Care, control and complications of hospitalised patients with type 1 diabetes in China: A nationwide-based registry study.

AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.

ACOT7 promotes retinoblastoma resistance to vincristine by regulating fatty acid metabolism reprogramming.

The rate of vincristine (VCR) resistance in the treatment of retinoblastoma (RB) is relatively high, and the exact role and mechanism of autophagy and fatty acid (FA) metabolism in RB are still unknown. The aim of this study was to elucidate the molecular mechanism by which acyl-CoA thioesterase 7 (ACOT7) regulates FA metabolism and autophagy, which may lead to potential therapeutic strategies for RB. In the present study, the relationship between FA metabolism and cellular drug sensitivity was evaluated through ACOT7 overexpression or inhibition tests in RB-resistant cells. The lipase inhibitor orlistat and the autophagy inhibitor CQ were used to determine the effects of ACOT7 on FA metabolism, autophagy, and cellular drug sensitivity, as well as the therapeutic value of ACOT7 targeting. The results showed that ACOT7 was upregulated in VCR-resistant RB cells, significantly enhancing cell resistance and indicating that ACOT7 may serve as a biomarker for VCR resistance in RB cells. Knockdown of ACOT7 inhibited FA metabolism and reduced cell viability in VCR-resistant RB cells. The effect of ACOT7 overexpression was opposite to that of ACOT7 knockdown, and ACOT7 overexpression promoted autophagy in VCR-resistant RB cells. After treatment with orlistat or CQ, FA metabolism in VCR-resistant RB cells decreased, cell viability and autophagy were inhibited, EMT was inhibited, and the sensitivity of RB cells to VCR was increased. In conclusion, ACOT7 knockdown can mediate FA metabolism to inhibit autophagy and the migration of RB cells, thereby improving the sensitivity of RB cells to VCR.

CTSB Nuclear Translocation Facilitates DNA Damage and Lysosomal Stress to Promote Retinoblastoma Cell Death.

Retinoblastoma (RB) is a pernicious tumor originating from photoreceptor precursor cells that often endangers the lives of children. The purpose of our study was to further investigate the influence of cathepsin B (CTSB) nuclear translocation on RB cell death. Y79 cells were injected into the vitreous cavity of nude mice at a dose of 4 µL/mouse to establish an animal model of RB. Real-time quantitative polymerase chain reaction (RT-qPCR), Western blot analysis, a comet assay, a Cell Counting Kit-8 (CCK-8) assay and flow cytometry were used to measure the levels of the interrelated genes and proteins and to evaluate alterations in autophagy, apoptosis, proliferation, DNA damage and cell cycle arrest. CTSB was found to be expressed at low levels in RB animal model samples and RB cell lines. Functionally, CTSB nuclear translocation promoted DNA damage, cell cycle arrest, ferroptosis and autophagy in Y79 cells and inhibited their proliferation. Downstream mechanistic studies showed that nuclear translocation of CTSB facilitates DNA damage and cell cycle arrest in RB cells by inhibiting breast cancer 1 protein (BRCA1) expression and also activates the signal transducer and activator of transcription 3/stimulator of interferon response cGAMP interactor 1 (STAT3/STING1) pathway to induce lysosomal stress, leading to ferroptosis and autophagy in Y79 cells and alleviating RB. Nuclear translocation of CTSB facilitates DNA damage and cell cycle arrest in RB cells by inhibiting BRCA1 expression and activating the STAT3/STING1 pathway and induces lysosomal stress, which eventually leads to ferroptosis and autophagy and mitigates RB.

Dynamic avoidance decision method for civil aircraft in a suborbital debris hazard zone.

Closing the static suborbital debris hazard zone method leads to low airspace resource utilization and long delays for civil aircraft, while the dynamic delineation of suborbital debris hazard zone method can solve the above phenomena. However, the existing research lacks the decision instruction for civil aircraft to avoid the dynamic suborbital debris hazard zone. To address the above problems, this paper creates probability ellipsoids of suborbital debris with different ballistic coefficients in the two-dimensional plane and use the divide-and-conquer algorithm for the dynamic delineation of the suborbital debris hazard zone. The suborbital debris hazard zone is extended outward by 10 km. Subsequently, the standard A* algorithm, the standard Lazy theta* algorithm, the improved Lazy theta* algorithm, and a flight path planning strategy are designed to avoid the suborbital debris hazard zone and provide safe dynamic avoidance commands for civil aircraft with fixed time intervals. The simulation results show that the average area of the dynamically delineated suborbital debris hazard zone is lower than the traditional static no-fly zone; the standard A* algorithm and improved Lazy theta* algorithm provides shorter flight path lengths and flight time and fewer waypoints in windless and windy conditions, respectively.

