TERT activates endogenous retroviruses to promote an immunosuppressive tumour microenvironment.

Telomerase plays a pivotal role in tumorigenesis by both telomere-dependent and telomere-independent activities, although the underlying mechanisms are not completely understood. Using single-sample gene set enrichment analysis (ssGSEA) across 9,264 tumour samples, we observe that expression of telomerase reverse transcriptase (TERT) is closely associated with immunosuppressive signatures. We demonstrate that TERT can activate a subclass of endogenous retroviruses (ERVs) independent of its telomerase activity to form double-stranded RNAs (dsRNAs), which are sensed by the RIG-1/MDA5-MAVS signalling pathway and trigger interferon signalling in cancer cells. Furthermore, we show that TERT-induced ERV/interferon signalling stimulates the expression of chemokines, including CXCL10, which induces the infiltration of suppressive T-cell populations with increased percentage of CD4+ and FOXP3+ cells. These data reveal an unanticipated role for telomerase as a transcriptional activator of ERVs and provide strong evidence that TERT-mediated ERV/interferon signalling contributes to immune suppression in tumours.

Is there any difference in urinary continence between bilateral and unilateral nerve sparing during radical prostatectomy? A systematic review and meta-analysis.

CONTEXT: In men with prostate cancer, urinary incontinence is one of the most common long-term side effects of radical prostatectomy (RP). The recovery of urinary continence in patients is positively influenced by preserving the integrity of the neurovascular bundles (NVBs). However, it is still unclear if bilateral nerve sparing (BNS) is superior to unilateral nerve sparing (UNS) in terms of post-RP urinary continence. The aim of this study is to systematically compare the differences in post-RP urinary continence outcomes between BNS and UNS. METHODS: The electronic databases of PubMed and Web of Science were comprehensively searched. The search period was up to May 31, 2023. English language articles comparing urinary continence outcomes of patients undergoing BNS and UNS radical prostatectomy were included. Meta-analyses were performed to calculate pooled relative risk (RR) estimates with 95% confidence intervals for urinary continence in BNS and UNS groups at selected follow-up intervals using a random-effects model. Sensitivity analyses were performed in prospective studies and robotic-assisted RP studies. RESULTS: A meta-analysis was conducted using data from 26,961 participants in fifty-seven studies. A meta-analysis demonstrated that BNS improved the urinary continence rate compared to UNS at all selected follow-up points. RRs were 1.36 (1.14-1.63; p = 0.0007) at ≤ 1.5 months (mo), 1.28 (1.08-1.51; p = 0.005) at 3-4 mo, 1.12 (1.03-1.22; p = 0.01) at 6 mo, 1.08 (1.05-1.12; p < 0.00001) at 12 mo, and 1.07 (1.00-1.13; p = 0.03) at ≥ 24 mo, respectively. With the extension of the follow-up time, RRs decreased from 1.36 to 1.07, showing a gradual downward trend. Pooled estimates were largely heterogeneous. Similar findings were obtained through sensitivity analyses of prospective studies and robotic-assisted RP studies. CONCLUSION: The findings of this meta-analysis demonstrate that BNS yields superior outcomes in terms of urinary continence compared to UNS, with these advantages being sustained for a minimum duration of 24 months. It may be due to the real effect of saving the nerves involved. Future high-quality studies are needed to confirm these findings.

Development of a novel forensic age estimation strategy for aged blood samples by combining piRNA and miRNA markers.

