Enhancing Structural Rigidity of Ultrahigh-Ni Oxide Through Al and Nb Dual-Bulk-Doping for High-Voltage Lithium-Ion Batteries.

The pursuit of high energy densities propels the design of next-generation nickel-based layered oxide cathodes. The utilization of low-cobalt, ultrahigh-nickel layered oxide cathodes, and the extension of operating voltages promise enhanced energy density. However, stability and safety face challenges associated with nickel content, including structural degradation, lattice oxygen evolution, and thermal instability. In this study, a promising strategy of Al and Nb dual-bulk-doping is presented in high-Ni cathode materials of LiNi0.96Co0.04O2 (NC) to stabilize the bulk structure, suppress oxygen release, and attain superior electrochemical performance at high voltages. The introduction of Al and Nb effectively raises the migration energy of Ni2+ into Li sites and stabilizes lattice oxygen through strengthened Al─O and Nb─O bonds. Furthermore, the substitution of high-valence Nb ions reduces the charge depletion of lattice oxygen and induces an ordered microstructure. The Al and Nb dual-bulk-doping strategy mitigates strain and stress associated with the H2↔H3 phase transition, reducing the generation and propagation of microcracks. The resulting Li(Ni0.96Co0.04)0.985Al0.01Nb0.005O2 (NCAN) cathode exhibits superior cycling stability, with a capacity retention of 77.8% after 300 cycles, even when operating at a high-voltage of 4.4 V, outperforming the NC (48.5%). This work provides a promising perspective for developing high-voltage and high-Ni cathode materials.

Ga-Doped Ultrahigh-Nickel Oxide Microspheres with Radially Aligned Primary Grains as a Cathode for Stable Cycling Li-Ion Batteries.

Owing to the high energy density, ultrahigh-nickel (Ni > 0.9) layered oxides are used as promising cathode materials for next-generation Li-ion batteries. Unfortunately, the serious pulverization and rapid capacity fading during cycling limit the commercial viability of an ultrahigh-nickel oxide cathode. Herein, the introduction of Ga into LiNi0.96Co0.04O2 brings a radially aligned microstructural change of oxide microspheres during the lithiation of the Ni0.96Co0.04(OH)2 precursor. As expected, such radially aligned needle-like primary grains on microspheres have a positive influence to reduce the anisotropic volume change and suppress the formation of microcracks of Ga-induced Li(Ni0.96Co0.04)0.99Ga0.01O2 during cycling. Specifically, compared with irregular primary grains of LiNi0.96Co0.04O2, Ga-induced oxide presents a high initial discharge capacity of 227.9 mA h g-1 at 0.1C rate between 2.8 and 4.3 V. Especially, Ga-induced oxide delivers higher initial discharge capacities of 233.9 and 240.3 mA h g-1 with higher cutoff charge voltages of 4.4 and 4.5 V at 0.1C, respectively. Furthermore, a good capacity retention of 74.1% at 1 C rate is obtained after 300 cycles, which is almost 85% higher than that of the pristine sample, mainly due to the generation of microcracks of oxide microspheres during the long-term cycle. Therefore, the introduction of Ga into LiNi0.96Co0.04O2 is a feasible approach for improving the microstructure and cycling stability of the ultrahigh-Ni layered oxides.

La-Doped Ultrahigh-Nickel Layered Oxide Cathode with Enhanced Cycle Stability for Li-Ion Batteries.

Currently, ultrahigh-nickel layered oxide is one of the most promising cathodes for lithium-ion batteries, with the advantages of high theoretical capacity and low cost. However, some problems in ultrahigh-nickel layered oxides are more serious, such as irreversible structural transformation, particle cracking, and side reactions at the electrode/electrolyte interface, resulting in the fast decay of the discharge capacity and midpoint potential. In this work, La doping is introduced into ultrahigh-nickel layered LiNi0.9Co0.1O2 oxide to improve the cycle stability on both discharge capacity and midpoint potential. As demonstrated, La can be doped successfully into the subsurface of LiNi0.9Co0.1O2 oxide, and the morphology of the oxide microspheres is not changed obviously by La doping. Compared with the pristine sample, the La-doped sample presents improved electrochemical performance, especially good cycle stabilization on both discharge capacity and midpoint potential. In addition, after a long-term cycle, the La-doped sample still maintains a relatively complete spherical morphology. It means that the pillaring effect of La with a large radius is helpful in accommodating the volume change caused by the insertion/extraction of Li ions, thus easing the anisotropic stress accumulation and microcrack growth inside the microspheres of the La-doped sample.

