Melatonin enhances resistance to Botryosphaeria dothidea in pear by promoting jasmonic acid and phlorizin biosynthesis.

Ring rot, caused by Botryosphaeria dothidea, is an important fungal disease of pear fruit during postharvest storage. Melatonin, as a plant growth regulator, plays an important role in enhancing the stress resistance of pear fruits. It enhances the resistance of pear fruits to ring rot by enhancing their antioxidant capacity. However, the underlying mechanism remains unclear. In this study, we examined the effect of melatonin on the growth of B. dothidea. Results showed that melatonin did not limit the growth of B. dothidea during in vitro culture. However, metabolomics and transcriptomics analyses of 'Whangkeumbae' pear (Pyrus pyrifolia) revealed that melatonin increased the activity of antioxidant enzymes, including peroxidase (POD), superoxide dismutase (SOD), and polyphenol oxidase (PPO), in the fruit and activated the phenylpropanoid metabolic pathway to improve fruit resistance. Furthermore, melatonin treatment significantly increased the contents of jasmonic acid and phlorizin in pear fruit, both of which could improve disease resistance. Jasmonic acid regulates melatonin synthesis and can also promote phlorizin synthesis, ultimately improving the resistance of pear fruit to ring rot. In summary, the interaction between melatonin and jasmonic acid and phlorizin enhances the antioxidant defense response and phenylpropanoid metabolism pathway of pear fruit, thereby enhancing the resistance of pear fruit to ring rot disease. Our results provide new insights into the application of melatonin in the resistance to pear fruit ring rot.

Knockdown of LRCH4 Remodels Tumor Microenvironment Through Inhibiting YAP and TGF-ß/Smad Signaling Pathway in Colorectal Cancer.

BACKGROUND: Colorectal cancer is one of the most common gastrointestinal malignancies worldwide. LRCH4 is the top 1 gene associated with an unfavorable prognosis in colorectal cancer. METHODS: Here, we reported that the knockdown of LRCH4 inhibited the proliferation, migration and invasion in HT29 cells. RESULTS: The activity of Yes-Associated Protein (YAP), a transcription factor in the Hppo-YAP signaling pathway, was significantly inhibited by LRCH4-siRNA. LRCH4 knockdown also reversed the EMT and regulated the expression of extracellular matrix (ECM) protein, Fibronectin and Collagen IV in HT29 cells. In addition, the TGF-ß/Smad signaling pathway, as the downstream pathway of Yap, was also inhibited by LRCH4 knockdown. CONCLUSION: Knockdown of LRCH4 involved in the regulation of ECM and EMT and inhibited YAP and the TGF-ß/Smad signaling pathway in colorectal cancer cells. Our study provided a mechanism of LRCH4 on colorectal cancer cells, and a new potential target for clinical tumor treatment.

Spatially selective defect management of CsPbI3 films for high-performance carbon-based inorganic perovskite solar cells.

Defects formed at the surface, buried interface and grain boundaries (GB) of CsPbI3 perovskite films considerably limit photovoltaic performance. Such defects could be passivated effectively by the most prevalent post modification strategy without compromising the photoelectric properties of perovskite films, but it is still a great challenge to make this strategy comprehensive to different defects spatially distributed throughout the films. Herein, a spatially selective defect management (SSDM) strategy is developed to roundly passivate various defects at different locations within the perovskite film by a facile one-step treatment procedure using a piperazine-1,4-diium tetrafluoroborate (PZD(BF4)2) solution. The small-size PZD2+ cations could penetrate into the film interior and even make it all the way to the buried interface of CsPbI3 perovskite films, while the BF4- anions, with largely different properties from I- anions, mainly anchor on the film surface. Consequently, virtually all the defects at the surface, buried interface and grain boundaries of CsPbI3 perovskite films are effectively healed, leading to significantly improved film quality, enhanced phase stability, optimized energy level alignment and promoted carrier transport. With these films, the fabricated CsPbI3 PSCs based on carbon electrode (C-PSCs) achieve an efficiency of 18.27%, which is among the highest-reported values for inorganic C-PSCs, and stability of 500 h at 85 °C with 65% efficiency maintenance.

