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Abstract Obsessive–compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors, with childhood trauma recognized as a contributing factor to its pathophysiology. This study aimed to delineate brain functional aberrations in OCD patients and explore the association between these abnormalities and childhood trauma, to gain insights into the neural underpinnings of OCD. Forty-eight drug-naive OCD patients and forty-two healthy controls (HC) underwent resting-state functional magnetic resonance imaging and clinical assessments, including the Yale–Brown Obsessive Compulsive Scale (Y–BOCS) and Childhood Trauma Questionnaire-Short Form (CTQ-SF). Compared to HCs, OCD patients exhibited significantly decreased amplitude of low-frequency fluctuations (ALFF) in the right cerebellum, decreased regional homogeneity (ReHo) in the right cerebellum and right superior occipital lobes (FWE-corrected p

Abstract Cimicifugae Rhizoma, generally known as “Sheng Ma” in China, has great medicinal and dietary values. Cimicifugae Rhizoma is the dried rhizome of Cimicifuga foetida L., Cimicifuga dahurica (Turcz.) Maxim. and Cimicifuga heracleifolia Kom., which has been used to treat wind-heat headache, tooth pain, aphtha, sore throat, prolapse of anus and uterine prolapse in traditional Chinese medicine. This review systematically presents the traditional uses, phytochemistry, pharmacology, clinical studies, quality control and toxicity of Cimicifugae Rhizoma in order to propose scientific evidence for its rational utilization and product development. Herein, 348 compounds isolated or identified from the herb are summarized in this review, mainly including triterpenoid saponins, phenylpropanoids, chromones, alkaloids, terpenoids and flavonoids. The crude extracts and its constituents had various pharmacological properties such as anti-inflammatory, antitumor, antiviral, antioxidant, neuroprotective, anti-osteoporosis and relieving menopausal symptoms. The recent research progress of Cimicifugae Rhizoma in ethnopharmacology, phytochemistry and pharmacological effects demonstrates the effectiveness of its utilization and supplies valuable guidance for further research. This review will provide a basis for the future development and utilization of Cimicifugae Rhizoma.

Aberration of Notch signaling is one of the key events involved in the development and progression of head and neck squamous cell carcinoma (HNSCC). The Notch pathway controls the tissue-specific differentiation of normal squamous epithelial cells and is frequently altered in squamous carcinomas, thus affecting their proliferation, growth, survival, and chemosensitivity or resistance against anti-cancer agents. In this study, we show that the use of novel, small-molecule inhibitors of Notch signaling, such as FLI-06, can have a beneficial effect on increasing the chemosensitivity of HNSCC to taxane-based chemotherapy. Inhibition of Notch signaling by FLI-06 alone virtually blocks the proliferation and growth of HNSCC cells in both 2D and 3D cultures and the zebrafish model, which is accompanied by down-regulation of key Notch target genes and proteins. Mechanistically, FLI-06 treatment causes cell cycle arrest in the G1-phase and induction of apoptosis in HNSCC, which is accompanied by increased c-JunS63 phosphorylation. Combining FLI-06 with Docetaxel shows a synergistic effect and partially blocks the cell growth of aggressive HNSCC cells via enhanced apoptosis and modification of c-JunS243 phosphorylation via GSK-3β inhibition. In conclusion, inhibition of Notch signaling in HNSCC cells that retain active Notch signaling significantly supports taxane-based anticancer activities via modulation of both the GSK-3β and the c-Jun.

The multiple species characteristics of traditional Chinese medicines (TCMs) are crucial for expanding TCMs sources, meeting the needs of the pharmaceutical industry and ensuring clinical requirements. It’s also one of the significant factors affecting the quality control of TCMs. Systematic differential analysis of original species in TCMs is an important link in achieving comprehensive quality control, ensuring the effectiveness and safety of clinical medication. The study aims to establish a reliable and efficient approach to screen combinatorial discriminatory quality markers for rapid differentiation of original species by metabolomics coupled with DNA barcoding as a case of Cimicifugae Rhizoma. DNA barcoding is used to identify the origin of Cimicifugae Rhizoma. The data-dependent acquisition mode integrated with the computerized intelligent filtering system was established for in-depth characterization of metabolites from Cimicifugae Rhizoma using ultra-high performance liquid chromatography to quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The untargeted metabolomics combined with multivariate statistical analysis was performed to screen and identify the potential combinatorial discriminatory quality markers. Finally, quantitative analysis and predictive model of these markers were employed to validate the feasibility of this strategy to distinguish the original species. Based on the scores of variable importance in projection greater than 1.0 and t-test (p

