated two types of extreme drought (chronic/intense) of once‐in‐20‐year occurrence.AM fungal richness and community composition exhibited high sensitivity to extreme drought and were more sensitive to intense drought than chronic drought. This community sensitivity (i.e. decline in richness and shifts in community composition) of AM fungi can be jointly explained by soil moisture, plant richness, and aboveground productivity. Notably, the robustness of the plant–AM fungal community co‐response increased with drought intensity.Our results indicate that AM fungal communities are sensitive to climate extremes, and we propose that the plant community mediates AM fungal community responses. Given the ubiquitous nature of AM associations, their climate sensitivity may have profound consequences on plant communities and ecosystem stability under climate change. [ABSTRACT FROM AUTHOR]

Probiotic-based therapy for ulcerative colitis (UC) is a novel and promising approach that has gained much popularity in recent years. However, probiotics may be easily captured and destroyed by the harsh in vivo environment, which limits their application prospects to a large extent. This work introduces a versatile facile approach for decorating individual probiotics with nanozyme coatings, named Pt-Lipid@EcN. A bimolecular lipid coating is deposited on the surface of probiotics used in the oral treatment of UC using simple self-assembly with a liposome under cytocompatible conditions, and it acts as armor to effectively protect the probiotics from strong digestive acids and enzymes. The obtained results indicated that the liposome-coated Escherichia coli Nissle (EcN) 1917 could significantly improve the colonization rate of the microorganisms in the intestinal tract. We also explored the specific mechanism of Pt-Lipid@EcN to improve the behavior of murine UC models, including reduction of inflammatory effects and histological injury, and regulation of epithelial barrier homeostasis in the intestine. The nanozyme-shielded probiotic exhibited enhanced anti-inflammatory ability in vivo, introducing novel strategies for the application of nanozyme biomedicine in the treatment of colonic inflammatory diseases. [ABSTRACT FROM AUTHOR]

Karst is the most common ore-controlling structure in Mississippi Valley-type (MVT) Pb–Zn deposits. However, the formation process of karst caves that contain ores and their related Pb–Zn mineralization in fold-thrust belts is poorly understood. The Changdong MVT Pb–Zn deposit is hosted by karst caves located in the fold-thrust system of the Simao basin, Sanjiang metallogenic belt, Tibetan Plateau. The Changdong deposit is an ideal natural laboratory for studying the effects of karst on Pb–Zn mineralization in MVT deposits. The ore bodies in this deposit are hosted by a large-scale carbonate breccia and bedded sediments belt within the late Permian limestones, which are situated in the hanging wall of the regional Longshu thrust fault. The δ13CV-PDB values of the limestone fragments from the breccias range from − 4.2 to 4.1‰. They are similar to those of overlying limestone strata, indicating that the fragments were mainly derived from autochthonous limestones in the overlying strata. Energy-dispersive spectroscopy analysis indicates that the bedded sediments and the matrices of the carbonate breccias contain K–Al silicate clay minerals, quartz, rock fragments, and calcite fragments. Detrital zircons from bedded sediments contain five discrete age populations ranging from the Jurassic to the Paleoproterozoic, indicating that the matrix materials were derived from the weathered sediments of metamorphic and magmatic rocks along the western margin of the Simao basin. Bedded sediments dominated by exogenous materials are actually speleothems. When contextualized with recently published data placing the Changdong deposit formation in the early to middle Oligocene, our data suggest that the Changdong deposit formed within a meteoric paleokarst system. The Pb–Zn ores are hosted by the speleothems in the breccia belt and comprise microspherulitic or colloidal sphalerite and euhedral galena. The sphalerite and galena precipitated by filling voids and replacing calcite crystals in faded speleothems. The pyrite and galena δ34SV-CDT values from the Changdong deposit range from − 16.9 to 15.8‰, indicating a pre-existing H2S reservoir interpreted as a result of bacterial sulfate reduction (BSR). A three-stage process for the Changdong deposit was proposed as last. First, the Permian limestone was uplifted to the near-surface by regional thrusting during the India-Eurasia collision, and karst caves formed by meteoric dissolution. Second, a reduced sulfur trap formed by BSR in the paleokarst caves during continual regional compression. Third, metal-rich fluids migrated into the Changdong deposit via tensile faults formed during the transition from compressive stress to extensional strike-slip stress as a result of progressive rotation of the regional strain axes. The Pb–Zn sulfides were likely precipitated by low-temperature fluid mixing. This study provides new data to establish a geologically consistent framework for the evaluation of karst caves and related MVT Pb–Zn mineralization in fold-thrust systems. [ABSTRACT FROM AUTHOR]