In forensic investigations, age estimation is vital for determining whether a suspect is under or over the legally defined adult age. With breakthroughs in RNA sequencing technology, small noncoding RNAs have provided new ways to solve problems related to the age estimation of trace or aged samples, owing to their small molecular weight and better stability. In our previous study, we had applied miRNAs for the age estimation of bloodstains; however, further improvement of the existing model is needed. PIWI-interacting RNAs (PiRNAs), which are 24-32 nt noncoding small RNA molecules involved in the PIWI-piRNA pathway, play an important role in the aging process. In this study, we explored the possibility of simultaneously analyzing piRNAs and miRNAs for better age estimation purpose. Through massively parallel sequencing, five age-related piRNAs were identified in blood samples that had been stored for eight years. Further real-time PCR analysis revealed that two piRNAs (piR-000753 and piR-020548) showed relatively higher efficiency in age estimation. Additionally, two age-related miRNAs (miR-324-3p and miR-330-5p) were used to build the estimation model. Among all algorithms tested, gradient boosting showed the lowest mean absolute error (MAE) and root mean square error (RMSE) values (3.171 and 4.403 years, respectively) for the validation dataset (n = 110). The errors of the model were less than 5 years and 10 years for 81.82% and 96.36% of the samples, respectively. The results suggest that the combined use of piRNA and miRNA markers may increase the accuracy of age estimation, and our new model has great potential for application in forensic casework.

Recent Advances in Fluorescent Nanoprobes for Food Safety Detection.

Fluorescent nanoprobes show similar fluorescence properties to traditional organic dyes, but the addition of nanotechnology accurately controls the size, shape, chemical composition, and surface chemistry of the nanoprobes with unique characteristics and properties, such as bright luminescence, high photostability, and strong biocompatibility. For example, modifying aptamers or antibodies on a fluorescent nanoprobe provides high selectivity and specificity for different objects to be tested. Fluorescence intensity, life, and other parameters of targets can be changed by different sensing mechanisms based on the unique structural and optical characteristics of fluorescent nanoprobes. What's more, the detection of fluorescent nanoprobes is cost-saving, simple, and offers great advantages in rapid food detection. Sensing mechanisms of fluorescent nanoprobes were introduced in this paper, focusing on the application progress in pesticide residues, veterinary drug residues, heavy metals, microbes, mycotoxins, and other substances in food safety detection in recent years. A brief outlook for future development was provided as well.

Long noncoding RNA Gas5 induces cell apoptosis and inhibits tumor growth via activating the CHOP-dependent endoplasmic reticulum stress pathway in human hepatoblastoma HepG2 cells.

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to be important tumor-associated regulatory factors. LncRNA growth arrest-specific transcript 5 (Gas5) acts as an anti-oncogene in most cancers. Whether Gas5 acts as an oncogene or anti-oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription-polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull-down experiments and analyzed by mass spectrometry. A series of novel Gas5-interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78 kDa glucose-regulated protein (GRP78) was identified as a direct target of Gas5 by Rip-qPCR and Western blot analysis assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5-mediated apoptosis in HepG2 cells. Magnetic resonance imaging showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.

First report of Fusarium fujikuroi causes leaf spot in Polygonatum odoratum (Mill.) Druce in China.

