Preserved C-peptide is common and associated with higher time in range in Chinese type 1 diabetes.

Objective: The aim of this study is to determine the residual C-peptide level and to explore the clinical significance of preserved C-peptide secretion in glycemic control in Chinese individuals with type 1 diabetes (T1D). Research design and methods: A total of 534 participants with T1D were enrolled and divided into two groups, low-C-peptide group (fasting C-peptide ≤10 pmol/L) and preserved-C-peptide group (fasting C-peptide >10 pmol/L), and clinical factors were compared between the two groups. In 174 participants who were followed, factors associated with C-peptide loss were also identified by Cox regression. In addition, glucose metrics derived from intermittently scanned continuous glucose monitoring were compared between individuals with low C-peptide and those with preserved C-peptide in 178 participants. Results: The lack of preserved C-peptide was associated with longer diabetes duration, glutamic acid decarboxylase autoantibody, and higher daily insulin doses, after adjustment {OR, 1.10 [interquartile range (IQR), 1.06-1.14]; OR, 0.46 (IQR, 0.27-0.77); OR, 1.04 (IQR, 1.02-1.06)}. In the longitudinal analysis, the percentages of individuals with preserved C-peptide were 71.4%, 56.8%, 71.7%, 62.5%, and 22.2% over 5 years of follow-up. Preserved C-peptide was also associated with higher time in range after adjustment of diabetes duration [62.4 (IQR, 47.3-76.6) vs. 50.3 (IQR, 36.2-63.0) %, adjusted P = 0.003]. Conclusions: Our results indicate that a high proportion of Chinese patients with T1D had preserved C-peptide secretion. Meanwhile, residual C-peptide was associated with favorable glycemic control, suggesting the importance of research on adjunctive therapy to maintain ß-cell function in T1D.

A new peptide, VD11, promotes structural and functional recovery after spinal cord injury.

The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury. It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury. Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue. While amphibians have a pronounced ability to regenerate the spinal cord, few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury. Here we report for the first time the successful identification and isolation of a new polypeptide, VD11 (amino acid sequence: VDELWPPWLPC), from the spinal cord of an endemic Chinese amphibian (Odorrana schmackeri). In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide, as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia. In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury, alleviated pathological damage, and promoted axonal regeneration. Furthermore, RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways. In summary, we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.

Molecular physiology of iron trafficking in Drosophila melanogaster.

Iron homeostasis in insects is less-well understood comparatively to mammals. The classic model organism Drosophila melanogaster has been recently employed to explore how iron is trafficked between and within cells. An outline for iron absorption, systemic delivery, and efflux is thus beginning to emerge. The proteins Malvolio, ZIP13, mitoferrin, ferritin, transferrin, and IRP-1A are key players in these processes. While many features are shared with those in mammals, some physiological differences may also exist. Notable remaining questions include the existence and identification of functional transferrin and ferritin receptors, and of an iron exporter like ferroportin, how systemic iron homeostasis is controlled, and the roles of different tissues in regulating iron physiology. By focusing on aspects of iron trafficking, this review updates on presently known complexities of iron homeostasis in Drosophila.

[Fire resistance of bark of 11 tree species]. / 11ç§æ ‘ç§çš„æ ‘çš®æŠ—ç«æ€§.

China is one of the countries with serious forest fires. Besides the methods of strengthening management of fire source and increasing forest fire monitoring and rescue efforts, improving the ability of forest itself to resist fire is also the key to prevent forest fires. In this study, we examined the characteristics of the bark across 11 main tree species in Korean pine broad-leaved forest at Jiaohe Forestry Experimental Area in Jilin Province. Fire resistance of bark acorss the tree species was evaluated comprehensively with four indices of water content, ash content, calorific value and oxygen index, using the methods of entropy weight, variance analysis and cluster analysis. Results showed that water content of bark was the highest in Phellodendron amurense. Calorific value of bark was the lowest and ash content was the highest in Ulmus davidiana. Oxygen index of bark was the highest in Fraxinus mandshurica. Bark fire resistance of 11 tree species followed the order of U. davidiana > Acer mono > Acer triflorum > Acer mandshuricum > F. mandshurica > Quercus mongolica > P. amurense > Tilia amurensis > Juglans mandshurica > Pinus koraiensis > Betula costata. The tree species in Korean pine broad-leaved forest could be classified to five categories according to bark fire resistance: U. davidiana belonged to the category of strongest fire-resistance; A. mono and A. triflorum belonged to the category of strong fire-resistance; A. mandshuricum, F. mandshurica, Q. mongolica, P. amurense, T. amurensis belonged to the category of common fire-resistance; J. mandshurica and P. koraiensis belonged to the category of weak fire-resistance; and B. costata belonged to the category of poor fire-resistance.

Peripheral monocyte counts predict the clinical outcome for patients with colorectal cancer: a systematic review and meta-analysis.

