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Although the starting event in COVID-19 is a viral infection some patients present with an over-exuberant inflammatory response, leading to acute lung injury (ALI) and adult respiratory distress syndrome (ARDS). Since IL-6 plays a critical role in the inflammatory response, we assessed the efficacy and safety of tocilizumab (TCZ) in this single-centre, observational study in all Covid-19 in-patient with a proven SARS-CoV-2 rapidly progressing infection to prevent ALI and ARDS. 104 patients with COVID-19 treated with TCZ had a lower mortality rate (5·8%) compared with the regional mortality rate (11%), hospitalized patient's mortality (10%), and slightly lower than hospitalized patients treated with our standard of care alone (6%). We found that TCZ rapidly decreased acute phase reactants, ferritin and liver release of proteins. D-Dimer decreased slowly. We did not observe specific safety concerns. Early administration of IL6-R antagonists in COVID-19 patients with impending hyperinflammatory response, may be safe and effective treatment to prevent, ICU admission and further complications., Graphical abstract Unlabelled Image, Highlights • The lack of RCT forced the use of potential treatments in an emergency context, and results are of particular relevance. • Early administration of IL6-R antagonist tocilizumab, may be an effective and safe treatment for moderate to severe SARS-CoV2 positive patients. • Tocilizumab may prevent irreversible cytokine release syndrome CRS. • Tocilizumab reduced intubation, ICU admission, and decreased the risk of mortality. • Future prospective RCT will give answer about which are the first line drugs to treat COVID-19.

Citrus fruit creasing or cracking is a complex pre-harvest physiological disorder that causes significant economic losses. Recent studies have indicated that citrus fruit creasing or cracking is caused not only by genetic factors but also by environmental factors. By reviewing the relationship between citrus fruit creasing or cracking and peel mechanical properties, the cellular wall ultrastructure, cellular wall metabolism and modification, this paper summarized the mechanism of citrus creasing or cracking and further explained the effects of genetic factors and environmental factors (light, temperature, humidity, mineral nutrition and plant growth regulators) on citrus fruit creasing or cracking rate. Further studies were proposed to provide a sound theoretical basis on citrus fruit creasing or cracking.

Both arbuscular mycorrhizal fungi (AMF) and phosphorus (P) can regulate the lateral root (LR) formation of plants; however, the differences in their regulation and whether auxin is involved in the regulation are less understood, especially for woody plants. In this study, trifoliate orange ( Poncirus trifoliata (L.) Raf) plants were inoculated with AMF strain, Rhizophagus irregularis BGC JX04B, under two P levels in pot culture. The influences of AMF and P level on LR formation were investigated, and the expression of LR- and auxin-related genes were quantified. Results showed that the mycorrhizal colonization at low P level was higher than that at high P level. AMF increased shoot biomass and decreased R/S ratio. The numbers of 1st and 2nd LR were significantly increased by AMF, while high P level only increased 2nd LR number. Variation partitioning analysis indicates that AMF was more effective than P level in regulating LR formation. At 2 MAT (month after transplanting), AMF significantly increased the expression of PSK6 and RSI-1 , and high P level significantly increased the expression of KRP6 . At 4 MAT, AMF significantly increased the expression of PSK6 , but decreased the expression of KRP6 . High P level significantly inhibited the expression of NAC1 , while AMF increased the expression of NAC1 at low P level at 2 MAT, promoting the LR formation. AMF also significantly increased the expression of NAC1 at 4 MAT. Besides, the development of 1st and 2nd LR presented a positively significantly relation with the expression of PSK6 and NAC1 , and 2nd LR also with the expression of TIR1 . Taken together, these data suggest that AMF and P level differentially affect the LR formation in P. trifoliata via auxin signaling.