Polygonatum odoratum (Mill.) Druce, a member of Liliaceae, is one of the traditional Chinese herbal plants mainly used in Jilin, Hubei, Guangxi, Zhejiang, Liaoning, Hunan and Guangdong provinces. Leaf spot disease of P. odoratum was continuously observed in the Planting Demonstration Garden in Changsha (28 °48 N; 113° 34E), Hunan Province of China, in May 2021 and May 2022. The symptoms initially appeared as tiny reddish-brown spots and continued to expand, resulting in round, oval, or irregular tan lesions with necrotic, film-shaped, or perforated central tissues. Leaf spot disease affects approximately 60-70% of plants. For pathogen isolation, symptomatic leaf samples were collected and disinfected with 70% ethanol for 30 s and 3% sodium hypochlorite for 2 min, followed by rinsing with sterile distilled water. Subsequently, small pieces (3 × 3 mm) of diseased tissues were placed on potato dextrose agar (PDA) and incubated in the dark at 25 °C for 24 h to 36 h. The emerging fungal hyphal tips were transferred to PDA and purified by the single-spore method (Yu, et al., 202). In total, 50 disease spots were isolated, and 10 cultures with the same appearance were obtained. Two strains coded as hnxryzy and hnxryzy01 were randomly selected for identification. After 6 days of culture in PDA, dense pink colonies were observed with a mean radial growth rate of 7.5 mm/day. Strains cultured 6 days on synthetic low nutrient medium, microconidia were oval or ovate (7.5-9.67 µm × 2.49-3.57 µm(n = 50)), and macroconidia were sickle-shaped and slightly curved, gradually tapering at both ends, with 2-5 pseudoseptate (10.01-22.14 µm × 2.07-4.22 µm (n = 50)). These morphological characteristics were consistent with the description of Fusarium fujikuroi (Fang, et al., 2021). Furthermore, primers ITS1/ITS4, EF728F/EF986R, Bt2a/Bt2b, RPB1-F5/RPB1-R8 and fRPB2-5F2/fRPB2-7cR (Li, et al., 2013, Xie, et al., 2022) were used to amplify the partial region of the internal transcribed spacer (ITS) , the translation elongation factor EF-1α,ß-tubulin,polymerase II largest subunit (RPB1) and RNA polymerase II second largest subunit (RPB2) genes from strains hnxryzy and hnxryzy01, respectively. Amplicons were sequenced by Tsingke Biotechnology Co., Ltd. The expected sequences of ITS, EF-1α, ß-tubulin, RPB1 and RPB2 of hnxryzy and hnxryzy01 were obtained. The sequence alignment of hnxryzj and hnxryzj01 with the Fusarium ID databased and NCBI shows the following results: The sequences of ITS region, EF-1α, ß-tubulin , RPB1 and RPB2 of strain hnxryzy (GenBank accession nos. ON797440, ON820553, ON820554, OP413443, and OP413445, respectively) and strain hnxryzy01 (GenBank accession nos. ON965284, ON968721, ON968722, OP413444, and OP413446, respectively) were 99% to 100% identical to those of F. fujikuroi (GenBank accession numbers CP023090, KC874784, MN490089, MN193916, and MN193888, respectively). Then a phylogenetic tree based on EF-1α, RPB1, and RPB2 sequences was constructed (Torres-Cruz, et al., 2022). The strains hnxryzy and hnxryzy01 were more closely related to F. fujikuroi ( NRRL13566 GenBank accession nos. AF160279, JX171456, and JX171570, respectively), with bootstrap values of 99%. Two sets (5 plants in each set) of potted plants were used in pathogenicity assays. Wounded leaves were sprayed with conidial suspensions (100 µL, 1 × 107 spores/mL) and sterile water as control. Inoculated plants were covered with plastic bags for 24 h, and maintained at 25 ° C in 12/12 h light/dark conditions in the greenhouse (Yu, et al., 2022). Pathogenicity assays were repeated thrice. Dark brown spots identical to those seen in the field were observed 14 days after inoculation, while the control leaves did not exhibit any symptoms. In this study, the pathogen F. fujikuroi was successfully reisolated from the leaves of inoculated samples showing symptoms, thereby verifying Koch's postulate. To our knowledge, this is the first report of F. fujikuroi inducing leaf spot on P. odoratum in China. Since F. fujikuroi is a common pathogenic fungus that infects different plant species(Qiu, et al., 2020), more attention should be paid to its prevalence in P. odoratum and the potential risk of outbreak in other provinces of China.

Identification of key genes in benign prostatic hyperplasia using bioinformatics analysis.

