Multiomics analysis reveals the molecular mechanisms underlying virulence in Rhizoctonia and jasmonic acid-mediated resistance in Tartary buckwheat (Fagopyrum tataricum).

Rhizoctonia solani is a devastating soil-borne pathogen that seriously threatens the cultivation of economically important crops. Multiple strains with a very broad host range have been identified, but only 1 (AG1-IA, which causes rice sheath blight disease) has been examined in detail. Here, we analyzed AG4-HGI 3 originally isolated from Tartary buckwheat (Fagopyrum tataricum), but with a host range comparable to AG1-IA. Genome comparison reveals abundant pathogenicity genes in this strain. We used multiomic approaches to improve the efficiency of screening for disease resistance genes. Transcriptomes of the plant-fungi interaction identified differentially expressed genes associated with virulence in Rhizoctonia and resistance in Tartary buckwheat. Integration with jasmonate-mediated transcriptome and metabolome changes revealed a negative regulator of jasmonate signaling, cytochrome P450 (FtCYP94C1), as increasing disease resistance probably via accumulation of resistance-related flavonoids. The integration of resistance data for 320 Tartary buckwheat accessions identified a gene homolog to aspartic proteinase (FtASP), with peak expression following R. solani inoculation. FtASP exhibits no proteinase activity but functions as an antibacterial peptide that slows fungal growth. This work reveals a potential mechanism behind pathogen virulence and host resistance, which should accelerate the molecular breeding of resistant varieties in economically essential crops.

Identification macrophage signatures in prostate cancer by single-cell sequencing and machine learning.

BACKGROUND: The tumor microenvironment (TME) encompasses a variety of cells that influence immune responses and tumor growth, with tumor-associated macrophages (TAM) being a crucial component of the TME. TAM can guide prostate cancer in different directions in response to various external stimuli. METHODS: First, we downloaded prostate cancer single-cell sequencing data and second-generation sequencing data from multiple public databases. From these data, we identified characteristic genes associated with TAM clusters. We then employed machine learning techniques to select the most accurate TAM gene set and developed a TAM-related risk label for prostate cancer. We analyzed the tumor-relatedness of the TAM-related risk label and different risk groups within the population. Finally, we validated the accuracy of the prognostic label using single-cell sequencing data, qPCR, and WB assays, among other methods. RESULTS: In this study, the TAM_2 cell cluster has been identified as promoting the progression of prostate cancer, possibly representing M2 macrophages. The 9 TAM feature genes selected through ten machine learning methods and demonstrated their effectiveness in predicting the progression of prostate cancer patients. Additionally, we have linked these TAM feature genes to clinical pathological characteristics, allowing us to construct a nomogram. This nomogram provides clinical practitioners with a quantitative tool for assessing the prognosis of prostate cancer patients. CONCLUSION: This study has analyzed the potential relationship between TAM and PCa and established a TAM-related prognostic model. It holds promise as a valuable tool for the management and treatment of PCa patients.

LI-RADS CT and MRI Ancillary Feature Association with Hepatocellular Carcinoma and Malignancy: An Individual Participant Data Meta-Analysis.

Background The independent contribution of each Liver Imaging Reporting and Data System (LI-RADS) CT or MRI ancillary feature (AF) has not been established. Purpose To evaluate the association of LI-RADS AFs with hepatocellular carcinoma (HCC) and malignancy while adjusting for LI-RADS major features through an individual participant data (IPD) meta-analysis. Materials and Methods Medline, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched from January 2014 to January 2022 for studies evaluating the diagnostic accuracy of CT and MRI for HCC using LI-RADS version 2014, 2017, or 2018. Using a one-step approach, IPD across studies were pooled. Adjusted odds ratios (ORs) and 95% CIs were derived from multivariable logistic regression models of each AF combined with major features except threshold growth (excluded because of infrequent reporting). Liver observation clustering was addressed at the study and participant levels through random intercepts. Risk of bias was assessed using a composite reference standard and Quality Assessment of Diagnostic Accuracy Studies 2. Results Twenty studies comprising 3091 observations (2456 adult participants; mean age, 59 years ± 11 [SD]; 1849 [75.3%] men) were included. In total, 89% (eight of nine) of AFs favoring malignancy were associated with malignancy and/or HCC, 80% (four of five) of AFs favoring HCC were associated with HCC, and 57% (four of seven) of AFs favoring benignity were negatively associated with HCC and/or malignancy. Nonenhancing capsule (OR = 3.50 [95% CI: 1.53, 8.01]) had the strongest association with HCC. Diffusion restriction (OR = 14.45 [95% CI: 9.82, 21.27]) and mild-moderate T2 hyperintensity (OR = 10.18 [95% CI: 7.17, 14.44]) had the strongest association with malignancy. The strongest negative associations with HCC were parallels blood pool enhancement (OR = 0.07 [95% CI: 0.01, 0.49]) and marked T2 hyperintensity (OR = 0.18 [95% CI: 0.07, 0.45]). Seventeen studies (85%) had a high risk of bias. Conclusion Most LI-RADS AFs were independently associated with HCC, malignancy, or benignity as intended when adjusting for major features. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Crivellaro in this issue.