Background The aim of the study was to retrospectively evaluate the incidence and outcomes of inferior vena cava (IVC) filter thrombus during catheter-directed thrombolysis (CDT) for acute proximal deep venous thrombosis (DVT). Methods From October 2006 to June 2015, patients diagnosed with acute proximal DVT and received CDT after a retrievable IVC filter was placed were included. The incidence, treatment, and outcomes of IVC filter thrombus during CDT were recorded and analyzed. Results A total of 189 patients (91 women, 98 men; mean age, 57.6 ± 9.8 years; range, 24-85 years) were included in this study. Among the 189 cases, the DVTs involved popliteal iliofemoral veins in 54 patients, iliofemoral veins in 113 patients, and iliac veins in 22 patients, of which 18 patients had thrombus extended into the IVC. Of the 189 patients, a total of 8 (4.2%, 8 of 189) patients were identified with IVC filter thrombus during CDT. The IVC filter thrombus was detected on a median of 2 days (range, 2-4 days) of CDT therapy, including small-size (n = 6) and large-size (n = 2) filter thrombus. Of the 8 patients, CDTs were performed with a mean 7.6 ± 1.1 days (range, 6-11 days) after the presence of symptoms for the treatment of proximal DVT, and all the IVC filter thrombi were lysed during CDT for the proximal DVT. All the IVC filters were removed successfully with a mean of 12.8 ± 0.93 days from placement. There were no procedure- or thrombolysis-related major complications, and no symptomatic pulmonary embolism breakthrough was seen in any of the patients after the filter placement. Conclusions IVC filter thrombus during CDT for the acute proximal DVT is uncommon, and all of them did not need any additional treatment.

‘Shatangju’ mandarin creasing results is serious economic loss in many ‘Shatangju’ mandarin orchards. Based on developing accurate preventive strategies for creasing fruit, the creasing of eight-year-old ‘Shatangju’ ( Citrus reticulata Blanco cv. Shatangju) onto Poncirus trifoliate (L.) rootstock was investigated. It was treated twice with either Zn or Zn + NAA application in the fruit enlargement stage (18th and 27th of May, 2011), and Zn + NAA (18th and 28th of May, 2012), respectively. The Zn and Zn + NAA treatments at the fruit enlargement stage of ‘Shatangju’ significantly enhanced the levels of IAA, GA 3 , and tryptophan in the early peel development stage, promoted the growth and division of cells, decreased the range of peel hardness variation during fruit development, reduced creasing abnormalities in peel tissue, especially in albedo, postponed the peel thickness transition time of peel development, and significantly lowered the creasing fruit rate and cumulative abscission rate of ‘Shatangju’ mandarin. Compared with the control and Zn treatment, Zn + NAA treatment could be recommended in the fruit enlargement stage as a cultivation technique to lower the creasing fruit rate of Shatangju mandarin.

Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape the attack from immune cells. Cancer cells can express many immune inhibitory signalling proteins to cause immune cell dysfunction and apoptosis. One of these inhibitory molecules is programmed death-ligand-1 (PD-L1), which binds to programmed death-1 (PD-1) expressed on T-cells, B-cells, dendritic cells and natural killer T-cells to suppress anti-cancer immunity. Therefore, anti-PD-L1 and anti-PD-1 antibodies have been used for the treatment of cancer, showing promising outcomes. However, only a proportion of patients respond to the treatments. Further understanding of the regulation of PD-L1 expression could be helpful for the improvement of anti-PD-L1 and anti-PD-1 treatments. Studies have shown that PD-L1 expression is regulated by signalling pathways, transcriptional factors and epigenetic factors. In this review, we summarise the recent progress of the regulation of PD-L1 expression in cancer cells and propose a regulatory model for unified explanation. Both PI3K and MAPK pathways are involved in PD-L1 regulation but the downstream molecules that control PD-L1 and cell proliferation may differ. Transcriptional factors hypoxia-inducible factor-1α and signal transducer and activation of transcription-3 act on the promoter of PD-L1 to regulate its expression. In addition, microRNAs including miR-570, miR-513, miR-197, miR-34a and miR-200 negatively regulate PD-L1. Clinically, it could increase treatment efficacy of targeted therapy by choosing those molecules that control both PD-L1 expression and cell proliferation.

Translationally controlled tumour protein TCTP (gene symbol: TPT1) is a highly-conserved, cyto-protective protein implicated in many physiological and disease processes, in particular cancer, where it is associated with poor patient outcomes. To understand the mechanisms underlying the accumulation of high TCTP levels in cancer cells, we studied the signalling pathways that control translation of TCTP mRNA, which contains a 5?-terminal oligopyrimidine tract (5?-TOP). In HT29 colon cancer cells and in HeLa cells, serum increases the expression of TCTP two- and four-fold, respectively, and this is inhibited by rapamycin or mTOR kinase inhibitors. Polysome profiling and mRNA quantification indicate that these effects occur at the level of mRNA translation. Blocking this pathway upstream of mTOR complex 1 (mTORC1) by inhibiting Akt also prevented increases in TCTP levels in both HeLa and HT29 colon cancer cells, whereas knockout of TSC2, a negative regulator of mTORC1, led to derepression of TCTP synthesis under serum starvation. Overexpression of eIF4E enhanced the polysomal association of the TCTP mRNA, although it did not protect its translation from inhibition by rapamycin. Conversely, expression of a constitutively-active mutant of the eIF4E inhibitor 4E-BP1, which is normally inactivated by mTORC1, inhibited of TCTP mRNA translation in HEK293 cells. Our results demonstrate that TCTP mRNA translation is regulated by signalling through the PI3-K/Akt/mTORC1 pathway. This explains why TCTP levels are frequently increased in cancers, since mTORC1 signalling is hyperactive in ~ 80% of tumours.

