Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function.

Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.

O-GlcNAcylation orchestrates porcine oocyte maturation through maintaining mitochondrial dynamics and function.

O-linked ß-N-acetylglucosamine (O-GlcNAc) modification exists widely in cells, playing a crucial role in the regulation of important biological processes such as transcription, translation, metabolism, and the cell cycle. O-GlcNAc modification is an inducible reversible dynamic protein post-translational modification, which regulates complex cellular activities through transient glycosylation and deglycosylation. O-GlcNAc glycosylation is specifically regulated by O-GlcNAc glycosyltransferase (O-GlcNAc transferase, OGT) and O-GlcNAc glycoside hydrolase (O-GlcNAcase). However, the mechanisms underlying the effects of O-GlcNAc modification on the female reproductive system, especially oocyte quality, remain unclear. Here, we found that after OGT was inhibited, porcine oocytes failed to extrude the first polar body and exhibited abnormal actin and microtubule assembly. Meanwhile, the mitochondrial dynamics and function were also disrupted after inhibition of OGT function, resulting in the occurrence of oxidative stress and autophagy. Collectively, these results inform our understanding of the importance of the glycosylation process for oocyte maturation, especially for the maturation quality of porcine oocytes, and the alteration of O-GlcNAc in oocytes to regulate cellular events deserves further investigation.

Licochalcone A Induces Ferroptosis in Hepatocellular Carcinoma via Reactive Oxygen Species Activated by the SLC7A11/GPX4 Pathway.

Liver cancer is a common malignant tumor, and its incidence is increasing yearly. Millions of people suffer from liver cancer annually, which has a serious impact on global public health security. Licochalcone A (Lico A), an important component of the traditional Chinese herb licorice, is a natural small molecule drug with multiple pharmacological activities. In this study, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma cell lines (HepG2 and Huh-7), and explored the inhibitory mechanism of Lico A on hepatocellular carcinoma. First, we evaluated the inhibitory effects of Lico A on hepatocellular carcinoma, and showed that Lico A significantly inhibited and killed HepG2 and Huh-7 cells in vivo and in vitro. Transcriptomic analysis showed that Lico A inhibited the expression of solute carrier family 7 member 11 (SLC7A11), which induced ferroptosis. We confirmed through in vivo and in vitro experiments that Lico A promoted ferroptosis in hepatocellular carcinoma cells by downregulating SLC7A11 expression, thereby inhibiting the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway and inducing activation of reactive oxygen species (ROS). In this study, we suggest that Lico A is a potential SLC7A11 inhibitor that induces ferroptotic death in hepatocellular carcinoma cells, thereby providing a theoretical basis for the development of natural small molecule drugs against hepatocellular carcinoma.

Preparation of polyvinyl alcohol/chitosan nanofibrous films incorporating graphene oxide and lanthanum chloride by electrospinning method for potential photothermal and chemical synergistic antibacterial applications in wound dressings.

Electrospun fibres have been widely used as skin dressings due to their unique structur. However, due to the lack of intrinsic antimicrobial activity, it is easy for the wound to become infected. Bacterial infection, which leads to chronic inflammation, severely hinders the normal process of skin regeneration. In this study, a polyvinyl alcohol/chitosan (PVA/CS) composite films with chemical sterilization and near-infrared (NIR) photothermal antibacterial activity was fabricated by electrospinning. Graphene oxide (GO), a photosensitiser, was incorporated into the films, and lanthanum chloride (Lacl3) as a chemical antibacterial agent was also doped in the electrospun films. The structure, morphology, mechanical properties, wettability, and antimicrobial and photothermal antibacterial activity of the PVA/CS-based fibre films were investigated. The results showed that the addition of Lacl3 to the PVA/CS/GO nanofibres (PVA/CS/GO-La) improved the hydrophilicity, tensile strength and resistance to elastic deformation of the nanofibres. The PVA/CS/GO-La12.5 mM sample exhibited the best antibacterial performance, showing high inhibition against Staphylococcus aureus (82% antibacterial efficacy) and Escherichia coli (99.7% antibacterial efficacy). Furthermore, the antibacterial efficacy of the films surface was further enhanced after exposure to NIR light (808 nm, 0.01 W) for 20 min. In addition, the nanofibre films showed no cytotoxicity against human skin fibroblasts (HSFs), indicating its potential application in the field of broad-spectrum antibacterial materials.

