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1.
Differences in background environment and fertilization method mediate plant response to nitrogen fertilization in alpine grasslands on the Qinghai-Tibetan Plateau.
He, S, Du, J, Wang, Y, Cui, L, Liu, W, Xiao, Y, Ran, Q, Li, L, Zhang, Z, Tang, L, et al
The Science of the total environment. 2024;:167272
Abstract
Grassland degradation threatens ecosystem function and livestock production, partly induced by soil nutrient deficiency due to the lack of nutrient return to soils, which is largely ascribed to the intense grazing activities. Therefore, nitrogen (N) fertilization has been widely adopted to restore degraded Qinghai-Tibetan Plateau (QTP) grasslands. Despite numerous field manipulation studies investigating its effects on alpine grasslands, the patterns and thresholds of plant response to N fertilization remain unclear, thus hindering the prediction of its influences on the regional scale. Here, we established a random forest model to predict N fertilization effects on plant productivity based on a meta-analysis synthesizing 88 publications in QTP grasslands. Our results showed that N fertilization increased the aboveground biomass (AGB) by 46.51 %, varying wildly among plant functional groups. The positive fertilization effects intensified when the N fertilization rate increased to 272 kg ha-1 yr-1, and decreased after three years of continuous fertilization. These effects were more substantial when applying ammonium nitrate compared to urea. Further, a machine learning model was used to predict plant productivity response to N fertilization. The total explained variance and mean squared residuals ranged from 49.41 to 75.13 % and 0.011-0.058, respectively, both being the highest for grasses. The crucial predictors were identified as climatic and geographic factors, background AGB without N fertilization, and fertilization methods (i.e., rate, form, and duration). These predictors with easy access contributed 62.47 % of the prediction power of grasses' response, thus enhancing the generalizability and replicability of our model. Notably, if 30 % of yak dung is returned to soils on the QTP, the grassland productivity and plant carbon pool are predicted to increase by 5.90-6.51 % and 9.35-10.31 g C m-2 yr -1, respectively. Overall, the predictions of this study based on literature synthesis enhance our understanding of plant responses to N fertilization in QTP grasslands, thereby providing helpful information for grassland management policies. Conflict of interest: The authors declare no conflict of interest.
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2.
Meta-analysis of changes in thiol-disulfide homeostasis during preeclampsia.
Wang, D, Yang, G, You, X, Zhang, Z
Biomolecules & biomedicine. 2024;(1):30-39
Abstract
The present study systematically assessed alterations in thiol-disulfide homeostasis among women with preeclampsia (PE) through meta-analysis. This was conducted as such changes are believed to be associated with the oxidative stress underlying this condition. A comprehensive search of Medline, Web of Science, and Embase databases was conducted from their inception until 22 March 2023, to identify studies comparing levels of native thiol, total thiol, and disulfide between pregnant women with PE and those without PE. Results were pooled using a random-effects model to account for study heterogeneity. The analysis included a total of 631 women diagnosed with PE and 668 healthy pregnant women, encompassing 13 case-control studies and 1 prospective study. Pooled outcomes revealed that women with PE had significantly lower blood levels of native thiol, (mean difference [MD] -51.42 umol/L; 95% confidence interval [CI] -79.75 to -23.10 umol/L; P < 0.001; I2 = 0% and total thiol (MD -65.56 umol/L; 95% CI -104.97 to -26.15 umol/L; P = 0.001; I2 = 0%) compared to the control group. In contrast, no significant difference was observed in blood disulfide levels between the two groups (MD -1.10 umol/L; 95% CI -4.41 to -2.21 umol/L; P = 0.51; I2 = 0%). Subgroup analyses indicated that the results were consistent across studies matched by gestational age and body mass index, as well as those with varying quality scores (P for subgroup differences all > 0.05). In conclusion, women with PE are associated with significantly reduced blood levels of native and total thiols but show no change in blood disulfide levels, suggesting a state of reduced antioxidants in PE.
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3.
Efficacy of polyethylene glycol loxenatide for type 2 diabetes mellitus patients: a systematic review and meta-analysis.