To reduce the inpatient mortality and improve the quality of hospital management, we explore the relationship between temperatures and in-hospital mortality in a large sample across 10 years in Nanjing, Jiangsu. We collected 10 years' data on patient deaths from a large research hospital. Distributed lag non-linear model (DLNM) was used to find the association between daily mean temperatures and in-hospital mortality. A total of 6160 in-hospital deaths were documented. Overall, peak RR appeared at 8 °C, with the range of 1 to 20 °C having a significantly high mortality risk. In the elderly (age ≥ 65 years), peak RR appeared at 5 °C, with range − 3 to 21 °C having a significantly high mortality risk. In males, peak RR appeared at 8 °C, with the range 0 to 24 °C having a significantly high mortality risk. Moderate cold (define as 2.5th percentile of daily mean temperatures to the MT), not extreme temperatures (≤ 2.5th percentile or ≥ 97.5th percentile of daily mean temperatures), increased the risk of death in hospital patients, especially in elderly and male in-hospital patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Declaring the drought-resistance of plant communities in grassland and the underlying mechanisms is crucial under climatic change scenario. Here we aimed to quantify aboveground & belowground net primary productivity (ANPP & BNPP) and their allocation in response to extreme droughts, and to uncover any underlying factors of drought resistance. Methods: We experimentally reduced growing season rainfall by 66% for four years in two grassland sites (Sandy and Loamy site respectively), and measured ANPP and BNPP yearly and evaluated the relatedness of drought-induced changes for them to plant traits (Plant height, δ13C, SLA and LNC) and community composition. Results: Experimental drought decreased species richness, ANPP of forbs and the total at both sites, but decreased ANPP of grasses only at the Sandy site. Experimental drought has non-significant effect on total BNPP at both sites, but increased 10–20 cm BNPP and decreased 0–10 cm BNPP. BNPP ratio was kept unchanged at the Loamy site but increased at the Sandy site. Moreover, the communities at the Loamy site showed lower δ13C, SLA and LNC, but greater height. Conclusions: Our study demonstrates that extreme drought can impact community productivity and structure, and highlights the importance of plant traits, community composition and soil properties in modulating the responses and resistance of steppe communities to extreme drought. [ABSTRACT FROM AUTHOR]

Chemotherapy resistance in breast cancer is an important factor affecting the prognosis of breast cancer patients. We computationally analyzed the differences in gene expression before and after chemotherapy in breast cancer patients, drug-sensitive groups, and drug-resistant groups. Through functional enrichment analysis, immune microenvironment analysis, and other computational analysis methods, we identified PRC1, GGTLC1, and IRS1 as genes that may mediate breast cancer chemoresistance through the immune pathway. After validation of certain other clinical datasets and in vitro cellular assays, we found that the above three genes influenced drug resistance in breast cancer patients and were closely related to the tumor immune microenvironment. Our finding that chemoresistance in breast cancer could be influenced by the mediation of tumor immunity expanded our knowledge of how to address this problem and could guide future research involving chemoresistance. [ABSTRACT FROM AUTHOR]

Prostate cancer is still a significant global health burden in the coming decade. Novel biomarkers for detection and prognosis are needed to improve the survival of distant and advanced stage prostate cancer patients. The tumor microenvironment is an important driving factor for tumor biological functions. To investigate RNA prognostic biomarkers for prostate cancer in the tumor microenvironment, we obtained relevant data from The Cancer Genome Atlas (TCGA) database. We used the bioinformatics tools Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm and weighted coexpression network analysis (WGCNA) to construct tumor microenvironment stromal-immune score-based competitive endogenous RNA (ceRNA) networks. Then, the Cox regression model was performed to screen RNAs associated with prostate cancer survival. The differentially expressed gene profile in tumor stroma was significantly enriched in microenvironment functions, like immune response, cancer-related pathways, and cell adhesion-related pathways. Based on these differentially expressed genes, we constructed three ceRNA networks with 152 RNAs associated with the prostate cancer tumor microenvironment. Cox regression analysis screened 31 RNAs as the potential prognostic biomarkers for prostate cancer. The most interesting 8 prognostic biomarkers for prostate cancer included lncRNA LINC01082, miRNA hsa-miR-133a-3p, and genes TTLL12, PTGDS, GAS6, CYP27A1, PKP3, and ZG16B. In this systematic study for ceRNA networks in the tumor environment, we screened out potential biomarkers to predict prognosis for prostate cancer. Our findings might apply a valuable tool to improve prostate cancer clinical management and the new target for mechanism study and therapy. [ABSTRACT FROM AUTHOR]