Zinc deficiency compromises the maturational competence of porcine oocyte by inducing mitophagy and apoptosis.

Zinc, an essential trace mineral, plays a pivotal role in cell proliferation, maintenance of redox homeostasis, apoptosis, and aging. Serum zinc concentrations are reduced in patients with polycystic ovary syndrome (PCOS). However, the underlying mechanism of the effects of zinc deficiency on the female reproductive system, especially oocyte quality, has not been fully elucidated. Thus, we established an in vitro experimental model by adding N,N,N',N'-Tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) into the culture medium, and to determine the potential regulatory function of zinc during porcine oocytes maturation. In the present study, we found that zinc deficiency caused aberrant meiotic progress, accompanied by the disrupted cytoskeleton structure in porcine oocytes. Zinc deficiency impaired mitochondrial function and dynamics, leading to the increase of reactive oxygen species (ROS) and acetylation level of the antioxidative enzyme superoxide dismutase 2 (SOD2), eventually induced the occurrence of oxidative stress and early apoptosis. Moreover, zinc deficiency perturbed cytosolic Ca2+ homeostasis, lipid droplets formation, demonstrating the aberrant mitochondrial function in porcine oocytes. Importantly, we found that zinc deficiency in porcine oocytes induced the occurrence of mitophagy by activating the PTEN-induced kinase 1/Parkin signaling pathway. Collectively, our findings demonstrated that zinc was a critical trace mineral for maintaining oocyte quality by regulating mitochondrial function and autophagy in porcine oocytes.

A bZIP transcription factor (CiFD) regulates drought- and low-temperature-induced flowering by alternative splicing in citrus.

Drought and low temperature are two key environmental factors that induce adult citrus flowering. However, the underlying regulation mechanism is poorly understood. The bZIP transcription factor FD is a key component of the florigen activation complex (FAC) which is composed of FLOWERING LOCUS T (FT), FD, and 14-3-3 proteins. In this study, isolation and characterization of CiFD in citrus found that there was alternative splicing (AS) of CiFD, forming two different proteins (CiFDα and CiFDß). Further investigation found that their expression patterns were similar in different tissues of citrus, but the subcellular localization and transcriptional activity were different. Overexpression of the CiFD DNA sequence (CiFD-DNA), CiFDα, or CiFDß in tobacco and citrus showed early flowering, and CiFD-DNA transgenic plants were the earliest, followed by CiFDß and CiFDα. Interestingly, CiFDα and CiFDß were induced by low temperature and drought, respectively. Further analysis showed that CiFDα can form a FAC complex with CiFT, Ci14-3-3, and then bind to the citrus APETALA1 (CiAP1) promoter and promote its expression. However, CiFDß can directly bind to the CiAP1 promoter independently of CiFT and Ci14-3-3. These results showed that CiFDß can form a more direct and simplified pathway that is independent of the FAC complex to regulate drought-induced flowering through AS. In addition, a bHLH transcription factor (CibHLH96) binds to CiFD promoter and promotes the expression of CiFD under drought condition. Transgenic analysis found that CibHLH96 can promote flowering in transgenic tobacco. These results suggest that CiFD is involved in drought- and low-temperature-induced citrus flowering through different regulatory patterns.

Alternarialone A, a new curvularin-type metabolite from the mangrove-derived fungus Alternaria longipes.

