Pulmonary Transit Time Derived from First-Pass Perfusion Cardiac MR Imaging: A Potential New Marker for Cardiac Involvement and Prognosis in Light-Chain Amyloidosis.

BACKGROUND: First-pass perfusion cardiac MR imaging could reflect pulmonary hemodynamics. However, the clinical value of pulmonary transit time (PTT) derived from first-pass perfusion MRI in light-chain (AL) amyloidosis requires further evaluation. PURPOSE: To assess the clinical and prognostic value of PTT in patients with AL amyloidosis. STUDY TYPE: Prospective observational study. POPULATION: 226 biopsy-proven systemic AL amyloidosis patients (age 58.62 ± 10.10 years, 135 males) and 43 healthy controls (age 42 ± 16.2 years, 20 males). FIELD STRENGTH/SEQUENCE: SSFP cine and phase sensitive inversion recovery late gadolinium enhancement (LGE) sequences, and multislice first-pass myocardial perfusion imaging with a saturation recovery turbo fast low-angle shot (SR-TurboFLASH) pulse sequence at 3.0T. ASSESSMENT: PTT was measured as the time interval between the peaks of right and left ventricular cavity arterial input function curves on first-pass perfusion MR images. STATISTICAL TESTS: Independent-sample t test, Mann-Whitney U test, Chi-square test, Fisher's exact test, analysis of variance, or Kruskal-Wallis test, as appropriate; univariable and multivariable Cox proportional hazards models and Kaplan-Meier curves, area under receiver operating characteristic curve were used to determine statistical significance. RESULTS: PTT could differentiate AL amyloidosis patients with (N = 188) and without (N = 38) cardiac involvement (area under the curve [AUC] = 0.839). During a median follow-up of 35 months, 160 patients (70.8%) demonstrated all-cause mortality. After adjustments for clinical (Hazard ratio [HR] 1.061, confidence interval [CI]: 1.021-1.102), biochemical (HR 1.055, CI: 1.014-1.097), cardiac MRI-derived (HR 1.077, CI: 1.034-1.123), and therapeutic (HR 1.063, CI: 1.024-1.103) factors, PTT predicted mortality independently in patients with AL amyloidosis. Finally, PTT could identify worse outcomes in patients demonstrating New York Heart Association class III, Mayo 2004 stage III, and transmural LGE pattern. DATA CONCLUSION: PTT may serve as a new imaging predictor of cardiac involvement and prognosis in AL amyloidosis. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Myeloperoxidase-Sensitive Magnetic Resonance Imaging Assesses Inflammatory Activation State in Experimental Mouse Acute Gout.

BACKGROUND: A novel myeloperoxidase-activatable manganese-based (MPO-Mn) MRI probe may enable the activation state of inflammatory foci to be detected and monitored noninvasively. PURPOSE: To evaluate the inflammatory response in a mouse model of acute gout using MPO as an imaging biomarker and a potential therapeutic target. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 40 male Swiss mice with monosodium urate crystals induced acute gout. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted imaging with 2D fast spoiled gradient recalled echo and T2-weighted imaging with fast recovery fast spin-echo sequences. ASSESSMENT: The difference in contrast-to-noise ratio between left hind limb (lesion) and right hind limb (internal reference) (ΔCNR), and normalized signal-to-noise ratio (nSNR) on the right hind limb were calculated and compared. The expression level and activity of myeloperoxidase (MPO) were analyzed using western blotting and spectrophotometric quantitation activity assay. MPO-positive cell infiltration and lesion volume were evaluated using immunofluorescence staining and T2-weighted images, respectively. STATISTICAL TESTS: Student's t test. A P-value less than 0.05 was considered to be statistically significant. RESULTS: MPO-Mn resulted in a significantly higher ΔCNR than Gd-DTPA (22.54 ± 1.86 vs. 13.90 ± 2.22) but lower nSNR on the reference right hind limb (1.08 ± 0.07 vs. 1.21 ± 0.08). Compared to the nontreatment group, MPO-inhibition resulted in a significantly reduced contrast enhancement at the lesion (17.81 ± 1.58 vs. 22.96 ± 3.12), which was consistent with a remission of the inflammatory response, as evidenced by a substantial reduction of lesion volume (0.55 ± 0.16 mm3 /g vs. 1.14 ± 0.15 mm3 /g), myeloperoxidase expression level (0.98 ± 0.09 vs. 1.48 ± 0.19) and activity (0.75 ± 0.12 vs. 1.12 ± 0.07), and inflammatory cell recruitment. DATA CONCLUSION: MPO-Mn MRI has potential to evaluate the activation state of inflammatory foci in the experimental model of acute gout. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 1.