The effect of different pterygium surgery techniques on the ocular surface parameters in different durations: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of different pterygium surgery techniques on ocular surface (OS) in different follow-up periods. METHODS: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, and China Biology Medicine disc were searched for studies reporting pre- and post-operative OS parameters in pterygium. RESULTS: A total of 33 articles were finally included. Three OS parameters showed relatively consistent changing trends after surgery including ocular surface disease index (OSDI), tear film break-up time (BUT), and score of corneal fluorescein staining (SCFS). They worsened significantly at 1w post-operation and then gradually improved: OSDI and BUT showed obvious improvement in 1 m post-operation (SMD = - 0.58, 95%CI = [- 1.04, - 0.13]; SMD = 0.42, 95%CI = [0.06, 0.78]); SCFS was restored to preoperative levels in 3 m after surgery (SMD = - 0.54, 95%CI = [- 1.16, 0.07]). Another parameter, Schirmer test without anesthesia (SIT), presented transient increase at 1w post-operation (SMD = 0.87, 95%CI = [0.27, 1.47]) and presented a relatively stable improvement after 1 m post-operation (SMD = 0.52, 95%CI = [0.16, 0.89]). All parameters in amniotic membrane graft (AMT) showed better improvement in early stage and they showed non-inferior improvements in the long term compared with conjunctival autograft (CAG). Limbal-conjunctival autograft (LCAG) made excellent improvement to OS in the long term while pterygium excision (PE) showed the worst OS. The type of pterygium (primary and secondary), diabetes mellitus (DM) status, and fixation method had certain effects on the results. CONCLUSIONS: OS of pterygium is deteriorated at 1w post-operation then gradually improved to preoperative levels after 1 m post-operation. Among various surgery techniques, LCAG had the best improvement to OS which especially displayed in the long-term outcomes.

Short-term exposure to extreme temperature and outpatient visits for respiratory diseases among children in the northern city of China: a time-series study.

BACKGROUND: Although studies have indicated that extreme temperature is strongly associated with respiratory diseases, there is a dearth of studies focused on children, especially in China. We aimed to explore the association between extreme temperature and children's outpatient visits for respiratory diseases and seasonal modification effects in Harbin, China. METHODS: A distributed lag nonlinear model (DLNM) was used to explore the effect of extreme temperature on daily outpatient visits for respiratory diseases among children, as well as lag effects and seasonal modification effects. RESULTS: Extremely low temperatures were defined as the 1st percentile and 2.5th percentile of temperature. Extremely high temperatures were defined as the 97.5th percentile and 99th percentile of temperature. At extremely high temperatures, both 26 °C (97.5th) and 27 °C (99th) showed adverse effects at lag 0-6 days, with relative risks (RRs) of 1.34 [95% confidence interval (CI): 1.21-1.48] and 1.38 (95% CI: 1.24-1.53), respectively. However, at extremely low temperatures, both - 26 °C (1st) and - 23 °C (2.5th) showed protective effects on children's outpatient visits for respiratory diseases at lag 0-10 days, with RRs of 0.86 (95% CI: 0.76-0.97) and 0.85 (95% CI: 0.75-0.95), respectively. We also found seasonal modification effects, with the association being stronger in the warm season than in the cold season at extremely high temperatures. CONCLUSIONS: Our study indicated that extremely hot temperatures increase the risk of children's outpatient visits for respiratory diseases. Efforts to reduce the exposure of children to extremely high temperatures could potentially alleviate the burden of pediatric respiratory diseases, especially during the warm season.