Alternarialone A (1), one new curvularin derivative, and two known compounds (2 and 3) were isolated from the crude extract of the mangrove-derived fungus Alternaria longipes. Their structures were elucidated by comprehensive spectroscopic analyses, including MS and NMR spectroscopic data. The absolute configuration of 1 was assigned by 13C NMR calculations and a comparison of electronic circular dichroism (ECD) spectra. All compounds were evaluated for their antibacterial activities against Helicobacter pylori. Compounds 2 and 3 showed antibacterial activities against H. pylori G27 with MIC values of 8 and 16 µg/ml, respectively, while compound 3 also displayed antibacterial activity against H. pylori BHKS159 with the MIC value of 16 µg/ml.

[Accumulation of Cry proteins in soil released from Bt rice after planting for multiple years]. / 多年种植Bt稻后外源蛋白在土壤中的积累.

Cry protein residue and accumulation in soil are two important components of the environmental safety assessment for the plantation of transgenic Bt crops. Several Bt rice lines with good commercial prospects have been developed in China, but it is unclear whether Cry proteins will accumulate in soils after multiple years of Bt rice cultivation. We planted the transgenic Bt rice lines cry1Ab/1Ac Minghui 63 (Huahui No. 1) and cry2A Minghui 63 for 9 years in the same field. The Cry proteins in the rhizosphere soil were estimated with enzyme linked immunosorbent assay (ELISA) at tillering stage and on the 60th day after harvest in each year. The Cry protein residues during the seedling, flowering and ripening stages were estimated in the first year (2012) and the last year (2020) of the experiment. In 2012, the concentration of Cry1Ab/1Ac in the rhizosphere soil of Huahui No. 1 was 1.25, 1.77, 1.97, 1.71 and 0.30 ng·g-1 at the seedling, tillering, flowering, ripening stages and on the 60th day after harvest, respectively. In 2020, the corresponding values were 1.30, 1.69, 2.03, 1.77, and 0.43 ng·g-1. In 2012, the concentration of Cry2A in rhizosphere soil of line cry2A Minghui 63 was 0.91, 1.52, 1.53, 1.37, and 0.12 ng·g-1 at the seedling, tillering, flowering, ripening stages and on the 60th day after harvest, respectively. The corresponding values in 2020 were 0.95, 1.43, 1.61, 1.40, and 0.15 ng·g-1. Results of multi-way ANOVA showed that the effect of year was not significant, but the effects of rice variety and growth stage were significant. Our results indicated that Cry proteins could be detected in rhizosphere soil during the growth stages of Bt rice, but would be degraded by 60 d after harvest, and that the concentrations of Cry proteins in the soil would not accumulate across multiple planting years.

A systematic review of the quality of reporting and risk of bias for randomized crossover trials in digestive disease journals.

BACKGROUND: The quality of randomized crossover studies on digestive diseases is unclear. We aimed to review crossover trials in digestive disease journals and evaluate their reporting quality and risk of bias. METHODS: We searched the PubMed, Web of Science, and Scopus databases for all crossover trials in 39 digestive journals between January 2011 and September 2021. Reporting adherence was based on the CONSORT 2010 statement: extension to randomized crossover trials published in July 2019. A newly released Cochrane risk of bias tool 2.0 extension for crossover trials was applied to assess the risk of bias. RESULTS: In total, 173 studies were included in the analysis, and 16.2% were published following the CONSORT statement extension. The crossover design was not only widely used in drug efficacy trials (48.6%) but also in endoscopic ultrasound trials (23.7%) and dietary studies (17.9%) in the field of digestive diseases. The overall reporting adherence was 37.6% for full texts and 43.4% for abstracts. The proportions of trials with low, some concerns, and high risk of bias were 13.9%, 15.6%, and 70.5%, respectively. The difference in reporting adherence and high risk of bias between pre- and post-CONSORT was not significant. Having a sample size plan, defining primary end points, and pre-registration showed higher reporting adherence and lower risk of bias than those who did not. CONCLUSION: These findings demonstrated the inadequate quality of randomized crossover trials for digestive diseases. Compliance with the CONSORT extension for crossover trials must be strengthened and improved (PROSPERO CRD: 42021248723).

Potential mechanism of Ziyin Tongluo Formula in the treatment of postmenopausal osteoporosis: based on network pharmacology and ovariectomized rat model.