Effects of Metabolic Syndrome and Its Components on Chronic Kidney Disease and Renal Function: A Two-Sample Mendelian Randomization Study.

Objective: The association of metabolic syndrome (MetS) and its components with chronic kidney disease (CKD) and renal function remains controversial in observational studies. To comprehensively investigate the association between MetS and its components with CKD and renal function, a Mendelian randomization (MR) study was performed. Methods: The inverse variance weighting (IVW) of random effects was used as the main estimation method, while MR-Egger and weighted median analysis results were used for auxiliary judgments. Cochran's Q test, MR-Egger intercept test, leave-one-out analysis, and funnel plots were used to assess heterogeneity and pleiotropy. Results: The MR analyses of genetically predicted MetS and its components' association with CKD risk and renal function showed the following causal associations: hypertension with CKD risk; MetS and obesity with increased blood urea nitrogen and decreased estimated glomerular filtration rate based on cystatin C; hypertension and diabetes with increased urine albumin-creatinine ratio and increased risk of microalbuminuria; and CKD with increased triglyceride. Conclusion: Based on genetic data, this study demonstrated an association between hypertension and CKD risk and a causal association between other MetS components and renal function. The early diagnosis and prevention of MetS and its components might be essential for CKD management.

Effects of trunk training using motor imagery on trunk control ability and balance function in patients with stroke.

OBJECTIVE: To explore the effects of trunk training using motor imagery on trunk control and balance function in patients with stroke. METHODS: One hundred eligible stroke patients were randomly divided into a control group and trial group. The control group was given routine rehabilitation therapy, while the trial group was given routine rehabilitation therapy and trunk training using motor imagery. RESULTS: Prior to treatment, there was no significant difference between the two groups (P > 0.05) in Sheikh's trunk control ability, Berg rating scale (BBS), Fugl-Meyer assessment (FMA), movement length, movement area, average front-rear movement speed, average left-right movement speed, and surface electromyography (sEMG) signal of the bilateral erector spinae and rectus abdominis. After treatment, Sheikh's trunk control ability, FMA, and BBS in the two groups were significantly higher than those before treatment (P < 0.05). The movement length, movement area, the average front-rear movement speed, and the average left-right movement speed in the two groups decreased significantly (P < 0.05). The differences of these indicators between the two groups were statistically significant (P < 0.05). After treatment, the rectus abdominis and erector spinae on the affected side of the two groups improved when compared with those before treatment (P < 0.05). The rectus abdominis and erector spinae on the healthy side of the trial group descended after treatment (P < 0.05), while little changes were observed on the healthy side of the control group after treatment (P > 0.05). The rectus abdominis and erector spinae on the affected side of the trial group improved when compared with those in the control group (P < 0.05). There was no significant difference between the two groups in the decline of abdominalis rectus and erector spinal muscle on the healthy side. CONCLUSION: Trunk training using motor imagery can significantly improve the trunk control ability and balance function of stroke patients and is conducive to promoting the recovery of motor function.

Anion Confinement for Homogeneous Mixed Halide Perovskite Film Growth by Electrospray.

Wide-bandgap perovskites are promising absorbers for state-of-the-art tandem solar cells to feasibly surpass Shockley-Queisser limit with low cost. However, the commonly used mixed halide perovskites suffer from poor stability; particularly, photoinduced phase segregation. Electrospray deposition is developed to bridge the gap of growth rate between iodide and bromide components during film growth by spatially confining the anion diffusion and eliminating the kinetic difference, which universally improves the initial homogeneity of perovskite films regardless of device architectures. It thus promotes the efficiency and stability of corresponding solar cells based on wide-bandgap (1.68 eV) absorbers. Remarkable power conversion efficiencies (PCEs) of 21.44% and 20.77% are achieved in 0.08 cm2 and 1.0 cm2 devices, respectively. In addition, these devices maintain 90% of their initial PCE after 1550 h of stabilized power output (SPO) tracking upon one sun irradiation (LED) at room temperature.

