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Some citrus orchards in China often experience nitrogen (N) deficiency. For the first time, targeted metabolomics was used to examine N-deficient effects on hormones in sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) leaves and roots. The purpose was to validate the hypothesis that hormones play a role in N deficiency tolerance by regulating root/shoot dry weight ratio (R/S), root system architecture (RSA), and leaf and root senescence. N deficiency-induced decreases in gibberellins and indole-3-acetic acid (IAA) levels and increases in cis(+)-12-oxophytodienoic acid (OPDA) levels, ethylene production, and salicylic acid (SA) biosynthesis might contribute to reduced growth and accelerated senescence in leaves. The increased ethylene formation in N-deficient leaves might be caused by increased 1-aminocyclopropanecarboxylic acid and OPDA and decreased abscisic acid (ABA). N deficiency increased R/S, altered RSA, and delayed root senescence by lowering cytokinins, jasmonic acid, OPDA, and ABA levels and ethylene and SA biosynthesis, increasing 5-deoxystrigol levels, and maintaining IAA and gibberellin homeostasis. The unchanged IAA concentration in N-deficient roots involved increased leaf-to-root IAA transport. The different responses of leaf and root hormones to N deficiency might be involved in the regulation of R/S, RSA, and leaf and root senescence, thus improving N use efficiency, N remobilization efficiency, and the ability to acquire N, and hence conferring N deficiency tolerance. [ABSTRACT FROM AUTHOR]

Several studies have confirmed that the pathophysiological progression of Alzheimer's disease (AD) is closely related to changes in the intestinal microbiota; thus, modifying the intestinal microbiota has emerged as a new way to treat AD. Effective interventions for gut microbiota include the application of probiotics and other measures such as fecal microbiota transplantation (FMT). However, the application of probiotics ignores that the intestine is a complete microecosystem with competition among microorganisms. FMT also has issues when applied to patient treatment. In a previous study, we found that eight species of bacteria that are isolated with high frequency in the normal intestinal microbiota (i.e., intestinal dominant microbiota) have biological activities consistent with the effects of FMT. In this article, we confirmed that the treatment of intestinal dominant microbiota significantly restored intestinal microbiota abundance and composition to normal levels in APP/PS1 mice; downregulated brain tissue pro-inflammatory cytokines (IL-1β and IL-6) and amyloid precursor protein (APP) and β-site APP cleavage enzyme 1 (BACE1) expression levels; and reduced the area of Aβ plaque deposition in the brain hippocampus. Our study provides a new therapeutic concept for the treatment of AD, adjusting the intestinal microecological balance through dominant intestinal microbiota may be an alternative to FMT. [ABSTRACT FROM AUTHOR]

Citrus sinensis seedlings were supplied with a nutrient solution containing 15 (control) or 0 (nitrogen (N) deficiency) mM N for 10 weeks. Extensive metabolic and gene reprogramming occurred in 0 mM N-treated roots (RN0) to cope with N deficiency, including: (a) enhancing the ability to keep phosphate homeostasis by elevating the abundances of metabolites containing phosphorus and the compartmentation of phosphate in plastids, and/or downregulating low-phosphate-inducible genes; (b) improving the ability to keep N homeostasis by lowering the levels of metabolites containing N but not phosphorus, upregulating N compound degradation, the root/shoot ratio, and the expression of genes involved in N uptake, and resulting in transitions from N-rich alkaloids to carbon (C)-rich phenylpropanoids and phenolic compounds (excluding indole alkaloids) and from N-rich amino acids to C-rich carbohydrates and organic acids; (c) upregulating the ability to maintain energy homeostasis by increasing energy production (tricarboxylic acid cycle, glycolysis/gluconeogenesis, oxidative phosphorylation, and ATP biosynthetic process) and decreasing energy utilization for amino acid and protein biosynthesis and new root building; (d) elevating the transmembrane transport of metabolites, thus enhancing the remobilization and recycling of useful compounds; and (e) activating protein processing in the endoplasmic reticulum. RN0 had a higher ability to detoxify reactive oxygen species and aldehydes, thus protecting RN0 against oxidative injury and delaying root senescence. [ABSTRACT FROM AUTHOR]