α-MSH-catabolic enzyme prolylcarboxypeptidase in nucleus accumbens shell ameliorates stress susceptibility in mice through regulating synaptic plasticity.

Emerging evidence demonstrates the vital role of synaptic transmission and structural remodeling in major depressive disorder. Activation of melanocortin receptors facilitates stress-induced emotional behavior. Prolylcarboxypeptidase (PRCP) is a serine protease, which splits the C-terminal amino acid of α-MSH and inactivates it. In this study, we asked whether PRCP, the endogenous enzyme of melanocortin system, might play a role in stress susceptibility via regulating synaptic adaptations. Mice were subjected to chronic social defeat stress (CSDS) or subthreshold social defeat stress (SSDS). Depressive-like behavior was assessed in SIT, SPT, TST and FST. Based on to behavioral assessments, mice were divided into the susceptible (SUS) and resilient (RES) groups. After social defeat stress, drug infusion or viral expression and behavioral tests, morphological and electrophysiological analysis were conducted in PFX-fixed and fresh brain slices containing the nucleus accumbens shell (NAcsh). We showed that PRCP was downregulated in NAcsh of susceptible mice. Administration of fluoxetine (20 mg·kg-1·d-1, i.p., for 2 weeks) ameliorated the depressive-like behavior, and restored the expression levels of PRCP in NAcsh of susceptible mice. Pharmacological or genetic inhibition of PRCP in NAcsh by microinjection of N-benzyloxycarbonyl-L-prolyl-L-prolinal (ZPP) or LV-shPRCP enhanced the excitatory synaptic transmission in NAcsh, facilitating stress susceptibility via central melanocortin receptors. On the contrary, overexpression of PRCP in NAcsh by microinjection of AAV-PRCP alleviated the depressive-like behavior and reversed the enhanced excitatory synaptic transmission, abnormal dendritogenesis and spinogenesis in NAcsh induced by chronic stress. Furthermore, chronic stress increased the level of CaMKIIα, a kinase closely related to synaptic plasticity, in NAcsh. The elevated level of CaMKIIα was reversed by overexpression of PRCP in NAcsh. Pharmacological inhibition of CaMKIIα in NAcsh alleviated stress susceptibility induced by PRCP knockdown. This study has revealed the essential role of PRCP in relieving stress susceptibility through melanocortin signaling-mediated synaptic plasticity in NAcsh.

[Feasibility of Single-Breath-Hold Compressed Sensing Real-Time Cine Imaging for Assessment of Ventricular Function and Left Ventricular Strain in Cardiac Magnetic Resonance].

Objective: To explore the feasibility of single-breath-hold compressed sensing real-time cine imaging (CS-cine) in the assessment of ventricular function and left ventricular (LV) strain. Methods: A total of 70 subjects were enrolled prospectively, and all subjects underwent cardiac magnetic resonance imaging (cardiac MRI) using both the standard steady-state free procession cine (sta-cine) acquisition and a prototype CS-cine sequence. For both CS-cine and sta-cine imaging, continuous short-axis cine images were acquired from the base to the apex to cover the entire left ventricle, and long-axis cine images including two-, three-, and four-chamber views were also acquired. The scanning range, number of slices, slice thickness and intervals were kept identical for the two cine images of the same participant. Subjective evaluation of the image quality was performed on all cine images. For both sequences, the conventional function parameters of the left and the right ventricles and LV strain values were assessed with post-processing software analysis. The cine image quality, conventional ventricular function parameters, and LV strain values were compared between the two cine groups and the differences were examined. Inter- and intraobserver agreements for CS-cine images were measured using intraclass correlation coefficient ( ICC). Bland-Altman analysis was performed to assess reproducibility between the two cine methods. Results: The median scanning time of CS-cine was 21 s versus 272 s for sta-cine ( P<0.001). The median image quality scores of two groups were significantly different, 4 points for sta-cine and 2 points for CS-cine ( P<0.001). Bi-ventricular end-diastolic volumes (EDV), stroke volume (SV) and ejection fraction (EF) were significantly smaller in CS-cine ( P<0.001). Nevertheless, no significant differences between the two groups in bi-ventricular ESV or LV mass were observed ( P>0.05). LV strain parameters, including the peak radial strain, peak circumferential strain and peak longitudinal strain derived from LV mid-ventricular slice, were significantly different in the two sequences ( P<0.001). Moreover, CS-cine-derived functional parameters and strain measurements have a good correlation with those of sta-cine (for RV function parameters, and left ventricular PLS, PCS values, more than 95% points fell within the limits of agreement [ LoA]; meanwhile, more than 91% points fell within the LoA for other parameters) and inter- and intraobserver agreements were strong ( ICC=0.88 to 0.99) for CS-cine. Conclusion: CS-cine can well realize the rapid acquisition of cine images for quantitative analysis of cardiac function, and the conventional ventricular function parameters and LV globalized strain values obtained from CS-cine imaging have good reproducibility.