Review of fruit cork spot disorder of Asian pear (Pyrus spp.).

Cork spot disorder has affected the fruit of Asian pear since the 1990s and has become serious in recent years with increasingly affected cultivars and areas. The commodity value of affected fruit is greatly decreased, resulting in severe economic losses. Cork spot disorder of pear fruit is a physiological disorder, and the factors responsible are relatively complex. Research on the cause of cork spot disorder is still at an early stage and, thus, further investigations are needed to elucidate the underlying mechanism of the disorder. In this review, current knowledge of the factors associated with the incidence of cork spot disorder in Asian pear fruit is summarized, including fruit growth and development, fruit nutrient status, and environmental factors. Potential preventive measures and priorities for future research are outlined.

Carboxypeptidase A6 suppresses the proliferation and invasion of colorectal cancer cells and is negatively regulated by miR-96-3p.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor, and this study aims to explore the role and the regulatory mechanism of carboxypeptidase A6 (CPA6) in CRC cells. METHODS: Specific shRNA targeting CPA6 mRNA was transfected into NCM460 and HT29 cells to down-regulate CPA expression, and expression plasmid was transfected into HCT116 cells to exogenously overexpress CPA6. The dual luciferase assay was used to detect the direct binding of miR-96-3p to CPA6 3'UTR. Phosphorylation and activation of Akt were detected using Western blot. Cells were treated with miR-96-3p mimics, Akt inhibitor (MK-2206) or agonist (SC79) for rescue experiments. The cell functions were evaluated using CCK-8, clone formation, transwell, and Western blot assays. Xenograft tumor assay was also used to analyze the effect of altered CPA6 expression on tumor growth. RESULTS: Knockdown of CPA6 promoted the proliferation, clone formation, migration, and invasion of NCM460 and HT29 cells in vitro, and the tumor growth of nude mouse xenograft tumor in vivo. Moreover, over-expression of CPA6 significantly inhibited the malignant proliferation and invasion of HCT116 cells in vitro, and the tumor growth of xenograft tumor in vivo. Furthermore, miR-96-3p could directly regulate CPA6 expression by targeting its 3'UTR, and miR-96-3p mimics rescued the inhibitory effects of CPA6 overexpression on the malignant proliferation and invasion of CRC cells. Finally, CPA6 knockdown enhanced Akt/mTOR phosphorylation and activation, while CPA6 overexpression inhibited Akt/mTOR activation. The regulatory effect of CPA6 on Akt/mTOR signaling was naturally regulated by miR-96-3p. Akt inhibitor or agonist rescued the effects of CPA6 knockdown or overexpression on proliferation and EMT of colon cancer cells. CONCLUSION: CPA6 has a significant tumor suppressive effect on CRC by inhibiting the activation of Akt/mTOR signaling, and miR-96-3p negatively regulates the expression of CPA6.

Identification of QTLs and Putative Candidate Genes for Plant Architecture of Lotus Revealed by Regional Association Mapping.

The lotus (Nelumbo Adans.) is one of the most economically relevant ornamental aquatic plants. Plant architecture (PA) is an important trait for lotus classification, cultivation, breeding, and applications. However, the underlying genetic and molecular basis controlling PA remains poorly understood. In this study, an association study for PA-related traits was performed with 93 genome-wide microsatellite markers (simple sequence repeat, SSR) and 51 insertion-deletion (InDel) markers derived from the candidate regions using a panel of 293 lotus accessions. Phenotypic data analysis of the five PA-related traits revealed a wide normal distribution and high heritability from 2013 to 2016, which indicated that lotus PA-related traits are highly polygenic traits. The population structure (Q-matrix) and the relative kinships (K-matrix) of the association panels were analyzed using 93 SSR markers. The mixed linear model (MLM) taking Q-matrix and K-matrix into account was used to estimate the association between markers and the traits. A total of 26 markers and 65 marker-trait associations were identified by considering associations with p < 0.001 and Q < 0.05. Based on the significant markers, two QTLs on Chromosome 1 were identified, and two candidate genes were preliminarily determined. The results of our study provided useful information for the lotus breeding aiming at different PA phenotypes using a molecular-assisted selection (MAS) method and also laid the foundation for the illustration of the molecular mechanism underlying the major QTL and key markers associated with lotus PA.