BACKGROUND: Amending from ancient classic, Ziyin Tongluo Formula (ZYTLF) has been prescribed to treat postmenopausal osteoporosis (PMOP) for decades with good curative effect. However, the possible mechanisms of it are still unknown. METHODS: Ovariectomized rat model was established to validate the therapeutic effect of ZYTLF on PMOP by Micro-CT bone analysis and pathological observation. Subsequently, active ingredients of ZYTLF and corresponding putative targets were identified by online databases. Overlapping genes were first obtained from mining genes associated with PMOP and then overlapped them with the putative targets. Key genes were selected from the multiple constructed and analyzed networks. GO and KEGG pathway enrichment analysis were performed by importing the key genes to the DAVID database. Moreover, validation of the binding association between key targets and their corresponding active compounds were accomplished by AutoDock Tools and other software. Lastly, Enzyme linked immunosorbent assay (Elisa) detection and Western blot analysis were utilized to further explore the possible mechanism of ZYTLF on PMOP. RESULTS: With 129 target genes interacting with PMOP, 92 active compounds of ZYTLF corresponded to 243 targets, and 50 key genes were chosen. Network analysis revealed the top 10 active ingredients, such as quercetin and kaempferol and the top 50 key genes, such as ERα, p38 MAPK, p-AKT and TGF-ß1. Enrichment analysis uncovered multiple signaling pathways, including estrogen signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Furthermore, our finding of the foremost active compounds was tightly bound to the core proteins, which were verified by molecular docking analysis. Through experimental studies, we confirmed that the prescription of ZYTLF could ameliorate the OVX-induced bone loss, suppress the osteoclast activity and boost osteoblast ability through experimental studies. CONCLUSION: The potential mechanisms and therapeutic effects of ZYTLF against PMOP may be ascribed to inhibition of osteoclast activity, boost of osteoblast activity and enhancement of the expression of ERα.

A MADS-Box Gene CiMADS43 Is Involved in Citrus Flowering and Leaf Development through Interaction with CiAGL9.

MADS-box genes are involved in various developmental processes including vegetative development, flower architecture, flowering, pollen formation, seed and fruit development. However, the function of most MADS-box genes and their regulation mechanism are still unclear in woody plants compared with model plants. In this study, a MADS-box gene (CiMADS43) was identified in citrus. Phylogenetic and sequence analysis showed that CiMADS43 is a GOA-like Bsister MADS-box gene. It was localized in the nucleus and as a transcriptional activator. Overexpression of CiMADS43 promoted early flowering and leaves curling in transgenic Arabidopsis. Besides, overexpression or knockout of CiMADS43 also showed leaf curl phenotype in citrus similar to that of CiMADS43 overexpressed in Arabidopsis. Protein-protein interaction found that a SEPALLATA (SEP)-like protein (CiAGL9) interacted with CiMADS43 protein. Interestingly, CiAGL9 also can bind to the CiMADS43 promoter and promote its transcription. Expression analysis also showed that these two genes were closely related to seasonal flowering and the development of the leaf in citrus. Our findings revealed the multifunctional roles of CiMADS43 in the vegetative and reproductive development of citrus. These results will facilitate our understanding of the evolution and molecular mechanisms of MADS-box genes in citrus.

A Robust Discriminant Framework Based on Functional Biomarkers of EEG and Its Potential for Diagnosis of Alzheimer's Disease.

(1) Background: Growing evidence suggests that electroencephalography (EEG), recording the brain's electrical activity, can be a promising diagnostic tool for Alzheimer's disease (AD). The diagnostic biomarkers based on quantitative EEG (qEEG) have been extensively explored, but few of them helped clinicians in their everyday practice, and reliable qEEG markers are still lacking. The study aims to find robust EEG biomarkers and propose a systematic discrimination framework based on signal processing and computer-aided techniques to distinguish AD patients from normal elderly controls (NC). (2) Methods: In the proposed study, EEG signals were preprocessed firstly and Maximal overlap discrete wavelet transform (MODWT) was applied to the preprocessed signals. Variance, Pearson correlation coefficient, interquartile range, Hoeffding's D measure, and Permutation entropy were extracted as the input of the candidate classifiers. The AD vs. NC discriminant performance of each model was evaluated and an automatic diagnostic framework was eventually developed. (3) Results: A classification procedure based on the extracted EEG features and linear discriminant analysis based classifier achieved the accuracy of 93.18 ± 3.65 (%), the AUC of 97.92 ± 1.66 (%), the F-measure of 94.06 ± 4.04 (%), separately. (4) Conclusions: The developed discrimination framework can identify AD from NC with high performance in a systematic routine.