Background: Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limit the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment. Results: In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner. Conclusions: This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level. [ABSTRACT FROM AUTHOR]

Mississippi Valley-type (MVT) Pb-Zn deposits serve as the world's major supply of Pb-Zn resources. However, the age constraint of MVT Pb-Zn deposits has long been a big challenge, due to the lack of minerals that are unequivocally related to ore deposition and that can be used for radioisotopic dating. Here we show sporopollens can provide useful chronological information on the Changdong MVT Pb-Zn deposit in the Simao basin, Sanjiang belt, West China. The Pb-Zn ores in the Changdong deposit are hosted by internal sediments in paleo-karst caves of meteoric origin. Sphalerite and galena occur as replacements of carbonate minerals and void infillings in the internal sediments. The relations suggest that the Pb-Zn mineralization occurred after the deposition of the internal sediments. A palynological assemblage mainly composed of angiosperm pollen dominated by Castanea, Quercus, and Carya and fern spores dominated by Polypodiaceae, Pteris, and Athyriaceae was identified. These pollen and spores place the ore-hosting internal sediments and the Changdong paleo-karst at early to middle Oligocene. Consequently, the Changdong Pb-Zn deposit must have formed after the early Oligocene (∼34 Ma). These age constraints, together with the geological characteristics, indicate that the Changdong Pb-Zn deposit is a paleo-karst-controlled MVT deposit related to fold-thrust systems in the Sanjiang belt. The Changdong deposit is similar to other MVT Pb-Zn deposits in the northern part of the Sanjiang belt, making it possible to extend this Pb-Zn belt 500 km further to the South. Results presented here highlights the potential of sporopollens in dating the age of MVT deposits related to paleo-karst formation in young orogenic belts. [ABSTRACT FROM AUTHOR]

Background: The oleaginous microorganism Schizochytrium sp. is widely used in scientific research and commercial lipid production processes. However, low glucose-to-lipid conversion rate (GLCR) and low lipid productivity of Schizochytrium sp. restrict the feasibility of its use. Results: Orlistat is a lipase inhibitor, which avoids triacylglycerols (TAGs) from hydrolysis by lipase. TAGs are the main storage forms of fatty acids in Schizochytrium sp. In this study, the usage of orlistat increased the GLCR by 21.88% in the middle stage of fermentation. Whereas the productivity of lipid increased 1.34 times reaching 0.73 g/L/h, the saturated fatty acid and polyunsaturated fatty acid yield increased from 21.2 and 39.1 to 34.9 and 48.5 g/L, respectively, indicating the advantages of using a lipase inhibitor in microbial lipids fermentation. Similarly, the system was also successful in Thraustochytrid Aurantiochytrium. The metabolic regulatory mechanisms stimulated by orlistat in Schizochytrium sp. were further investigated using transcriptomics and metabolomics. The results showed that orlistat redistributed carbon allocation and enhanced the energy supply when inhibiting the TAGs' degradation pathway. Therefore, lipase in Schizochytrium sp. prefers to hydrolyze saturated fatty acid TAGs into the β-oxidation pathway. Conclusions: This study provides a simple and effective approach to improve lipid production, and makes us understand the mechanism of lipid accumulation and decomposition in Schizochytrium sp., offering new guidance for the exploitation of oleaginous microorganisms. [ABSTRACT FROM AUTHOR]