Propensity score-matched comparison between totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction and conventional laparoscopic surgery with mini-laparotomy in the treatment of ascending colon cancer (with video).

BACKGROUND AND AIMS: Now that the debate about the safety and effectiveness of laparoscopic versus open surgery is over, attention has turned to innovations that can verify whether minimizing the impact of laparoscopy on the abdominal wall can further reduce pain, improve patient comfort, lead to superior cosmesis, and reduce morbidity. The aim of this study was to further explore the application value of totally laparoscopic right hemicolectomy with transcolonic natural orifice specimen extraction (NOSE) and to evaluate the short-term efficacy of transcolonic NOSE surgery for resecting specimens of ascending colon cancer. METHODS: From January 2016 to May 2017, a retrospective study was conducted in Guangxi. Propensity score matching was used to minimize the bias from nonrandomized treatment assignment. Patients were followed up through May 2020. RESULTS: Forty-nine patients underwent totally laparoscopic right hemicolectomy with transcolonic NOSE and 116 patients laparoscopic right hemicolectomy with mini-laparotomy (ML) procedures at our institution. After propensity score matching, each group included 45 patients, and all covariate imbalances were alleviated. The transcolonic NOSE group and the ML group did not differ significantly in terms of baseline clinical characteristics. The transcolonic NOSE group was associated with a shorter time to first flatus (NOSE vs ML: 1.8 ± .5 vs 3.2 ± .8, P = .032), a shorter length of hospital stay (11.3 ± 2.5 days vs 13.0 ± 3.1 days, P = .034), a shorter time to first liquid intake (2.6 ± .8 vs 3.8 ± .9, P = .068), less pain (1.8 ± .8 vs 4.2 ± .7, P = .013), less analgesia requirement (6 [13.3%] vs 21 [46.7%], P = .001), and lower C-reactive protein levels on postoperative day 1 (3.6 ± 1.7 vs 8.2 ± 2.2, P = .001) and postoperative day 3 (NOSE 2.4 ± 1.4 vs M: 4.6 ± 1.7 [P = .013]) than the ML group. The median follow-up was 28.4 months (interquartile range, 18.0-36.0). The 3-year overall survival rates were similar between the transcolonic NOSE group and the ML group. CONCLUSIONS: In total, laparoscopic right hemicolectomy with transcolonic specimen extraction appears to be safe for selected patients with ascending colon cancer as a minimally invasive surgery.

First report of Fusarium fujikuroi causing bulb rot on Lilium lancifolium in China.