A Homogalacturonan from Peel of Winter Jujube (Zizyphus jujuba Mill. cv. Dongzao): Characterization and Protective Effects against CCl4-Induced Liver Injury.

A homogalacturonan pectin (HG, designated as WJP-F80) was extracted from the peel of winter jujube (Zizyphus jujuba Mill. Cv. Dongzao) and separated via ethanol-graded precipitation. The structural and conformational features were elucidated through HPAEC-PAD, GC-MS, 2D NMR, and HPSEC-MALLS studies. In vivo assessments were carried out to evaluate the hepatoprotective effects of WJP-F80 against CCl4-induced injury of mice. Results showed that WJP-F80 was a linear 1,4-α-galacturonan with partially methyl-esterified at O-6 of GalpA and occasionally acetylation. The Mw of WJP-F80 was determined as 45.3 kDa, the polydispersity was calculated as 1.56, and the Rg was measured as 22.7 nm in 0.1 M NaNO3. The conformational analysis revealed that WJP-F80 exhibited as rigid stiff chain in low Mw range, while aggregation by self-assembly of HG chains lead to high Mw and random coil conformation. In vivo studies indicated that WJP-F80 can protect the livers of mice from acute injury induced via CCl4 by decreasing the serum biochemical markers of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to normal levels. This work provides a theoretical basis for the value-added deep processing of winter jujube.

An integrated learning algorithm for early prediction of melon harvest.

Different modeling techniques must be applied to manage production and statistical estimation to predict the expected harvest. By calculating advanced production methods and the rational valuation of different factors, we can accurately capture the variety of growth characteristics and the expected yield. This paper obtained 32 feature variables related to melons, including phenological features, shape features, and color features. The Gradient Boosted Decision Tree (GBDT) network and the Grid Search (GS) hyperparameter seeking method was applied to calculate the degree of importance of all melon fruits' characteristics and construct prediction models for three expected harvest indexes of melon yield, sugar content, and endocarp hardness. To facilitate growers to carry out prediction and estimation in the field without destroying the melon fruits. The reduced feature variables were selected as inputs. The GBDT model was used to provide a significant advantage in prediction compared to both Random Forest (RF) and Support Vector Regression (SVR) methods. In addition, to verify the feasibility of using only reduced feature variables as input for the evaluation work, this study also compares the predictive effects of the model when all feature variables and only reduced feature variables are used. The GBDT prediction model proposed in this paper predicted melon yield, sugar content, and hardness using reduced features as input, and the model R2 could reach more than 90%. Therefore, this method can effectively help growers carry out early non-destructive inspection and growth prediction of melons in the field.

Advances in the research of plant-derived natural products against retinoblastoma.

Retinoblastoma (RB) is a highly aggressive ocular tumor, and due to socioeconomic and medical constraints, many children receive treatment only in the metaphase and advanced clinical stages, resulting in high rates of blindness and disability. Although several approaches exist in the treatment of RB, some children with the disease do not have satisfactory results because of various factors. Plant-derived natural products have shown definite therapeutic effects in the treatment of various tumors and are also widely used in the study of RB. We review plant-derived natural products used in the study of anti-RB to provide ideas for the clinical application of these drugs and the development of new therapeutic drugs.

Panax notoginseng saponins induce apoptosis in retinoblastoma Y79 cells via the PI3K/AKT signalling pathway.