Extreme drought decreases aboveground net primary production (ANPP) in most grasslands, but the magnitude of ANPP reductions varies especially in C3‐dominated grasslands. Because the mechanisms underlying such differential ecosystem responses to drought are not well resolved, we experimentally imposed an extreme 4‐yr drought (2015–2018) in two C3 grasslands that differed in aridity. These sites had similar annual precipitation and dominant grass species (Leymus chinensis) but different annual temperatures and thus water availability. Drought treatments differentially affected these two semiarid grasslands, with ANPP of the drier site reduced more than at the wetter site. Structural equation modeling revealed that community‐weighted means for some traits modified relationships between soil moisture and ANPP, often due to intraspecific variation. Specifically, drought reduced community mean plant height at both sites, resulting in a reduction in ANPP beyond that attributable to reduced soil moisture alone. Higher community mean leaf carbon content enhanced the negative effects of drought on ANPP at the drier site, and ANPP–soil‐moisture relationships were influenced by soil C:N ratio at the wetter site. Importantly, neither species richness nor functional dispersion were significantly correlated with ANPP at either site. Overall, as expected, soil moisture was a dominant, direct driver of ANPP response to drought, but differential sensitivity to drought in these two grasslands was also related to soil fertility and plant traits. [ABSTRACT FROM AUTHOR]

B4GALNT2 gene encodes the enzyme β1,4-N-acetylgalactosaminyltransferase 2 that biosynthesizes the histo-blood group antigen Sda, which is expressed on the surface of erythrocytes and in body secretions. Analysis of The Cancer Genome Atlas (TCGA) database revealed that this gene was highly expressed in breast cancer tissues in comparison with adjacent healthy ones. In-vitro lentivirus-assisted B4GALNT2 gene knockdown experiments in model triple negative breast cancer (TNBC) cell lines (HCC1937 and MDA-MB-231) showed inhibition in cell proliferation, decrease in cell viability, promotion of cell apoptosis and inhibitions in cell migration and invasiveness abilities in comparison with empty lentivirus transfectant controls. Also, in cell cycle tests, the number of cells in the G1 phase increased, in the S phase decreased and did not change in the G2/M phase (indicative of the presence of a block in the G1 phase). In-vivo tumor formation experiments in mice revealed that knockdown of the B4GALNT2 gene in MDA-MB-231 cells inhibited their proliferation. Using co-immunoprecipitation (Co-IP) mass spectroscopy-assisted analysis, it was found that HLA-B protein [a product of the human leukocyte antigen (HLA) class I gene] interacts with B4GALNT2 protein. In-vitro overexpression of HLA-B in B4GALNT2-knocked down MDA-MB-231 cell lines significantly recovered the cell proliferation, viability and migration ability of B4GALNT2 gene. These indicate that HLA-B is one of the interaction proteins in the downstream pathway of the B4GALNT2 gene. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BCa) is the most commonly diagnosed cancer and the leading cause of cancer death among females around the world. Recent studies have indicated that long non-coding RNAs (lncRNAs) can serve as an independent biomarker for diagnosis and prognosis in many types of cancer, including pancreatic adenocarcinoma, gastric cancer, liver cancer, and lung cancer. Previous studies have shown that many lncRNAs are associated with the occurrence and development of BCa. However, few studies have combined multiple lncRNAs to predict the prognosis of early-stage BCa patients. Methods: Systematic and comprehensive analysis of data from The Cancer Genome Atlas (TCGA) was conducted to identify lncRNA signatures with prognostic value in BCa. Additionally, the relative expression levels of the 8 lncRNA of several BCa cell lines were detected by quantitative real-time PCR (qPCR) and the results were substituted into a risk score formula. Finally, migration assays were used to verify the result from prognostic analysis according to the risk scores among cell lines with different risk scores. Results: Our study included 808 BCa patients with complete clinical data. A panel of 8 lncRNAs was identified using Wilcox tests as different between normal and tumor tissue of the BCa patients. This panel was used to analyze the survival of BCa patients. Patients with low risk scores had greater overall survival (OS) than those with high risk scores. Multivariate Cox regression analyses demonstrated that the lncRNA signature was an independent prognostic factor. Gene Set Enrichment Analysis (GSEA) suggested that the lncRNAs might be involved in several molecular signaling pathways implicated in BCa such as the DNA replication pathway, the cell cycle pathway, and the pentose phosphate pathway. Validation experiments in breast cancer cells to test cell migration by using wound-healing assays supported the results of the model. Conclusion: Our study demonstrated that a panel of 8 lncRNAs has the potential to be used as an independent prognostic biomarker of BCa. [ABSTRACT FROM AUTHOR]

