bluuebunny/crossref_metadata_2025 huggingface dataset:
Network pharmacology and molecular docking to explore Siraitia grosvenorii’s potential mechanism in preventing and treating proliferative diabetic retinopathy
Authors: Zhou Yehong , Shu Fuxing , Sarsaiya Surendra , Jiang Hu , Jiang Chengyan , Qu Tingnian , Wang Ruixia
Published: October 2022

Although Siraitia grosvenorii (abbreviated as S.g.) is frequently used to prevent and cure diabetes problems, the precise mechanism underlying its ability to do so remains unknown. Through network pharmacology and molecular docking techniques, we studied the early molecular mechanisms of S.g in the treating of proliferative diabetic retinopathy (PDR) in this study. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to screen the active compounds and related targets of S.g. Oral bioavailability (OB) 30% and drug likeness (DL) 0.18 were used as screening criteria. The active compounds without knowledge of a probable target were excluded. The Uniprot database included converted symbols for the associated targets. GEO2R was used to explore several genes related to PDR. Using jvenn web service to intersect targets of S.g and PDR. The Xiantao Academic Online website was used to examine the expression patterns of intersect targets in PDR samples. The STRING database was used to create a protein-protein interaction (PPI) network of intersecting targets. Cytoscape software was used to show the PPI network, MCODE software was used to evaluate the network’s core proteins, and CytoHubba software was used to extract the important networks of the top three targets. Omicshare platform carried a functional analysis using the Gene Ontology (GO) and pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Pymol, AutoDock Vina software, Schrödinger Software were used to conduct molecular docking experiments or pockets search on the top three targets. The results showed that 85 targets were matched to six active compounds of S.g. 18 intersect targets were found. Seven DEGs were up-regulated and eleven genes were down-regulated when these targets were divided into two groups. TNF, PTGS2, and CASP3 were the main targets, according to the PPI network. The intersect targets were mostly related to angiogenesis, cell proliferation, oxidative stress, inflammatory response, and metabolism. It was discovered that the core targets TNF, PTGS2, and CASP3 had various levels of affinity for their respective compounds. Interestingly, multiple good drug-forming pockets for CASP3 and PTGS2 targets were identified through Schrödinger software. In particular, six compounds bind to the top three core targets to inhibit IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Pathways in cancer and 14 other signaling pathways to inhibit inflammation, apoptosis, oxidative stress, arachidonic acid metabolism, and angiogenesis to prevent and treat PDR. The study’s findings, which served as a guide for the widespread use of S.g in PDR clinical practise, included multi-substances and targets of S.g to prevent and cure PDR.
Characterization of KLH-driven immune responses in clinical studies: A systematic review
Authors: Saghari Mahdi , Jansen Manon A. A. , Grievink Hendrika W. , Rissmann Robert , Moerland Matthijs
Published: October 2022

The pharmacological activity assessment of novel immunomodulatory drugs in early-stage drug development is challenging as healthy volunteers do not express relevant immune biomarkers. Alternatively, the immune system can be challenged with keyhole limpet hemocyanin (KLH), a suitable antigen for studying adaptive immune responses. This report systemically reviews the KLH challenge in clinical studies focusing on the characterization of the KLH-driven systemic and local immune responses, identification of the KLH-induced biomarkers, and the evaluation of the effect of pharmacological interventions and diseases on the KLH response. A systematic literature review was carried out in PubMed spanning from 1967 to 2022. The systemic humoral KLH responses could be characterized by ELISA after 3 weeks following immunization. For the systemic cellular and molecular immune responses multiple KLH immunizations and the use of novel techniques such as flow cytometry and ELISpot yield optimal results. The objective evaluation of dermal KLH rechallenge allows for more accurate and sensitive quantification of the local response compared to subjective scoring. For the local cellular and molecular assays after KLH dermal rechallenge we also advocate the use of multiple KLH immunizations. Furthermore, oral KLH feeding, age, physical activity, alcohol consumption, stress, as well as certain auto-immune diseases also play a role in the KLH-induced immune response. Importantly, based on the KLH challenges, the effect of (novel) immunomodulatory drugs could be demonstrated in healthy volunteers, providing valuable information for the clinical development of these compounds. This review underlines the value of KLH challenges in clinical studies, but also the need for standardized and well-controlled methodology to induce and evaluate KLH responses.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifierCRD42022335419
NG2/CSPG4 regulates cartilage degeneration during TMJ osteoarthritis
Authors: Reed David A. , Zhao Yan , Bagheri Varzaneh Mina , Shin Jun Soo , Rozynek Jacob , Miloro Michael , Han Michael
Published: October 2022