PURPOSE: This study aimed to identify differentially expressed genes (DEGs) and pathways in benign prostatic hyperplasia (BPH) by comprehensive bioinformatics analysis. METHODS: Data of the gene expression microarray (GSE6099) were downloaded from GEO database. DEGs were obtained by GEO2R. Functional and enrichment analyses of selected genes were performed using DAVID database. Protein-protein interaction network was constructed through STRING. Anterior gradient 2 (ARG2) and lumican (LUM) staining in paraffin-embedded specimens from BPH and normal prostate (NP) were detected by immunohistochemistry (IHC). Differences between groups were analyzed by the Student's t test. RESULTS: A total of 24 epithelial DEGs and 39 stromal DEGs were determined. The GO analysis results showed that epithelial DEGs between BPH and NP were enriched in biological processes of glucose metabolic process, glucose homeostasis and negative regulation of Rho protein signal transduction. For DEGs in stroma, enriched biological processes included response to ischemia, antigen processing and presentation, cartilage development, T cell costimulation and energy reserve metabolic process. ARG2, as one of the epithelial DEGs, was mainly located in epithelial cells of prostate. In addition, LUM is primarily expressed in the stroma. We further confirmed that compared with NP, the BPH have the lower ARG2 protein level (p = 0.029) and higher LUM protein level (p = 0.003) using IHC. CONCLUSIONS: Our study indicated that there are possible differentially expressed genes in epithelial and stromal cells, such as ARG2 and LUM, which may provide a novel insight for the pathogenesis of BPH.

Efficacy and safety of prostatic artery embolization for benign prostatic hyperplasia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the efficacy and safety of prostatic artery embolization (PAE) vs. transurethral resection of the prostate (TURP) in patients affected by benign prostatic hyperplasia (BPH). We also reviewed mean changes from baseline in PAE at selected follow-up points. METHODS: PubMed, Web of Science, and Embase were searched up to May 1, 2020. Randomized controlled trials on PAE were collected according to specific inclusion and exclusion criteria. Meta-analyses were performed using RevMan 5.3, STATA 14, and GraphPad Prism 8. Pooled patient-reported scores and functional outcomes were calculated by using a fixed or random-effect model. RESULTS: Eleven articles met our selection criteria and ten independent patient series were included in the final analysis. Pooled estimates suggested no significant difference between TURP and PAE for patient-reported outcomes including International Prostate Symptom Score (2.32 (- 0.44 to 5.09)) and quality of life (0.18 (- 0.41 to 0.77)) at 12 months. PAE was less effective regarding improvements in most functional outcomes such as maximum flow rate, prostate volume, and prostate-specific antigen. Moreover, PAE may be associated with relatively fewer complications, lower cost, and shorter hospitalization. After the PAE procedure, the overall weighted mean differences for all outcomes except sexual health scores were significantly improved from baseline during follow-up to 24 months. CONCLUSION: PAE is non-inferior to TURP with regard to improving patient-reported outcomes, though most functional parameters undergo more changes after TURP than after PAE. Moreover, PAE can significantly continue to relieve symptoms for 24 months without causing serious complications. KEY POINTS: • PAE is as effective as TURP in improving subjective symptom scores, with fewer complications and shorter hospitalization times. • PAE is inferior to TURP in the improvement of most functional outcomes. • Improvements due to PAE are durable during follow-up to 24 months.

Robust compressive multimode fiber imaging against bending with enhanced depth of field.

Imaging through single multimode fiber prevails its counterpart using single mode fiber bundle on spatial resolution limit and minimum radius. Current multimode fiber imaging suffers from fussy calibration, which can be reduced by recent developed compressive sensing scheme [ [L. V. Amitonova, Opt. Lett. 43, 5427 (2018)]. Experiments demonstrate improvement on depth of field by more than three orders of magnitude, together with robustness against macro fiber bending, which is vital to endoscopic applications.

Evaluations of acoustic damping performances of double-layer in-duct perforated plates at low Mach and Helmholtz number.