This study aimed to investigate the effects of Panax notoginseng saponins (PNS) on the proliferation, apoptosis, and PI3K/AKT signalling pathways of retinoblastoma Y79 cells to explore the possible mechanism of action of PNS on retinoblastoma. The effects of PNS and carboplatin on the proliferation of Y79 cells were examined using cell counting kit-8 assay. And the apoptosis rate, the mRNA and protein levels of apoptosis-related genes and the expression of PI3K/AKT pathway protein were assessed. PNS effectively inhibited the proliferation (P < 0.05) and increased apoptosis of Y79 cells (P < 0.05). Compared with the negative control, the Y79 cells treated with PNS had significantly increased (P < 0.05) mRNA and protein expression of Bax, caspase-3, caspase-8, and caspase-9 and elevated levels of cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 proteins (P < 0.05). The mRNA and protein expression of the apoptosis suppressor gene Bcl-2 was inhibited (P < 0.05), while the Bax/Bcl-2 values of the cells in the drug group were significantly higher than those in the negative group (P < 0.01). After treatment with PNS, the total protein expression of PI3K and AKT1 in the Y79 cells did not show significant differences compared with the negative group (P > 0.05), although the expression of phosphorylated proteins p-PI3K, p-AKT (Thr308), p-AKT (Ser473), and p-mTOR were significantly reduced (P < 0.05). Meanwhile, the antagonist protein of the pathway phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression was increased (P < 0.01). Cellular alterations following inhibition of the PI3K/AKT pathway using LY294002 were similar to those of PNS, the proliferation of Y79 cells was also inhibited, and cell apoptosis increased (P < 0.001). The expression of Bax, caspase-3, caspase-8, caspase-9, and activation proteins cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9 was also significantly higher than that in the negative control (P < 0.05). Bcl-2 protein expression was decreased (P < 0.01), and the Bax/Bcl-2 ratio was higher than that in the negative control (P < 0.001). Overall, we demonstrated that PNS effectively inhibited the proliferation and promoted the apoptosis of retinoblastoma Y79 cells. The apoptosis-promoting effect of PNS may involve the inhibition of the PI3K/AKT signalling pathway, which subsequently regulates the expression of apoptosis-related genes.

Case Report: Treatment of Oral Lichen Planus With a Focus on Psychological Methods.

Oral lichen planus (OLP) is one of the most common chronic diseases; however, its etiology remains unknown. More and more studies have revealed that emotional instability is one of the risk factors for the onset and expansion of OLP, especially in patients suffering from depression, anxiety disorder, and acute stress. In this case report, we had a 32-year-old female OLP patient who had no obvious response to conventional OLP drugs. Then we switched to a combination of psychotropic drugs and psychotherapies. By regulating mood through drugs and psychological counseling, the patient's oral disease was alleviated. Our case shows that clinicians should consider the mental problems of OLP patients. It also emphasizes the importance of medications and psychological counseling in the treatment of somatic diseases.

Anti-proliferation and apoptosis-inducing effects of sodium aescinate on retinoblastoma Y79 cells.

AIM: To investigate the anti-proliferation and apoptosis-inducing effects of sodium aescinate (SA) on retinoblastoma Y79 cells and its mechanism. METHODS: Y79 cells were cultured at different drug concentrations for different periods of time (24, 48, and 72h). The inhibitory effect of SA on proliferation of Y79 cells was detected by the cell counting kit-8 (CCK-8) assay, and the morphology of Y79 cells in each group was observed under an inverted microscope. An IC50 of 48h was selected for subsequent experiments. After pretreatment with SA for 24 and 48h, cellular DNA distribution and apoptosis were detected by flow cytometry. Real-time qunatitative polymerase chain reaction (RT-qPCR) and Western blot were used to assess changes in related genes (CDK1, CyclinB1, Bax, Bcl-2, caspase-9, caspase-8, and caspase-3). RESULTS: SA inhibited proliferation and induced apoptosis of Y79 cells in a time-dependent and concentration-dependent manner. Following its intervention in the cell cycle pathway, SA can inhibit the expression of CDK1 and CyclinB1 at the mRNA and protein levels, and block cells in the G2/M phase. In caspase-related apoptotic pathways, up-regulation of Bax and down-regulation of Bcl-2 caused caspase-9 to self-cleave and further activate caspase-3. What's more, the caspase-8-mediated extrinsic apoptosis pathway was activated, and the activated caspase-8 was released into the cytoplasm to activate caspase-3, which as a member of the downstream apoptotic effect group, initiates a caspase-cascade reaction that induces cell apoptosis. CONCLUSION: SA inhibits the proliferation of Y79 cells by arresting the cell cycle at the G2/M phase, and induces apoptosis via the caspase-related apoptosis pathway, indicating that SA may have promising potential as a chemotherapeutic drug.

Using Relaxation Time to characterize biological effects of different mutagens.