Changes in the mechanical homeostasis of the temporomandibular joint (TMJ) can lead to the initiation and progression of degenerative arthropathies such as osteoarthritis (OA). Cells sense and engage with their mechanical microenvironment through interactions with the extracellular matrix. In the mandibular condylar cartilage, the pericellular microenvironment is composed of type VI collagen. NG2/CSPG4 is a transmembrane proteoglycan that binds with type VI collagen and has been implicated in the cell stress response through mechanical loading-sensitive signaling networks including ERK 1/2. The objective of this study is to define the role of NG2/CSPG4 in the initiation and progression of TMJ OA and to determine if NG2/CSPG4 engages ERK 1/2 in a mechanical loading-dependent manner. In vivo, we induced TMJ OA in control and NG2/CSPG4 knockout mice using a surgical destabilization approach. In control mice, NG2/CSPG4 is depleted during the early stages of TMJ OA and NG2/CSPG4 knockout mice have more severe cartilage degeneration, elevated expression of key OA proteases, and suppression of OA matrix synthesis genes. In vitro, we characterized the transcriptome and protein from control and NG2/CSPG4 knockout cells and found significant dysregulation of the ERK 1/2 signaling axis. To characterize the mechanobiological response of NG2/CSPG4, we applied mechanical loads on cell-agarose-collagen scaffolds using a compression bioreactor and illustrated that NG2/CSPG4 knockout cells fail to mechanically activate ERK 1/2 and are associated with changes in the expression of the same key OA biomarkers measured in vivo. Together, these findings implicate NG2/CSPG4 in the mechanical homeostasis of TMJ cartilage and in the progression of degenerative arthropathies including OA.
A complex patchwork of magma bodies that fed the Bishop Tuff supereruption (Long Valley Caldera, CA, United States): Evidence from matrix glass major and trace-element compositions
Authors: Gualda Guilherme A. R. , Ghiorso Mark S. , Hurst Aaron A. , Allen Madeline C. , Bradshaw Richard W.
Published: October 2022

The geologic record reveals events in which enormous volumes (100–1000s of km3) of magma were erupted in a matter of days to months. Yet, the architecture of magmatic systems that feed supereruptions can only be investigated through the study of ancient systems. For more than 40 years, the Bishop Tuff (Long Valley, California) has been the archetypal example of a single, zoned magma body that fed a supereruption. Early-erupted material is pyroxene-free and crystal poor (< 20 wt%), presumably erupted from the upper parts of the magma body; late-erupted material is orthopyroxene and clinopyroxene-bearing, commonly more crystal rich (up to 30 wt% crystals), and presumably tapped magma from the lower portions of the magma body. Fe-Ti oxide compositions suggest higher crystallization temperatures for late-erupted magmas (as high as 820°C) than for early-erupted magmas (as low as 700°C). Pressures derived from major-element compositions of glass inclusions were used to suggest an alternative model of lateral juxtaposition of two main magma bodies—each one feeding early-erupted and late-erupted units. Yet, this interpretation has proven controversial. We present a large dataset of matrix glass compositions for 227 pumice clasts that span the stratigraphy of the deposit. We calculate crystallization pressures based on major-element glass compositions using rhyolite-MELTS geobarometry and crystallization temperatures based on Zr in glass using zircon-saturation geothermometry. Additionally, we apply the same methods to 1,538 major-element and 615 trace-element analyses from a dataset from the literature. The results overwhelmingly demonstrate that the variations in crystallization temperature and pressure are not consistent with vertical stratification of a single magma body. All crystallization pressures and temperatures are very similar, with modes of ∼150 MPa and ∼730°C. Our results support lateral juxtaposition of three main magma bodies. Magmas represented by smaller stratigraphic units crystallized at similar pressures as the main bodies, which suggests coexistence of larger and smaller magma bodies at the time of eruption. We compare our findings with results for other very large eruptions and supereruptions. We argue that supereruptions typically mobilize a complex patchwork of magma bodies that reside within specific levels of the crust. These eruptions reveal the architecture of the crust during moments of high abundance of eruptible magma, revealing crustal states that differ from what is inferred for magmatic systems currently present on Earth.
Mw ≥ 5 aftershocks of the 2008 Sichuan earthquake: Analysis of temporal variation of Omori Law p-value
Authors: Gupta Harsh K. , Rekapalli Rajesh
Published: October 2022

Strong to great earthquakes considerably weaken the structural strength of the subsurface strata and civil constructions. The occurrence of Mw ≥ 5 aftershocks further contributes to the loss of human lives and damage to property. Therefore, the estimate of the duration of such aftershocks occurring near a metropolitan area is of major concern. In a previous study (Gupta et al., 2008), aftershocks for the destructive Sichuan earthquake, China (12 May 2008 Mw 7.9) for 23 days were used to estimatep-value and it was proposed that the M ≥ 5 aftershocks may continue for 7 months. In the present study, we analyze aftershock activity of Mw≥ 5 for 2-year duration within an area of 300 km radius from the epicenter, using modified Omori Law, which is well-known for analyzing aftershock rate and duration. We compare our results with the duration of aftershocks estimated using the exponential scaling law for the M ≥ 5 aftershock duration for major to great Himalayan earthquakes. Our analysis suggests that a highp-value (>1) indicates a slow decay of aftershocks as observed. As thep-value changes with time, the estimates of the duration of the occurrence of aftershocks of M ≥ 5 may change. Using a dynamic approach, the data of the first 100 days has been used in this study and the duration of occurrence of Mw ≥ 5 earthquakes is estimated to be ∼300 days, which is found to be true. Our analysis suggests that the temporal variation of thep-value from the onset of the mainshock and the slope of its variation are the key elements in comprehending the duration of the occurrence of the aftershocks of a certain magnitude. We infer that a highp-value (p>1) after the main earthquake, indicates a longer duration of larger aftershocks, which has been found in the case of the Sichuan earthquake. Thep-value decreases with time, however, an intermittent increase in thep-value could be an indicator of an increased chance for the occurrence of a higher magnitude aftershock. The proposed dynamic approach to estimating temporalp-values may help in forecasting the occurrence of stronger aftershocks more effectively. We believe that this is the first time, where the temporal variation ofp-values is estimated and related to the occurrence of aftershocks.
Discovering hydrothermalism from Afar: In Situ methane instrumentation and change-point detection for decision-making
Authors: Preston Victoria , Flaspohler Genevieve , Kapit Jason , Pardis William , Youngs Sarah , Martocello Donald E. , Roy Nicholas , Girguis Peter R. , Wankel Scott D. , Michel Anna P. M.
Published: October 2022