In this work, acoustic damping performances of double-layer in-duct perforated plates are studied at low Mach (Ma) and Helmholtz number (He) to evaluate the effects of (1) Ma, (2) the porosities (i.e., open-area ratio) σ1 and σ2 of the front and back plates, and (3) the axial distance Lc between these two plates. The orifices' damping is characterized by sound absorption coefficient α denoting the fraction of incident sound energy being absorbed. For this, a quasi-steady acoustic model is developed first and experiments are then conducted. When Ma = 0, α is experimentally found to oscillate with He, whatever the porosities of σ1 and σ2 are set. However, when Ma is increased to and above 0.037, the power absorption troughs, i.e., local αmin of the double-layer plates with σ1,2 ≤ 9% are more separated and shallower. Furthermore, when σ1= 9% or σ2 = 9%, the damping performances are quite different in terms of the local αmax peaks and their number. In addition, increasing Lc with respect to the downstream pipe length Ld gives rise to an increase of αmin and αmax by 10%. Finally, the double-layer plates are shown to involve a larger α than that of single-layer one over a broader He range.

Modeling the crosstalk between the circadian clock and ROS in Neurospora crassa.

The circadian clock regulates the expression of clock-controlled genes and adapts to environmental changes. Reactive oxygen species (ROS) also undergo circadian rhythms and have a role in circadian timekeeping. To elucidate crosstalk between ROS and the circadian clock in Neurospora crassa, we build an integrative network model, characterizing the circadian oscillator, ROS system and their interactions. Notably, the (de)phosphorylation and nuclear-cytoplasmic shuttling of clock proteins are modeled in detail. Simulation results quantitatively reproduce the essential features of circadian rhythm (both in constant darkness and under light/dark cycles) and the changes in period length and phase when ROS levels are altered under diverse conditions. This work clarifies the effects of three interactions between ROS and the clock on the circadian rhythm, suggesting that the regulation of WCC activity by protein phosphatase 2A in an O2--dependent manner plays a predominant role. The functional significance of such modulations is also discussed.

Rapid detection of unconjugated estriol in the serum via superparamagnetic lateral flow immunochromatographic assay.

Unconjugated estriol (uE3) is one of the main naturally occurring estrogens that plays an important role in growth and development of the fetus. Usually, the level of uE3 is very low in men and non-pregnant women, but in pregnant women, the level of estriol has been found to be quite high. Therefore, the combination of uE3, AFP, and hCG is now widely used for Down Syndrome screening as a triple marker. Here, we developed a superparamagnetic lateral flow immunochromatographic assay to quantitatively detect uE3. The detection limit of this assay was 0.86 nmol/L and the linear range for the determination of uE3 was from 1 to 100 nmol/L. The detection time was 15 min and the assay had very low cross-reactivity with estrone (E1), estradiol (E2), and progesterone. The coefficient of variation (CV) of intra- and inter-assay ranged from 5% to 13%. The magnetic signals were stable under 37 °C within 7 d. Moreover, the concentrations of uE3 measured by lateral flow immunochromatographic assay in 230 serum samples collected from pregnant women at the Chinese People's Liberation Army General Hospital had a good correlation with those measured by time-resolved fluorescence immunoassay (R = 0.946).

Down-regulation of p16 and MGMT promotes the anti-proliferative and pro-apoptotic effects of 5-Aza-dC and radiation on cervical cancer cells.

Cervical cancer is one of the most common malignancies of the female reproductive system. Therefore, it is critical to investigate the molecular mechanisms involved in the development and progression of cervical cancer. In this study, we stimulated cervical cancer cells with 5-aza-2'-deoxycytidine (5-Aza-dC) and found that this treatment inhibited cell proliferation and induced apoptosis; additionally, methylation of p16 and O-6-methylguanine-DNA methyltransferase (MGMT) was reversed, although their expression was suppressed. 5-Aza-dC inhibited E6 and E7 expression and up-regulated p53, p21, and Rb expression. Cells transfected with siRNAs targeting p16 and MGMT as well as cells stimulated with 5-Aza-dC were arrested in S phase, and the expression of p53, p21, and Rb was up-regulated more significantly. However, when cells were stimulated with 5-Aza-dC after transfection with siRNAs targeting p16 and MGMT, proliferation decreased significantly, and the percentage of cells in the sub-G1 peak and in S phase was significantly increased, suggesting a marked increase in apoptosis. But E6 and E7 overexpression could rescue the observed effects in proliferation. Furthermore, X-ray radiation caused cells to arrest in G2/M phase, but cells transfected with p16- and MGMT-targeted siRNAs followed by X-ray radiation exhibited a significant decrease in proliferation and were shifted toward the sub-G1 peak, also indicating enhanced apoptosis. In addition, the effects of 5-Aza-dC and X-ray radiation were most pronounced when MGMT expression was down-regulated. Therefore, down-regulation of p16 and MGMT expression enhances the anti-proliferative effects of 5-Aza-dC and X-ray radiation. This discovery may provide novel ideas for the treatment of cervical cancer.