Pedogenetic features of the soils could be a proxy for revealing the landform surface processes. Our work first analyzed the particle size distributions and lithological discontinuities (LDs) of the soils in the midstream of the Zoushui River, central Taiwan. The results showed that the parental materials of the soils derive from mixed sediments of the Zoushui River and its tributaries, and the LDs of some soils suggested multi-depositional events with homogeneous lithology. Then, we proposed a soil chronosequence of Inceptisols, Ultisols, and Oxisols, over the Pleistocene timescale. There was a very well-defined semilogarithmic relationship between weighted profile development index (WPDI) values and soil age with correlation coefficients (r) greater than 0.9. The age of the soils did not certainly agree with the interglacials of the main marine isotope stage (MIS). However, the soils started to develop only after being aggraded by relatively warm and humid periods or by extreme rain events in cool and dry periods. Irrespective of whether the soils had started to develop, tectonic downcutting, providing clear altitudinal separation of the terrace treads, could inevitably happen later (or almost synchronologically) to ensure stabilities of the tread surfaces. [ABSTRACT FROM AUTHOR]

The conversion of skeletal muscle fiber from fast-twitch to slow-twitch is crucial for sustained contractile and stretchable events, energy homeostasis, and anti-fatigue ability. The purpose of our study was to explore the mechanism and effects of garcinol on the regulation of skeletal muscle fiber type transformation. Forty 21-day-old male C57/BL6J mice (n = 10/diet) were fed a control diet or a control diet plus garcinol at 100 mg/kg (Low Gar), 300 mg/kg (Mid Gar), or 500 mg/kg (High Gar) for 12 weeks. The tibialis anterior (TA) and soleus muscles were collected for protein and immunoprecipitation analyses. Dietary garcinol significantly downregulated (p < 0.05) fast myosin heavy chain (MyHC) expression and upregulated (p < 0.05) slow MyHC expression in the TA and soleus muscles. Garcinol significantly increased (p < 0.05) the activity of peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) and markedly decreased (p < 0.05) the acetylation of PGC-1α. In vitro and in vivo experiments showed that garcinol decreased (p < 0.05) lactate dehydrogenase activity and increased (p < 0.05) the activities of malate dehydrogenase and succinic dehydrogenase. In addition, the results of C2C12 myotubes showed that garcinol treatment increased (p < 0.05) the transformation of glycolytic muscle fiber to oxidative muscle fiber by 45.9%. Garcinol treatment and p300 interference reduced (p < 0.05) the expression of fast MyHC but increased (p < 0.05) the expression of slow MyHC in vitro. Moreover, the acetylation of PGC-1α was significantly decreased (p < 0.05). Garcinol promotes the transformation of skeletal muscle fibers from the fast-glycolytic type to the slow-oxidative type through the p300/PGC-1α signaling pathway in C2C12 myotubes. [ABSTRACT FROM AUTHOR]

Sex-related differences among comorbid conditions associated with surgical site infection (SSI) after total knee arthroplasty (TKA) are unclear. This population-based cohort study used a novel approach with a Phecode system to evaluate preoperative clinical phenotypes (i.e., comorbid conditions) associated with SSI after TKA and delineate sex-related differences in phenotypes. Using the Taiwan National Health Insurance Research Database (2014–2018), 83,870 patients who underwent TKA were identified. Demographic and SSI data during the 90-day postoperative follow-up were obtained. Comorbidities identified by the International Classification of Diseases within 1 year before TKA were recorded and mapped into Phecodes representing phenotypes. The overall rate of 90-day SSI was 1.3%. In total, 1663 phenotypes were identified among 83,870 patients—1585 and 1458 phenotypes for female (n = 62,018) and male (n = 21,852) patients, respectively. According to multivariate logistic regression analysis, the SSI odds ratio significantly increased with the presence of each of the 16 phenotypes. Subgroup analysis revealed that the presence of 10 and 4 phenotypes significantly increased SSI risk in both sexes; only one phenotype was common to both sexes. Therefore, comorbid conditions and sex should be considered in preoperative SSI risk evaluation in patients undergoing primary TKA. These findings provide new perspectives on susceptibility, prevention, and treatment in these patients. [ABSTRACT FROM AUTHOR]

Allergic respiratory disease is a worldwide and increasingly prevalent health problem. Many researchers have identified complex changes in the microbiota of the respiratory and intestinal tracts in patients with allergic respiratory diseases. These affect immune response and influence the progression of disease. However, the diversity of bacterial changes in such cases make it difficult to identify a specific microorganism to target for adjustment. Recent research evidence suggests that common bacterial variations present in allergic respiratory disease are associated with immune disorders. This finding could lead to the discovery of potential therapeutic targets in cases of allergic respiratory disease. In this review, we summarize current knowledge of bacteria changes in cases of allergic respiratory disease, to identify changes commonly associated with immune disorders, and thus provide a theoretical basis for targeting therapies of allergic respiratory disease through effective modulation of key bacteria. [ABSTRACT FROM AUTHOR]