Liu, Y, Ma, W, Fu, H, Zhang, Z, Yin, Y, Wang, Y, Liu, W, Yu, S, Zhang, Z
Frontiers in pharmacology. 2024;:1235639
Abstract
Objective: Some studies have proved that polyethylene glycol loxenatide (PEG-Loxe) has significant effects on controlling blood glucose and body weight in patients with type 2 diabetes mellitus (T2DM), but there is still some controversy over the improvement of blood lipid profiles (BLP) and blood pressure (BP), and more evidences are needed to verify such effects. Therefore, this study was conducted to provide a comprehensive evaluation of the efficacy of PEG-Loxe in improving blood glucose (BG), BLP, BP, body mass index (BMI), and body weight (BW) in patients with T2DM for clinical reference. Methods: Randomized controlled trials (RCT) in which PEG-Loxe was applied to treat T2DM were retrieved by searching PubMed, Cochrane Library, Embase, Medline, Scopus, Web of Science, China National Knowledge Infrastructure, China Scientific Journal, Wanfang Data, and SinoMed databases. Outcome measures included BG, BLP, BP, BMI, and BW. RevMan 5.3 software was used to perform data analysis. Results: Eighteen trials were identified involving 2,166 patients. In experimental group 1,260 patients received PEG-Loxe alone or with other hypoglycemic agents, while in control group 906 patients received placebo or other hypoglycemic agents. In the overall analysis, PEG-Loxe significantly reduced the levels of glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-h postprandial blood glucose (2-h PBG), BMI, and BW compared with control group. However, it had no obvious effect on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Conclusion: PEG-Loxe has better hypoglycemic effects compared with placebo in patients with T2DM, but could not significantly improved TG, LDL-C, HDL-C, SBP, and DBP. And the combination of conventional hypoglycemic drugs (CHD) and PEG-Loxe could more effectively improve the levels of HbA1c, FPG, 2-h PBG, TC, TG, BMI, and BW compared with CHD in T2DM patients. Systematic Review Registration: www.inplasy.com, identifier INPLASY202350106.
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4.
The mechanism of UNC-51-like kinase 1 and the applications of small molecule modulators in cancer treatment.
Sun, D, Zhang, Z, Yu, X, Li, H, Wang, X, Chen, L
European journal of medicinal chemistry. 2024;:116273
Abstract
Autophagy is a process of self-renewal in cells, which not only provides the necessary nutrients for cells, but also clears necrotic organelles. Autophagy disorders are closely related to diseases such as cancer. UNC-51-like kinase 1 (ULK1) is a serine/threonine protein kinase that plays a crucial role in receiving input from energy and nutrient sensors, activating autophagy to maintain cellular homeostasis under stressful conditions. In recent years, targeting ULK1 has become a highly promising strategy for cancer treatment. This review introduces the regulatory mechanism of ULK1 in autophagy through the AMPK/mTOR/ULK1 pathway and reviews the research progress of ULK1 activators and inhibitors and their applications in cancer treatment. In addition, we analyze the binding modes between ULK1 and modulators through virtual molecular docking, which will provide a reliable basis and theoretical guidance for the design and development of new therapeutic drugs targeting ULK1.
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5.
Role of sodium taurocholate cotransporting polypeptide (NTCP) in HBV-induced hepatitis: Opportunities for developing novel therapeutics.
Zhang, Z, Zhang, Q, Zhang, Y, Lou, Y, Ge, L, Zhang, W, Zhang, W, Song, F, Huang, P
Biochemical pharmacology. 2024;:115956
Abstract
Hepatitis B is an infectious disease caused by the HBV virus. It presents a significant challenge for treatment due to its chronic nature and the potential for developing severe complications, including hepatocirrhosis and hepatocellular carcinoma. These complications not only cause physical and psychological distress to patients but also impose substantial economic and social burdens on both individuals and society as a whole. The internalization of HBV relies on endocytosis and necessitates the involvement of various proteins, including heparin sulfate proteoglycans, epidermal growth factor receptors, and NTCP. Among these proteins, NTCP is pivotal in HBV internalization and is primarily located in the liver's basement membrane. As a transporter of bile acids, NTCP also serves as a receptor facilitating HBV entry into cells. Numerous molecules have been identified to thwart HBV infection by stifling NTCP activity, although only a handful exhibit low IC50 values. In this systematic review, our primary focus dwells on the structure and regulation of NTCP, as well as the mechanism involved in HBV internalization. We underscore recent drug breakthroughs that specifically target NTCP to combat HBV infection. By shedding light on these advances, this review contributes novel insights into developing effective anti-HBV medications.