Seafloor hydrothermalism plays a critical role in fundamental interactions between geochemical and biological processes in the deep ocean. A significant number of hydrothermal vents are hypothesized to exist, but many of these remain undiscovered due in part to the difficulty of detecting hydrothermalism using standard sensors on rosettes towed in the water column or robotic platforms performing surveys. Here, we use in situ methane sensors to complement standard sensing technology for hydrothermalism discovery and compare sensors on a towed rosette and an autonomous underwater vehicle (AUV) during a 17 km long transect in the Northern Guaymas Basin in the Gulf of California. This transect spatially intersected with a known hydrothermally active venting site. These data show that methane signalled possible hydrothermal-activity 1.5–3 km laterally (100–150 m vertically) from a known vent. Methane as a signal for hydrothermalism performed similarly to standard turbidity sensors (plume detection 2.2–3.3 km from reference source), and more sensitively and clearly than temperature, salinity, and oxygen instruments which readily respond to physical mixing in background seawater. We additionally introduce change-point detection algorithms—streaming cross-correlation and regime identification—as a means of real-time hydrothermalism discovery and discuss related data supervision technologies that could be used in planning, executing, and monitoring explorative surveys for hydrothermalism.
Physiological levels of adrenaline fail to stop pancreatic beta cell activity at unphysiologically high glucose levels
Authors: Sluga Nastja , Križančić Bombek Lidija , Kerčmar Jasmina , Sarikas Srdjan , Postić Sandra , Pfabe Johannes , Skelin Klemen Maša , Korošak Dean , Stožer Andraž , Slak Rupnik Marjan
Published: October 2022

Adrenaline inhibits insulin secretion from pancreatic beta cells to allow an organism to cover immediate energy needs by unlocking internal nutrient reserves. The stimulation of α2-adrenergic receptors on the plasma membrane of beta cells reduces their excitability and insulin secretion mostly through diminished cAMP production and downstream desensitization of late step(s) of exocytotic machinery to cytosolic Ca2+ concentration ([Ca2+]c). In most studies unphysiologically high adrenaline concentrations have been used to evaluate the role of adrenergic stimulation in pancreatic endocrine cells. Here we report the effect of physiological adrenaline levels on [Ca2+]c dynamics in beta cell collectives in mice pancreatic tissue slice preparation. We used confocal microscopy with a high spatial and temporal resolution to evaluate glucose-stimulated [Ca2+]c events and their sensitivity to adrenaline. We investigated glucose concentrations from 8-20 mM to assess the concentration of adrenaline that completely abolishes [Ca2+]c events. We show that 8 mM glucose stimulation of beta cell collectives is readily inhibited by the concentration of adrenaline available under physiological conditions, and that sequent stimulation with 12 mM glucose or forskolin in high nM range overrides this inhibition. Accordingly, 12 mM glucose stimulation required at least an order of magnitude higher adrenaline concentration above the physiological level to inhibit the activity. To conclude, higher glucose concentrations stimulate beta cell activity in a non-linear manner and beyond levels that could be inhibited with physiologically available plasma adrenaline concentration.
Myokines: Novel therapeutic targets for diabetic nephropathy
Authors: Yang Ming , Luo Shilu , Yang Jinfei , Chen Wei , He Liyu , Liu Di , Zhao Li , Wang Xi
Published: October 2022

With the increasing incidence of diabetic nephropathy (DN), there is an urgent need to find effective DN preventive and therapeutic modalities. It is widely believed that effective exercise is good for health. However, the beneficial role of exercise in kidney disease, especially in DN, and the underlying molecular mechanisms have rarely been reported. Muscle is not only an important motor organ but also an important endocrine organ, secreting a group of proteins called “myokines” into the blood circulation. Circulating myokines then move to various target organs to play different biological roles. In this review, we summarize the currently known myokines and the progress in research relating them to DN and discuss its potential as a therapeutic target for DN.
On airborne tire wear particles along roads with different traffic characteristics using passive sampling and optical microscopy, single particle SEM/EDX, and µ-ATR-FTIR analyses
Authors: Gao Zhiqiang , Cizdziel James V. , Wontor Kendall , Clisham Carly , Focia Kaylea , Rausch Juanita , Jaramillo-Vogel David
Published: October 2022