Lysine 2-hydroxyisobutyrylation of NAT10 promotes cancer metastasis in an ac4C-dependent manner.

Posttranslational modifications add tremendous complexity to proteomes; however, gaps remain in knowledge regarding the function and regulatory mechanism of newly discovered lysine acylation modifications. Here, we compared a panel of non-histone lysine acylation patterns in metastasis models and clinical samples, and focused on 2-hydroxyisobutyrylation (Khib) due to its significant upregulation in cancer metastases. By the integration of systemic Khib proteome profiling in 20 paired primary esophageal tumor and metastatic tumor tissues with CRISPR/Cas9 functional screening, we identified N-acetyltransferase 10 (NAT10) as a substrate for Khib modification. We further showed that Khib modification at lysine 823 in NAT10 functionally contribute to metastasis. Mechanistically, NAT10 Khib modification enhances its interaction with deubiquitinase USP39, resulting in increased NAT10 protein stability. NAT10 in turn promotes metastasis by increasing NOTCH3 mRNA stability in an N4-acetylcytidine-dependent manner. Furthermore, we discovered a lead compound #7586-3507 that inhibited NAT10 Khib modification and showed efficacy in tumor models in vivo at a low concentration. Together, our findings bridge newly identified lysine acylation modifications with RNA modifications, thus providing novel insights into epigenetic regulation in human cancer. We propose that pharmacological inhibition of NAT10 K823 Khib modification constitutes a potential anti-metastasis strategy.

ANO1 Reprograms Cholesterol Metabolism and the Tumor Microenvironment to Promote Cancer Metastasis.

SIGNIFICANCE: Metastatic cancer cells upregulate ANO1 to activate cell-intrinsic and -extrinsic mechanisms that alter cholesterol metabolism and stimulate fibroblasts, which can be targeted with ANO1 inhibitors to inhibit metastatic growth. See related commentary by Singh and Mehla, p. 1759.

PES1 reduces CD8+ T cell infiltration and immunotherapy sensitivity via interrupting ILF3-IL15 complex in esophageal squamous cell carcinoma.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has brought survival benefits to patients with specific cancer types, most of cancer patients remain refractory to the ICB therapy, which is largely attributed to the immunosuppressive tumor microenvironment. Thereby, it is urgent to profile key molecules and signal pathways responsible for modification of tumor microenvironment. METHODS: Multiple databases of esophageal squamous cell carcinoma (ESCC) were integratively analyzed to screen candidate genes responsible for infiltration of CD8+ T cells. Expression of pescadillo ribosomal biogenesis factor 1 (PES1) in clinical ESCC samples was examined by qRT-PCR, western blotting, and immunohistochemistry. The mechanisms of PES1 were investigated via RNA sequencing and mass spectrometry followed by immunoprecipitation and proximity ligation assay. The clinical and therapeutic significance of PES1 in ESCC was comprehensively investigated using ESCC cells and mouse model. RESULTS: PES1 was significantly upregulated and correlated with poor prognosis in ESCC patients. PES1 knockdown decreased ESCC cell growth in vitro and in vivo and enhanced the efficacy of ICB therapy in mouse model, which was established through subcutaneous inoculation with ESCC cells. Analyses on RNA sequencing and mass spectrometry suggested that PES1 expression was negatively correlated with IL15 and ILF3 was one of the PES1-associated proteins. It has been known that ILF3 interacts with and stabilizes IL15 mRNA to increase IL15 protein level. Our data further indicated that PES1 interfered with the interaction between ILF3 and IL15 mRNA and impaired ILF3-mediated stabilization of IL15 mRNA, which eventually reduced the protein level of IL15. Interestingly, the inhibitory effect of ICB therapy boosted by PES1 knockdown dramatically antagonized by knockdown of IL15, which suppressed the tumor-infiltrated CD8+ T cells in ESCC. Finally, we confirmed the relationships among PES1, IL15, and CD8+ T cell infiltration in 10 locally advanced ESCC patients receiving ICB neoadjuvant therapy and demonstrated that ICB therapy would be more effective in those with low expression of PES1. CONCLUSIONS: Altogether, our findings herein provided novel insights on biological function and clinical significance of PES1 and suggested that high expression of PES1 could suppress ILF3-IL15 axis-mediated immunosurveillance and promote resistance to ICB through restraining tumor-infiltrated CD8+ T cells.

N4-acetylcytidine modification of lncRNA CTC-490G23.2 promotes cancer metastasis through interacting with PTBP1 to increase CD44 alternative splicing.

Although N4-acetylcytidine (ac4C) modification affects the stability and translation of mRNA, it is unknown whether it exists in noncoding RNAs, and its biological function is unclear. Here, nucleotide-resolution method for profiling CTC-490G23.2 ac4C sites and gain- and loss-of-function experiments revealed that N-acetyltransferase 10 (NAT10) is responsible for ac4C modification of long noncoding RNAs (lncRNAs). NAT10-mediated ac4C modification leads to the stabilization and overexpression of lncRNA CTC-490G23.2 in primary esophageal squamous cell carcinoma (ESCC) and its further upregulation in metastatic tissues. CTC-490G23.2 significantly promotes cancer invasion and metastasis in vitro and in vivo. Mechanistically, CTC-490G23.2 acts as a scaffold to increase the binding of CD44 pre-mRNA to polypyrimidine tract-binding protein 1 (PTBP1), resulting in a oncogenic splicing switch from the standard isoform CD44s to the variant isoform CD44v(8-10). CD44v(8-10), but not CD44s, binds to and increases the protein stability of vimentin. Expression levels of CTC-490G23.2 and CD44v(8-10) can predict poor prognosis in cancer patients. Furthermore, the antisense oligonucleotide (ASO)/SV40-LAH4-L1 peptide self-assembled nanocomplexes targeting CTC490G23.2 exerts a significantly suppressive effect on cancer metastasis. The outcome of this study will provide new mechanistic insight into the ac4C modification of lncRNAs and useful clues for the development of novel systemic therapies and prognostic biomarkers.

A feasibility study of different GSI noise indexes and concentrations of contrast medium in hepatic CT angiography of overweight patients: image quality, radiation dose, and iodine intake.

PURPOSE: To conduct a comparative study of image quality, radiation dose, and iodine intake in hepatic computed tomographic angiography (CTA) of overweight patients with different Gemstone Spectral Imaging (GSI) noise indexes combined with different concentrations of contrast medium. MATERIALS AND METHODS: Ninety patients with a body mass index of ≥ 25 kg/m2 were divided into three groups (A, B and C), each with 30 patients. The three groups underwent hepatic CTA with different NI of 7, 11 and 15, respectively, and were injected with different iodine concentrations of 370, 350 and 320 mgI/mL, respectively. Five sets of images at 40-60 keV (interval, 5 keV) were reconstructed in each group. The CT value, image noise, contrast-to-noise ratio (CNR) and subjective score of the hepatic artery and vein, and portal vein in different monochromatic image sets were analyzed to select the optimal energy level in each group. The differences in CT value, image noise, CNR and a subjective score of hepatic artery and vein, portal vein in the optimal monochromatic images among the three groups were compared, the volume CT dose index (CTDIvol) and dose-length product (DLP) were recorded, and the effective dose and iodine intake were calculated. RESULTS: The 40 keV was determined to be the optimal energy level for the monochromatic image sets in each group. No significant group differences were noted in the CT value, image noise, CNR, and subjective image scores of the hepatic artery and vein, and portal vein for the optimal monochromatic images (P > 0.05). Compared with group A, the effective dose and iodine intake in group B were reduced by 50.18% and 9.3%, and by 58.12% and 14.23% in group C, respectively. CONCLUSION: A low-concentration contrast medium combined with a high-noise GSI index in hepatic CTA of overweight patients can reduce the radiation dose and iodine intake while ensuring image quality.

Extensive crystal fractionation of high-silica magmas revealed by K isotopes.

Fractional crystallization plays a critical role in generating the differentiated continental crust on Earth. However, whether efficient crystal-melt separation can occur in viscous felsic magmas remains a long-standing debate because of the difficulty in discriminating between differentiated melts and complementary cumulates. Here, we found large (~1 per mil) potassium isotopic variation in 54 strongly peraluminous high-silica (silicon dioxide >70 weight %) leucogranites from the Himalayan orogen, with potassium isotopes correlated with trace elemental proxies (e.g., strontium, rubidium/strontium, and europium anomaly) for plagioclase crystallization. Quantitative modeling requires up to ~60 to 90% fractional crystallization to account for the progressively light potassium isotopic composition of the fractionated leucogranites, while plagioclase accumulation results in enrichment of heavy potassium isotopes in cumulate leucogranites. Our findings strongly support fractional crystallization of high-silica magmas and highlight the great potential of potassium isotopes in studying felsic magma differentiation.

Comparing feasibility of different tube voltages and different concentrations of contrast medium in coronary CT angiography of overweight patients.

OBJECTIVES: To compare image quality, radiation dose, and iodine intake of coronary computed tomography angiography (CCTA) acquired by wide-detector using different tube voltages and different concentrations of contrast medium (CM) for overweight patients. MATERIALS AND METHODS: A total of 150 overweight patients (body mass index≥25 kg/m2) who underwent CCTA are enrolled and divided into three groups according to scan protocols namely, group A (120 kVp, 370 mgI/ml CM); group B (100 kVp, 350 mgI/ml CM); and group C (80 kVp, 320 mgI/ml CM). The CT values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and figure-of-merit (FOM) of all images are calculated. Images are subjectively assessed using a 5-point scale. In addition, the CT dose index volume (CTDIvol) and dose length product (DLP) of each patient are recorded. The effective radiation dose (ED) is also calculated. Above data are then statistically analyzed. RESULTS: The mean CT values, SNR, CNR, and subjective image quality of group A are significantly lower than those of groups B and C (P < 0.001), but there is no significant difference between groups B and C (P > 0.05). FOMs show a significantly increase trend from group A to C (P < 0.001). The ED values and total iodine intake in groups B and C are 30.34% and 68.53% and 10.22% and 16.85% lower than those in group A, respectively (P < 0.001). CONCLUSION: The lower tube voltage and lower concentration of CM based on wide-detector allows for significant reduction in iodine load and radiation dose in CCTA for overweight patients comparing to routine scan protocols. It also enhances signal intensity of CCTA and maintains image quality.

Feasibility and Efficacy of a Degradable Magnesium-Alloy GBR Membrane for Bone Augmentation in a Distal Bone-Defect Model in Beagle Dogs.

We explored the feasibility and efficacy of a degradable magnesium (Mg) alloy guided bone regeneration (GBR) in the treatment of bone defects after tooth extraction. A GBR membrane (MAR-Gide (MG)) was used to treat a mandibular second molar (M2M)-distal bone defect (DBD). In eight beagle dogs, bilateral mandibular second and fourth premolars were hemi-sected. The distal roots were removed to create a two-wall bony defect of dimension 5 mm × 5 mm × 5 mm to simulate M2M-DBD. Thirty-two bone defects were assigned randomly into four groups according to GBR membranes (MG and Bio-Gide (BG)) applied and the time of killing (3 months and 6 months after surgery). The osteogenesis of bone defects and MG degradation were analyzed using micro-CT, histology (staining, tartrate-resistant acid phosphatase), and inductively coupled plasma mass spectrometry. MG did not increase the prevalence of infection, wound dehiscence, or subcutaneous emphysema compared with those using BG. Trabecular volume/total volume at 3 months (63.71 ± 10.4% vs. 59.97 ± 8.94%) was significantly higher in the group MG than that in the group BG. Implanted MG was degraded completely within 3 months, and "island-shaped" new bone was found near MG degradation products. A significant difference was not found in vertical bone height or percent of new bone formation (45.44 ± 12.28% vs. 43.49 ± 7.12%) between the groups. The concentration of rare-earth elements in mandibular lymph nodes of the group MG was significantly higher than that of the group BG (P ≤ 0.017) but did not lead to histopathological changes. In summary, MG exhibited good biocompatibility and clinical applicability compared with BG in vivo. The osteogenic effect of MG could be enhanced by regulating the degradation rate of Mg-alloy.

Efficacy and safety of Zicuiyin decoction on diabetic kidney disease: A multicenter, randomized controlled trial.

BACKGROUD: Zicuiyin (ZCY) decoction created by Xichun Zhang in the Qing dynasty has been used on diabetes mellitus and complications for more than two centuries in China. Huangkui capsule (HKC) is a listed Chinese patent medicine to treat diabetic kidney disease (DKD). To determine whether ZCY is non-inferior to HKC in the treatment of DKD, a multicenter, parallel-control, open-label, randomized clinical trial was conducted. METHODS: In this clinical trial, 88 DKD patients were recruited at three centers in Tianjin from January 2018 to December 2019. They were randomized to receive HKC (2.5 g, TID) or ZCY (crude drug amount 75 g, 150 ml, BID) for eight weeks based on routine treatment. The primary outcome was the change of estimated glomerular filtration rate (eGFR). The secondary outcomes included change of serum creatinine (SCr), urinary albumin excretion rate, 24 h urinary protein, urinary albumin-creatinine ratio, glycosylated hemoglobin A1c, symptom scores, and microbiota compositions profiles. RESULTS: The change of eGFR in HKC and ZCY groups were -7.08 ± 24.65 and 2.57 ± 18.49 ml/min/1.73 m2, respectively (p < 0.05). The 95% lower confidence limit for the difference between the estimated means was 1.93 ml/min/1.73 m2, establishing the superiority of ZCY. Compared to HKC, ZCY could significantly decrease SCr and symptom scores (p < 0.05). There were no significant differences in other outcomes between the two groups (p > 0.05). ZCY ameliorated gut microbiota dysbiosis, including increased Prevotellaceae and Lactobacillaceae and decreased Enterobacteriales, Clostridiaceae and Micrococcaceae. No severe adverse events were reported in any group. CONCLUSIONS: ZCY had better efficacy in improving and protecting kidney function. It would be an alternative option to treat DKD, especially those who decline eGFR and gut microbiota dysbiosis. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-OON-17012076. Registered July 21, 2017.

[Efficacy of Yishen Huoxue Tongluo() medicated serum on apoptosis of nucleus pulposus cells of human intervertebral disc under overload static pressure].

OBJECTIVE: To explore the efficacy of Yishen Huoxue Tongluo() decoction containing serum on the apoptosis of human disc nucleus pulposus cells under the overload static pressure stress and its related mechanism. METHODS: Human nucleus pulposus cells were divided into three groups. The blank group had no intervention. The model group and traditional Chinese medicine serum intervention group were treated with 3 MPa compressive stress in vitro for 2, 4 and 6 hours. The changes and differences of morphology, growth status and ultrastructure of intervertebral disc nucleus pulposus cells were observed. The apoptosis rate of nucleus pulposus cells and nuclear factor kappa-B p65 (NF-κB p65), SRY-related high mobility group box 9 (SOX9), C/EBP-homologous protein (CHOP), matrix metalloprotein-13 (MMP-13) and corresponding gene expression were detected. RESULTS: At the same time, compared with the blank group, the nucleus pulposus cells in the model group were smaller in volume, less in cytoplasm and worse in growth; the nucleus pulposus cells in the traditional Chinese medicine serum intervention group were slightly larger in volume, more complete in morphology, richer in cytoplasm and better in growth. Under the same action time, the ultrastructure of nucleus pulposus cells in blank group was complete, and the structures of primary and secondary processes were not broken;and the ultrastructure of model group and traditional Chinese medicine serum intervention group were damaged, the main and secondary processes were broken to varying degrees, and there was no significant difference between the two groups. At the same time, the apoptosis rate of nucleus pulposus cells in model group was higher than that in blank group, while the apoptosis rate of nucleus pulposus cells in the traditional Chinese medicine serum intervention group was lower than that inmodel group, the difference was statistically significant (P<0.05); with the increase of action time, there was no significant difference in the apoptosis rate of nucleus pulposus cells between blank group and traditional Chinese medicine serum intervention group, and the apoptosis rate of nucleus pulposus cells in model group was increased. Compared with model group, the expression of NF-κB p65, CHOP, MMP-13 were decreased and SOX9 was increased in traditional Chinese medicine serum intervention group at the same time (P<0.05);with the increase of action time, the expression of NF-κB p65, CHOP and MMP-13 were increased, and the expression of SOX9 was decreased in blank group and model group(P<0.05), and the expression level of model group was higher than that of blank group(P<0.05). Overall observation by gene expression, under the same action time, the relative quantifications of NF-κB p65, CHOP and MMP-13 in traditional Chinese medicine serum intervention group were lower than that in model group, while SOX9 was increased (P<0.05);compared with model group, the relative quantifications of NF-κB p65, CHOP and MMP-13 in blank group were decreased(P<0.05), and the relative quantification of SOX9 was increased(P<0.05);with the increase of action time, the relative quantifications of NF-κB p65, CHOP and MMP-13 of nucleus pulposus cells in blank group and model group were increased and SOX9 was decreased(P<0.05). CONCLUSION: Yishen Huoxue Tongluo() decoction can reduce the apoptosis of nucleus pulposus cells under overload and static pressure, and has the effect of delaying the degeneration of nucleus pulposus cells. Its mechanism may be related to the decrease of CHOP, MMP-13 expression and the increase of SOX9 expression by inhibiting NF-κB p65 signal pathway of nucleus pulposus cells.

Insulin-Like Peptide and FoxO Mediate the Trehalose Catabolism Enhancement during the Diapause Termination Period in the Chinese Oak Silkworm (Antheraea pernyi).

In insects, trehalose accumulation is associated with the insulin/insulin-like growth factor signalling (IIS) pathway. However, whether insulin-like peptide is involved in the regulation of the trehalose metabolism during diapause termination remains largely unknown. This study assessed whether insulin-like peptide (ApILP) enhances the trehalose catabolism in the pupae of Antheraeapernyi during their diapause termination process. Injection of 10 µg of bovine insulin triggered diapause termination and synchronous adult eclosion in diapausing pupae. Moreover, treatment with bovine insulin increased the expression of trehalase 1A (ApTre-1A) and trehalase 2 (ApTre-2), as well as the activity of soluble and membrane-bound trehalase, resulting in a decline in trehalose levels in the haemolymph. Silencing ApILP via RNA interference significantly suppressed the expression of ApTre-1A and ApTre-2, thus leading to an increase in the trehalose concentration during diapause termination. However, neither injection with bovine insulin nor ApILP knockdown directly affected trehalase 1B (ApTre-1B) expression. Moreover, overexpression of the transcription factor forkhead box O (ApFoxO) induced an increase in trehalose levels during diapause termination; however, depletion of ApFoxO accelerated the breakdown of trehalose in diapausing pupae by increasing the expression of ApTre-1A and ApTre-2. The results of this study help to understand the contributions of ApILP and ApFoxO to the trehalose metabolism during diapause termination.

Acute hepatotoxicity and nephrotoxicity risk assessment of the Tibetan medicine 25 flavors of the turquoise pill based on 1H-NMR metabonomics.

ETHNOPHARMACOLOGICAL RELEVANCE: 25 flavors of the turquoise pill, a traditional Tibetan medicine for the treatment of various types of hepatitis, has not been investigated on its safety, especially the component mineral turquoise, which is believed to be essential but worried for its potential toxicity. AIM OF THE STUDY: To explore the potential acute toxicity and function of 25 flavors of the turquoise pill and turquoise, the possible mechanism of the effects of turquoise and 25 flavors of the turquoise pill were systematically studied based on 1H NMR metabolomics. MATERIALS AND METHODS: The rats were administered with turquoise and 25 flavors of the turquoise pill by gavage for 7 days, and samples of serum, liver, and kidney were collected. The potential toxicity and function of turquoise and 25 flavors of the turquoise pill on the liver and kidney of SD rats were evaluated by 1H NMR metabonomics, histopathology, and biochemical indexes. RESULTS: The results demonstrated that 25 flavors of the turquoise pill could scavenge free oxygen radicals, strengthen aerobic respiration and inhibit glycolysis in the liver. It did not cause oxidative stress in the kidney with no obvious damage. By modulation of branched-chain amino acids (BCAAs), 25 flavors of the turquoise pill can improve the utilization of glucose and promote aerobic respiration of the kidney. CONCLUSION: Considering the high dosage and short duration used in this study relative to their typical clinical usage, administration of 25 flavors of the turquoise pill and its component mineral turquoise are safe to livers and kidneys.

Automatic Detection and Measurement of Spinous Process Curve on Clinical Ultrasound Spine Images.

The ultrasound (US) imaging technique has been applied to scoliosis assessment, and the proxy Cobb angle can be acquired on the US coronal images. The spinous process angle (SPA) is a valuable parameter to indicate 3-D deformity of spine. However, the SPA cannot be measured on US images since the spinous process (SP) is merged in the soft tissue layer and impossible to be identified on the coronal view directly. A new method based on the gradient vector flow (GVF) snake model was proposed to automatically locate SP position on the US transverse images, and the density-based spatial clustering of application with noise (DBSCAN) was used to remove the outliers out of the detected location results. With marking the SP points on the US coronal image, the SP curve was interpolated and the SPA was measured. The algorithm was evaluated on 50 subjects with various severity of scoliosis, and two raters measured the SPA on both US images and radiographs manually. The mean absolute differences (MADs) of SPAs obtained from the two modalities were 3.4° ± 2.4° and 3.6° ± 2.8° for the two raters, respectively, which were less than the clinical acceptance error (5°), and the results reported a good linear correlation ( ) between the US method and radiography. It indicates that the proposed method can be a promising approach for SPA measurement using the US imaging technique.

Therapeutic assessment of fractions of Gastrodiae Rhizoma on chronic atrophic gastritis by 1H NMR-based metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodiae Rhizoma (GR), a well-known and commonly-used TCM (Traditional Chinese Medicine) for treating headache, dizziness, tetanus, epilepsy, and etc., has been proven to relieve chronic atrophic gastritis (CAG). Due to its complex ingredients, the active fractions responsible for the treatment of CAG remain largely unknown. AIM OF THE STUDY: To explore the underlying material and interpret its underlying mechanism, the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG was studied based on the 1H NMR metabolomics. MATERIALS AND METHODS: The rat model of CAG was established by autoimmune method. The modeled CAG rats were then treated with 4 polar parts (T1-4 in descending polarity, corresponding to water, n-butanol, ethyl acetate and petroleum ether extracts, respectively) of Gastrodiae Rhizoma for 21 consecutive days. The stomach and serum samples were collected and then subjected to histopathology observation, biochemical measurement (MDA, SOD, GSH, NO, XOD and pepsin), 1H NMR metabolic profiling and multivariate/univariate statistical analysis. RESULTS: The results showed that T1 had the best therapeutic effect, T2 the second, and T3 and T4 the poorest with no obvious therapeutic effect, demonstrating that the effective components of Gastrodiae Rhizoma should be compounds of high polarity. T1 achieved good therapeutic effects due to the anti-inflammatory and anti-oxidant activities, and by rectifying the disturbed energy and amino acid metabolism in CAG model. CONCLUSION: This integrated metabolomics approach proved the validity of the therapeutic effect of extract from different polar parts of Gastrodiae Rhizoma on autoimmune CAG, providing new insights into the underlying mechanisms, and demonstrating the feasibility of metabolomics to evaluate efficacy of herbal drug, which is often difficult by traditional means.

Potential hepatoxicity risk of the shell of Herpetospermum caudigerum Wall in rats based on 1H-NMR metabonomics.

The Herpetospermum caudigerum Wall (HCW) is a traditional Tibetan medicine and is widely used in clinical practice. However, the shell of the HCW (SHCW) has rarely been studied, and some researchers have suggested that the SHCW may be toxic. Therefore, in this study, SHCW was administered to rats at two doses (0.1 and 0.33 g/kg) once a day for 21 days. The hepatic stimuli induced by SHCW in rats were investigated for the first time by 1H-NMR-based metabolomics combined with histopathological observation and biochemical detection. Histopathological sections showed a certain degree of hepatocyte edema and hepatic sinus congestion in the liver tissue of the rats in the drug-administered group. Serum biochemical indicators revealed a significant increase in ALT, AST, and MDA, and a significant decrease in SOD. Metabolomic results showed that the metabolites in rats were changed after gavage administration of extracts from SHCW. By multivariate statistical analysis and univariate analysis, it was found that SHCW could cause the disorder of energy metabolism, oxidative stress and amino acid metabolism in rats, leading to liver damage. This comprehensive metabolomics approach demonstrates its ability to describe the global metabolic state of an organism and provides a powerful and viable tool for exploring drug-induced toxicity or side effects.

[Analysis of Transport and Transformation Characteristics Between Dissolved Phosphorus and Particulate Phosphorus in Water of the Three Gorges Reservoir].

To understand the difference between transport coefficients of water runoff, sand discharge, and phosphorus flux in each subsection of a river, a judgement method for analyzing the characteristics of phosphorus transport and transformation in water of rivers was established in this study. Based on the measured data of water runoff, sand discharge, and phosphorus fraction concentrations in the water of the Three Gorges Reservoir (TGR) in January and July 2015, characteristics of phosphorus transport and transformation in the water were analyzed by using the conceptual method. The results showed that the predominant phosphorus fraction in water of the TGR was total dissolved phosphorus (TDP), which accounted for 51%-96% of total phosphorus in water. The TDP flux relative to runoff in the TGR decreased in January 2015 That was caused by the adsorption of TDP by suspended particles in the dry season. In contrast, TDP flux showed additive effect relative to water runoff in July 2015 due to exogenous water inputs with high TDP concentrations in the wet season. Both sand and total particulate phosphorus (TPP) presence in the water showed obvious sediment and retention characteristics during the two periods. The TPP flux presented an additive effect relative to sand discharge, meaning that the major transformation direction of phosphorus fractions was from TDP to TPP. The subsection between Qingxichang and Wanzhou was the main retention area of water, sand, and phosphorus in the TGR, which can be associated with the enhancement of phosphorus adsorption capacity caused by particle size reduction of suspended particles in the subsection.

[Methylation level of MEG3 and semen quality].

OBJECTIVE: To study the relationship between semen quality and the methylation level of maternally expressed gene 3 (MEG3) in sperm. METHODS: We collected the general demographic data, semen samples and results of clinical semen analysis from 403 married men undergoing pre-conception examinations in March and April 2015 and March and April 2016. Using pyrosequencing, we quantitatively detected the methylation level at 8 CpG sites in the differentially methylated region of MEG3, and subjected the data obtained to variance analysis, Pearson correlation analysis, two-sample t-test and multivariate linear regression analysis. RESULTS: Both the individual and mean methylation levels at CpG sites 1－8 of MEG3 were correlated highly negatively with sperm concentration (P < 0.05), but not with the semen volume, sperm motility, or the percentage of morphologically normal sperm (P > 0.05). The men with an abnormal sperm concentration exhibited significantly higher individual and mean methylation levels at the 8 CpG sites than those with a normal one (P < 0.05). After adjusting for age as a confounding factor, multivariate linear regression analysis showed a decrease of 1.684 × 106/mL in sperm concentration for every 1% increase in the average methylation of MEG3 (P < 0.05). CONCLUSIONS: The imprinting gene MEG3 is involved in spermatogenesis and its methylation level may influence sperm concentration.