The unique properties of tear film breakup process in patients with nasal unilateral pterygium.

SIGNIFICANCE: This study found that the unique properties of tear film breakup process in eyes with pterygium, combined with ocular surface parameters, further revealed specific dynamic mechanism. It suggested that the thickness of pterygium was especially valuable in deciding the necessity of surgical management. PURPOSE: This study aimed to explore the dynamic mechanism of tear film instability in eyes with pterygium. METHODS: A paired-eye controlled cross-sectional study was conducted. Seventy-eight patients with nasal pterygium were enrolled. Fluorescein tear film breakup was observed. Several key parameters related to tear film quality were defined and analyzed, including total breakup area (mathematically derived from pixel size using MATLAB), breakup velocity, fluorescein breakup time, breakup location and pattern, tear meniscus height, score of fluorescein corneal staining, and meiboscore. RESULTS: With comparable tear meniscus height, score of fluorescein corneal staining, and meiboscore between paired eyes (p > 0.05), eyes with pterygium had shorter breakup time, larger breakup area, and faster breakup velocity (p < 0.05). In eyes with pterygium, a positive correlation between meiboscore and pterygium parameters including length, thickness, and size was observed (p > 0.001). As the thickness increased, difference of breakup time and area between paired eyes increased (p = 0.02 and 0.046). Eyes with pterygium had more fixed inferonasal breakup location and often presented as dimple break (60%), whereas random break was the most common in contralateral normal eyes (62%). A unique breakup pattern named pterygium-induced local dimple break was found. It displayed as an irregular but vertical line-like shape appearing after lipid layer spreading, which was adjacent to the lower margin of pterygium and presented with unique properties including inferonasal breakup location, local breakup area, shorten breakup time, and faster breakup velocity. CONCLUSIONS: Eyes with pterygium showed a unique tear film breakup process and novel breakup pattern named pterygium-induced local dimple break . Dynamic mechanism played a significant role in tear film instability of eyes with pterygium rather than aqueous deficiency and increased evaporation.

Individual Participant Data Meta-Analysis of LR-5 in LI-RADS Version 2018 versus Revised LI-RADS for Hepatocellular Carcinoma Diagnosis.

Background A simplification of the Liver Imaging Reporting and Data System (LI-RADS) version 2018 (v2018), revised LI-RADS (rLI-RADS), has been proposed for imaging-based diagnosis of hepatocellular carcinoma (HCC). Single-site data suggest that rLI-RADS category 5 (rLR-5) improves sensitivity while maintaining positive predictive value (PPV) of the LI-RADS v2018 category 5 (LR-5), which indicates definite HCC. Purpose To compare the diagnostic performance of LI-RADS v2018 and rLI-RADS in a multicenter data set of patients at risk for HCC by performing an individual patient data meta-analysis. Materials and Methods Multiple databases were searched for studies published from January 2014 to January 2022 that evaluated the diagnostic performance of any version of LI-RADS at CT or MRI for diagnosing HCC. An individual patient data meta-analysis method was applied to observations from the identified studies. Quality Assessment of Diagnostic Accuracy Studies version 2 was applied to determine study risk of bias. Observations were categorized according to major features and either LI-RADS v2018 or rLI-RADS assignments. Diagnostic accuracies of category 5 for each system were calculated using generalized linear mixed models and compared using the likelihood ratio test for sensitivity and the Wald test for PPV. Results Twenty-four studies, including 3840 patients and 4727 observations, were analyzed. The median observation size was 19 mm (IQR, 11-30 mm). rLR-5 showed higher sensitivity compared with LR-5 (70.6% [95% CI: 60.7, 78.9] vs 61.3% [95% CI: 45.9, 74.7]; P < .001), with similar PPV (90.7% vs 92.3%; P = .55). In studies with low risk of bias (n = 4; 1031 observations), rLR-5 also achieved a higher sensitivity than LR-5 (72.3% [95% CI: 63.9, 80.1] vs 66.9% [95% CI: 58.2, 74.5]; P = .02), with similar PPV (83.1% vs 88.7%; P = .47). Conclusion rLR-5 achieved a higher sensitivity for identifying HCC than LR-5 while maintaining a comparable PPV at 90% or more, matching the results presented in the original rLI-RADS study. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Sirlin and Chernyak in this issue.