Lilium lancifolium Thunb., commonly known as Juandan lily and tiger lily, is widely cultivated in China for its edible bulbs and medicinal properties, with a commercial value worth of ~RMB 6 billion Yuan per year. Bulb rot is an increasingly common disease on L. lancifolium, significantly impacting both the quantity and quality of the main product, the scaled bulbs. Typically, the causal pathogens invade the plant through wounds in the root or the ends of the bulb, causing the roots and bulb to brown and rot, which can eventually lead to stem wilt and death of the whole plants. During pathogenesis, the infected bulbs typically turn from white to brown, with sunken lesions and later the scales flaking off from the base of the bulb (Figure 1A and 1B). Plants growing from infected bulbs are generally short, with discolored leaves, wilting, and death at an early stage. Bulb rot is commonly observed in fields with excess water and a history of continuous Juandan lily cultivation. For this study, wilted L. lancifolium plants with rotted bulbs were collected from Longshan in Hunan, Enshi in Hubei, Yixing in Jiangsu, and Lu'an in Anhui in 2018 and 2019. Infected bulbs were surface sterilized with 75% ethanol for 30 seconds, followed by disinfection with 2% sodium hypochlorite for 5 minutes, and then rinsing with sterile water three times. The surface-sterilized tissue was divided into small pieces of 0.5 × 0.5 cm in size, placed on potato dextrose agar (PDA) medium containing 50 mg/l streptomycin sulfate, and incubated at 25℃. Mycelia growing from diseased tissues were sub-cultured onto fresh PDA medium to obtain pure culture, which formed dense white hyphae after a few days (Figure 1C and 1D). Colonies on PDA produced abundant condia about 15 days after subculturing. Microconidia were abundant, solitary, thin walled, hyaline, ovoid, 0 to 1 septate, with an average size of 6.1 × 2.6 µm (n=50) (Figure 1E). Macroconidia had a curved apical cell and foot-like basal cell with 3 to 5 septa, with an average size of 35.4 × 4.3 µm (n=30) (Figure 1E). No chlamydospore was observed. These morphological characteristics of the causal pathogen were similar to those of Fusarium spp. (Leslie et al., 2006). To identify the Fusarium isolates to species level, DNA fragments of the internal transcribed spacer (ITS) regions of the ribosomal RNA gene cluster, translation elongation factor subunit 1-alpha (TEF1-α), and RNA polymerase II subunit 2 (RPB2) genes were amplified using primers ITS1/ITS4, EF1/EF2, and 7cF/11aR respectively and sequenced (Choi et al. 2018; Jiang et al. 2018; Choi et al. 2017). BLAST analyses showed that the ITS (GenBank Accession No. MT549849), TEF1-α (GenBank Accession No. MT553348), and RPB2 (Accession No. MW201686) sequences of our isolates shared the highest sequence identities (98-100%) with those of F. fujikuroi reference strains in GenBank. A phylogenetic tree showing the relationship between one of our strains, S106, and those of the closely related species within the F. fujikuroi species complex was constructed by the maximum likelihood method using MEGA X (Kumar et al. 2018) (Figure 2). Based on the morphological characteristics and DNA sequences, the strains were identified as F. fujikuroi sensu stricto. We used two methods, an ex vivo assay using Juandan lily bulb scales and an in vivo assay using potted Juandan lily plants, to confirm pathogenicity for one representative F. fujikuroi strain from each of the four geographic regions to fulfill Koch's postulates (Bian et al. 2016; Zeng et al. 2019). In the ex vivo assay, actively growing mycelia on PDA plates were cut into 5mm diameter fungal blocks as inocula. To prepare healthy Juandan lily bulb scales as test tissues, healthy fresh scales were first surface sterilized using 75% alcohol for 30 seconds, followed by treatment of 2% sodium hypochlorite for 5 minutes, and then rinsed with sterile water 3 times. The scales were punctured with sterilized dissecting needles, the 5mm mycelial blocks containing the PDA medium were then inoculated on the punctured wound of the scales. Sterile PDA culture medium without mycelia was inoculated on the punctured wound as a negative control. After inoculation, Juandan lily scales were placed in sterile culture dishes with two layers of sterilized filter paper and 5ml of sterile water in each dish. Six Juandan lily scales were placed in each dish, with different treatments placed in different dishes, and the dishes were placed in an incubator in the dark at 25℃. After 10 days of incubation, we found that the F. fujikuroi-inoculated Juandan lily bulb scales showed disease symptoms (brownish lesion) similar to those in the original field collected infected bulb samples (Figure 1F). However, such symptoms were not observed in the negative control group. The pathogenicity test was performed 3 times for each isolate, each with six repeats. In the in vivo pathogenicity test using potted lily plants, we prepared actively growing cultures of our F. fujikuroi strains by incubating them in a liquid medium, the potato dextrose broth, for 3 days in a shaker-incubator at 25℃ and 180rpm. The asexual spores conidia from the fungal cultures were harvested by filtration through eight layers of sterile cheese clothes and with spore concentrations adjusted to 1×107 conidia per ml. Healthy Juandan lily bulbs were selected and one bulb was planted in each pot containing sterilized soil. Each pot was inoculated with 1ml conidia suspension, at the base soil where the bulbs were planted. The pots were placed in a growth chamber at 25℃ with a 12 h light and 12 h dark cycle. Symptoms similar to those observed in diseased bulbs in the field were observed, with symptoms at 30 days after inoculations shown in Figure 3. Specifically, most of the roots, bulb plate and scale tissues of Juandan lily plants inoculated with F. fujikuroi conidia were rotten and turned black, with few new roots. In addition, the infected plants showed stunted growth (Figure 3). In contrast, the uninoculated plants grew normally, with dense new roots and healthy-looking bulbs, and no rot symptom (Figure 3). The fungi were re-isolated from the infected Juandan lily tissues from both pathogenicity assays, following the procedures described above for isolating and identifying the fungal cultures from infected field samples. These re-isolated fungi were shown to have colony morphology and DNA sequences at the three loci identical to those of our inoculated F. fujikuroi strains. Several Fusarium species have been reported as pathogens of lily plants in China, including F. oxysporum, F. solani and F. tricinctum (Li, et al., 1995; Li, et al., 2013). In addition, F. redolens has been reported previously in ornamental lily in Ukraine (Zerova, 1940). Indeed, Fusarium moniliforme, one of the disused synonyms of F. fujikuroi (Seifert et al. 2003), has been reported as a causal agent for diseases in lily. However, it's now known that the originally defined F. fujikuroi sensu lato is in fact a large species complex consisting of over 60 recognized species, including F. fujikuroi sensu stricto (Moussa et al. 2017; Choi et al. 2018). In addition, there are over 100 species in the genus Lilium as well as many other species with their common names including the word "lily" but are not in the Lilium genus. To our knowledge, this is the first confirmed report of bulb rot of Juandan lily L. lancifolium caused by F. fujikuroi sensu stricto in China. Our result should help with future monitoring and control of Juandan lily diseases.