Abstract Notch signalling is one of the key molecular pathways involved in cell-to-cell signal transduction. Although the mechanisms of action of the NOTCH receptors are already relatively well known, their biological implications remain unclear, especially during the initiation and progression of head and neck squamous cell carcinoma (HNSCC). Here, we present the growth- and differentiation-modulating effects of various “next generation” small molecule Notch modulators represented by RIN-1, and CB-103, on HNSCC, compared to gamma secretase inhibitors as “conventional” NOTCH interfering compounds, like DAPT. These molecules were tested in different cell- and tissue culture conditions represented by 2D monolayer, non-adherent or spheroid culture, 3D organoid cultures, and zebrafish in vivo model. The most pronounced, pleiotropic effects were observed for the NOTCH modulator RIN-1. At the molecular level, RIN-1-dependent activation of Notch signalling led to characteristic changes in the expression of NOTCH-regulated targets, i.e., the transcriptional suppressors HES1 and HEY1, p21 (CDKN1A) cell cycle inhibitor, and pro-apoptotic BAX markers. These changes led to restriction of proliferation, growth, and reduced motility of HNSCC cells in 2D cultures. Consequently, cell cycle arrest in the G2-M phase and induction of apoptosis were observed. Similar anticancer effects were observed in 3D cultures and in the zebrafish model. In contrast, RIN-1 treatment resulted in inhibition of Notch signalling and the growth of HNSCC spheroids under non-adherent cell culture conditions. Our results suggest that modulation of Notch signalling could be used as a chemotherapeutic agent in selected patients with intact NOTCH signaling.

Abstract Background Depression and anxiety are common symptoms associated with significant morbidity in adolescents. Few studies have explored the relationship between latent profiles of adolescent depression-anxiety symptoms and executive function (EF), which is also a major pediatric public health concern. Methods The sample included 1,306 participants who were recruited from two schools in Ningxia. The Depression Self-Rating Scale for Children (DSRSC) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) were used to assess the level of depression-anxiety symptoms in adolescents, and their executive function state was assessed using the Behavior Rating Inventory of Executive Function-Self-Report version (BRIEF-SR). Latent profile analysis (LPA) was carried out using Mplus 7.0 to explore the most likely number of profiles based on the subscales of DSRSC and SCARED. The relationship between adolescents’ executive function and depression-anxiety symptoms were analyzed by multivariable logistic regression, and the odds ratio were used to test the impact of this relationship. Results The LPA results show that the three-profile model was the best-fitting model for adolescent depression and anxiety symptoms. The proportions of Profile-1 (“Healthy Group”), Profile-2 (“Anxiety Disorder Group”), and Profile-3 (“Depression-Anxiety Disorder Group”) were 61.4%, 23.9%, and 14.7%, respectively. Additional analyses using multivariable logistic regression suggested that poor shifting capacity and emotional control were significantly more likely to be classified into the depression and/or anxiety groups, and worse working memory, task completion, and better inhibition were significantly more likely to be classified into the anxiety group. Conclusions The findings contribute to our understanding of the heterogeneity of adolescents’ depression-anxiety symptoms and highlight the important role of executive function in influencing mental health outcomes. These findings will guide the improvement and delivery of interventions for the treatment of anxiety and depression in adolescents, mitigating functional impairments in patients and reducing disease risk.