Introduction: Metastatic prostate cancer (mPCa) is responsible for most prostate cancer (PCa) deaths worldwide. The present study aims to explore the molecular differences between mPCa and PCa.Methods: The authors downloaded GSE6752, GSE6919, and GSE32269 from the Gene Expression Omnibus and employed integrated analysis to identify differentially expressed genes (DEGs) between mPCa and PCa. Functional and pathway-enrichment analyses were performed, and a protein-protein interaction (PPI) network and modules were constructed. Clinical mPCa specimens were collected to verify the results by performing RT-qPCR. The Cancer Genome Atlas database was used to conduct a survival analysis, and an immunohistochemical assay was performed. The invasion ability of PCa cells was verified by Transwell assay.Results: One-hundred six consistently DEGs were found in mPCa compared with PCa. DEGs significantly enriched the positive regulation of cell proliferation, cell division, and cell adhesion in small cell lung cancer and PCa. Cell division, nucleoplasm, and cell cycle were selected from the PPI network, and the top 10 hub genes were selected. CDC20 and PTTG1 with genetic alterations were significantly associated with poorer disease-free survival. Immunohistochemical assay results showed that the expression levels of CDC20 and PTTG1 in mPCa were higher than those in PCa. The results of the migration assay indicated that CDC20 and PTTG1 could enhance the migration ability of PCa cells.Conclusion: The present study revealed that CDC20 and PTTG1 contribute more to migration, progression, and poorer prognoses in mPCa compared with PCa. CDC20 and PTTG1 could represent therapeutic targets in mPCa medical research and clinical studies. [ABSTRACT FROM AUTHOR]

Background: Although long non-coding RNA (lncRNA) RAET1K has been observed to be abnormally expressed in patients with various cancers, its role and molecular mechanism in acute myeloid leukemia (AML) remain unclear. Methods: The expression of RAET1K and miR-503-5p in bone marrow tissues and cell lines was detected by qRT-PCR. Cell proliferation was evaluated by cell counting kit-8 and 5-ethynyl-20-deoxyuridine (EdU) staining assay. Cell invasion and migration were detected by transwell assay. Cell apoptosis was evaluated by flow cytometry. The relationship between RAET1K and miR-503-5p, as well as miR-503-5p and INPP4B, was determined by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. In addition, the tumorigenesis of leukemia cells was evaluated by using a xenograft mouse model in vivo. Results: RAET1K was significantly upregulated and miR-503-5p was markedly downregulated in bone marrow tissues and cell lines (HL-60 and THP-1). Silencing of RAET1K (si-RAET1K) and overexpression of miR-503-5p inhibited cell proliferation, migration, and invasion but promoted apoptosis of HL-60 and THP-1 cells. RAET1K functioned as a sponge of miR-503-5p, and miR-503-5p inhibitor obviously attenuated the effect of si-RAET1K on AML progression in vitro. INPP4B was identified as a target of miR-503-5p, and INPP4B overexpression obviously reversed the effect of miR-503-5p mimics on cell proliferation, migration, invasion, and apoptosis of HL-60 and THP-1 cells in vitro. Knockdown of RAET1K effectively inhibited the tumorigenesis of leukemia cells in vivo. Conclusion: Our results demonstrated that RAET1K/miR-503-5p/INPP4B axis contributed to AML progression, suggesting that RAET1K might be a potential target for the treatment of AML. [ABSTRACT FROM AUTHOR]