Management Strategy for Prostate Imaging Reporting and Data System Category 3 Lesions.

PURPOSE OF REVIEW: Prostate Imaging Reporting and Data System (PI-RADS) category 3 lesions present a clinical dilemma due to their uncertain nature, which complicates the development of a definitive management strategy. These lesions have an incidence rate of approximately 22-32%, with clinically significant prostate cancer (csPCa) accounting for about 10-30%. Therefore, a thorough evaluation is warranted. RECENT FINDINGS: This review highlights the need for radiology peer review, including the confirmation of dynamic contrast-enhanced (DCE) compliance, as the initial step. Additional MRI models such as VERDICT or Tofts need to be verified. Current evidence shows that imaging and clinical indicators can be used for risk stratification of PI-RADS 3 lesions. For low-risk lesions, a safety net monitoring approach involving annual repeat MRI can be employed. In contrast, lesions deemed potentially risky based on prostate-specific antigen density (PSAD), 68 Ga-PSMA PET/CT, MPS, Proclarix, or AI/machine learning models should undergo biopsy. It is recommended to establish a multidisciplinary team that takes into account factors such as age, PSAD, prostate, and lesion size, as well as previous biopsy pathological findings. Combining expert opinions, clinical-imaging indicators, and emerging methods will contribute to the development of management strategies for PI-RADS 3 lesions.

Clinical observation of tear film breakup time with a novel smartphone-attachable technology.

PURPOSE: To demonstrate the practicability of a portable instrument in assessing tear film breakup time (TFBUT): a lens attachment for smartphones (LAS). METHODS: By applying LAS in combination with the iPhone 12 pro, and a recordable slit-lamp microscope, we obtained TFBUT videos from 58 volunteers. The comparison between the conventional slit-lamp microscope and LAS by an experienced ophthalmologist. Moreover, we also invited an ophthalmic postgraduate student and an undergraduate student with no clinical experience to assess TFBUT in those videos. The inter-observer reliability was assessed using intraclass correlation coefficients (ICC). RESULTS: The TFBUT of 116 eyes in total was recorded. Reliability indexes were adequate. The Spearman's correlation analysis and the intraclass correlation coefficient suggested a strong correlation between the 2 modalities (Right eye: Spearman's r = 0.929, 95% confidence interval (CI) = 0.847-0.963, ICC = 0.978, p < 0.001; Left eye: Spearman's r = 0.931, 95% CI = 0.866-0.964, ICC = 0.985, p < 0.001;). Between instruments, the majority of TFBUT measurements showed good agreement on Bland Altman plot. A high concordance was observed in TFBUT, when assessed by an ophthalmologist and an ophthalmic postgraduate student (Left eye: LAS ICC = 0.951, p < 0.001; Left eye: slit-lamp microscope ICC = 0.944, p < 0.001). CONCLUSIONS: Compared with the conventional slit-lamp microscope, the LAS has sufficient validity for evaluating TFBUT in clinics or at home.

Improvement of the stability and catalytic efficiency of heparan sulfate N-sulfotransferase for preparing N-sulfated heparosan.

The chemo-enzymatic and enzymatic synthesis of heparan sulfate and heparin are considered as an attractive alternative to the extraction of heparin from animal tissues. Sulfation of the hydroxyl group at position 2 of the deacetylated glucosamine is a prerequisite for subsequent enzymatic modifications. In this study, multiple strategies, including truncation mutagenesis based on B-factor values, site-directed mutagenesis guided by multiple sequence alignment, and structural analysis were performed to improve the stability and activity of human N-sulfotransferase. Eventually, a combined variant Mut02 (MBP-hNST-NΔ599-602/S637P/S741P/E839P/L842P/K779N/R782V) was successfully constructed, whose half-life at 37°C and catalytic activity were increased by 105-fold and 1.35-fold, respectively. After efficient overexpression using the Escherichia coli expression system, the variant Mut02 was applied to N-sulfation of the chemically deacetylated heparosan. The N-sulfation content reached around 82.87% which was nearly 1.88-fold higher than that of the wild-type. The variant Mut02 with high stability and catalytic efficiency has great potential for heparin biomanufacturing.