All kinds of mutagenic factors may cause physiological, biochemical and genetic changes of all organisms. To characterize their characteristic biology effects, the concept of Relaxation Time (RT) was introduced for the first time, and the specific process was as follows. After mutation of organisms, the offsprings will be continuingly cultured (or cultivated) to the next generation (Rx). Once a biological effect began to show no significant difference compared to the untreated controls, the Rx was defined as the RT of the effect. In this paper, three kinds of mutagenic factors were selected to treat the seeds or seedlings of Astragalus sinicus L., subsequently, the corresponding RT was calibrated. The results showed that the RT was diverse not only among different biological effects but also among different mutagenic factors. For the RT of chemical mutagens and gamma rays, most of which are concentrated on R1, whereas the heavy ion beams have significant differences among different tracks. Among biological effects, the SOD activity and superoxide anion free radical content in the Peak region are more prominent, and their RT reaches R3 and R4, respectively. Thus, the RT may characterize the characteristic biological effects from differently mutagenic factors.

Overexpression of NtSnRK2.2 enhances salt tolerance in Nicotiana tabacum by regulating carbohydrate metabolism and lateral root development.

SnRK2 is a plant-specific protein kinase family implicated in environmental stress tolerance. Individual SnRK2 genes have acquired distinct regulatory properties in response to various environmental stresses. In this study, NtSnRK2.2, a SnRK2 subclass II member in Nicotiana tabacum L., was cloned and characterised. Sequence alignment analysis showed that SnRK2.2 exhibits widespread sequence differences across Nicotiana species. The tissue expression pattern of NtSnRK2.2 showed a root-predominant expression. To investigate its biological function, NtSnRK2.2 was overexpressed in tobacco, which subsequently resulted in increased soluble sugars and more lateral roots under a normal condition. A salt-stress tolerance assay showed that NtSnRK2.2-overexpressing plants exhibited enhanced salt tolerance, which was further confirmed based on its better root architecture and increase in soluble sugars, thereby implying that NtSnRK2.2 is a multifunctional regulatory factor in plants. Together, our results indicated the possible role played by NtSnRK2.2 in maintaining metabolic homeostasis via the regulation of carbohydrate metabolism in response to environmental stress.

Selenium Modulates the Level of Auxin to Alleviate the Toxicity of Cadmium in Tobacco.

Cadmium (Cd) is an environmental pollutant that potentially threatens human health worldwide. Developing approaches for efficiently treating environmental Cd is a priority. Selenium (Se) plays important role in the protection of plants against various abiotic stresses, including heavy metals. Previous research has shown that Se can alleviate Cd toxicity, but the molecular mechanism is still not clear. In this study, we explore the function of auxin and phosphate (P) in tobacco (Nicotiana tabacum), with particular focus on their interaction with Se and Cd. Under Cd stress conditions, low Se (10 µM) significantly increased the biomass and antioxidant capacity of tobacco plants and reduced uptake of Cd. We also measured the auxin concentration and expression of auxin-relative genes in tobacco and found that plants treated with low Se (10 µM) had higher auxin concentrations at different Cd supply levels (0 µM, 20 µM, 50 µM) compared with no Se treatment, probably due to increased expression of auxin synthesis genes and auxin efflux carriers. Overexpression of a high affinity phosphate transporter NtPT2 enhanced the tolerance of tobacco to Cd stress, possibly by increasing the total P and Se content and decreasing Cd accumulation compared to that in the wild type (WT). Our results show that there is an interactive mechanism among P, Se, Cd, and auxin that affects plant growth and may provide a new approach for relieving Cd toxicity in plants.

The unique evolutionary pattern of the Hydroxyproline-rich glycoproteins superfamily in Chinese white pear (Pyrus bretschneideri).

BACKGROUND: The hydroxyproline-rich glycoprotein (HRGP) superfamily, comprising three families (arabinogalactan-proteins, AGPs; extensins, EXTs; proline-rich proteins, PRPs), is a class of proline-rich proteins that exhibit high diversity and are involved in many aspects of plant biology. RESULTS: In this study, 838 HRGPs were identified from Chinese white pear (Pyrus bretschneideri) by searching for biased amino acid composition and conserved motifs. 405 HRGPs were derived from whole genome duplication (WGD) events which is suggested to be the major force of driving HRGPs expansion and the recent WGD event shared by apple and pear generated most duplicated HRGPs in pear. This duplication event drived the structural variation of the HRGPs encoding hydroxyproline (Hyp)-rich motifs. The rate of HRGPs evolution mainly impacted the Hyp-rich motifs even in chimeric HRGPs. During the evolution of 53 PRPs that are also typified by 7-deoxyloganetin glucosyltransferase-like genes, the duplication from PRP to non-PRP was indirectly modified by positive selection. These results suggested that the rate of HRGP evolution mainly influenced the Hyp-rich motifs even in chimeric HRGPs. The expression divergence of HRGPs was higher than that of other commonly duplicated genes. In pear pistil, 601 HRGPs exhibited expression, while in pear pollen, 285 HRGPs were expressed. The qPCR results revealed that Pbr036330.1 and Pbr010506.1 showed different expression profile in self-incompatibility of pear pistil. CONCLUSIONS: The researches indicated that WGD events was the main duplication type during the evolution of HRGPs, and the highly variable Hyp-motifs might be accountable for the expansion, evolution and expression divergence of HRGPs and that this divergence may be responsible for the gain of new functions in plants.