What is known and objective: Hypofibrinogenaemia is major treatment‐related adverse event associated with tigecycline therapy, which in some cases can result in treatment termination. We aimed to identify the risk factors for tigecycline‐induced hypofibrinogenaemia. Methods: We retrospectively retrieved 426 Chinese patients who were undergoing tigecycline therapy ≥ 3 days. Results and discussion: There were 426 patients treated with tigecycline. The mean age was 60.31 ± 19.23 years, and 299 (70.19%) patients were male. Of the patients, 50.5% developed hypofibrinogenaemia and 10.1% of patients developed bleeding. Compared with before treatment, fibrinogen (FIB) significantly decreased after tigecycline was used while prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) significantly increased (all P <.001). There was no statistically significant difference in platelet count, hepatic function, and renal function before and after tigecycline treatment (all P >.05). In analysing relevant risk factors, extension of the tigecycline treatment course was found to be the main risk factor for tigecycline‐induced hypofibrinogenaemia. Regardless of whether patients received the standard dose or high dose of tigecycline, the long treatment course group (>14 days) had more patients with hypofibrinogenaemia than the routine treatment course group (52.21% vs 40.74%, 48.81% vs 19.44%, all P <.05). Renal failure (whether requiring or not requiring dialysis) is also a risk factor for tigecycline‐induced hypofibrinogenaemia (OR [95% CI]: 2.450 [1.335‐4.496]). What is new and conclusion: Tigecycline administration has been related to hypofibrinogenaemia, especially patients with renal failure and when long treatment course of tigecycline are used. We recommend that coagulation function be closely monitored in patients with the aforementioned risk factors for tigecycline‐induced hypofibrinogenaemia to ensure patient safety. [ABSTRACT FROM AUTHOR]

Background: The dysregulation of gut microbiota is pivotal in colorectal carcinogenesis. Meanwhile, altered gut microbiome may affect the development of intestinal diseases through interaction with the host genes. However, the synergy between the altered gut microbiota composition and differential expression of specific genes in colorectal cancer (CRC) remains elusive. Thus, we integrated the data from 16S rRNA gene sequences and RNA sequences to investigate the potential relationship between genes and gut microbes in patients with CRC. Results: Compared with normal samples, the presence of Proteobacteria and Fusobacteria increased considerably in CRC samples; conversely, the abundance of Firmicutes and Spirochaetes decreased markedly. In particular, the genera Fusobacterium, Catenibacterium, and Shewanella were only detected in tumor samples. Meanwhile, a closely interaction between Butyricimonas and Clostridium was observed in the microbiome network. Furthermore, a total of 246 (differentially expressed genes) DEGs were identified between tumor and normal tissues. Both DEGs and microbiota were involved in bile secretion and steroid hormone biosynthesis pathways. Finally, genes like cytochrome P450 family 3 subfamily A member 4 (CYP3A4) and ATP binding cassette subfamily G member 2 (ABCG2) enriched in these two pathways were connected with the prognosis of CRC, and CRC patients with low expression level of CYP3A4 and ABCG2 had longer survival time. Conclusion: Identifying the complicated interaction between gut microbiota and the DEGs contributed to further understand the pathogenesis of CRC, and these findings might enable better diagnosis and treatment of CRC patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation demonstrate only a median progression-free survival (PFS) of 8 to 10 months and undergo EGFR tyrosine kinase inhibitors (EGFR-TKIs) therapy. For decades, bilirubin has been reported to be associated with the onset and prognosis of lung cancer as a prooxidant. This study aimed to investigate the prediction of pretreatment circulating bilirubin for PFS in lung adenocarcinoma (LAC) patients who underwent EGFR-TKIs targeted therapy. Patients and Methods: LAC cases diagnosed and undergone EGFR-TKIs targeted therapy at The First Affiliated Hospital of Zhengzhou University between 2013 and 2015 were retrospectively reviewed. A total of 180 patients were studied according to inclusion and exclusion criteria. Follow-up data were collected for all patients until the disease progressed. Results: Univariate analysis showed that the levels of pretreatment total bilirubin (TBIL), indirect bilirubin (IBIL) and direct bilirubin (DBIL) were related to PFS (all p< 0.05). Considering the close relationship among the three factors, we combined TBIL, IBIL and DBIL into one total factor, which is called bilirubin. Kaplan–Meier survival curves and Log rank tests indicated that patients with lower bilirubin levels had a shorter median PFS than those with higher bilirubin levels (8 vs. 15 months; p= 0.002). Multivariate analysis demonstrated that pretreatment bilirubin is an independent prognostic factor (HR=0.454, CI: 0.267– 0.773, p= 0.004). Conclusion: This study confirms that bilirubin can predict the prognosis of LAC patients who had undergone EGFR-TKIs targeted therapy. [ABSTRACT FROM AUTHOR]