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/ß-catenin pathway in the myocardium of mice after myocardial infarction.

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/ß-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/ß-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.

Crosstalk between 5-Aminolevulinic Acid and Abscisic Acid Adjusted Leaf Iron Accumulation and Chlorophyll Synthesis to Enhance the Cold Tolerance in Solanum lycopersicum Seedlings.

Previous studies found that 5-aminolevulinic acid (ALA) and abscisic acid (ABA) can mitigate damage from adversity by enhancing photosynthesis. However, it is not clear whether they have positive effects on iron utilization and chlorophyll synthesis of tomato seedlings under low-temperature stress. To investigate the possible functional relationship between ABA and ALA and elucidate the possible mechanisms of action of ALA to alleviate low-temperature stress in tomato seedlings, this experiment analyzed the effects of ALA and ABA on chlorophyll synthesis in tomato seedling leaves sprayed with exogenous of ALA (25 mg·L-1) or ABA (100 µM) under low-temperature stress (8-18 °C/8-12 °C, day/night). The results show that exogenous ALA increased the Fv/Fm of tomato leaves by 5.31% and increased the accumulation of iron and chlorophyll by 101.15% and 15.18%, respectively, compared to the low-temperature treatment alone, and tomato resistance of low-temperature stress was enhanced. Meanwhile, exogenous application of ALA increased the ABA content by 39.43%, and subsequent application of exogenous ABA revealed that tomato seedlings showed similar effects to exogenous ALA under low-temperature stress, with increased accumulation of iron and chlorophyll in tomato seedlings, which eventually increased the maximum photochemical efficiency of PS II. Under low-temperature stress, application of exogenous ABA significantly reduced ALA content, but the expression of key enzyme genes (PPGD, HEMB1, HEME1, and HEMF1), precursors of chlorophyll synthesis by ALA, was significantly elevated, presumably because the increased activity of these enzymes after external application of ABA accelerated ALA consumption. In conclusion, ABA may crosstalk with ALA to improve the photochemical efficiency and low temperature resistance of tomatoes by regulating chlorophyll synthesis and iron accumulation.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.

Pigment Characterization of the Giant-Colony-Forming Haptophyte Phaeocystis globosa in the Beibu Gulf Reveals Blooms of Different Origins.

The giant-colony-forming haptophyte Phaeocystis globosa has caused several large-scale blooms in the Beibu Gulf since 2011, but the distribution and dynamics of the blooms remained largely unknown. In this study, colonies of P. globosa, as well as membrane-concentrated phytoplankton samples, were collected during eight cruises in the Beibu Gulf from September 2016 to August 2017. Pigments were analyzed by high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD). The pigment 19'-hexanoyloxyfucoxanthin (hex-fuco), generally considered a diagnostic pigment for Phaeocystis, was not detected in P. globosa colonies in the Beibu Gulf, whereas 19'-butanoyloxyfucoxanthin (but-fuco) was found in all colony samples. Moreover, but-fuco in membrane-concentrated phytoplankton samples exhibited a similar distribution pattern to that of P. globosa colonies, suggesting that but-fuco provided the diagnostic pigment for bloom-forming P. globosa in the Beibu Gulf. Based on the distribution of but-fuco in different water masses in the region prior to the formation of intensive blooms, it is suggested that P. globosa blooms in the Beibu Gulf could originate from two different sources. IMPORTANCE Phaeocystis globosa has formed intensive blooms in the South China Sea and even around the world, causing huge social economic losses and environmental damage. However, little is known about the formation mechanism and dynamics of P. globosa blooms. 19'-Hexanoyloxyfucoxanthin (hex-fuco) is often used as the pigment proxy to estimate Phaeocystis biomass, while this is challenged by the giant-colony-forming P. globosa in the Beibu Gulf, which contains only 19'-butanoyloxyfucoxanthin (but-fuco) but not hex-fuco. Using but-fuco as a diagnostic pigment, we traced two different origins of P. globosa blooms in the Beibu Gulf. This study clarifies the development process of P. globosa blooms in the Beibu Gulf, which provides a basis for the early monitoring and prevention of the blooms.