Jasmonic acid negatively regulates branch growth in pear.

The quality of seedlings is an important factor for development of the pear industry. A strong seedling with few branches and suitable internodes is ideal material as a rootstock for grafting and breeding. Several branching mutants of pear rootstocks were identified previously. In the present study, 'QAU-D03' (Pyrus communis L.) and it's mutants were used to explore the mechanism that affects branch formation by conducting phenotypic trait assessment, hormone content analysis, and transcriptome analysis. The mutant plant (MP) showed fewer branches, shorter 1-year-old shoots, and longer petiole length, compared to original plants (OP), i.e., wild type. Endogenous hormone analysis revealed that auxin, cytokinin, and jasmonic acid contents in the stem tips of MP were significantly higher than those of the original plants. In particular, the jasmonic acid content of the MP was 1.8 times higher than that of the original plants. Transcriptome analysis revealed that PcCOI1, which is a transcriptional regulatory gene downstream of the jasmonic acid signaling pathway, was expressed more highly in the MP than in the original plants, whereas the expression levels of PcJAZ and PcMYC were reduced in the MP compared with that of the original plants. In response to treatment with exogenous methyl jasmonate, the original plants phenotype was consistent with that of the MP in developing less branches. These results indicate that jasmonic acid negatively regulates branch growth of pear trees and that jasmonic acid downstream regulatory genes play a crucial role in regulating branching.

Association between hypertension and nonalcoholic fatty liver disease: a cross-sectional and meta-analysis study.

The association between hypertension and nonalcoholic fatty liver disease (NAFLD) is not completely understood. This study aimed to investigate the association between hypertension and hepatic ultrasound examination-diagnosed positive NAFLD in healthy people; to conduct a comprehensive meta-analysis combining the results of previous studies; to explore whether hypertension was a risk factor for NAFLD. This study included 2049 adults (male: 870 and female: 1179), aged ≥20 years, whose anthropometric parameters were measured to analyze the risk of hypertension on NAFLD. We also collected data from 11 cross-sectional studies relevant to this topic using PubMed, Embase, Web of Science, CNKI, Wanfang, and CQVIP from beginning till 31 August 2020 and combined it with our data for a meta-analysis to explore whether hypertension was a risk factor for NAFLD. After adjusting for confounding factors, the odds of NAFLD in hypertensive subjects was 1.473 (95%CI: 1.119-1.938). After combining with 10 selected studies, 42711 participants were enrolled in meta-analysis. Hypertension was a risk factor for NAFLD (Z = 13.46, P < 0.001); the odds of NAFLD in hypertensive subjects was 1.43 (95%CI: 1.36-1.51). The results were consistent with the results of the meta-analysis. Further studies are required to confirm these results.

Initializing film homogeneity to retard phase segregation for stable perovskite solar cells.

The mixtures of cations and anions used in hybrid halide perovskites for high-performance solar cells often undergo element and phase segregation, which limits device lifetime. We adapted Schelling's model of segregation to study individual cation migration and found that the initial film inhomogeneity accelerates materials degradation. We fabricated perovskite films (FA1-xCsxPbI3; where FA is formamidinium) through the addition of selenophene, which led to homogeneous cation distribution that retarded cation aggregation during materials processing and device operation. The resultant devices achieved enhanced efficiency and retained >91% of their initial efficiency after 3190 hours at the maximum power point under 1 sun illumination. We also observe prolonged operational lifetime in devices with initially homogeneous FACsPb(Br0.13I0.87)3 absorbers.

Bagging Strategy and Identification of Coloring Mode of 'Xinqihong' Pear.