In this research we employed layered double hydroxide nanoparticles (LDHs) to simultaneously deliver an anticancer drug 5-fluorouracil (5-FU) and Allstars Cell Death siRNA (CD-siRNA) for effective cancer treatment. The strategy takes advantage of the LDH anion exchange capacity to intercalate 5-FU into its interlayer spacing and load siRNA on the surface of LDH nanoparticles. LDH nanoparticles have been previously demonstrated as an effective cellular delivery system for 5-FU and siRNA separately in various investigations. More excitedly, the combination of CD-siRNA and anticancer drug 5-FU with the same LDH particles significantly enhanced cytotoxicity to three cancer cell lines, e.g. MCF-7, U2OS and HCT-116, compared to the single treatment with either CD-siRNA or 5-FU. This enhancement is probably a result of coordinate mitochondrial damage process. Thus, the strategy to co-deliver siRNA and an anticancer drug by LDHs has great potential to overcome the drug resistance and enhance cancer treatment.

The purpose of this study was to examine the hypothesis that serum levels of phospholipid (PL) fatty acids (FA) and minerals are associated with the components of metabolic syndrome (MetS) in the Chinese population and the profiles of changes may differ from patients with MetS from Western countries. The levels of serum PL, FA, and minerals were examined in 201 subjects (52 with MetS and 149 healthy controls without any MetS components) in China. The saturated FA proportion in serum was significantly higher, whereas the proportion of total polyunsaturated FA (PUFA), n-3 and n-6 PUFA (22:6n-3: -16%, P = .006; 20:4n-6: -36%, P < .001), and estimated δ-5 desaturase were significantly lower in the MetS group compared with those that are not MetS. Subjects with MetS had higher levels of serum Zn (P = .037) and Mg (P < .001) than subjects without MetS. The proportion of n-3 PUFA was significantly negatively correlated with body mass index and waist circumference. In conclusion, serum PL FA composition and serum minerals in Chinese men with MetS differed significantly from that of healthy individuals, reflecting a decrease in n-3 and n-6 PUFA, especially 22:6n-3 and 20:4n-6, and an increase in saturated FA, magnesium, and zinc. These changes may reflect improper dietary intake in subjects with MetS, and dietary modification could be useful to prevent MetS and as an adjunctive therapy.

Citrus creasing results in serious economic loss in many citrus orchards. Based on the different incidence of creasing, two sweet orange cultivars ‘Hong Jiang’ (grafting chimaera of which flesh is mostly from Citrus reticulata Blanco and peel is from Citrus sinensis Osbeck in) and ‘An Liu’ (Citrus sinensis Osbeck) were used to investigate the creasing rate. The ultrastructure in cellular wall, cellular wall component, cellular wall degradation-related enzymes and expansin (Ct-Exp1) of sweet orange during fruit ripening in field were comparatively analyzed. ‘Hong Jiang’ sweet orange had a higher creasing rate than ‘An Liu’ during ripening. The activities of polygalacturonase, cellulase and pectinesterase in cellular wall of ‘Hong Jiang’ increased more markedly compared with ‘An Liu’. The increases in the content of soluble pectin, ionically associated pectin, covalently bound pectin, hemicellulose and cellulose of ‘Hong Jiang’ were higher than those of ‘An Liu’. Furthermore, the enhanced degradation of the ultrastructure in the albedo cellular walls was observed in ‘Hong Jiang’. Moreover, the northern blot analysis indicated that the Ct-Exp1 gene expressed more strongly in peel of ‘Hong Jiang’ than ‘An Liu’ during fruit ripening. These data suggest that enhanced loss of pectin and cellulose in the cellular walls of peel tissue of sweet orange could result in fruit creasing.

Plant root system architecture is essential characteristics in relation to nutrient acquisition by root system from soil volume. Many environmental factors can affect the establishment of root system architecture, e.g. arbuscular mycorrhizal (AM) fungi. We inoculated the trifoliate orange ( Poncirus trifoliata L. Raf.) seedlings with four AM fungal species in rhizoboxes, with non-inoculated seedlings as control. Using the WinRHIZO ® image analysis system, the root system architecture of seedlings was characterized. Results indicated that AM colonization did not affect the tap root length, the average root diameter, the basal root growth angle in spite that four AM fungal species exerted differential influence on the plant growth. Contrastingly, AM colonization significantly reduced the total root length, the root volume, the root surface area, but promoted the formation of lateral roots of high order. In addition, AM colonization induced more fine roots and less coarse roots. To our knowledge, it is the first report on the influence of AM fungi on the distribution of root diameter size classes. The mechanisms and implication of AM fungi on root system architecture is discussed.

Interferon gamma (IFNgamma) plays a central role in the immune response against infection and tumur immune surveillance. Its functions include not only activation of the host immune system to control microbial infections but also repression of autoimmune responses by turning on T-regulatory cells and increasing T effector cell apoptosis. Defects in IFNgamma and IFNgamma receptor genes have been associated with autoimmune diseases such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis. However, treatment of autoimmune diseases by supplementing with IFNgamma has been satisfactory due to its broad biological effects. Instead, its target T-regulatory cells may be used for the clinical treatment of autoimmune diseases. Future study could also focus on promotion of the beneficial effects of IFNgamma and blocking those unwanted IFNgamma-induced activities.

Non-cellulosic beta-glucans are now recognized as potent immunological activators, and some are used clinically in China and Japan. These beta-glucans consist of a backbone of glucose residues linked by beta-(1--3)-glycosidic bonds, often with attached side-chain glucose residues joined by beta-(1--6) linkages. The frequency of branching varies. The literature suggests beta-glucans are effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia, and diabetes. Their mechanisms of action involve them being recognized as non-self molecules, so the immune system is stimulated by their presence. Several receptors have been identified, which include: dectin-1, located on macrophages, which mediates beta-glucan activation of phagocytosis and production of cytokines, a response co-ordinated by the toll-like receptor-2. Activated complement receptors on natural killer cells, neutrophils, and lymphocytes, may also be associated with tumour cytotoxicity. Two other receptors, scavenger and lactosylceramide, bind beta-glucans and mediate a series of signal pathways leading to immunological activation. Structurally different beta-glucans appear to have different affinities toward these receptors and thus generate markedly different host responses. However, the published data are not always easy to interpret as many of the earlier studies used crude beta-glucan preparations with, for the most part, unknown chemical structures. Careful choice of beta-glucan products is essential if their benefits are to be optimized, and a better understanding of how beta-glucans bind to receptors should enable more efficient use of their biological activities.

Seedlings of litchi ( Litchi chinensis Sonn.) were inoculated with two arbuscular mycorrhizal (AM) fungal species, Glomus intraradices and Gigaspora margarita . Plant growth response and morphological changes induced by AM inoculation were investigated. Plant endogenous indoleacetic acid (IAA) and isopentenyl adenosines (iPAs) concentrations were determined. With mycorrhizal infection rate of 9.0–18.8%, plant biomasses increased by 13.5–30.1%. Leaf number, leaflet number, total leaf area and first order lateral root number were significantly increased by AM inoculation. Although G. margarita significantly increased plant P content and uptake, no significant difference in N nutrition was observed between mycorrhizal and non-mycorrhizal plants. Enzyme-linked immunosorbent assay (ELISA) indicated the changes in IAA and iPAs induced by AM inoculation. IAA concentrations in shoots and in roots were 5–7 times and 2–5 times higher in mycorrhizal than in non-mycorrhizal plants, respectively. The iPAs concentrations increased by 1.7 times in shoots and by 1.9–2.5 times in roots, due to mycorrhizal inoculation. We suggest that the changes in endogenous phytohormone level may be responsible for morphological alteration induced by AM inoculation.

Fungal β-glucans have been well known for its medicinal implications including immune stimulation, wound healing, hypocholesterolemic effects and treatment of diabetes. We read with great interest the paper entitled “Induction of dendritic cell maturation by β-glucan isolated from Sparassis crispa” by Kim et al. in your journal. In the paper, it is shown that β-glucan from Sparassis crispa can induce the maturation of dendritic cells which is important in the immune system to bridge innate immune and adaptive immune... In summary, β-glucan can activate the PI3K/Akt pathway via several receptors and the activation of the pathway may play a critical role in β-glucan-induced DC maturation.