Exogenous 5-aminolevulinic acid alleviates low-temperature injury by regulating glutathione metabolism and ß-alanine metabolism in tomato seedling roots.

Food availability represents a major worldwide concern due to climate change and population growth. Low-temperature stress (LTS) severely restricts the growth of tomato seedlings. Exogenous 5-aminolevulinic acid (ALA) can alleviate the harm of abiotic stress including LTS; however, data on its protective mechanism on tomato seedling roots, the effects of organelle structure, and the regulation of metabolic pathways under LTS are lacking. In this study, we hope to fill the above gaps by exploring the effects of exogenous ALA on morphology, mitochondrial ultrastructure, reactive oxygen species (ROS) enrichment, physiological indicators, related gene expression, and metabolic pathway in tomato seedlings root under LTS. Results showed that ALA pretreatment could increase the activity of antioxidant enzymes and the content of antioxidant substances in tomato seedlings roots under LTS to scavenge the massively accumulated ROS, thereby protecting the mitochondrial structure of roots and promoting root development under LTS. Combined transcriptomic and metabolomic analysis showed that exogenous ALA pretreatment activated the glutathione metabolism and ß-alanine metabolism of tomato seedling roots under LTS, further enhanced the scavenging ability of tomato seedling roots to ROS, and improved the low-temperature tolerance of tomato seedlings. The findings provide a new insight into the regulation of the low-temperature tolerance of tomato by exogenous ALA.

A Method for Detection of Corn Kernel Mildew Based on Co-Clustering Algorithm with Hyperspectral Image Technology.

Hyperspectral imaging can simultaneously acquire spectral and spatial information of the samples and is, therefore, widely applied in the non-destructive detection of grain quality. Supervised learning is the mainstream method of hyperspectral imaging for pixel-level detection of mildew in corn kernels, which requires a large number of training samples to establish the prediction or classification models. This paper presents an unsupervised redundant co-clustering algorithm (FCM-SC) based on multi-center fuzzy c-means (FCM) clustering and spectral clustering (SC), which can effectively detect non-uniformly distributed mildew in corn kernels. This algorithm first carries out fuzzy c-means clustering of sample features, extracts redundant cluster centers, merges the cluster centers by spectral clustering, and finally finds the category of corresponding cluster centers for each sample. It effectively solves the problems of the poor ability of the traditional fuzzy c-means clustering algorithm to classify the data with complex structure distribution and the complex calculation of the traditional spectral clustering algorithm. The experimental results demonstrated that the proposed algorithm could describe the complex structure of mildew distribution in corn kernels and exhibits higher stability, better anti-interference ability, generalization ability, and accuracy than the supervised classification model.

Application of afatinib combined with np regimen in the treatment of stage iv non-small cell lung cancer and its effect on patient survival.

To explore the application of afatinib combined with NP regimen in the treatment of stage IV non-small cell lung cancer and its effect on patient survival, the data of 100 patients with stage IV non-small cell lung cancer admitted to our hospital from February 2017 to February 2018 were retrospectively analyzed. They were equally divided into observation group and control group, with 50 in each group. The control group was treated with an NP regimen and the observation group was treated with afatinib. The disease control rate (DCR) of the observation group was remarkably higher than that of the control group (P<0.05). The observation group witnessed a markedly higher clinical benefit rate relative to the control group (P<0.05). A remarkably longer median treatment failure time of the observation group was observed as compared to the control group (P<0.001). There was no statistical difference in the incidence of adverse reactions between the observation group and the control group (P>0.05). Afatinib combined with NP regimen treatment increases the clinical benefit rate of patients with stage IV non-small cell lung cancer, improves its short-term efficacy and helps prolong the survival time of patients, with excellent safety profile.