'Xinqihong' is a recently selected and well-colored red pear (Pyrus bretschneideri Rehd.) cultivar that is popular in the marketplace owing to the bright red color and high quality of the fruit. The red pigmentation is strongly associated with the light signal. However, its responses to bagging treatment and to light exposure after shading are unknown. In this study, the fruit were treated with three types of fruit bags. 'Xinqihong' fruit colored rapidly in response to light stimulation. A white fruit bag was optimal for bagging of 'Xinqihong' fruit. To ensure satisfactory red pigmentation, the fruit required exposure to 30 days of light after bag removal. A transcriptome analysis was conducted to screen light-signal-related genes and identify their possible functions. PbCRY1 activated the promoter of PbHY5.2 and enhanced its expression. PbHY5.2 activated the promoter activity of PbUFGT and induced anthocyanin synthesis, and also showed self-activation characteristics. Both PbCRY2 and PbPHY1 induced anthocyanin accumulation. Thus, blue-light receptors played an important role in anthocyanin synthesis. This study provides a theoretical basis for the bagging cultivation of new varieties of 'Xinqihong', and lays a foundation for the study of the mechanisms of red pear fruit coloring in response to light signals.

3D Bioprinting of Living Materials for Structure-Dependent Production of Hyaluronic Acid.

3D bioprinting of living materials represents an interesting paradigm toward the efficacy enhancement for the biosynthesis of various functional compounds in microorganisms. Previous studies have shown the success of 3D-printed bioactive systems in the production of small molecular compounds. However, the feasibility of such a strategy in producing macromolecules and how the geometry of the 3D scaffold influences the productivity are still unknown. In this study, we printed a series of 3D gelatin-based hydrogels immobilized with fermentation bacteria that can secrete hyaluronic acid (HA), a very useful natural polysaccharide in the fields of biomedicine and tissue engineering. The 3D-printed bioreactor was capable of producing HA, and an elevated yield was obtained with the system bearing a grid structure compared to that either with a solid structure or in a scaffold-free fermentation condition. As for the grid structure, bioreactors with a 90° strut angel and a median interfilament distance displayed the highest HA yield. Our findings highlighted the significant role of 3D printing in the spatial control of microorganism-laden hydrogel structures for the enhancement of biosynthesis efficiency.

Avoiding Structural Collapse to Reduce Lead Leakage in Perovskite Photovoltaics.

Perovskite solar cells (PSCs) have become a promising candidate for the next-generation photovoltaic technologies. As an essential element for high-efficiency PSCs however, the heavy metal Pb is soluble in water, causing a serious threat to the environment and human health. Due to the weak ionic bonding in three-dimensional (3D) perovskites, drastic structure decomposition occurs when immersing the perovskite film in water, which accelerates the Pb leakage. By introducing the chemically stable Dion-Jacobson (DJ) 2D perovskite at the 3D perovskite surface, the film dissolution is significantly slowed down, which retards lead leakage. As a result, the Pb contamination is dramatically reduced under various extreme conditions. In addition, the PSCs device deliver a power conversion efficiency (PCE) of 23.6 % and retain over 95 % of their initial PCE after the maximum power point tracking for over 1100 h.

Variations in Pedicel Structural Properties Among Four Pear Species (Pyrus): Insights Into the Relationship Between the Fruit Characteristics and the Pedicel Structure.

Fruit pedicel is the bridge linking the parent tree and the fruit, which is an important channel for water and nutrients transport to the fruit. The genetic specificity determines the characteristics of the pedicel and the fruit, but the relationship between the pedicel structure and the fruit characteristics is unexplored. Combining the investigation of fruit characteristics, the statistical analysis of the pedicel structural properties, and the 2D and 3D anatomical observation of the pedicel, this study found distinctive contributions of the pedicel elements to the fruit characteristics in four pear species. The European pear (Conference) showed distinct fruit shape index and pedicel structural properties compared with the oriental pears (Akizuki, Yali, and Nanguoli). The fruit size positively correlated with pedicel length, fiber area, pedicel diameter, the area percentage of the cortex, and the area percentage of phloem; however, fruit firmness and soluble solids concentration are showed a stronger positive correlation with xylem area, pith area, the area percentage of xylem, the area percentage of sieve tube, and the area percentage of pith. Pedicel elements, including pith, fiber, and cortex, likely play a certain role in the fruit growth due to the variations of their characteristics demonstrated in the four pear species. The porosity, the ratio of the surface area to the volume, and the spatial arrangement of the vessels showed significant variations across the pear species, indicating the distinction of the hydraulic conductance of the pedicels. Our findings provided direct evidence that pedicel structural elements contributed distinctively to the fruit characteristics among pear species.