The microglia, displaying diverse phenotypes, play a significant regulatory role in the development, progression, and prognosis of Parkinson’s disease. Research has established that glycolytic reprogramming serves as a critical regulator of inflammation initiation in pro-inflammatory macrophages. Furthermore, the modulation of glycolytic reprogramming has the potential to reverse the polarized state of these macrophages. Previous studies have shown that Levistilide A (LA), a phthalide component derived from Angelica sinensis, possesses a range of pharmacological effects, including anti-inflammatory, antioxidant, and neuroprotective properties. In our study, we have examined the impact of LA on inflammatory cytokines and glucose metabolism in microglia induced by lipopolysaccharide (LPS). Furthermore, we explored the effects of LA on the AMPK/mTOR pathway and assessed its neuroprotective potential both in vitro and in vivo. The findings revealed that LA notably diminished the expression of M1 pro-inflammatory factors induced by LPS in microglia, while leaving M2 anti-inflammatory factor expression unaltered. Additionally, it reduced ROS production and suppressed IκB-α phosphorylation levels as well as NF-κB p65 nuclear translocation. Notably, LA exhibited the ability to reverse microglial glucose metabolism reprogramming and modulate the phosphorylation levels of AMPK/mTOR. In vivo experiments further corroborated these findings, demonstrating that LA mitigated the death of TH-positive dopaminergic neurons and reduced microglia activation in the ventral SNpc brain region of the midbrain and the striatum. In summary, LA exhibited neuroprotective benefits by modulating the polarization state of microglia and altering glucose metabolism, highlighting its therapeutic potential.

It is widely acknowledged that the climacteric syndrome negatively affects women’s quality of life and leads to cerebral ischemic injury, osteoporosis and cardiovascular disease. One of the main active ingredients in Radix Scutellariae, Baicalin, has been established to possess a wide range of pharmacological effects and is beneficial in enhancing osteogenic differentiation and cardiovascular disease. Baicalin’s profound metabolic impact on various stem cell populations and their fate specification could improve the efficiency of stem cell therapy for climacteric syndrome. However, Baicalin-mediated processes are complex and many of the underlying mechanisms are not fully fathomed yet. This review aims to shed light on the regulatory role of Baicalin on the diverse behaviors of distinct stem cell populations and provide a good cell source for stem cell therapy to broaden the therapeutic landscape for climacteric syndrome patients.

Soil water deficit is an important factor affecting the source–sink balance of sweet potato during its late-season growth, but water regulation during this period has not been well studied. Therefore, the aim of this study was to determine the appropriate irrigation level in late-season sweet potato, and the effect of irrigation level on accumulation and allocation of photosynthetic products. In this study, two yield-based field trials (2021–2022) were conducted in which five late-season irrigation levels set according to the crop evapotranspiration rate were tested (T0: non-irrigation, T1: 33% ETc, T2: 75% ETc, T3: 100% ETc, T4: 125% ETc). The effects of the different irrigation levels on photosynthetic physiological indexes, 13C transfer allocation, water use efficiency (WUE), water productivity (WP), and the yield and economic benefit of sweet potato were studied. The results showed that late-season irrigation significantly increased the total chlorophyll content and net photosynthetic rate of functional leaves, in addition to promoting the accumulation of above-ground-source organic biomass (p < 0.05). The rate of 13C allocation, maximum accumulation rate (Vmax), and average accumulation rate (Vmean) of dry matter in storage root were significantly higher under T2 irrigation than under the other treatments (p < 0.05). This suggests that both non-irrigation (T0) and over-irrigation (T4) were not conducive to the transfer and allocation of photosynthetic products to storage roots in late-season sweet potato. However, moderate irrigation (T2) effectively promoted the source–sink balance, enhanced the source photosynthetic rate and stimulated the sink activity, such that more photosynthate was allocated to the storage sink. The results also showed that T2 irrigation treatments significantly increased yield, WUE and WP compared to T0 and T4 (p < 0.05), suggesting that moderate irrigation (T2) can significantly promote the potential of storage root production and field productivity. There was a close relationship between economic benefit and marketable sweet potato yield, and both were highest under T2 (p < 0.05), increasing by 36.1% and 59.9% compared with T0 over the two-year study period. In conclusion, irrigation of late-season sweet potato with 75% evapotranspiration (T2) can improve both the yield and production potential. Together, these results support the use of late-season water management in the production of sweet potato.