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6.
Comparative physiological and transcriptome analysis between potassium-deficiency tolerant and sensitive sweetpotato genotypes in response to potassium-deficiency stress.
Jin, R, Yan, M, Li, G, Liu, M, Zhao, P, Zhang, Z, Zhang, Q, Zhu, X, Wang, J, Yu, Y, et al
BMC genomics. 2024;(1):61
Abstract
BACKGROUND Sweetpotato is a typical ''potassium (K+) favoring'' food crop, which root differentiation process needs a large supply of potassium fertilizer and determine the final root yield. To further understand the regulatory network of the response to low potassium stress, here we analyze physiological and biochemical characteristics, and investigated root transcriptional changes in two sweetpotato genotypes, namely, - K tolerant "Xu32" and - K susceptible"NZ1". RESULT We found Xu32 had the higher capability of K+ absorption than NZ1 with better growth performance, higher net photosynthetic rate and higher chlorophyll contents under low potassium stress, and identified 889 differentially expressed genes (DEGs) in Xu32, 634 DEGs in NZ1, 256 common DEGs in both Xu32 and NZ1. The Gene Ontology (GO) term in molecular function enrichment analysis revealed that the DEGs under low K+ stress are predominately involved in catalytic activity, binding, transporter activity and antioxidant activity. Moreover, the more numbers of identified DEGs in Xu32 than that in NZ1 responded to K+-deficiency belong to the process of photosynthesis, carbohydrate metabolism, ion transport, hormone signaling, stress-related and antioxidant system may result in different ability to K+-deficiency tolerance. The unique genes in Xu32 may make a great contribution to enhance low K+ tolerance, and provide useful information for the molecular regulation mechanism of K+-deficiency tolerance in sweetpotato. CONCLUSIONS The common and distinct expression pattern between the two sweetpotato genotypes illuminate a complex mechanism response to low potassium exist in sweetpotato. The study provides some candidate genes, which can be used in sweetpotato breeding program for improving low potassium stress tolerance.
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7.
Unlocking the health potential of anthocyanins: a structural insight into their varied biological effects.
Li, F, Sun, Q, Chen, L, Zhang, R, Zhang, Z
Critical reviews in food science and nutrition. 2024;:1-21
Abstract
Anthocyanins have become increasingly important to the food industry due to their colorant features and many health-promoting activities. Numerous studies have linked anthocyanins to antioxidant, anti-inflammatory, anticarcinogenic properties, as well as protection against heart disease, certain types of cancer, and a reduced risk of diabetes and cognitive disorders. Anthocyanins from various foods may exhibit distinct biological and health-promoting activities owing to their structural diversity. In this review, we have collected and tabulated the key information from various recent published studies focusing on investigating the chemical structure effect of anthocyanins on their stability, antioxidant activities, in vivo fate, and changes in the gut microbiome. This information should be valuable in comprehending the connection between the molecular structure and biological function of anthocyanins, with the potential to enhance their application as both colorants and functional compounds in the food industry.
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8.
The NAD+ Precursor Nicotinamide Riboside Rescues Mitochondrial Defects and Neuronal Loss in iPSC derived Cortical Organoid of Alpers' Disease.
Hong, Y, Zhang, Z, Yangzom, T, Chen, A, Lundberg, BC, Fang, EF, Siller, R, Sullivan, GJ, Zeman, J, Tzoulis, C, et al
International journal of biological sciences. 2024;(4):1194-1217
Abstract
Alpers' syndrome is an early-onset neurodegenerative disorder usually caused by biallelic pathogenic variants in the gene encoding the catalytic subunit of polymerase-gamma (POLG), which is essential for mitochondrial DNA (mtDNA) replication. The disease is progressive, incurable, and inevitably it leads to death from drug-resistant status epilepticus. The neurological features of Alpers' syndrome are intractable epilepsy and developmental regression, with no effective treatment; the underlying mechanisms are still elusive, partially due to lack of good experimental models. Here, we generated the patient derived induced pluripotent stem cells (iPSCs) from one Alpers' patient carrying the compound heterozygous mutations of A467T (c.1399G>A) and P589L (c.1766C>T), and further differentiated them into cortical organoids and neural stem cells (NSCs) for mechanistic studies of neural dysfunction in Alpers' syndrome. Patient cortical organoids exhibited a phenotype that faithfully replicated the molecular changes found in patient postmortem brain tissue, as evidenced by cortical neuronal loss and depletion of mtDNA and complex I (CI). Patient NSCs showed mitochondrial dysfunction leading to ROS overproduction and downregulation of the NADH pathway. More importantly, the NAD+ precursor nicotinamide riboside (NR) significantly ameliorated mitochondrial defects in patient brain organoids. Our findings demonstrate that the iPSC model and brain organoids are good in vitro models of Alpers' disease; this first-in-its-kind stem cell platform for Alpers' syndrome enables therapeutic exploration and has identified NR as a viable drug candidate for Alpers' disease and, potentially, other mitochondrial diseases with similar causes.