Association Between the Polymorphism of Aldehyde Dehydrogenase 2 Gene and Cerebral Infarction in a Hakka Population in Southern China.

Genetic factors play an important role in determining the susceptibility to ischemic stroke. Herein, we examined the association of an aldehyde dehydrogenase 2 (ALDH2) gene polymorphism with cerebral infarction. Patients with cerebral infarction (n = 963) and healthy controls (n = 921) were included. Genotyping was performed using gene chip platform analysis, and Sanger sequencing was used to confirm ALDH2 genotypes. The risk prediction of ALDH2 polymorphisms for cerebral infarction was examined under three genetic modes of inheritance. For males, ALDH2*2/*2 genotype was a significant risk factor for cerebral infarction in the co-dominant model (age-, smoking-, and drinking-adjusted OR 1.514, 95% CI 1.005-2.282, p = 0.047) and the recessive model (age-, smoking-, and drinking-adjusted OR 1.601, 95% CI 1.078-2.379, p = 0.020). However, for females, ALDH2*2/*2 genotype was a protective factor for cerebral infarction in the co-dominant model (age-, smoking-, and drinking-adjusted OR 0.450 95% CI 0.215-0.941, p = 0.034) and the recessive model (age-, smoking-, and drinking-adjusted OR 0.440, 95% CI 0.214-0.903, p = 0.025). Further, logistic regression analysis revealed that age, smoking, hypertension, hyperlipidemia, and hypercholesterolemia were significant risks for the presence of cerebral infarction. In conclusion, these findings support an association of ALDH2 gene polymorphisms with ischemic stroke in a Chinese Hakka population. In particular, homozygote ALDH2*2/*2 may be a risk factor for cerebral infarction in males, but contribute to reduced risk for cerebral infarction in females.

Secretory overproduction of a raw starch-degrading glucoamylase in Penicillium oxalicum using strong promoter and signal peptide.

Raw starch-degrading enzymes (RSDEs) are capable of directly degrading raw starch granules below the gelatinization temperature of starch, which may significantly reduce the cost of starch-based biorefining. However, low yields of natural RSDEs from filamentous fungi limit their industrial application. In this study, transcriptomic and secretomic profiling was employed to screen strongest promoters and signal peptides for use in overexpression of a RSDE gene in Penicillium oxalicum. Top five strong promoters and three signal peptides were detected. Using a green fluorescent protein (GFP) as the reporter, the inducible promoter pPoxEgCel5B of an endoglucanase gene PoxEgCel5B and the signal peptide spPoxGA15A of a raw starch-degrading glucoamylase PoxGA15A were respectively identified as driving the highest GFP production in P. oxalicum. PoxGA15A-overexpressed P. oxalicum strain OXPoxGA15A, which was constructed based on both pPoxEgCel5B and spPoxGA15A, produced significantly higher amounts of recombinant PoxGA15A than the parental strain ∆PoxKu70. Furthermore, crude enzyme from the OXPoxGA15A strain exhibited high activities towards raw starch from cassava, potato, and uncooked soluble starch. Specifically, raw cassava starch-degrading enzyme activity reached 241.6 U/mL in the OXPoxGA15A, which was 3.4-fold higher than that of the ∆PoxKu70. This work provides a feasible method for hyperproduction of RSDEs in P. oxalicum.