[Preliminary establishment of quantitative detection for luteinizing hormone based on superparamagnetic particles labeled immuno chromatography method].

OBJECTIVE: To develop a quick quantitative detecting method for luteinizing hormone(LH) based on superparamagnetic particles labeled immunochromatography technology. METHODS: Magnetic particles were catalyzed by EDC/NHS, LH monoclonal antibody were coupled with magnetic particles, another antibody were coated with the NC membrane, established a quantitative detecting method combined sand wish assay format with immunochromatography. The performance of this method was evaluated by linear range, precision, accuracy, specificity and stability. Detecting the serum sample that were tested by chemiluminescence immunoassay (CLIA) which was high credibility to verify the reliability. RESULTS: The reaction time of LH antibody coupled magnetic particles, LH and LH antibody coated in nitrocellulose membrane was 20 min; the coefficient of variation (CV) values for low, median, high were 8%-12%, the bias was less than 10%, recovery rate was 90%-120%, the minimum detection limit was 0.63 mIU/ml, no obvious cross reaction with human chorionic gonadotropin (HCG), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH). Test results of clinical sample had good correlation with CLIA (R² =0.96, P<0.05). CONCLUSION: The superparamagnetic particles labeled immuno-chromatography method is simple and rapid, and is expected to become a direction in the development for point-of-care test (POCT) quantitative detection of micro components in biological sample.

MicroRNA-350 induces pathological heart hypertrophy by repressing both p38 and JNK pathways.

Recent studies have identified important roles for microRNAs (miRNAs) in many cardiac pathophysiological processes, including the regulation of cardiomyocyte hypertrophy. However, the role of miR-350 in the cardiac setting is still unclear. The objective of this study is to determine whether miR-350 alone can induce pathological cardiac hypertrophy by repressing the SAPK pathway in cardiomyocytes. Here we report that miR-350 plays a key role in determining pathological cardiomyocyte hypertrophy and apoptosis. Comprehensive microarray profiling of miRs and qPCR showed that this unique miRNA was significantly up-regulated in rat hearts in response to late-stage transverse aortic constriction. Western blotting and luciferase assays confirmed that the target mRNAs of miR-350 are mitogen activated protein kinase (MAPK) 11/14 and MAPK8/9 gene transcripts. Gain-of-unction and loss-of-function approaches were used to investigate the functional roles of miR-350. The forced over-expression of miR-350 was sufficient to induce hypertrophy of cardiomyocytes through the posttranslational suppression of p38 and JNK protein synthesis. Moreover, miR-350 led to an increase in unphosphorylated NFATc3 and its nuclear translocation, resulting in the over-expression of pathological hypertrophy markers. As predicted, these effects could effectively be imitated by siR-JNK/p38 through the degeneration of p38 and JNK mRNAs. Conversely, antagomir-350 could lower the levels of miR-350, reverse the expression of target proteins and reduce cell size and apoptosis relative to the administration of mutant antagomir-350. Our data provide the first evidence that miR-350 is a critical regulator of pathological cardiac hypertrophy and apoptosis in rats.

Surface-induced hydrogelation inhibits platelet aggregation.