[Functions and applications of Multi-Tower Platform of Qingyuan Forest Ecosystem Research Station of Chinese Academy of Sciences]. / ä¸­å›½ç§‘å­¦é™¢æ¸ åŽŸæ£®æž—ç”Ÿæ€ç³»ç»Ÿè§‚æµ‹ç ”ç©¶ç«™å¡”ç¾¤å¹³å°çš„åŠŸèƒ½å’Œåº”ç”¨.

The relationship between the structure and function of forest ecosystems is the main intere-sts in the research area of forest ecology and management. However, over complex terrains in particular, these studies had been challenged as uneasy tasks due to the limitations in the forest survey and measurement techniques and other supporting technologies. Chinese Academy of Sciences (CAS) funded "Multi-Tower LiDAR/ECFlux Platform for Monitoring the Structure and Function of Secondary Forest Ecosystems" (Multi-Tower Platform, MTP) as a field station network corner-stone research infrastructure project, which was completed by Qingyuan Forest CERN (Chinese Ecosystem Research Network). In a distinctively-bounded and monitored-outlet watershed, the MTP was integrated by light detection and ranging (LiDAR) scanners, eddy covariance (EC) flux instrument systems, whole- and sub-watershed hydrology station network, long-term forest plot arrays, and live data center. Using LiDAR scanning, the MTP can get cloud data for holographic information on canopy structure. The EC-flux instrument system and hydrology station network along with forest plot arrays could ensure the reliability of water and carbon observations over this complex terrain, which allows to verify the studies on flux measurement technologies and methods, as well as to understand the processes of ecohydrology and CO2 exchange between forest ecosystem and the atmosphere. Further, we can also assess the primary ecosystem services, including water conservation and carbon sequestration. All the data from "tower-station" were streamed through wireless network, which would facilitate data monitoring, management, and sharing. There are three tasks of MTP team: 1) defining innovative methods and descriptors to quantify three-dimensional forest structure; 2) developing theories and techniques to measure CO2/H2O fluxes and other trace gases over complex terrains; 3) understanding the relationship between structure and function of forest ecosystems, providing information and rationales for forest management practices to assure broad and sustainable benefits from forests.

Flavobacterium alkalisoli sp. nov., isolated from rhizosphere soil of Suaeda salsa.

A Gram-negative, strictly aerobic, gliding motility, none-spore forming, yellow, rods bacterial strain, designated XS-5T, was isolated from rhizosphere soil of Suaeda salsa, in Tumd Right Banner, Inner Mongolia, PR China. A phylogenetic tree based on the 16S rRNA gene sequences and the phylogenomic tree both showed that strain XS-5T clustered with Flavobacterium beibuense F44-8T (shared 97.2 % of 16S rRNA gene similarity) and Flavobacterium rakeshii FCS-5T (97.6 %), and shared <96.0 % of 16S rRNA gene similarities with all other type strains. Strain XS-5T contained MK-6 as the major respiratory quinone. Its major polar lipids were phosphatidylethanolamine, an unidentified aminolipid and an unidentified lipid; and the major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 0, iso-C15 : 0 3-OH, Summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c), and Summed feature 9 (iso-C17 : 1 ω9c and/or C16 : 0 10-methyl). The genome consisted of a 3 985 855 bp circular chromosome, with a G+C content of 37.9 mol%, predicting 3616 coding sequences genes, 45 tRNA genes and three rRNA operons. The average nucleotide identity, amino acid identity and digital DNA-DNA hybridization values of strain XS-5T to F. beibuense F44-8T and F. rakeshii FCS-5T were 79.2 and 79.2 %, 81.7 and 81.6 %, 22.3 and 22.2 %, respectively. The results of phylogenetic, physiological and biochemical tests allowed the discrimination of strain XS-5T from its phylogenetic relatives. Flavobacterium alkalisoli sp. nov. is therefore proposed with strain XS-5T (=CGMCC 1.17077T=KCTC 72459T) as the type strain.