Enantioselective Friedel-Crafts Alkylation Reactions of 3-Substituted Indoles with Electron-Deficient Alkenes.

Highly enantioselective Friedel-Crafts C2-alkylation reactions of 3-substituted indoles with α,ß-unsaturated esters and nitroalkenes were developed using chiral Lewis acids as catalysts, which afforded chiral indole derivatives bearing C2-benzylic stereogenic centers in good to excellent yields (up to 99%) and enantioselectivities (up to 96% ee).

Redox-neutral α-allylation of amines by combining palladium catalysis and visible-light photoredox catalysis.

An unprecedented α-allylation of amines was achieved by combining palladium catalysis and visible-light photoredox catalysis. In this dual catalysis process, the catalytic generation of allyl radical from the corresponding π-allylpalladium intermediate was achieved without additional metal reducing reagents (redox-neutral). Various allylation products of amines were obtained in high yields through radical cross-coupling under mild reaction conditions. Moreover, the transformation was applied to the formal synthesis of 8-oxoprotoberberine derivatives which show potential anticancer properties.

Design, synthesis and evaluation of novel quinazoline-2,4-dione derivatives as chitin synthase inhibitors and antifungal agents.

A series of novel 1-methyl-3-substituted quinazoline-2,4-dione derivatives were designed, synthesized, and characterized by (1)H NMR, (13)C NMR and MS spectral data. Their inhibition against chitin synthase (CHS) and antifungal activities were evaluated in vitro. Results showed compounds 5b, 5c, 5e, 5f, 5j, 5k, 5l, and 5o had strong inhibitory potency against CHS. Compound 5c, which has the highest potency among these compounds, had a half-inhibition concentration (IC50) of 0.08mmol/L, while polyoxin B as positive drug had IC50 of 0.18mmol/L. These IC50 values of compounds 5i, 5m, 5n, and 5s were greater than 0.75mmol/L, which revealed that those compounds had weak inhibition activity against CHS. Moreover, most of these compounds exhibited moderate to excellent antifungal activities. In detail, to Candida albicans, the activities of compound 5g and 5k were 8-fold stronger than that of fluconazole and 4-fold stronger than that of polyoxin B; to Aspergillus flavus, the activities of 5g, 5l and 5o were16-fold stronger than that of fluconazole and 8-fold stronger than that of polyoxin B; to Cryptococcus neoformans, the minimum-inhibition-concentration (MIC) values of compounds 5c, 5d, 5e and 5l were comparable to those of fluconazole and polyoxin B. The antifungal activities of these compounds were positively correlated to their IC50 values against CHS. Furthermore, these compounds had negligible actions to bacteria. Therefore, these compounds were promising selective antifungal agents.

[Effects of different K fertilizer and water level on growth and physiological characteristics of Isatis indigotica].

The experiment included three potassium levels (K0 0 g x kg(-1), K1 0.33 g x kg(-1), K2 0.67 g x kg(-1)) and two water gradients (well watered and drought stress), then measured growth indicators, SOD, POD, CAT activities and concents of osmotic regulation substances. To explore the effects of K fertilizer and water on growth and physiological characteristics of Isatis indigotica, providing reference for improving drought resistance of I. indigotica. The result showed drought stress inhibited the growth and decreased the biomass of I. indigotica but K fertilizer can alleviate the drought stress. Compared with K0 treatment, K1, K2 treatment increased the biomass of overground part of by 89. 13% ,60. 87% under drought stress. The corresponding increase in soluble sugar content was 16.67%, 5.00%, and in proline content was 42.41%, 65.62%, respectively. SOD,POD and CAT activities was significantly improved in K1, K2 treatment in comparison with K0 treatment under drought stress, but soluble protein content significantly reduced. The conclusion is that appropriate amount of K fertilizer can increase the activities of antioxidase and the content of osmoregulation substance under drought stress, and improve drought resistance of I. indigotica.

[Influence of drying method on content of epigoitrin and uridine in isatidis radix].

OBJECTIVE: To study the influence of different drying methods on the content of epigoitrin and uridine in Isatidis Radix. METHODS: Fresh Isatidis Radix was processed by four drying methods including airing drying and drying in far infrared oven at different temperature,drying in the sun and drying in the shade. The contents of epigoitrin and uridine were determined by HPLC. RESULTS: The contents of epigoitrin as well as uridine in samples valued from 3.847 - 5.204 mg/g and 0.701 - 1.028 mg/g, respectively. CONCLUSION: The optimal drying method is airing drying at 55 degrees C, which will be serviced in the large-scale processing of Isatidis Radix.