We demonstrate that a tripeptide hydrogelator, Nap-FFG, can selectively self-assemble at the surface of platelets, thus inhibiting ADP-, collagen-, thrombin- and arachidonic acid (AA)-induced human platelet aggregations with the IC(50) values of 0.035 (41), 0.14 (162), 0.062 (68), and 0.13 mg/mL (148 µM), respectively. Other tripeptide hydrogelators with chemical structures of Nap-FFX (X = A, K, S, or E) could not or possessed less potencies to inhibit platelet aggregations. We observed higher amounts of Nap-FFG at the platelet surface by the techniques of LC-MS and confocal microscopy. We also observed self-assembled nanofibers around the platelet incubated with the Nap-FFG by cryo-TEM. The ζ potential of Nap-FFG treated platelets was a little bit more negative than that of untreated ones. The amount of Nap-FFG at the surface of NIH 3T3 cells was much less than that of platelets. These observations suggested that Nap-FFG could selectively self-assemble through unknown ligand-receptor interactions and form thin layers of hydrogels at the surface of platelets, thus preventing the aggregation of them. This study not only broadened the application and opened up a new door for biomedical applications of molecular hydrogels but also might provide a novel strategy to counteract infection diseases through selective surface-induced hydrogelations at pathogens, such as bacteria and virus.

Metabolomics Study of the Effect of Transcription Factor NOR-like1 on Flavonoids in Tomato at Different Stages of Maturity Using UPLC-MS/MS.

Tomato fruits are rich in flavonoids. This study explores the effect of transcription factor SlNOR-like1 on the accumulation of flavonoids in tomato fruits at different ripening stages. We used ultra-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to analyze wild-type (WT) and NOR-like1 CRISPR/Cas9-edited (NOR-like1) tomato fruits. A total of 50 flavonoid metabolites were accurately identified and determined in tomatoes. The flavonoid metabolic differences were observed among the different tomato sample groups using PCA and OPLS-DA analysis. There were 16 differential flavonoids (13 upregulated and 3 downregulated) identified between WT-GR (WT tomato at the green-ripening stage) and NOR-like1-GR (NOR-like1 tomato at the green-ripening stage), 9 differential flavonoids (six upregulated and three downregulated) identified between WT-BR3 (WT tomato at the color-breaking stage) and NOR-like1-BR3 (NOR-like1 tomato at the color-breaking stage), and 12 differential flavonoids (11 upregulated and 1 downregulated) identified between WT-BR9 (WT tomato at the red-ripening stage) and NOR-like1-BR9 (NOR-like1 tomato at the red-ripening stage). Rutin, nicotiflorin, naringenin chalcone, eriodictyol, and naringenin-7-glucoside were the five flavonoids with the highest content in the ripening stages (BR3 and BR9) in both WT and NOR-like1 tomato fruits. The overall flavonoid contents in WT tomato fruits changed little from GR to BR3 and decreased from BR3 to BR9; meanwhile, in the NOR-like1 tomato fruits, the total amounts of the flavonoids exhibited an increasing trend during all three ripening stages. The accumulation pattern of flavonoid metabolites in NOR-like1 tomato fruits differed from that in WT tomato fruits, especially in the later ripening process of BR9. The transcription factor SlNOR-like1 has an impact on the accumulation of flavonoids in tomato fruits. The results provide a preliminary basis for subsequent research into its regulatory mechanism and will be helpful for attaining future improvements in the nutritional quality and postharvest treatment of tomato fruits.

[Effects of Equal Amounts Silicon Fertilizer Application on Soil Bioavailability of Cadmium and Cadmium Uptake by Rice].