Control of the spatial characteristics of femtosecond laser filamentation in glass via feedback-based wavefront shaping with an annular phase mask.

We propose a feedback-based wavefront shaping with an annular phase mask to control the spatial characteristics of femtosecond laser filamentation in K9 glass. A closed-loop feedback driven by a genetic algorithm was used to search for the optimal phase profile for generating the specified filaments. We demonstrate the flexibility of this method to extend or shorten filaments, improve continuity, and simultaneously control the position of filaments with specified lengths. Our approach offers a flexible regulation of the spatial characteristics of femtosecond laser filamentation for its potential applications.

Predictive role of T2WI and ADC-derived texture parameters in differentiating Gleason score 3 + 4 and 4 + 3 prostate cancer.

BACKGROUND: Since Gleason score (GS) 4 + 3 prostate cancer (PCa) has a worse prognosis than GS 3 + 4 PCa, differentiating these two types of PCa is of clinical significance. OBJECTIVE: To assess the predictive roles of using T2WI and ADC-derived image texture parameters in differentiating GS 3 + 4 from GS 4 + 3 PCa. METHODS: Forty-eight PCa patients of GS 3 + 4 and 37 patients of GS 4 + 3 are retrieved and randomly divided into training (60%) and testing (40%) sets. Axial image showing the maximum tumor size is selected in the T2WI and ADC maps for further image texture feature analysis. Three hundred texture features are computed from each region of interest (ROI) using MaZda software. Feature reduction is implemented to obtain 30 optimal features, which are then used to generate the most discriminative features (MDF). Receiver operating characteristic (ROC) curve analysis is performed on MDF values in the training sets to achieve cutoff values for determining the correct rates of discrimination between two Gleason patterns in the testing sets. RESULTS: ROC analysis on T2WI and ADC-derived MDF values in the training set (n = 51) results in a mean area under the curve (AUC) of 0.953±0.025 (with sensitivity 0.9274±0.0615 and specificity 0.897±0.069), and 0.985±0.013 (with sensitivity 0.9636±0.0446 and specificity 0.9726±0.0258), respectively. Using the corresponding MDF cutoffs, 95.3% (ranges from 76.5% to 100%) and 94.1% (ranged from 76.5% to 100%) of test cases (n = 34) are correctly discriminated using T2WI and ADC-derived MDF values, respectively. CONCLUSIONS: The study demonstrates that using T2WI and ADC-derived image texture parameters has a potential predictive role in differentiating GS 3 + 4 and GS 4 + 3 PCa.

Improving production of Streptomyces griseus trypsin for enzymatic processing of insulin precursor.

BACKGROUND: Trypsin has many applications in food and pharmaceutical manufacturing. Although commercial trypsin is usually extracted from porcine pancreas, this source carries the risks of infectivity and immunogenicity. Microbial Streptomyces griseus trypsin (SGT) is a prime alternative because it possesses efficient hydrolysis activity without such risks. However, the remarkable hydrolysis efficiency of SGT causes autolysis, and five autolysis sites, R21, R32, K122, R153, and R201, were identified from its autolysate. RESULTS: The tbcf (K101A, R201V) mutant was screened by a directed selection approach for improved activity in flask culture (60.85 ± 3.42 U mL-1, increased 1.5-fold). From the molecular dynamics simulation, in the K101A/R201V mutant the distance between the catalytical residues D102 and H57 was shortened to 6.5 Å vs 7.0 Å in the wild type, which afforded the improved specific activity of 1527.96 ± 62.81 U mg-1. Furthermore, the production of trypsin was increased by 302.8% (689.47 ± 6.78 U mL-1) in a 3-L bioreactor, with co-overexpression of chaperones SSO2 and UBC1 in Pichia pastoris. CONCLUSIONS: SGT protein could be a good source of trypsin for insulin production. As a result of the hydrolysates analysis and direct selection, the activity of the tbcf (K101A, R201V) mutant increased 1.5-fold. Furthermore, the production of trypsin was improved threefold by overexpressing chaperone protein in Pichia pastoris. Future studies should investigate the application of SGT to insulin and pharmaceutical manufacturing.