Sphingomonas suaedae sp. nov., a chitin-degrading strain isolated from rhizosphere soil of Suaeda salsa.

A Gram-stain-negative, aerobic, chitin-degrading, motile bacterial strain with a single polar flagellum, designated XS-10T, was isolated from saline soil sampled from the rhizosphere of Suaeda salsa, Tumd Right Banner, Inner Mongolia, PR China. Strain XS-10T grew at 10-40 °C (optimum, 35 °C), pH 5.0-9.0 (optimum, pH 8.0) and 0-12.5% NaCl (optimum 2.0 %). The phylogenetic analysis based on both the 16S rRNA gene and the phylogenomic tree revealed that strain XS-10T formed a clade with Sphingomonas turrisvirgatae MCT13T and Sphingomonas koreensis JSS-26T, sharing 98.4 and 97.5 % 16S rRNA gene similarities to S. koreensis JSS-26T and S. turrisvirgatae MCT13T, respectively. Spermidine and Q-10 were the major polyamine and the major respiratory quinone, respectively. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid, two unidentified lipids and an unidentified aminophospholipid. The major fatty acids were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C16 : 0 and C17 : 1 ω6c. The genome of strain XS-10T consisted of a 4 154 291 bp chromosome with a DNA G+C content of 65.5 mol%. The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values of strain XS-10T with S. turrisvirgatae MCT13T and S. koreensis JSS-26T were 77.8 and 78.6 %, 75.9 and 76.3 %, and 22.0 and 22.9 %, respectively. Based on the phylogenetic, phenotypic, and genotypic characteristics, strain XS-10T is considered to represent a novel species of the genus Sphingomonas, for which the name Sphingomonas suaedae sp. nov. is proposed. The type strain is XS-10T (=CGMCC 1.17078T=JCM 33850T).

Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn's disease patients.

BACKGROUND: Thiopurine-induced leukopenia (TIL) is a life-threatening toxicity and occurs with a high frequency in the Asian population. Although nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) variants significantly improve the predictive sensitivity of TIL, more than 50% of cases of this toxicity cannot be predicted by this mutation. The potential use of the 6-thioguanine nucleotide (6TGN) level to predict TIL has been explored, but no decisive conclusion has been reached. Can we increase the predictive sensitivity based on 6TGN by subgrouping patients according to their NUDT15 R139C genotypes? AIM: To determine the 6TGN cut-off levels after dividing patients into subgroups according to their NUDT15 R139C genotypes. METHODS: Patients' clinical and epidemiological characteristics were collected from medical records from July 2014 to February 2017. NUDT15 R139C, thiopurine S-methyltransferase, and 6TGN concentrations were measured. RESULTS: A total of 411 Crohn's disease patients were included. TIL was observed in 72 individuals with a median 6TGN level of 323.4 pmol/8 × 108 red blood cells (RBC), which was not different from that of patients without TIL (P = 0.071). Then, we compared the 6TGN levels based on NUDT15 R139C. For CC (n = 342) and CT (n = 65) genotypes, the median 6TGN level in patients with TIL was significantly higher than that in patients without (474.8 vs 306.0 pmol/8 × 108 RBC, P = 9.4 × 10-5; 291.7 vs 217.6 pmol/8 × 108 RBC, P = 0.039, respectively). The four TT carriers developed TIL, with a median 6TGN concentration of 135.8 pmol/8 × 108 RBC. The 6TGN cut-off levels were 411.5 and 319.2 pmol/8 × 108 RBC for the CC and CT groups, respectively. CONCLUSION: The predictive sensitivity of TIL based on 6TGN is dramatically increased after subgrouping according to NUDT15 R139C genotypes. Applying 6TGN cut-off levels to adjust thiopurine therapies based on NUDT15 is strongly recommended.