Cadmium (Cd) contamination of paddy fields is a global concern, as it can cause the accumulation of Cd in food. To explore the effects of equal application of silicon fertilizers on the bioavailability of cadmium and soil Cd uptake at different growth stages of rice, a field experiment was conducted with five silicon fertilizers under the same silicon dose (225 kg·hm-2). The results revealed that the Cd contents in roots, stems, and leaves increased with the extension of the rice growth stage. The application of silicon fertilizers reduced the Cd contents in roots, stems, and leaves in brown rice by 14.9%, 28.2%, and 12.2%, respectively. Compared with that in the control, the Cd content of brown rice in the SiCaMgFe and SiW treatments was decreased by 21.1% (P<0.05) and 21.2% (P<0.05), respectively. Similarly, Cd content in iron plaque (DCB-Cd) increased with the extension of the rice growth period, which accounted for 15.8%-42.8% of the total Cd content in roots, and the DCB-Cd content was different in each stage of rice. The content of exchangeable Cd (Exc-Cd) in soil at the mature stage of rice decreased by 36.4%, and the other fractions increased by 12.5%-48.2%. The results showed significant negative correlations between the Cd contents and Si in roots, DCB-Cd and soil available Cd and available Si, Exc-Cd and Car-Cd, and soil available Cd and pH value. Cd content in roots was positively correlated with DCB-Cd. With the equal dose of silicon fertilizer, the treatments of SiCaMgFe and SiW could effectively reduce the Cd content in rice. The application of silicon fertilizer promoted the transfer of Exc-Cd to Carb-Cd by increasing the soil pH value and the soil available Si content, meanwhile reducing the soil available Cd, Exc-Cd contents, the adsorption of Cd by the iron film on the root surface, and the adsorption capacity of iron plaque and root, thereby reducing the absorption of Cd by rice.

MITF-siRNA formulation is a safe and effective therapy for human melasma.

It is unclear whether siRNA-based agents can be a safe and effective therapy for diseases. In this study, we demonstrate that microphthalmia-associated transcription factor-siRNA (MITF-siR)-silenced MITF gene expression effectively induced a significant reduction in tyrosinase (TYR), tyrosinase-related protein 1, and melanocortin 1 receptor (MC1R) levels. The siRNAs caused obvious inhibition of melanin synthesis and melanoma cell apoptosis. Using a novel type of transdermal peptide, we developed the formulation of an MITF-siR cream. Results demonstrated that hyperpigmented facial lesions of siRNA-treated subjects were significantly lighter after 12 weeks of therapy than before treatment (P < 0.001); overall improvement was first noted after 4 weeks of siRNA treatment. At the end of treatment, clinical and colorimetric evaluations demonstrated a 90.4% lightening of the siRNA-treated lesions toward normal skin color. The relative melanin contents in the lesions and adjacent normal skin were decreased by 26% and 7.4%, respectively, after treatment with the MITF-siR formulation. Topical application of siRNA formulation significantly lightens brown facial hypermelanosis and lightens normal skin in Asian individuals. This treatment represents a safe and effective therapy for melasma, suggesting that siRNA-based agents could be developed for treating other diseases such as melanoma.

Study on Mechanical Properties of Multi-Cavity Steel-Concrete Composite Beam.

This paper proposes a new form of composite beam: a multi-cavity steel-concrete composite beam. This composite beam uses internal perforated steel plate to connect the concrete with the steel structure, and shear connectors are no longer required, which is more suitable for industrial production. The mechanical properties of a multi-cavity steel-concrete composite beam in industrial applications are studied to avoid failures. In this paper, two multi-cavity steel-concrete composite beams with a size of 2500 mm × 200 mm × 300 mm were prepared, in which the angle of internal porous steel plate was set as 60° and 75°, respectively. A full-scale static load test was conducted on the beams to research its deformation and failure modes. The finite element software ANSYS was used to perform finite element modeling of multi-cavity steel-concrete composite beams and to analyze the influence of concrete strength, steel strength, porosity, and the angle of internal porous steel plate on the mechanical properties of composite beams. The results are as follows: before the composite beam reaches its serviceability limit state, its deformation basically shows a linear change; with the increase of load, the plastic deformation is gradually obvious, which can still provide a certain bearing capacity in the failure stage; the bearing capacity of the composite beam is positively correlated with the strength of concrete and steel, while negatively correlated with the porosity and the angle of internal porous steel plate; composite beams have large bearing capacity, good ductility and integrity.