Wear-resistant Cu-Zr-Al-Ag-Co amorphous coatings were fabricated by high-velocity air-fuel spray technology using (Cu43Zr47Al7Ag3)99.5Co0.5 powder at different temperatures (i.e., 645, 725, and 805 K). The feedstock powders (98.6 wt.% amorphous phase) were produced by a gas atomization method. Thermal properties and microstructure of the powders and the coatings were comparably investigated by differential scanning calorimeter, scanning electron microscope, and transmission electron microscopy techniques. Wear properties were studied by a dry sliding wear tester under the linear reciprocating sliding in a ball-on-plate mode using a GCr15 ball as the counterpart at room temperature in air. A large fraction of amorphous phase (~67.5 wt.%) and crystalline phases (ZrO2, Al2.5Cu0.5Zr, and AlZr3) are found in the coating fabricated at a temperature (725 K) between the glass transition temperature (Tg) and the onset crystallization temperature (Tx). In addition, the coating also exhibits the highest Vickers hardness (554 HV0.1), bonding strength (59.3 MPa), a relatively low porosity (1.65%), and superior wear resistance. The wear mechanism of the coating is primarily abrasive wear and slight adhesive wear. [ABSTRACT FROM AUTHOR]

An Al86Ni6Y4.5Co2La1.5 amorphous coating was prepared on a ZM5 magnesium alloys substrate by using high-velocity air fuel (HVAF) spray. The coating contained a 75.8% amorphous phase (volume fraction) in addition to the crystallization phases of α-Al, Al4NiY, and Al9Ni5Y3. The microhardness reached 420 HV0.05 for the coating. The coating could endure 500 h neutral salt spray tests without apparent corrosion. Moreover, the coating exhibited a much nobler corrosion potential and two orders of magnitude smaller corrosion current density compared to the substrate. These improvements can be attributed to the compact coating structure and the passive film formed during corrosion. [ABSTRACT FROM AUTHOR]

Five new oleanane-type saponins, named ligushicosides A-E, and three known oleanane-type saponins were isolated from the roots of Ligulariopsis shichuana. Their structures were established by a combination of spectroscopic techniques, including 1D and 2D NMR and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Furthermore, all isolates were evaluated for their yeast α-glucosidase inhibitory effects and exhibited potent inhibition against α-glucosidase, while compounds 1 and 2 showed excellent inhibitory activities. The 3-O-glycoside moiety in oleanane-type saponin is important for the α-glucosidase inhibitory effects. [ABSTRACT FROM AUTHOR]

Clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is highly expressed in cancer, and is a selective killing ligand for oral cancer. Signaling proteins in the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt), Sonic hedgehog (SHH), and transforming growth factor β (TGFβ) pathways may regulate cell proliferation, migration, and apoptosis. Accordingly, the genes encoding these signaling proteins are potential targets for oral cancer therapy. In this review, we focus on recent advances in targeting therapies for oral cancer and discuss the gene targets within TRAIL, Wnt, SHH, and TGFβ signaling for oral cancer therapies. Oncogenic microRNAs (miRNAs) and tumor suppressor miRNAs targeting the genes encoding these signaling proteins are summarized, and the interactions between Wnt, SHH, TGFβ, and miRNAs are interpreted. With suitable combination treatments, synergistic effects are expected to improve targeting therapies for oral cancer. [ABSTRACT FROM AUTHOR]

In the current study, two new flavones, 4'-O-geranyltricin (1) and 3'-O-geranylpolloin (2), and a new 2-(2-phenylethyl)-4H-chromen-4-one derivative, 7-hydroxyl-6- methoxy-2-(2-phenylethyl)chromone (3), have been isolated from the stem barks of A. sinensis, together with 21 known compounds 4-24. The structures of new compounds 1-3 were determined through spectroscopic and MS analyses. Compounds 2, 3, 5, 6, and 8-10 exhibited inhibition (IC50 ≤ 12.51 μM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 3, 6, 8, 10, and 19 inhibited fMLP/CB-induced elastase release with IC50 values ≤ 15.25 μM. This investigation reveals bioactive isolates (especially 2, 3, 5, 6, 8, 9, 10, and 19) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases. [ABSTRACT FROM AUTHOR]