Tire wear particles (TWPs) are a major category of microplastic pollution produced by friction between tires and road surfaces. This non-exhaust particulate matter (PM) is transported through the air and with runoff leading to environmental pollution and health concerns. Here, we collected airborne PM along paved roads with different traffic volumes and speeds using Sigma-2 passive samplers. Particles entering the samplers deposit onto substrates for analysis, or, as we modified it, directly into small (60 ml) separatory funnels, which is particularly useful with high particle loads, where a density separation aids in isolating the microplastics. We quantified putative TWPs (∼10–80 µm) deposited on the substrates (primarily adhesive tape on glass slides) and in the funnels using stereomicroscopy. Putative TWP deposition rates (particles/cm2/day ± SD) at 5 m from the road were highest near a busy highway (324 ± 129), followed by a boulevard with moderate traffic (184 ± 93), and a slow traffic avenue (29 ± 7). We observed that deposition rates increased within proximity to the highway: 99 ± 54, 180 ± 88, and 340 ± 145 at 30, 15, and 5 m, respectively. We show that TWP abundances (i.e., deposition and mass concentration) increase with vehicle braking (driving behavior). We observed no differences (p > 0.05) between the separatory funnel and adhesive tape collection methods. In addition, we were able to obtain FTIR spectra of TWPs (>10 µm) using µ-ATR-FTIR. Both deserve further scrutiny as novel sampling and analytical approaches. In a separate sampling campaign, we differentiated 1438 particles (∼1–80 µm) deposited on boron substrates into TWP, metal, mineral, and biogenic/organic classes with single particle SEM/EDX analysis based on morpho-textural-chemical classification and machine learning. The results revealed similar concentration trends with traffic (high > moderate > low), with the distribution of particle sources alike for the highway and the moderate road: TWPs (∼38–39%) > biogenic (∼34–35%) > minerals (∼23–26%), and metallic particles (∼2–3%). The low traffic road yielded a much different distribution: biogenic (65%) > minerals (27%) > TWPs (7%) > metallic particles (1%). Overall, this work provides much-needed empirical data on airborne TWPs along different types of roads.
Impact of climate change shocks on economic growth: A new insight from non-linear analysis
Authors: Khurshid Nabila , Fiaz Asma , Khurshid Jamila , Ali Kashif
Published: October 2022

Despite the fact that Pakistan’s contribution to GHG emissions is low (0.8%) when compared to other countries but it is one of the hardest hit by climate change. The present study is an attempt to identify the impact of climate change on economic growth. The non-linear autoregressive distributional lag (NARDL) technique is used to estimate the asymmetric effect of climate change on the economic growth of Pakistan. Annual data covering the years 1980–2021 are used for empirical analysis. It is noteworthy to reiterate that CO2 emissions and mean temperature pose asymmetrical results concerning economic growth, both in the long-run and short-run. CO2_POS and CO2_NEG have a negative impact on economic growth, whereas MEANT_POS has a positive impact on economic growth and MEANT_NEG has a negative impact. Precipitation has a positive and significant long-term influence on economic growth. Research findings indicate that comprehensive mitigation policies at the nationwide and worldwide levels are required to limit human-caused climate change in Pakistan. At national level, tree planting projects and safeguard greenery at all costs while at international level, policies needed for adoption of mitigation strategies to control climate change.
Land use change and its effect on ecosystem services in an Oxisol of the eastern High Plains of meta department in Colombia
Authors: Moreno-Conn Lina M. , Rodríguez-Hernandez Nubia S. , Arguello José Orlando , Gallo Gordillo Oscar , Bernal-Riobo Jaime H. , Arango Miguel , Baquero José E.
Published: October 2022

Increasing cultivation on acid soils of Colombia’s Eastern High Plains in the Orinoquia region require crop management strategies that balance commercial and environmental interests. Previous research showed the effects of land preparation and management on certain aspects of ecosystem services of these acid soils. This research aimed to comprehensively evaluate the impact of use and soil management in a native savanna Oxisol converted to five production systems gaining traction among local farmers: Annual crops rotation–sugarcane (ACR-S); Annual crops rotation-maize-soybean (ACR-MS); Sugarcane monocrop (SM); Rubber associated with Desmodium ovalifollium (R-Do) as a cover crop; Pasture Brachiaria decumbens - Annual crops rotation (PBd-ACR) and native savanna (NS) as a control. The experimental design consisted of conditioning the soil with two doses of dolomitic lime and incorporating three tillage methods over 5 years. A Principal Components Analysis (PCA) constructed indicators of ecosystem services (ES), such as fertility, water regulation, macroinvertebrate diversity, climate control related to greenhouse gas emissions (GHG) and carbon stock. The indicator values were adjusted between 0.10 and 1.0. Physicochemical variables with the greatest statistical weight were identified for components 1 and 2 each year. The fertility indicator of the native savanna for year one had a low range with a value of 0.11 compared to the other systems (p ≤ 0.05). During the years two, three, and four, soil fertility increased in the PBd-ACR (0.51) production system compared to the other systems. PBd-ACR generally improved water supply, although with lower indicator values than ACR-MS and R-Do. PBd-ACR show high biodiversity for edaphic macroinvertebrates compared to other systems. Field measurements detected methane emissions only in the SM system. Oxisols changed with the introduction of crops. The positive and negative tradeoffs of production systems and their agronomic practices should be considered in agricultural development of these acid soils.
Rice-fish-duck system regulation of soil phosphorus fraction conversion and availability through organic carbon and phosphatase activity
Authors: Wang Chao , Yang Qiannan , Zhang Chi , Li Xiangdong , Chen Jing , Zhang Xiaolong , Chen Jinjie , Liu Kexue
Published: October 2022