Context Naoxintong (NXT), a prescribed traditional Chinese medicine, widely used in cerebrovascular and cardiovascular diseases, could be effective in diabetic wounds. Objective This study evaluates the wound healing activity of NXT by employing an excisional wound splinting model. Materials and methods NXT was dissolved in saline and given daily by gavage. Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with saline or 700 mg/kg/d NXT for 16 days. Wound closure was measured every four days. Extracellular matrix (ECM) remodelling, collagen deposition, leukocyte infiltration and expression of Col-3, CK14, CXCL1, CXCL2, MPO, Ly6G, CD68, CCR7, CD206, p-JAK1, p-STAT3 and p-STAT6 was analysed. Results NXT significantly accelerated rate of wound closure increased from 70% to 84%, accompanied by up-regulation of collagen deposition and ECM at days 16 post-injury. Moreover, NXT alleviated neutrophil infiltration, accompanied by down-regulation of CXCL1 and CXCL2 mRNA expression. In addition, NXT markedly augmented neutrophil efferocytosis. In diabetic wounds, the levels of M1 marker gene (CCR7) increased, while M2 marker gene (CD206) decreased, demonstrating a pro-inflammatory shift. Application of NXT increased M2 macrophage phenotype in db/db mice. Mechanistically, NXT treatment increased expression level of p-STAT3 and p-STAT6 at days 3 post-injury, indicating NXT mediated macrophages towards M2 phenotype and alleviated inflammation in diabetic wounds by activation of STAT3 and STAT6. Conclusions Our study provides evidence that NXT accelerates diabetic wound healing by attenuating inflammatory response, which provides an important basis for use of NXT in the treatment of chronic diabetic wound healing.

Context Cryptotanshinone (CT) is a diterpene quinone compound from Salvia miltiorrhiza Bge. Labiatae has been widely used in cardio-cerebral vascular diseases, which could be potentially effective in treating diabetic wounds. Objective This study evaluates the wound healing activity of CT by employing an excisional wound splinting model in db/db mice. Materials and methods Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with sodium carboxymethyl cellulose (CMC-Na) or 300 mg/kg/d CT for 16 days. Wound closure was measured every two days. Body weight, fasting blood glucose, re-epithelialization, granulation, leukocyte infiltration, capillary density, collagen deposition and expressions of CXCL1, CXCL2, VEGF, Ang-1, p-eNOS, eNOS, α-SMA, MMP2 and MMP9 were analysed. Expression of VEGF and tube formation was measured in vitro with human umbilical vein endothelial cells (HUVECs). Results CT significantly accelerated rate of wound closure, as the contraction ratio increased from 68% (non-treated group) to 83% (CT-treated group) at days 16 post-injury. A significant increase was observed in re-epithelialization and granulation tissue formation. Mechanistically, CT suppressed leukocyte infiltration and CXCL1 and CXCL2 expression. CT treatment also increased blood vessel density and expression level of VEGF, Ang-1 and p-eNOS. In vitro, CT boosted expression of VEGF and tube formation of endothelial cells. Moreover, extracellular matrix (ECM) remodelling was enhanced by CT via promoting fibroblast transformation and inhibiting MMP2 and MMP9. Conclusions Our study provides evidence that CT could be developed as a potential therapeutic agent for the treatment of chronic diabetic wound healing.

Background/Aims: Psoralen and bakuchiol are the main active compounds found in the traditional Chinese medicine Psoralea corylifolia L., and have been used to treat osteoporosis. This study aims to investigate the anti-osteoporosis effects of these two compounds using osteoclasts precursor differentiation and bone absorption assays in vitro. Methods: Primary mouse osteoclasts precursor cells were induced by M-CSF (macrophage colony stimulating factor) plus RANKL (receptor activator of nuclear factor kappa-B ligand) in vitro. TRACP (tartrate-resistant acid phosphatase) enzyme activity and toluidine blue staining were used to observe the effects of psoralen and bakuchiol on osteoclast differentiation and bone resorption, respectively. Gelatin zymography was used to assess MMP (matrix metalloproteinase) activity, and ELISA was performed to measure cathepsin K activity. Western blotting analysis for expression of phosphorylated AKT, ERK, NF-kB, and c-jun; and immunofluorescence analysis for c-jun and p65 nuclear translocation in induced osteoclasts were then used to determine the mechanism of anti-bone resorption of psoralen and bakuchiol. Results: Mature osteoclasts were induced by M-CSF plus RANKL from primary bone marrow macrophages in vitro. Both psoralen and bakuchiol significantly inhibited TRACP enzyme activity and slightly decreased the number of TRACP+ multinuclear osteoclasts induced by M-CSF plus RANKL. Bakuchiol significantly decreased bone lacunae area and attenuated MMP-2 activity induced by M-CSF plus RANKL in osteoclasts. Both psoralen and bakuchiol significantly decreased the expression and nuclear translocation of phosphorylated c-jun stimulated by M-CSF plus RANKL, but no significant effect on p65 translocation was observed in osteoclasts. Additionally, bakuchiol significantly attenuated the increased of M-CSF plus RANKL-induced phosphorylation of AKT in osteoclasts. Conclusions: Psoralen and bakuchiol ameliorated M-CSF plus RANKL-induced osteoclast differentiation and bone resorption via inhibition of AKT and AP-1 pathways activation in vitro.