Genome-Wide Analysis of KNOX Transcription Factors and Expression Pattern of Dwarf-Related KNOX Genes in Pear.

KNOTTED1-like homeobox (KNOX) transcription factors (TFs) belonging to the homeobox TF family play important roles in plant growth, development, and responses to abiotic and biotic stress. However, little information is available on KNOX TF in pear (Pyrus). In this study, 19 PbKNOXs TFs were re-identified in pear (Pyrus bretschneideri Rehd.). Phylogenetic analysis revealed that the TFs were clustered into three groups with 10 conserved motifs, some of which were group- or subgroup-specific, implying that they are important for the functions of the KNOX in these clades. PbKNM1 and PbKNM2 are KNM (encodes a MEINOX domain but not a homeodomain) genes identified in pear for the first time. KNOX genes in Pyrus and Malus were closely related, and a collinear relationship among PbKNOX genes in Pyrus and Malus was observed. Analysis of the expression patterns of PbKNOX genes in different tissues, at various growth stages, and in response to abiotic and biotic stress revealed that PbKNOXs are involved in plant growth and development. Our comparative transcriptional analysis of dwarf mutant varieties revealed that genes belonging to class I are highly expressed compared with genes in other classes. Analysis of the expression of PbKNOX genes in the hybrid offspring of vigorous and dwarf varieties revealed that PbKNOX genes were highly expressed in the vigorous offspring and weakly expressed in the dwarf offspring. These findings provide new insight into the function of KNOX TFs in pear and will aid future studies of dwarf fruit trees.

[Mechanism of oxymatrine in treatment of collagen-induced arthritis in mice].

Sophorae Flavescentis Radix, the root of Sophora flavescens Ait., has been widely applied in the medical field due to its anti-inflammatory, analgesic, bacteriostatic, antiviral, antitumor, and other pharmacological effects. The present study investigated the anti-rheumatoid arthritis effect of oxymatrine(OMT), the active component of Sophorae Flavescentis Radix by observing its effect on the function of B lymphocytes in collagen-induced arthritis(CIA) mice through the Toll-like receptor 9(TLR9)/myeloid differentiation factor 88(MyD88)/signal transducer and activator of transcription 3(STAT3) pathway. The CIA model in DBA/1 J mice was induced by bovine type Ⅱ collagen and complete Freund's adjuvant(CFA). Fifteen days after the primary immunization, mice were treated with OMT for 30 days by intraperitoneal injection. Paw swelling and arthritis index(AI) score were evaluated every 3 days. Joint histopathologic changes were observed by HE staining. Magnetic-activated cell sorting(MACS) was used to isolate B lymphocytes from the spleen of CIA mice spleen. The serum expression level of interleukin(IL)-21 was examined by the enzyme-linked immunosorbent assay(ELISA). The expression of TLR9, STAT3, p-STAT3, and IL-21 in B lymphocytes was detected by Western blot. The mRNA expression of TLR9, STAT3, and IL-21 in B lymphocytes was detected by real-time fluorescence-based quantitative PCR(qRT-PCR). The results showed that OMT could significantly alleviate the paw swelling, decrease the AI score, relieve synovial inflammatory cell infiltration and hyperplasia, reduce the level of inflammatory cytokines, and inhibit the expression of TLR9, STAT3, p-STAT3, and IL-21 of B lymphocytes in CIA mice. Therefore, OMT may alleviate rheumatoid arthritis by regulating TLR9/MyD88/STAT3 pathway in B lymphocytes, providing a valuable reference for the application of OMT in the clinical treatment of rheumatoid arthritis.