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9.
Self-Zincophilic Dual Protection Host of 3D ZnO/Zn⊂CF to Enhance Zn Anode Cyclability.
Lu, H, Hua, W, Zhang, Z, An, X, Feng, J, Xi, B, Xiong, S
Small (Weinheim an der Bergstrasse, Germany). 2024;:e2312187
Abstract
Zn dendrite growth and side reactions restrict the practical use of Zn anode. Herein, the design of a novel 3D hierarchical structure is demonstrated with self-zincophilic dual-protection constructed by ZnO and Zn nanoparticles immobilized on carbon fibers (ZnO/Zn⊂CF) as a versatile host on the Zn surface. The unique 3D frameworks with abundant zinc nucleation storage sites can alleviate the structural stress during the plating/stripping process and overpower Zn dendrite growth by moderating Zn2+ flux. Moreover, given the dual protection design, it can reduce the contact area between active zinc and electrolyte, inhibiting hydrogen evolution reactions. Importantly, density functional theory calculations and experimental results confirm that the introduced O atoms in ZnO/Zn⊂CF enhance the interaction between Zn2+ and the host and reduce Zn nucleation overpotential. As expected, the ZnO/Zn⊂CF-Zn electrode exhibits stable Zn plating/stripping with low polarization for 4200 h at 0.2 mA cm-2 and 0.2 mAh cm-2 . Furthermore, the symmetrical cell displays a significantly long cycling life of over 1800 h, even at 30 mA cm-2 . The fabricated full cells also show impressive cycling performance when coupled with V2 O3 cathodes.
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10.
Association Between Circulating Zinc and Risk for Childhood Asthma and Wheezing: A Meta-analysis on 21 Articles and 2205 Children.
Xue, M, Wang, Q, Pang, B, Zhang, X, Zhang, Y, Deng, X, Zhang, Z, Niu, W
Biological trace element research. 2024;(2):442-453
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Abstract
Asthma is one of the most frequent chronic diseases in children, and growing focus is placed on the exploration of attributable risk factors. Currently, no consensus has been reached on the implication of circulating zinc in the development of asthma. We aimed to conduct a meta-analysis to examine the association between circulating zinc and risk for childhood asthma and wheezing. We searched PubMed, Web of Science, EMBASE, and Google Scholar from inception until December 1, 2022. All procedures were performed independently and in duplicate. Random-effects model was adopted to derive standardized mean difference (SMD) and 95% confidence interval (95% CI). Statistical analyses were completed using the STATA software. Twenty-one articles and 2205 children were meta-analyzed. Overall, there was a statistically significant association between circulating zinc and risk for childhood asthma and wheezing (SMD: -0.38; 95% CI: -0.60 to -0.17; I2=82.6%, p<0.001), without evidence of publication bias as revealed by Begg's (p=0.608) and Egger (p=0.408) tests. Subgroup analyses showed that children with asthma or wheezing in Middle Eastern countries had significantly lower circulating zinc levels than controls (SMD: -0.42; 95% CI: -0.69 to -0.14; p<0.001; I2=87.1%). Additionally, average circulating zinc levels in asthma children were 0.41 μg/dl lower than that in controls, and the difference was statistically significant (SMD: -0.41; 95% CI: -0.65 to -0.16; p<0.001; I2=83.7%). By contrast, children with wheezing were 0.20 μg/dl lower than that in controls, and no between-group difference was noted (SMD=-0.20; 95% CI: -0.58 to 0.17; p=0.072; I2=69.1%). Our findings indicated that circulating zinc was associated with a significant risk for childhood asthma and its related symptom wheezing.