In this work, gold and bismuth bimetallic nanoparticles decorated L-cysteine functionalized graphene oxide nanocomposites (Au-BiNPs/SH-GO) were prepared and applied to selective detection of Fe(III) in lake and seawater samples by modifying onto glassy carbon electrodes. Bimetallic nanoparticles have various excellent properties and better catalytic properties because of the unique synergistic effect between metals. The modified electrode was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and Raman spectroscopy. Under optimized conditions, current peak intensity increased linearly with increasing Fe(III) concentration over the range of 0.2–50 μM and a detection limit of 0.07 μM (S/N = 3). The Au-BiNPs/SH-GO/GCE was used for the determination of Fe(III) in lake and seawater samples with recoveries ranged from 90 to 103%. Those satisfactory results revealed the potential application of the Au-BiNPs/SH-GO electrochemical sensor for heavy metals detection in environmental monitoring.

Abstract Background Salvianolate lyophilized injection (SLI) has been clinically used in China for the treatment of acutely cerebral infarction. Clinical and experimental studies have shown that Diabetes mellitus (DM) not only increases the risk of ischemic stroke recurrence but also leads to poor outcomes and increases fatality rates after stroke. Our previous study has proved that SLI can reduce the infarct volume after stroke in type 1 diabetic rats. The aim of the study is to explore the mechanism of SLI on stroke outcome in type 1 diabetic (T1DM) rats. Methods Type 1 diabetes rats model (T1DM) was induced in male Wistar rats by intraperitoneal (i.p) injection of streptozotocin (60 mg/kg) and T1DM rats were subjected to intraluminal middle cerebral artery occlusion (MCAO). The T1DM + MCAO rats were randomly divided into six groups: sham-operated, model-vehicle, positive control group (Edaravone-treating, DE 6 mg/kg) and SLI-treating group (10.5 mg/kg, 21 mg/kg and 42 mg/kg). SLI and DE were administered by tail vein injection at 3 h after MCAO, then daily for 14 days. Micro-CT scans of the brain tissue revealed vessel characteristics and distribution in the ischemia zone. Glucose uptake was analyzed by PET/CT. RAGE, MMP9 and inflammatory factors (COX-2, TNF-α and ICAM-1), HQ-1, HQO-1 and Nrf-2 expression levels in the ischemic brain tissue were analyzed by Immunofluorescence staining and Western blot at 14 days after MCAO. Results In this study, we have demonstrated that SLI treatment significantly increased the number of brain microvasculature in ipsilateral and glucose uptake in cortex, hippocampus and penumbra in the T1DM + MCAO rats. SLI also significantly decreased the expression of RAGE, MMP9 and inflammatory factors expression, and increased the expression of HQ-1, HQO-1 and Nrf-2 in T1DM + MCAO rats. Conclusion The study showed that SLI could protect against cerebral ischemia injury in T1DM + MCAO rats and the mechanism is related to decrease inflammatory factors and activate of the Nrf2/HO-1 signaling pathway.