Efficiency of Zoledronic Acid in Inhibiting Accelerated Periprosthetic Bone Loss After Cementless Total Hip Arthroplasty in Osteoporotic Patients: A Prospective, Cohort Study.

OBJECTIVE: To investigate the influence of preoperative osteopenia/osteoporosis on periprosthetic bone loss after total hip arthroplasty (THA) and the efficiency of zoledronate (ZOL) treatment in periprosthetic bone preservation. METHODS: This multicenter, prospective cohort study was conducted in four centers between April 2015 and October 2017. Patients were assigned to Normal BMD, Osteopenia, and Osteoporosis+ZOL groups. Patients with osteopenia received daily oral calcium (600 mg/d) and vitamin D (0.5 µg/d), while patients in the Osteoporosis+ZOL group received additional ZOL annually (5 mg/year). Periprosthetic bone mineral density (BMD) in seven Gruen zones, radiographic parameters, Harris hip score, EuroQol 5-Dimensions (EQ-5D) score, and BMD in hip and spine were measured within 7 days, 3 months, 12 months postoperation and annually thereafter. RESULTS: A total of 266 patients were enrolled, while 81 patients that completed the first year follow-up were involved in the statistical analysis. The mean follow-up time was 1.3 years. There were significant decreases of mean BMD in total Gruen zones (-4.55%, P < 0.05) and Gruen zone 1 (-10.22%, P < 0.01) in patients with osteopenia during the first postoperative year. Patients in the Osteoporosis+ZOL group experienced a marked increase in BMD in Gruen zone 1 (+16%) at the first postoperative year, which had a significant difference when compared with the Normal BMD group (P < 0.05) and the Osteopenia Group (P < 0.001). Low preoperative BMD in hip and spine was predictive of bone loss in Gruen zone 1 at 12 months after THA in patients with normal BMD (R2 = 0.40, P < 0.05). CONCLUSIONS: Patients with osteopenia are prone to higher bone loss in the proximal femur after cementless total hip arthroplasty (THA). ZOL, not solely calcium and vitamin D, could prevent the accelerated periprosthetic bone loss after THA in patients with osteopenia and osteoporosis.

Response of sap flow rate of apple trees to environmental factors in Loess Platea of Western Shanxi Province, China.

To clarify the effects of environmental factors on transpiration process of apple trees in rain-fed ecosystem, the dynamics of sap flow in apple trees from Loess Plateau area in western Shanxi Province of China were monitored using the thermal diffusion technique. Meanwhile, environmental factors including meteorological elements and soil moisture content were measured. The results showed that both net solar radiation (Rn) and atmospheric vapor deficit (VPD) were closely correlated with sap flow rate (Js), as the main ones among all the measured environmental factors. At both hourly and daily scales, the cumulative variances of the three principal components of the environmental factor were above 86%. The first principal component contained VPD and Rn, and explained the variance of over 52% (at hour scale) and 63% (at daily scale), which could be classified as the evaporation demand index (EDI) and as the key comprehensive environmental varia-bles affecting tree sap flow. The second principal component mainly included soil moisture content (SWC) and other factors, which were referred to the soil water and heat supply index. The third principal component mainly included wind speed and other factors, and could be classified into the hydrothermal dissipation index. At the scale of hourly or daily, the response of Js to EDI showed a significant exponential growth relationship. At the hourly time scale, Js of apple trees could be accurately modelled based on the first principal component EDI (R2=0.72). At the daily scale, Js of apple trees could be better modelled based on potential evapotranspiration (ET0) (R2=0.88). Our results were of great significance for clarifying the responses of water transport in apple tree to environmental factors, estimating water consumption of apple tree based on meteorological factors, as well as directing orchard water management.