The fruit of Cnidium monnieri is commercially used as healthcare products for the improvement of impotence and skin diseases. Three new coumarins, 3'-O-methylmurraol (1), rel-(1'S,2'S)-1'-O-methylphlojodicarpin (2), and (1'S,2'S)-1'-O-methylvaginol (3), have been isolated from the fruits of C. monnieri, together with 14 known compounds (4-17). The structures of these new compounds were determined through spectroscopic and MS analyses. Compounds 1, 4-12, and 14-17 exhibited inhibition (IC50 = 7.31 µg/mL) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-LOPEN leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 7, 9-11, 15, and 17 inhibited fMLP/CB-induced elastase release with IC50 values =7.83 µg/mL. This investigation reveals that bioactive isolates (especially 6, 7, 14, and 17) could be further developed as potential candidates for the treatment or prevention of various inflammatory diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is the leading cause of cancer-related death worldwide as patients are burdened with incredibly poor prognosis. Low survival rates are primarily attributed to lack of early detection and, therefore, timely therapeutic interventions. Late diagnosis is essentially caused by absent and non-specific symptoms, and compounded by inadequate diagnostic tools. We show here that a lung cancer biomarker, based on a simple blood test, might provide promising advantages for diagnostic assessment. Small extracellular vesicles (sEVs) are miniscule messengers that carry cancer biomarkers and are easily detected in the blood. We identify that the abundance of a specific micro-RNA, miR-3182, in these sEVs can be detected in the blood of lung cancer patients but not in controls with benign lung conditions. This demonstrates the potential use of miR-3182 as a biomarker for lung cancer diagnosis. With five-year survival rates as low as 3%, lung cancer is the most common cause of cancer-related mortality worldwide. The severity of the disease at presentation is accredited to the lack of early detection capacities, resulting in the reliance on low-throughput diagnostic measures, such as tissue biopsy and imaging. Interest in the development and use of liquid biopsies has risen, due to non-invasive sample collection, and the depth of information it can provide on a disease. Small extracellular vesicles (sEVs) as viable liquid biopsies are of particular interest due to their potential as cancer biomarkers. To validate the use of sEVs as cancer biomarkers, we characterised cancer sEVs using miRNA sequencing analysis. We found that miRNA-3182 was highly enriched in sEVs derived from the blood of patients with invasive breast carcinoma and NSCLC. The enrichment of sEV miR-3182 was confirmed in oncogenic, transformed lung cells in comparison to isogenic, untransformed lung cells. Most importantly, miR-3182 can successfully distinguish early-stage NSCLC patients from those with benign lung conditions. Therefore, miR-3182 provides potential to be used for the detection of NSCLC in blood samples, which could result in earlier therapy and thus improved outcomes and survival for patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite curative resection, high recurrence of HCC remains a big threat, leading to poor patient outcomes. Hepatitis B virus (HBV) pre-S mutants, which harbor deletions over pre-S1 and pre-S2 gene segments of large surface proteins, have been implicated in HCC recurrence. Therefore, a reliable approach for detection of pre-S mutants is urgently needed for predicting HCC recurrence to improve patient survival. In this study, we used a next-generation sequencing (NGS)-based platform for quantitative detection of pre-S mutants in the plasma of HBV-related HCC patients and evaluated their prognostic values in HCC recurrence. We demonstrated that the presence of deletions spanning the pre-S2 gene segment and the high percentage of pre-S2 plus pre-S1 + pre-S2 deletions, either alone or in combination, was significantly and independently associated with poor recurrence-free survival and had greater prognostic performance than other clinicopathological and viral factors in predicting HCC recurrence. Our data suggest that the NGS-based quantitative detection of pre-S mutants in plasma represents a promising approach for identifying patients at high risk for HBV-related HCC recurrence after surgical resection in a noninvasive manner. [ABSTRACT FROM AUTHOR]

To maintain sustainability and availability of regional water resources, appropriate integrated water resource management (IWRM) should be based on an assessment of water resource background and responses to regional development and utilization policies. The study proposed an assessment method combining hydrological variation analysis with a system dynamics (SD) model to support IWRM in the Baiyangdian Region, Northern China. Integrated variation analysis and attributive analysis were used to identify variation time and causes of runoff. Then, based on the current water resource situation, an accessibility analysis examined the possibility of achieving a water resources supply and demand balance of social economic development and the ecological environment within individual internal management. Finally, an SD model simulated water resource response to development policies to predict future policy impacts. Results showed that 65.18% of the impact on runoff was from human activities. Sustainability goals were impossible through internal management, but with eco-migration policies and 1 × 108 m3 inter-basin transferred water, it could quickly be achieved, and water ecosystem function could also be recovered. Establishment of the Xiong'an New Area necessitated introduction of integrated cross-basin management to protect the Baiyangdian Region from degradation of its ecological function. Our study proposed a new method for comparation of internal and cross-basin IWRM. [ABSTRACT FROM AUTHOR]