Worldwide solar dimming from the 1960s to the 1980s has been widely recognized, but the occurrence of solar brightening since the late 1980s is still under debate—particularly in China. This study aims to properly examine the biases of urbanization in the observed sunshine duration series from 1987 to 2016 and explore the related driving factors based on five meteorological stations around Hangzhou City, China. The results inferred a weak and insignificant decreasing trend in annual mean sunshine duration (−0.09 h/d decade−1) from 1987 to 2016 in the Hangzhou region, indicating a solar dimming tendency. However, large differences in sunshine duration changes between rural, suburban, and urban stations were observed on the annual, seasonal, and monthly scales, which can be attributed to the varied urbanization effects. Using rural stations as a baseline, we found evident urbanization effects on the annual mean sunshine duration series at urban and suburban stations—particularly in the period of 2002–2016. The effects of urbanization on the annual mean sunshine duration trends during 1987−2016 were estimated to be −0.16 and −0.35 h/d decade−1 at suburban and urban stations, respectively. For urban stations, the strongest urbanization effect was observed in summer (−0.46 h/d decade−1) on the seasonal scale and in June (−0.63 h/d decade−1) on the monthly scale. The notable negative impact of urbanization on local solar radiation changes was closely related to the changes in anthropogenic pollutions, which largely reduced the estimations of solar radiation trends in the Hangzhou region. This result highlights the necessity to carefully consider urbanization impacts when analyzing the trend in regional solar radiation and designing cities for sustainable development.

Increasing zinc (Zn) concentration in wheat grain is an important global challenge due to high incidence of Zn deficiency in human populations. In this study, a two-year field experiment was conducted to investigate the effects of foliar ZnSO4 combined with various biostimulants (fulvic acid (FA), seaweed extract (SE), amino acids (AA), and microbial incubates (MI)) on Zn concentration and bioavailability in wheat grain under different soil nitrogen (N) levels (0, 120, and 240 kg N/ha). Grain Zn concentration and bioavailability were significantly enhanced by foliar Zn plus various biostimulants and soil N supply. Compared to foliar Zn alone, foliar Zn + FA resulted in 16% increase in grain Zn, mainly from insoluble Zn increases, while foliar Zn + AA caused 11% increase in grain Zn, mainly from soluble (at N0) and insoluble Zn increases (at N120). Foliar Zn + FA and Zn + AA generally resulted in higher Zn bioavailability than foliar Zn alone. Additionally, N concentration and Fe concentration and bioavailability in grain were enhanced with foliar Zn + AA and soil N application. Thus, foliar ZnSO4 plus FA and AA under optimal soil N rate (120 kg N/ha) can be an effective and economically friendly approach for achieving agronomic biofortification.

Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of β-amyloid (Aβ42) deposited in hippocampus in Alzheimer's patients. Whether it has the therapeutic effect on Parkinson's disease, however, is unclear. In this study, we found that isobavachalcone could effectively remit Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), prolong the residence time of mice on Rota-rod and alleviate the neuronal necrosis. It also inhibited the over-activation of microglia, and decreased the expression of IL-6 and IL-1β in the brain of PD mice. In vitro, isobavachalcone could inhibit nuclear factor-kappaB (NF-κB) pathway through inhibiting the LPS-induced transfer of NF-κB subunit from cytoplasm to nucleus in BV-2 cells. Isobavachalcone decreased the LPS-induced oxidative stress and the expression of inflammatory cytokines, and provided a neuroprotective effect by antagonizing microglia-mediated inflammation. Our results indicated that isobavachalcone may be a candidated drug against Parkinson's disease with great clinical potential.

Organic matter plays a key role in availability and transformation of soil Zn (zinc), which greatly controls Zn concentrations in cereal grains and human Zn nutrition level. Accordingly, soils homogenized with the wheat straw (0, 12 g straw kg-1) and Zn fertilizer (0, 7 mg Zn kg-1) were buried and incubated in the field over 210 days to explore the response of soil Zn availability and the ageing of exogenous Zn to straw addition. Results indicated that adding straw alone scarcely affected soil DTPA-Zn concentration and Zn fractions because of the low Zn concentration of wheat straw and the high soil pH, and large clay and calcium carbonate contents. However, adding exogenous Zn plus straw increased the DTPA-Zn abundance by about 5-fold and had the similar results to adding exogenous Zn alone, corresponding to the increased Zn fraction loosely bounded to organic matter, which had a more dominant presence in Zn reaction than soil other constituents such as carbonate and minerals in calcareous soil. The higher relative amount of ineffective Zn (~50%) after water soluble Zn addition also occurred, and at the days of 120-165 and 180-210when the natural temperature and rainfall changed mildly, the ageing process of exogenous Zn over time was well evaluated by the diffusion equation, respectively. Consequently, combining crop residues with exogenous water soluble Zn application is promising strategy to maximize the availability of Zn in calcareous soil, but the higher ageing rate of Zn caused by the higher Zn mobility should be considered.