Monocytes originating from bone marrow play a key role in the inflammatory response. Divergent findings regarding the prognostic value of inflammatory factors like absolute monocyte count (AMC) in colorectal cancer (CRC) exist in the current literature. Thus, we sought to perform a systemic meta-analysis to comprehensively estimate whether the peripheral AMC affects the clinical outcome of CRC patients. A comprehensive literature search was performed in PubMed, Web of Science and EMBASE last updated to 23 December 2018, to identify studies reporting the prognostic value of AMC in patients with CRC. Hazard ratios and corresponding 95% confidence intervals (CIs) or P values were used as the effect size estimates for clinical outcomes including overall survival (OS), disease-free survival (DFS), cancer-specific survival (CSS) and progression-free survival (PFS) with the random-effect inverse variance weighted method. The potential heterogeneity was assessed with Q test and I statistics. Subgroup analyses with respect to some clinicopathological parameters were conducted. A total of 16 clinical studies comprising 3826 patients were included for analysis. Pooled analyses revealed that CRC patients with elevated AMC were significantly associated with worse OS (hazard ratio = 1.708, 95% CI: 1.480-1.971, P < 0.001), DFS (hazard ratio = 1.817, 95% CI: 1.289-2.560, P = 0.001), CSS (hazard ratio = 1.551, 95% CI: 1.187-2.027, P = 0.001) and PFS (hazard ratio = 1.487, 95% CI: 1.259-1.756, P < 0.001). In addition, subgroup analyses provided more information and demonstrated the prognostic effect of elevated preoperative AMC in patients with CRC. There were no significant heterogeneity and publication bias. In conclusion, elevated AMC seems to be served as an unfavorable and robust predicative indicator in CRC patients.

Drosophila multicopper oxidase 3 is a potential ferroxidase involved in iron homeostasis.

Multicopper oxidases (MCOs) are a specific group of enzymes that contain multiple copper centers through which different substrates are oxidized. Main members of MCO family include ferroxidases, ascorbate oxidases, and laccases. MCO type of ferroxidases is key to iron transport across the plasma membrane. In Drosophila, there are four potential multicopper oxidases, MCO1-4. No convincing evidence has been presented so far to indicate any of these, or even any insect multicopper oxidase, to be a ferroxidase. Here we show Drosophila MCO3 (dMCO3) is highly likely a bona fide ferroxidase. In vitro activity assay with insect-cell-expressed dMCO3 demonstrated it has potent ferroxidase activity. Meanwhile, the ascorbate oxidase and laccase activities of dMCO3 are much less significant. dMCO3 expression in vivo, albeit at low levels, appears mostly extracellular, reminiscent of mammalian ceruloplasmin in the serum. A null dMCO3 mutant, generated by CRISPR/Cas9 technology, showed disrupted iron homeostasis, evidenced by increased iron level and reduced metal importer Mvl expression. Notably, dMCO3-null flies phenotypically are largely normal at normal or iron stressed-conditions. We speculate the likely existence of a similar iron efflux apparatus as the mammalian ferroportin/ferroxidase in Drosophila. However, its importance to fly iron homeostasis is greatly minimized, which is instead dominated by another iron efflux avenue mediated by the ZIP13-ferritin axis along the ER/Golgi secretion pathway.

Functional studies of Drosophila zinc transporters reveal the mechanism for zinc excretion in Malpighian tubules.

BACKGROUND: Zinc is an essential metal involved in many physiological processes. Previous work has identified a set of zinc transporters involved in Drosophila dietary zinc absorption. However, zinc excretion and reabsorption, the other two important processes to maintain zinc homeostasis, are not as well understood. In this work, we screened all the potential zinc transporter Zip (SLC39) and ZnT (SLC30) members for their likely roles in zinc excretion in Malpighian tubules, an insect organ functionally analogous to mammalian kidneys. RESULTS: Zip71B (CG10006, most homologous to hZIP5), in addition to the previously characterized ZnT35C (CG3994), was identified as being critical in zinc excretion. Tubule-specific knockdown of Zip71B/dZip5 reduces zinc accumulation in the tubules, but increases zinc levels in the body, resulting in survival defect under zinc excess conditions. Zip71B/dZip5 is localized to the plasma membrane at the basolateral side of the tubules, and is functionally epistatic to the apically localized ZnT35C in regulating the tubule zinc homeostasis. Our results indicate that Zip71B/dZip5 is involved in zinc import into the tubular cells from the circulation, and ZnT35C in turn effluxes the tubular zinc out. Notably, mammalian ZIP5, which is expressed in the kidney, functions analogously to Zip71B/dZip5 in the fly while hZIP4 cannot complement the loss of Zip71B/dZip5 function. Furthermore, Zip71B/dZip5 expression is regulated by zinc so that, in response to toxic levels of zinc, the tubules can increase zinc efflux capability. We also characterized the role of dZnT1 (CG17723) in zinc reabsorption in Malpighian tubules. Finally, using a tubule calcification model, we were able to show that knockdown of Zip71B/dZip5 or ZnT35C was able to mitigate stone formation, consistent with their roles in tubular zinc homeostasis. CONCLUSIONS: Our results start to sketch out a relatively complete picture of the zinc excretion process in Drosophila Malpighian tubules, and may provide a reference for relevant mammalian studies.

Cloning and characterization of cDNA for the Oryza sativa phosphate transporter.

A putative high-affinity phosphate (Pi) transporter gene in rice (Oryza sativa), OsLPT1, was isolated by RT-PCR from the leaves of the plants. The 1635-bp nucleotide sequence of OsLPT1 spans an open reading frame encoding a polypeptide of 535 amino acids with sequence similarity to phosphate transporters from other plant species. Southern blot analysis showed that the OsLPT1 gene might be present in three transcripts in the rice genome. RT-PCR analysis demonstrated the expression of OsLPT1 in both leaves and roots. The expression of OsLPT1 in the roots was enhanced by Pi deprivation. In situ hybridization revealed OsLPT1 expression in mesophyll cells, xylem parenchyma and phloem cells in the leaves, and in the epidermis, exodermis, and in the vasculature surrounding metaxylem vessels in the roots. The data suggests that the OsLPT1 protein may be involved in enhancing phosphate uptake under conditions of Pi starvation, and in the translocation of Pi among cells in shoots to increase the efficiency of internal Pi use.