Three dimensional approach to investigating biological effects along energetic ion beam pathways.

Heavy ion beams have many exciting applications, including radiotherapy of deep-seated tumors and simulation tests of space irradiation for astronauts. These beams often use a feature that concentrates the energy deposition largely along the end of the energy pathway, leading to different distributions of biological effects along the axial direction. Currently, there is relatively little information regarding the radial directional difference of biological effects along the heavy ion paths. This study utilized a filter membrane that was quantatively applied with cells to demonstrate a 3D distribution model of irradiation on biological effects in living organisms. Some results have indicated that there is excitatory effect on the non-irradiated regions with energetic ions, which may give new insights into the distribution of biological effects along the paths of heavy ion beams with mid-high energy.

Study on the possible factors leading to complications of hydroxyapatite orbital implantation / 国际眼科杂志(Guoji Yanke Zazhi)

·Hydroxyapatite ( HA ) orbital implant has been widely used since it was developed due to its many advantages. It is one of the ideal materials to fill the orbital volume after enucleation or evicseration. However, it still causes complications, and some complications such as severe eye exposure may require reimplant surgery. The paper reviews the clinical application of HA orbital implant, the possible factors leading to complications of HA orbital implantation and the treatments for several common complications. The review aims to provide some help to readers.

Effects of Leptin on Na+/Ca2+ Exchanger in PC12 Cells.

BACKGROUND/AIMS: Alzheimer's disease (AD) is known to be related to alterations in neuronal intracellular calcium activity ([Ca2+]i). The present study revealed the distinct role of leptin in Na+/Ca2+-exchanger activity. METHODS: [Ca2+]i was determined utilizing Fura-2 fluorescence. The activity of NCX was measured by removal of extracellular Na+ in the presence of external Ca2+. Na+/Ca2+-exchanger activity was further quantified from whole cell currents following removal of extracellular Na+. Na+/Ca2+-exchanger isoform NCX1 transcript levels and protein abundance were quantified by RT-PCR and Western blotting, respectively. RESULTS: Exposure of PC12 cells to 30 µM amyloid (Aß42) increased [Ca2+]i, an effect significantly blunted by 6 hours incubation with leptin before Aß42 treatment. Moreover, leptin treatment significantly increased Na+/Ca2+-exchanger mediated Ca+ transport and current, NCX1 transcript level as well as NCX1 membrane protein abundance. CONCLUSION: We show that leptin blunts Aß42-evoked [Ca2+]i increase by increasing expression and activity of Na+/Ca2+-exchanger NCX1.

The complete mitochondrial genome of the Southern bluefin tuna Thunnus maccoyii.

The complete mitochondrial genome of the juvenile Southern bluefin tuna Thunnus maccoyii collected from Sea of Japan was determined by next-generation sequencing. The mitogenome is a circular molecule 16,529 bp in length, including the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and a control region. The TAS, central CSB and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes.

The complete mitochondrial genome of the juvenile Pacific bluefin tuna Thunnus orientalis (Perciformes, Scombridae).

The complete mitochondrial genome of the juvenile Pacific bluefin tuna Thunnus orientalis collected from Sea of Japan was determined by next-generation sequencing. The mitogenome is a circular molecule 16,529 bp in length, including the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and a control region. The termination-associated sequence (TAS), central conserved sequence blocks (CSB) and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes.

The complete mitochondrial genome of the juvenile Atlantic bluefin tuna Thunnus thynnus (Perciformes, Scombridae).

The complete mitochondrial genome of the juvenile Atlantic bluefin tuna Thunnus thynnus collected from Sea of Japan was determined by next-generation sequencing. The mitogenome is a circular molecule 16,529 bp in length, including the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and a control region. The TAS, central CSB and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes.