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.

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.

[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.

[Persistent chlamydial genital infection in Tianjin area: An epidemiological study].

OBJECTIVE: To investigate the epidemic features of persistent genital chlamydial infection (GCI) in Tianjin area. METHODS: We statistically analyzed the clinical data about the persistent GCI patients received at the Venereal Disease Clinic of Tianjin Medical University General Hospital from 2009 to 2011. RESULTS: A total of 158 patients with persistent GCI were received from Tianjin area. The patients ranged in age from 19 to 67 years, 39.24% from 20 to 29 and 34.81% from 30 to 39 years, 36.71% with commercial occupation, and 55.06% with college education or above. The sex partners of the patients included their spouses (32.91%) and waitresses (41.77%). The incidence probability of persistent GCI was higher in the females (59.49%) than in the males. Many of the patients were complicated with infections of mycoplasma, syphilis, candida albicans, or condyloma acuminatum. CONCLUSIONS: The epidemic trend of persistent GCI is rather grim in Tianjin area. New measures have to be developed targeting the epidemiological features of persistent GCI for better prevention and control of the disease.

Granary Temperature Measurement Network Based on Chirped FBG.

In conventional optical fiber grating temperature measuring system, it can be loaded into a small number of fibers grating probe. At the same time, the intensity of back waves is relatively weak, and its multiplexing capability is poor. In order to solve these problems, temperature measurement system was designed based on chirped Fiber Bragg Grating. Its purpose is to obtain large-scale, multi-point temperature measurement data. The bandwidth of back waves was improved by chirp modulation techniques, so that available processing power of signal was increased, and the number of the chirped FBG probe in one fiber was greatly increased. Grating period expression was derived in chirp modulation, and modulation method and the wavelength range was provided. In the experiment, LPT-102 broadband light source and the FP optical fiber demodulator were used, and the modulation bandwidth of the system was from 1 535.0 to 1 555.0 nm. It used the WR-201 type temperature sensor as calibrated detector. Experimental results show that when the temperature changed by 1 ℃ from 20~60 ℃, the test temperature error would be closed with traditional Fiber Bragg Grating probe and chirped Fiber Bragg Grating probe, and they both meet the design requirements. In contrast, the wavelength shift data of chirped FBG was more monotone linear than the characteristic FBG, so its data was more stable. Meanwhile, in one fiber, the number of probes in the chirped FBG system was greatly more than the Uniform FBG system. In the original FBG system, without increasing the number of optical fiber or reduced the temperature measurement accuracy, design requirements for increase with the number of probe points in the system was achieved.

[The Research and Application of Transient Temperature Test Based on Apodized-Chirped FBG].

In order to quickly and accurately obtain the transient temperature field information of the barrel when the gun is firing, the transient temperature measurement system was designed with apodized-chirped fiber Bragg grating (FBG) probe. In the system, chirped fiber grating was used to modulate the bandwidth of echo light. The bandwidth of echo light had been greatly improved. So the number of apodized-chirped FBGs in one fiber could be greatly increased, and the energy of echo light was increased too. The performances of five common apodization functions were analyzed, and the super-Gaussian function was used to process the echo signals in the system. This function effectively suppressed sidelobe increases and spectral dispersion caused by chirp modulation, which indicated that it could meet the design requirements of the transient temperature measurement. 50 apodized-chirped FBGs, which evenly wound on the barrel, were used in the experiments, and they modulation range was from 1 532.0 to 1 548.0 nm. Transient temperature of a certain type of gun barrel was tested when it fired, and test data from the system were compared to WRP-130S high-speed temperature detector. Experimental results show that the two methods are similar ones with average error of less than 2%, and better than 1% in the region of temperature steady drop. 1 ℃ can cause 0.041 3 nm wavelength shift in temperature-wavelength data. Transient temperatures of 50 independent positions can be obtained in an acquisition, so the efficiency of the barrel temperature field reconstruction is greatly improving.

[Preparation and Dissolution Evaluation of Breviscapine Self-microemulsion].