Hypertension development with an increased intake of added sugar, especially excessive fructose intake, was shown in the National Health and Nutrition Examination Survey (NHANES) data. However, the mechanism underlying blood pressure (BP) elevation with increased fructose intake is still unclear. First, the present study showed that in rats fed 10% fructose for one week, BP and fructose/glucose levels increased in the central and peripheral nervous system. Furthermore, increased fructose intake resulted in an upregulation of fructose concentration in the cerebrospinal fluid. Second, consumption of excess fructose increased serum triglycerides. However, the inhibition of triglyceride production did not mitigate sympathetic nerve hyperactivity, but contributed to an insignificant decrease in BP. Finally, increased fructose intake reduced nitric oxide (NO) levels in the nucleus tractus solitarii (NTS) and reduced baroreflex sensitivity within a week. Collectively, the data suggested that fructose intake reduced NO levels in the NTS and caused baroreflex dysfunction, which further stimulated sympathetic nerve activity and induced the development of high BP. [ABSTRACT FROM AUTHOR]

The Zhengchong gold deposit is located in the central segment of the Jiangnan Orogen in northeastern Hunan Province, South China. The host rocks of this deposit are the Neoproterozoic slates of the Lengjiaxi Group and granodiorite. The structures in the Zhengchong gold deposit are dominated by NE-trending reverse faults, which control the gold-bearing veins. The orebody consists of NE-trending laminated quartz veins and NW-trending quartz veins. The alteration styles include silicification, carbonatization, sulfidation, sericitization and chloritization. The Zhengchong gold mineralization can be divided into four stages: Quartz-pyrite (stage I), quartz-pyrite-arsenopyrite (stage II), quartz-polysulfide (stage III) and quartz-carbonate (stage IV). Three generations of hydrothermal pyrite were identified: Disseminated euhedral to subhedral cubes in altered wall-rock (PyI), euhedral to subhedral cubes inter-grown with arsenopyrite and tetrahedrite in quartz veins and wall-rock (PyII), and euhedral cubes with microinclusions (native gold, galena, sphalerite, chalcopyrite, tetrahedrite, and pyrrhotite) or metasomatic textures in sulfide-rich veins or veinlets (PyIII). PyII and PyIII are arsenian pyrite and represent the main Au-bearing minerals. PyI records the lowest concentrations of Au; PyII and PyIII record similar amounts of Au, Cu, Pb, Zn, and Bi, but PyIII is more enriched in Co, Ni, Te, and Se. The substitution of As, Se and Te for S and that of Co and Ni for Fe occurs by direct-ion exchange. Invisible gold is uniformly distributed within the arsenian pyrite, and visible gold fills microfractures in PyII or occurs as inclusions in PyIII. Co, Ni, Cu exhibit positive correlations with Au and a negative correlation between Au + Cu + Co + Ni and Fe reflect that Fe vacancies may have been a major cause of the precipitation of invisible Au and other metal elements in pyrite structure. There are systematic trace element differences between the three generations of pyrite (PyI, PyII, PyIII). The more Co, Ni and Se, Te substitution that occurred for Fe and S, respectively, the greater the increase in the Co/Ni ratio (<1) and the decrease in the Se/Te ratio (<10) in stage III, indicating that a more reduced, lower-temperature metamorphic hydrothermal fluid was present in stage III. [ABSTRACT FROM AUTHOR]

Five new oleanane-type saponins, named ligushicosides A-E, and three known oleanane-type saponins were isolated from the roots of Ligulariopsis shichuana . Their structures were established by a combination of spectroscopic techniques, including 1D and 2D NMR and high resolution electrospray ionization mass spectroscopy (HR-ESI-MS). Furthermore, all isolates were evaluated for their yeast α -glucosidase inhibitory effects and exhibited potent inhibition against α -glucosidase, while compounds 1 and 2 showed excellent inhibitory activities. The 3- O -glycoside moiety in oleanane-type saponin is important for the α -glucosidase inhibitory effects., Competing Interests: The authors declare no conflict of interest.