Integrated ecological farming combines rice growing with aquaculture, and is an effective way to improve soil productivity by increasing soil nutrient supply. However, the long-term effects of such integrated farming on phosphorus fractions and phosphorus availability of paddy soils in the Pearl River Delta (PRD) remain unknown. A four-year field experiment compared the phosphorus fractions with paddy field in rice-fish-duck system (RFD), rice-vegetable cropping system (RVS) and conventional rice system (CRS) in the PRD. SOC and phosphorus fractions were significantly influenced by cropping systems. RFD significantly increased SOC and phosphorus in the soil. Soil phosphorus was dominated by moderately labile P (40.67–49.41%). RFD also significantly increased soil microbial biomass carbon, microbial biomass phosphorus, and acid phosphatase activity (ACP) by 67.68, 46.68, and 15.87% compared to RVS, and by 134.14, 65.99, and 30.20% compared to CRS, respectively. SOC and ACP were the primary factors influencing the conversion and effectiveness of soil phosphorus. The RFD can alleviate low phosphorus activity in PRD paddy soils through the combined effect of chemical and biological process, while promoting a sustainable soil nutrient cycle within the ecosystem and guiding the sustainable development of rational soil fertilization in the PRD.
Calculation of surface settlement and pile foundation deformation caused by shield machine tunnelling along curve section
Authors: Zeng Feng , Gao Yang , Chen Fujiang , He Qingqing , He Zhihao
Published: October 2022

The shield machine tunnelling along the curve section causes more disturbance to the surrounding environment than the straight section. Pile foundation is the most commonly used foundation form in high-rise buildings, and high-rise buildings have extremely high requirements for controlling non-uniform deformation. Therefore, it is necessary to study the surface settlement and the deformation law of pile foundations caused by shield machine tunnelling along the curve section. Considering the shield machine tunnelling factors along the curve section and the coupling effect of piles and soil, the analytical calculation formula of the ground settlement and the pile foundation deformation caused by the shield machine tunnelling along the curve section is deduced. According to the actual project situation, a finite difference model (FDM) is constructed, and the correctness of the FDM and analytical prediction formula is verified by comparing the on-site monitoring data. The research shows that the error among the FDM results, the analytical prediction results, and the on-site monitoring data are small, and the surface settlement and pile foundation deformation meet the construction control standards. The friction resistance of the shield shell, the integrative gap at the shield tail (IGST), and the over-cutting gap (OG) are the main factors leading to the surface settlement. However, the shield shell friction and OG are the main reasons leading to the inner settlement of the curve section being more prominent than the outer side. The difference in the pile foundation settlement on both sides of the curve section is slight, the maximum settlement difference rate is 1.8%, and the maximum horizontal deformation rate of the pile foundation on the inner and outer sides is 9.2%, which shows that the horizontal deformation of the pile foundation is more sensitive to the asymmetrically distributed construction factors.
Impact of soil types and root exudates on cadmium and petroleum hydrocarbon phytoremediation by Sorghum sudanense, Festuca arundinace, and Lolium perenne
Authors: He Mengfan , Li Zhongbao , Chen Cheng , Mei Ping
Published: October 2022

With the development of industrialization, soils around the world have been polluted by heavy metals and oil to different degrees in recent years, and soil remediation has become a global problem. Phytoremediation has a wide application prospect because of its environmental friendliness and easy availability of materials.

Objective

To explore the effects of soil types and root exudates on the removal of cadmium and petroleum hydrocarbon in soils.

Method

A pot experiments with three soil types (sandy, loamy and clayey) of the Changning-Weiyuan area of Sichuan province and three root exudates (citric acid, glycine, and maltose) were carried out using Sorghum sudanense (Piper) Stapf., Lolium perenne L., and Festuca arundinacea L. as test materials. Plants were grown in soils contaminated by cadmium and petroleum at different concentrations.

Result

The biomass of S. sudanense, the translocation ratio and removal rate of cadmium in S. sudanense decreased gradually with increasing soil cadmium concentration. The promotion effects of the three root exudates on S. sudanense were in the following order: citric acid > glycine > maltose. At the same cadmium pollution conditions, the biomass levels of S. sudanense in sandy, loamy, and clayey soils were in the following order: clayey soil > loamy soil > sandy soil. On the contrary, the concentration, translocation ratio, and removal rate of cadmium in S. sudanense grown in the different soils treated with root exudates were in the following order: sandy soil > loamy soil > clayey soil. Under the three soil conditions, the fresh weight of F. arundinacea (0.36 ~ 0.68 g) and S. sudanense (0.51 ~ 0.99 g) increased significantly (p < 0.05). The total petroleum hydrocarbons degradation efficiencies of F. arundinacea, L. perenne, and S. sudanense were high in sandy soil (34.27% ~ 60.52%). Changing the type of root exudate had a significant impact on the degradation of total petroleum hydrocarbons in sandy soil (p < 0.05).