OBJECTIVE: To study the prescription and preparation technology of breviscapine self-microemulsion for oral administration, and to evaluate the quality, stability and in vitro dissolution. METHODS: The prescription and preparation technology were selected and optimized through the solubility experiment, compatibility test, and pseudo-ternary phase diagram method, using the self-emulsifying time, appearance, particle diameter and stability as indexes. The droplet morphous, drug content, stability and dissolution were evaluated. Results:The prescription composition of breviscapine self-microemulsion was caprylic/capric triglyceride(GTCC,40%), Cremophor RH-40(50%), and PEG-400 (10%), with the drug loading of 7. 0 mg/g. The breviscapine self-microemulsion exhibited uniform and transparent,with the particle size of 38. 57 nm,Zeta potential of - 8. 80 mV. The results of dissolution indicated that the accumulative dissolution in 0. 1 mol/L hydrochloric acid was able to reach 90. 30% after 90 min, being 5. 9 times to that of the raw material medicine. The stability result showed that the content of breviscapine self-microemulsion was affected by high temperature, indicating it should be stored at low temperature. CONCLUSION: The preparation of breviscapine self-microemulsion is simple, which can increase the solubility of breviscapine in water and the absorption of breviscapine in the stomach and intestine, and conform to the main indexes of oral drug delivery system. It offers the basis for further research of breviscapine.

[Research on spectrum correction algorithm of temperature measurement system based on FBG].

In order to solve the problem that temperature sensor laying is complex and maintenance cost is high in the large-scale, multi-point real-time temperature monitoring process, the temperature monitoring system based on Fiber Bragg Grating was designed and developed. Using wavelength selectivity by optical fiber diffraction grating, a function of temperature and wavelength was established. Temperature of the measured position was inversed by calculating the wavelength variation through the optical fiber Bragg grating. Due to environmental, materials and other factors, the spectral distribution and temperature changes do not satisfy linear relationship. Therefore, designed the spectrum correction algorithm was designed, and function curve fitting of wavelength and temperature was completed with a degree of fitting greater than 99.7%. Experiments used FB136L-IAC-proof oven, LPT-200 diode, and 1 550 nm optical fiber to detect 20 to 280 degrees C temperature range of multi-point in real-time. The results show that when the temperature is changed by 1 degrees C, the corresponding center wavelength shifts about 0.04 nm to longer wavelengths. Compared with the test data from standard device, the error is less than +/- 0.3 degrees C. Meanwhile, the spectral correction algorithm was applied to the system to further improve the uniformity and accuracy of the temperature detection. Because the system uses fiber-optic sensor network, it has a strong anti-electromagnetic interference capability. The diffraction grating can achieve precise measurements, so it has big dynamic range and high accuracy. The innovation of the system is to ensure high-precision measurements, while still satisfy large-scale, multi-point, high anti-jamming capability of rapid laying, and has a strong practical value.

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.

Evaluation of biomechanical properties of anterior atlantoaxial transarticular locking plate system using three-dimensional finite element analysis.

PURPOSE: To evaluate a new anterior atlantoaxial transarticular locking plate system using finite element analysis. METHODS: Thin-section spiral computed tomography was performed from occiput to C2 region. A finite element model of an unstable atlantoaxial joint, treated with an anterior atlantoaxial transarticular locking plate system, was compared with the simple anterior atlantoaxial transarticular screw system. Flexion, extension, lateral bending, and axial rotation were imposed on the model. Displacement of the atlantoaxial transarticular screw and stress at the screw-bone interface were observed for the two internal fixation systems. RESULTS: Screw displacement was less using the anterior atlantoaxial transarticular locking plate system compared to simple anterior atlantoaxial transarticular screw fixation under various conditions, and stability increased especially during flexion and extension. CONCLUSIONS: The anterior atlantoaxial transarticular locking plate system not only provided stronger fixation, but also decreased screw-bearing stress and screw-bone interface stress compared to simple anterior atlantoaxial transarticular screw fixation.

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.

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.

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.

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.

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.

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.

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.

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.

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.