[Characteristic fingerprint analysis and determination of main components on Andrographis paniculata extract by UPLC].

OBJECTIVE: To establish an analytical method for characteristic fingerprint and determination of main components of Andrographis paniculata Extract by UPLC. METHODS: The chromatographic conditions were Waters ACQUITY UPLC BEH-C18 (2. 1 mm x 0 mm,1.7 µm)by gradient elute using acetonitrile-water as mobile phase(0 -2 min,20% ~ 25% A;2 ~ 5 min,25% ~ 35% A;5 ~ 7 min,35% A;7 ~10 min,35%~ 55% A) at a flow rate of 0. 5 min/mL,detecting wavelength at 220 nm. Results:Contents of the andrographolide, neoandrographolide, 14-deoxyandrographolide and 14-deoxy-l11,12-didehydroandrographolide had good resolution with the correlation coefficients exceed 0. 9999 and the average percent recovery lied in 97. 2% to 103.9%, RSD was less than 3.0% (n = 6). The chromatograms of Andrographis paniculata Extract shared seven common peaks in which four of them were recognized by reference standard with the similarities over 0. 9. CONCLUSION: It is a fast,accurate and validated method,and can be useful in quality evaluations of Andrographis paniculata Extract.

[Analysis of multicomponent drug metabolism used in clinical pharmacy research of traditional Chinese medicine].

Multicomponent drug metabolism can be defined as a research area that, rather than pharmacokinetics and pharmacodynamics, is a concerted dynamic metabolic variation of one component in several other compounds circumstance with the interaction of transport protein and drug metabolizing enzymes, and the study of the dynamic course of multiple components must be simultaneously determined. By the use of multicomponent drug metabolism in the clinical pharmacy research of traditional Chinese medicine (TCM), it can become a useful tool with the integration of the overall dialectical method and the concrete molecular approach.

Photocatalytic generation of N-centered hydrazonyl radicals: a strategy for hydroamination of ß,γ-unsaturated hydrazones.

A visible-light photocatalytic generation of N-centered hydrazonyl radicals has been accomplished for the first time. This approach allows efficient intramolecular addition of hydrazonyl radical to terminal alkenes, thus providing hydroamination and oxyamination products in good yields. Importantly, the protocol involves deprotonation of an N-H bond and photocatalytic oxidation to an N-centered radical, thus obviating the need to prepare photolabile amine precursors or the stoichiometric use of oxidizing reagents.

Mastering Surface Sulfidation of MnP-MnO2 Heterostructure to Facilitate Efficient Polysulfide Conversion in Li─S Batteries.

The development of lithium-sulfur (Li─S) batteries has been hampered by the shuttling effect of lithium polysulfides (LiPSs). An effective method to address this issue is to use an electrocatalyst to accelerate the catalytic conversion of LiPSs. In this study, heterogeneous MnP-MnO2 nanoparticles are uniformly synthesized and embedded in porous carbon (MnP-MnO2/C) as core catalysts to improve the reaction kinetics of LiPSs. In situ characterization and density functional theory (DFT) calculations confirm that the MnP-MnO2 heterostructure undergo surface sulfidation during the charge/discharge process, forming the MnS2 phase. Surface sulfidation of the MnP-MnO2 heterostructure catalyst significantly accelerated the SRR and Li2S activation, effectively inhibiting the LiPSs shuttling effect. Consequently, the MnP-MnO2/C@S cathode achieves outstanding rate performance (10 C, 500 mAh g-1) and ultrahigh cycling stability (0.017% decay rate per cycle for 2000 cycles at 5 C). A pouch cell with MnP-MnO2/C@S cathode delivers a high energy density of 429 Wh kg-1. This study may provide a new approach to investigating the surface sulfidation of electrocatalysts, which is valuable for advancing high-energy-density Li-S batteries.

Deep learning for the automatic detection and segmentation of parotid gland tumors on MRI.