Conclusion

This study showed that soil types impacted the accumulation of cadmium and petroleum in plants. Phytoremediation of cadmium and petroleum contaminated soil could be enhanced by the application of root exudates. This study recommend that the method is suitable for field remediation of soils contaminated with mild cadmium and petroleum hydrocarbons.
Soil pyrogenic carbon in southern Amazonia: Interaction between soil, climate, and above-ground biomass
Authors: de Oliveira Edmar Almeida , Feldpausch Ted R. , Marimon Beatriz Schwantes , Morandi Paulo Sérgio , Phillips Oliver L. , Bird Michael , Murakami Alejandro Araujo , Arroyo Luzmila , Quesada Carlos Alberta , Marimon-Junior Ben Hur
Published: October 2022

The Amazon forest represents one of the world’s largest terrestrial carbon reservoirs. Here, we evaluated the role of soil texture, climate, vegetation, and distance to savanna on the distribution and stocks of soil pyrogenic carbon (PyC) in intact forests with no history of recent fire spanning the southern Amazonia forest-Cerrado Zone of Transition (ZOT). In 19 one hectare forest plots, including three Amazonian Dark Earth (ADE, terra preta) sites with high soil PyC, we measured all trees and lianas with diameter ≥ 10 cm and analyzed soil physicochemical properties, including texture and PyC stocks. We quantified PyC stocks as a proportion of total organic carbon using hydrogen pyrolysis. We used multiple linear regression and variance partitioning to determine which variables best explain soil PyC variation. For all forests combined, soil PyC stocks ranged between 0.9 and 6.8 Mg/ha to 30 cm depth (mean 2.3 ± 1.5 Mg/ha) and PyC, on average, represented 4.3% of the total soil organic carbon (SOC). The most parsimonious model (based on AICc) included soil clay content and above-ground biomass (AGB) as the main predictors, explaining 71% of soil PyC variation. After removal of the ADE plots, PyC stocks ranged between 0.9 and 3.8 Mg/ha (mean 1.9 ± 0.8 Mg/ha–1) and PyC continued to represent ∼4% of the total SOC. The most parsimonious models without ADE included AGB and sand as the best predictors, with sand and PyC having an inverse relationship, and sand explaining 65% of the soil PyC variation. Partial regression analysis did not identify any of the components (climatic, environmental, and edaphic), pure or shared, as important in explaining soil PyC variation with or without ADE plots. We observed a substantial amount of soil PyC, even excluding ADE forests; however, contrary to expectations, soil PyC stocks were not higher nearer to the fire-dependent Cerrado than more humid regions of Amazonia. Our findings that soil texture and AGB explain the distribution and amount of soil PyC in ZOT forests will help to improve model estimates of SOC change with further climatic warming.
Diagnostic accuracy of circulating free DNA testing for the detection of KRAS mutations in non-small cell lung cancer: A systematic review and meta-analysis
Authors: Palmieri Maria , Zulato Elisabetta , Wahl Sissel Gyrid Freim , Guibert Nicolas , Frullanti Elisa
Published: October 2022

Kirsten rat sarcoma viral oncogene homolog (KRAS) gene encodes a GTPase that acts as a molecular switch for intracellular signal transduction, promoting cell growth and proliferation. Mutations in the KRAS gene represent important biomarkers for NSCLC targeted therapy. However, detection of KRAS mutations in tissues has shown some limitations. During the last years, analyses of circulating free DNA (cfDNA) has emerged as an alternative and minimally invasive, approach to investigate tumor molecular changes. Here, we assessed the diagnostic performance of cfDNA analysis, compared to tissues through a meta-analysis and systematic review of existing literature. From 561 candidate papers, we finally identified 40 studies, including 2,805 NSCLC patients. We extracted values relating to the number of true-positive, false-positive, false-negative, and true-negative. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio, each with 95% CI, were calculated. A summary receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the overall diagnostic performance. The pooled sensitivity was 0.71 (95% CI 0.68–0.74) and the specificity was 0.93 (95% CI 0.92–0.94). The diagnostic odds ratio was 35.24 (95% CI 24.88–49.91) and the area under the curve was 0.92 (SE = 0.094). These results provide evidence that detection of KRAS mutation using cfDNA testing is of adequate diagnostic accuracy thus offering to the clinicians a new promising screening test for NSCLC patients.
An integrative analysis of the lncRNA-miRNA-mRNA competitive endogenous RNA network reveals potential mechanisms in the murine hair follicle cycle
Authors: Ding Yuxin , Chen Yuhong , Yang Xiaoshuang , Xu Piaopiao , Jing Jing , Miao Yujie , Mao Meiqi , Xu Jiali , Wu Xianjie , Lu Zhongfa
Published: October 2022

Alopecia is a common progressive disorder associated with abnormalities of the hair follicle cycle. Hair follicles undergo cyclic phases of hair growth (anagen), regression (catagen), and rest (telogen), which are precisely regulated by various mechanisms. However, the specific mechanism associated with hair follicle cycling, which includes noncoding RNAs and regulation of competitive endogenous RNA (ceRNA) network, is still unclear. We obtained data from publicly available databases and performed real-time quantitative polymerase chain reaction validations. These analyses revealed an increase in the expression of miRNAs and a decrease in the expression of target mRNAs and lncRNAs from the anagen to telogen phase of the murine hair follicle cycle. Subsequently, we constructed the ceRNA networks and investigated their functions using enrichment analysis. Furthermore, the androgenetic alopecia (AGA) microarray data analysis revealed that several novel alopecia-related genes were identified in the ceRNA networks. Lastly, GSPT1 expression was detected using immunohistochemistry. Our analysis revealed 11 miRNAs (miR-148a-3p, miR-146a-5p, miR-200a-3p, miR-30e-5p, miR-30a-5p, miR-27a-3p, miR-143-3p, miR-27b-3p, miR-126a-3p, miR-378a-3p, and miR-22-3p), 9 target mRNAs (Atp6v1a, Cdkn1a, Gadd45a, Gspt1, Mafb, Mitf, Notch1, Plk2, and Slc7a5), and 2 target lncRNAs (Neat1 and Tug1) were differentially expressed in hair follicle cycling. The ceRNA networks were made of 12 interactive miRNA-mRNA pairs and 13 miRNA-lncRNA pairs. The functional enrichment analysis revealed the enrichment of hair growth–related signaling pathways. Additionally, GSPT1 was downregulated in androgenetic alopecia patients, possibly associated with alopecia progression. The ceRNA network identified by our analysis could be involved in regulating the hair follicle cycle.
Transcriptomic profiling of Indian breast cancer patients revealed subtype-specific mRNA and lncRNA signatures
Authors: Manjunath Meghana , Nirgude Snehal , Mhatre Anisha , Vemuri Sai G. , Nataraj Mallika , Thumsi Jayanti , Choudhary Bibha
Published: October 2022