Although application of Zn combined with macronutrients (K, P, and N) can be used to fortify wheat grain with Zn, little is known about their interactions when foliar application is employed or the influences of common soil fertility management practices (e.g. N and straw management) on their efficiency. Therefore, the effects of foliar-applied Zn and N, P, or K on grain nutritional quality (especially Zn) were investigated in wheat grown under different soil N rates at two sites with (Sanyuan) or without (Yangling) employing straw return. A 4-year-long field experiment was also conducted to evaluate the environmental stability of the foliar formulations. Across 6 site-years, foliar Zn application alone or combined with N, P, or K fertilizers resulted in 95.7%, 101%, 67.9% and 121% increases in grain Zn concentration, respectively. In terms of increasing grain Zn concentration, foliar-applied Zn positively interacted with N (at Sanyuan) and K (at Yangling), but negatively interacted with P at any condition tested, suggesting depressive effects of foliarly-applied P on physiological availability of Zn. Although these interaction effects were the major factor that governing the efficiency of foliar-applied Zn combined with N, P, or K on grain Zn concentration, the magnitude of the increase/decrease in grain Zn (-3.96~5.71 mg kg-1) due to these interactions was much less than the average increases following Zn+K (31.3), Zn+P (18.7), and Zn+N (26.5 mg kg-1) treatments relative to that observed in foliar Zn-only treatment. The combined foliar application of Zn with N, P, or K did not cause any adverse impact on grain yield and other nutritional quality and in some cases slightly increased grain yield and macronutrient concentrations. Grain phytic acid:Zn molar ratios were respectively 52.0%, 53.1%, 43.4% and 63.5% lower in the foliar Zn, Zn+N, Zn+P and Zn+K treatments than in the control treatment. These effects were consistent over four years and across three soil N rates. Overall, combined foliar application of Zn with N, P, or K can successfully fortify wheat grain with Zn (above 40 mg kg-1), and including Zn in foliar N or K application are preferred for practically increasing dietary Zn intake.

Incorporating foliar zinc (Zn) spray into existing pesticide application is considered highly cost-effective to biofortify wheat (Triticum aestivum) with Zn. However, the effectiveness of this combined approach in terms of Zn enrichment and bioavailability in grain and its milling fractions is not well examined. Two-year field experiments were conducted in 2017 and 2018 with three sets of foliar applications (nil Zn as control, foliar Zn alone, and foliar Zn plus pesticides) at the anthesis, milk stage, or both. Compared to the control, grain yield was not affected by foliar Zn application alone or combined with pesticides, while the Zn concentrations and bioavailability substantially increased in the whole-grain, bran, and flour irrespective of spray timing. Yield losses by 28%–39% (2018 vs. 2017) led to 7%–18% and 18%–38% increase of Zn density in grain and flour, respectively. Further, such negative responses were uncoupled by foliar spray of Zn or Zn plus pesticides, and absent from the control plants. Nonetheless, grain Zn biofortification was achieved in both low- and high-yield plants with either Zn spray alone or combined with pesticides. Together with the enhanced Zn bioavailability in grain, bran, and flour, the effectiveness of this combined strategy is validated to biofortify wheat with Zn.