OBJECTIVES: Parotid gland tumors (PGTs) often occur as incidental findings on magnetic resonance images (MRI) that may be overlooked. This study aimed to construct and validate a deep learning model to automatically identify parotid glands (PGs) with a PGT from normal PGs, and in those with a PGT to segment the tumor. MATERIALS AND METHODS: The nnUNet combined with a PG-specific post-processing procedure was used to develop the deep learning model trained on T1-weighed images (T1WI) in 311 patients (180 PGs with tumors and 442 normal PGs) and fat-suppressed (FS)-T2WI in 257 patients (125 PGs with tumors and 389 normal PGs), for detecting and segmenting PGTs with five-fold cross-validation. Additional validation set separated by time, comprising T1WI in 34 and FS-T2WI in 41 patients, was used to validate the model performance. RESULTS AND CONCLUSION: To identify PGs with tumors from normal PGs, using combined T1WI and FS-T2WI, the deep learning model achieved an accuracy, sensitivity and specificity of 98.2% (497/506), 100% (119/119) and 97.7% (378/387), respectively, in the cross-validation set and 98.5% (67/68), 100% (20/20) and 97.9% (47/48), respectively, in the validation set. For patients with PGTs, automatic segmentation of PGTs on T1WI and FS-T2WI achieved mean dice coefficients of 86.1% and 84.2%, respectively, in the cross-validation set, and of 85.9% and 81.0%, respectively, in the validation set. The proposed deep learning model may assist the detection and segmentation of PGTs and, by acting as a second pair of eyes, ensure that incidentally detected PGTs on MRI are not missed.

SIVA-1 enhances acquired chemotherapeutic drug resistance of gastric cancer in vivo by regulating the ARF/MDM2/p53 pathway.

SIVA-1 has been shown to affect apoptotic processes in various different cell lines, and SIVA-1 significantly contributes to the decreased responsiveness of cancer cells to some chemotherapy agents. However, whether SIVA-1 has potential application in gastric cancer remains unknown. Therefore, the objective of this investigation was to clarify the distinct function of SIVA-1 in chemotherapeutic drug resistance within a living murine model with gastric malignancy, and initially elucidate the underlying mechanisms. In an established multidrug-resistant gastric cancer xenograft mouse model, lentivirus, named Lv-SIVA-1, was injected into xenograft tumors, and increased the mRNA and protein expression of endogenous SIVA-1 in tumors. Immunohistochemical assays of xenograft tumor showed that SIVA-1 was significantly upregulated, and the protein expression levels of SIVA-1 were highly increased, as detected by Western blotting. In addition, we detected the role of SIVA-1 in cell proliferation and cell apoptosis in gastric cancer cells by TUNEL and found that SIVA-1 decreased tumor cell apoptosis and promoted tumor growth in vivo. Using a TMT assay between tumor tissues of experimental and control groups, differentially expressed proteins were examined and three potential biomarkers of multidrug resistance (ARF, MDM2, and p53) were screened. We further investigated the molecular mechanism by which SIVA-1 played an efficient role against chemotherapies and found that overexpressed SIVA-1 leads to increased ARF and MDM2 expression and suppressed expression of p53 in tumor tissue. In conclusion, SIVA-1 plays a significant role in the multidrug resistance of gastric tumors. In addition, overexpressed SIVA-1 positively regulates cell proliferation, adjusts cycle progression, and reduces the response to drug treatment for gastric cancer in an ARF/MDM2/p53-dependent manner. This novel research provides a basis for chemical management of gastric cancer through regulation of SIVA-1 expression.

SIVA-1 interaction with PCBP1 serves as a predictive biomarker for cisplatin sensitivity in gastric cancer and its inhibitory effect on tumor growth in vivo.

Background: SIVA-1 has been reported to play a key role in cell apoptosis and gastric cancer (GC) chemoresistance in vitro. Nevertheless, the clinical significance of SIVA-1 in GC chemotherapy remains unclear. Methods and results: Immunohistochemistry and histoculture drug response assays were used to determine SIVA-1 expression and the inhibition rate (IR) of agents to GC and to further analyze the relationship between these two phenomena. Additionally, cisplatin (DDP)-resistant GC cells were used to elucidate the role and mechanism of SIVA-1 in vivo. The results demonstrated that SIVA-1 expression was positively correlated with the IR of DDP to GC but not with those of 5-fluorouracil (5-FU) or adriamycin (ADM). Furthermore, SIVA-1 overexpression with DDP treatment synergistically inhibited tumor growth in vivo by increasing PCBP1 and decreasing Bcl-2 and Bcl-xL expression. Conclusions: Our study demonstrated that SIVA-1 may serve as an indicator of the GC sensitivity to DDP, and the mechanism of SIVA-1 in GC resistance to DDP was preliminarily revealed.