Breast cancer (BC) is one of the leading causes of cancer-associated death in women. Despite the progress in therapeutic regimen, resistance and recurrence of breast cancer have affected the overall survival of patients. The present signatures, such as PAM50 and Oncotype DX, do not segregate the Indian breast samples based on molecular subtypes. This study aims at finding signatures of long noncoding RNA (lncRNA) and mRNA in Indian breast cancer patients using RNA-seq. We have analyzed the survival based on the menopausal and hormone status of 380 Indian breast cancer patients, and of these, we have sequenced and analyzed matched tumor–normal transcriptome of 17 (pre- and postmenopausal) Indian breast cancer patients representing six different subtypes, namely, four patients in triple-positive, three patients in estrogen receptor–positive (ER+ve), three patients in estrogen and progesterone receptors–positive (ER+ve, PR+ve), two patients in human epidermal growth factor receptor (Her2+ve), three patients in triple-negative, and one patient in ER+ve and Her2+ve subtypes. We have identified a 25 mRNA–27 lncRNA gene set, which segregated the subtypes in our data. A pathway analysis of the differentially expressed genes revealed downregulated ECM interaction and upregulated immune regulation, cell cycle, DNA damage response and repair, and telomere elongation in premenopausal women. Postmenopausal women showed downregulated metabolism, innate immune system, upregulated translation, sumoylation, and AKT2 activation. A Kaplan–Meier survival analysis revealed that menopausal status, grade of the tumor, and hormonal status displayed statistically significant effects (p < 0.05) on the risk of mortality due to breast cancer. Her2+ve patients showed low overall survival. One of the unique lncRNA-mRNA pairs specific to the EP-subtype, SNHG12 and EPB41, showed interaction, which correlates with their expression level; SNHG12 is downregulated and EPB41 is upregulated in EP samples.
Case Report: Two cases of apparent discordance between non-invasive prenatal testing (NIPT) and amniocentesis resulting in feto-placental mosaicism of trisomy 21. Issues in diagnosis, investigation and counselling
Authors: Feresin Agnese , Stampalija Tamara , Cappellani Stefania , Bussani Rossana , Faletra Flavio , Murru Flora , Ulivi Sheila , Suergiu Sarah , Savarese Pasquale , Pedicini Antonio , Policicchio Margherita , Ruggiero Raffaella , Bosio Barbara , Savarese Giovanni , Ardisia Carmela
Published: October 2022

The sequencing of cell-free fetal DNA in the maternal plasma through non-invasive prenatal testing (NIPT) is an accurate genetic screening test to detect the most common fetal aneuploidies during pregnancy. The extensive use of NIPT, as a screening method, has highlighted the limits of the technique, including false positive and negative results. Feto-placental mosaicism is a challenging biological issue and is the most frequent cause of false positive and negative results in NIPT screening, and of discrepancy between NIPT and invasive test results. We are reporting on two cases of feto-placental mosaicism of trisomy 21, both with a low-risk NIPT result, identified by ultrasound signs and a subsequent amniocentesis consistent with a trisomy 21. In both cases, after the pregnancy termination, cytogenetic and/or cytogenomic analyses were performed on the placenta and fetal tissues, showing in the first case a mosaicism of trisomy 21 in both the placenta and the fetus, but a mosaicism in the placenta and a complete trisomy 21 in the fetus in the second case. These cases emphasize the need for accurate and complete pre-test NIPT counselling, as well as to identify situations at risk for a possible false negative NIPT result, which may underestimate a potential pathological condition, such as feto-placental mosaicism or fetal trisomy. Post-mortem molecular autopsy may discriminate between placental, fetal and feto-placental mosaicism, and between complete or mosaic fetal chromosomal anomalies. A multidisciplinary approach in counselling, as well as in the interpretation of biological events, is essential for the clarification of complex cases, such as feto-placental mosaicisms.
Akkermansia muciniphila: The state of the art, 18 years after its first discovery
Authors: Iwaza Rim , Wasfy Reham Magdy , Dubourg Grégory , Raoult Didier , Lagier Jean-Christophe
Published: October 2022