Background: To investigate the renal pathophysiologyin rhabdomyolysis-induced acute kidney injury (AKI) in rats under hypoxia and deprivation of food and water (HDFW), thus broadening the knowledge about rhabdomyolysis-induced AKI in massive earthquake. Methods: Male Wistar rats weighing 200-230g were randomized into control, rhabdomyolysis (R), HDFW and rhabdomyolysis in combination with HDFW (R/HDFW) group. Experimental rhabdomyolysis rat model was established through clamping hind limb muscles, HDFW model rats were kept in 10% hypoxic chamber unavailable to food and water. At 1, 3, 5, 7, 9, 11d after treatment, serum creatinine (Scr) level, renal index, renal structural changes and cell apoptosis were analyzed. Results: After R, HDFW, R/HDFW treatment, the animals showed significantly higher Scr levels than the control group. Renal index in R and R/HDFW groups elevated remarkably compared with that in control and HDFW group. The results of histopathology, ultra-structure and apoptosis assay suggested that rhabdomyolysis caused renal tubular injury, HDFW treatment resulted in renal vascular dilation, tissue congestion and tubular cell damage. In addition, more severe renal lesion appeared in R/HDFW. Conclusions: We conclude that the association of experimental rhabdomyolysis with HDFW results in a different functional and histological pattern. The rhabdomyolysis-HDFW combination causes more severe renal injury.

HJURP (Holliday Junction-Recognizing Protein) plays dual roles in DNA repair and in accurate chromosome segregation during mitosis. We examined whether the single nucleotide polymorphisms (SNPs) of HJURP were associated with the risk of occurrence of hepatocellular carcinoma (HCC) among chronic hepatitis B virus (HBV) carriers from well-known high-risk regions for HCC in China.Twenty-four haplotype-tagging SNPs across HJURP were selected from HapMap data using the Haploview software. We genotyped these 24 SNPs using the using Sequenom's iPLEX assay in the Fusui population, consisting of 348 patients with HCC and 359 cancer-free controls, and further investigated the significantly associated SNP using the TaqMan assay in the Haimen population, consisting of 100 cases and 103 controls. The genetic associations with the risk of HCC were analyzed by logistic regression.We observed an increased occurrence of HCC consistently associated with A/C or C/C genotypes of the non-synonymous SNP rs3771333 compared with the A/A genotype in both the Fusui and Haimen populations, with a pooled odds ratio 1.82 (95% confidence interval, 1.33-2.49; P = 1.9 × 10-4). Case-only analysis further indicated that carriers of the at-risk C allele were younger than those carrying the A/A genotype (P = 0.0016). In addition, the expression levels of HJURP in C allele carriers were lower than that in A/A genotype carriers (P = 0.0078 and 0.0010, for mRNA and protein levels, respectively).Our findings suggest that rs3771333 in HJURP may play a role in mediating the susceptibility to HCC among Chinese.

Although some epidemiological investigations showed a potential association between long-term exposure of extremely low frequency electromagnetic fields (ELF-EMF) and Alzheimer's disease (AD), no reasonable mechanism can explain this association, and the related animal experiments are rare. In this study, ELF-EMF exposure (50 Hz 400 µT 60 d) combined with D-galactose intraperitoneal (50 mg/kg, q.d., 42 d) and Aβ25-35 hippocampal (5 μl/unilateral, bilateral, single-dose) injection was implemented to establish a complex rat model. Then the effects of ELF-EMF exposure on AD development was studied by using the Morris water maze, pathological analysis, and comparative proteomics. The results showed that ELF-EMF exposure delayed the weight gain of rats, and partially improved cognitive and clinicopathologic symptoms of AD rats. The differential proteomic analysis results suggest that synaptic transmission, oxidative stress, protein degradation, energy metabolism, Tau aggregation, and inflammation involved in the effects mentioned above. Therefore, our findings indicate that certain conditions of ELF-EMF exposure could delay the development of AD in rats.

Besides climate change, intensive anthropogenic activities affect vegetation cover variations, particularly in highly populated regions. Herein, we investigated the impacts of anthropogenic activities in the Circum-Bohai-Sea (CBS) region in China using correlation analysis between the normalized difference vegetation index (NDVI) and indicators related to urban development, agricultural practices, and afforestation efforts; multivariate linear regression and residual analyses were used to quantify how anthropogenic activities contribute to NDVI change. We found that the vegetation cover in most of the study area significantly increased from 1982 to 2015. In major cities, the decrease in vegetation cover was not as expected because of the opposing effects of rapid urbanization and greening. Afforestation and improved agricultural practices dominated the increase in vegetation cover in different regions. Anthropogenic activities accounted for 42% of the increase in vegetation cover in the CBS region. Therefore, to achieve regional sustainable development, the effects of human activities in highly populated area must be heeded. [ABSTRACT FROM AUTHOR]