Akkermansia muciniphila (A. muciniphila) is an anaerobic, Gram negative and mucin-degrading bacterium of the phylum Verrucomicrobia isolated in 2004 from human feces. Although it is a common resident in the human intestinal tract, it has also been detected in other anatomical sites. Genomic studies have revealed that A. muciniphila can be divided into different phylogroups with distinct metabolic properties. There is growing evidence regarding its beneficial impact on human health. Indeed, A. muciniphila is considered as a promising next-generation probiotic for treating cancer and metabolic disorders. The large-scale production of A. muciniphila is, therefore, a challenge. Beside mucin-based medium, other culture strategies have enabled its isolation. The administration of both live and pasteurized forms of A. muciniphila has shown to be promising in animal models. Alternatively, the administration of various prebiotics has also been assessed for enhancing its abundance in the human gut. Future prospects include human clinical trials, some of which are currently ongoing. This paper provides an overview of what is currently known about A. muciniphila’s phenotypical and genotypic traits, as well as its culture techniques and its connections to a number of human diseases and its potential application as an effective next generation probiotic.
Comprehensive analysis of transient receptor potential channels-related signature for prognosis, tumor immune microenvironment, and treatment response of colorectal cancer
Authors: Wang Lei , Chen Xingte , Zhang Hejun , Hong Liang , Wang Jianchao , Shao Lingdong , Chen Gang , Wu Junxin
Published: October 2022

Background

Transient receptor potential channels (TRPC) play critical regulatory functions in cancer occurrence and progression. However, knowledge on its role in colorectal cancer (CRC) is limited. In addition, neoadjuvant treatment and immune checkpoint inhibitors (ICIs) have increasing roles in CRC management, but not all patients benefit from them. In this study, a TRPC related signature (TRPCRS) was constructed for prognosis, tumor immune microenvironment (TIME), and treatment response of CRC.

Methods

Data on CRC gene expression and clinical features were retrospectively collected from TCGA and GEO databases. Twenty-eight TRPC regulators (TRPCR) were retrieved using gene set enrichment analysis. Different TRPCR expression patterns were identified using non-negative matrix factorization for consensus clustering, and a TRPCRS was established using LASSO. The potential value of TRPCRS was assessed using functional enrichment analysis, tumor immune analysis, tumor somatic mutation analysis, and response to preoperative chemoradiotherapy or ICIs. Moreover, an external validation was conducted using rectal cancer samples that received preoperative chemoradiotherapy at Fujian Cancer Hospital (FJCH)viaqRT-PCR.

Results

Among 834 CRC samples in the TCGA and meta-GEO cohorts, two TRPCR expression patterns were identified, which were associated with various immune infiltrations. In addition, 266 intersected genes from 5564 differentially expressed genes (DEGs) between two TRPC subtypes, 4605 DEGs between tumor tissue and adjacent non-tumor tissue (all FDR< 0.05, adjusted P< 0.001), and 1329 prognostic related genes (P< 0.05) were identified to establish the TRPCRS, which was confirmed in the TCGA cohort, two cohorts from GEO, and one qRT-PCR cohort from FJCH. According to the current signature, the high-TRPC score group had higher expressions of PD-1, PD-L1, and CTLA4, lower TIDE score, and improved response to anti-PD-1 treatment with better predictive ability. Compared to the high-TRPC score group, the low-TRPC score group comprised an immunosuppressive phenotype with increased infiltration of neutrophils and activated MAPK signaling pathway, but was more sensitive to preoperative chemoradiotherapy and associated with improved prognosis

Conclusions

The current TRPCRS predicted the prognosis of CRC, evaluated the TIME in CRC, and anticipated the response to immune therapy and neoadjuvant treatment.
Prolactin promotes proliferation of germinal center B cells, formation of plasma cells, and elevated levels of IgG3 anti-dsDNA autoantibodies
Authors: Carreón-Talavera Ricardo , Santana-Sánchez Paola , Fuentes-Pananá Ezequiel Moisés , Legorreta-Haquet María Victoria , Chávez-Sánchez Luis , Gorocica-Rosete Patricia Sofia , Chávez-Rueda Adriana Karina
Published: October 2022

Systemic lupus erythematosus (SLE) mainly affects females at reproductive age, which has been associated with hormones, such as prolactin (PRL). Different studies suggest that PRL exacerbates the clinical manifestations of SLE both in patients and in mouse models (e.g., the MRL/lpr strain), increasing the production of autoantibodies, which can be deposited as immune complexes and trigger inflammation and damage to different tissues. The objective of this work was to explore the potential mechanisms by which PRL increases the concentration of self-reactive antibodies in the MRL/lpr SLE model. To this end, we determined the role of PRL on the activation and proliferation of germinal center B cells (B-GCs) and their differentiation into antibody-secreting cells (ASCs). We show that the absolute number and percentage of B-GCs were significantly increased by PRLin vivoor uponin vitrotreatment with anti-IgM and anti-CD40 antibodies and PRL. The augmented B-GC numbers correlated with enhanced proliferation, but we did not observe enhanced expression of CD80 and CD86 activation markers or the BCL6 transcription factor, arguing against a more effective differentiation. Nevertheless, we observed enhanced phosphorylation of STAT1, secretion of IL-6, expression of IRF4, numbers of ASCs, and levels of IgG3 antibodies directed against dsDNA. Altogether, these results support the hypothesis that a PRL-mediated expansion of B-GCs yields more self-reactive ASCs, potentially explaining the pathogenic immune complexes that steadily lead to tissue damage during SLE.