Regulatory role and molecular mechanism of MST1 in MPP+-induced Parkinson's disease cell model.

Parkinson's disease (PD) is a multi-factorial degenerative disease in the elder. Given the involvement of mammalian sterile 20-like kinase 1 (MST1) in PD, this paper was to illustrate the mechanism of MST1 in 1-methyl-4-phenylpyridinium ion (MPP+)-induced PD cell model. Cells were treated with different concentrations of MPP+ to establish a PD cell model. RT-qPCR and Western blot revealed that MST1 expression and iron ion concentration increased but cellular activity decreased with MPP+ concentration. Inhibition of MST1 decreased ferroptosis, increased cellular viability, iron ion content, and levels of glutathione peroxidase 4, and decreased reactive oxygen species, lactate dehydrogenase release. Upregulation of ferroptosis levels using ferroptosis agonist Erastin reduced the protective effect of MST1 inhibition on PD cells. Mechanistically, dual-luciferase analysis identified that miR-23b-3p targeted MST1 and inhibited its expression. Overexpression of miR-23b-3p inhibited MST1 levels, thereby reducing cellular ferroptosis and attenuating MPP+-induced cell injury. Collectively, MST1 expression increased with increasing MPP+ concentration and miR-23b-3p targeted MST1 to reduce ferroptosis and MPP+-induced cell injury.

Application of agricultural pesticides in a peak period induces an abundance decline of metazoan zooplankton in a lake ecosystem.

The contamination of pesticides has been recognized as a major stressor in fresh water ecosystems in terms of the losses of services and population declines and extinctions. However, information on the adverse effects of pesticides on zooplankton communities under natural field conditions are still lacking, although zooplankton is quite sensitive to most of pesticides in laboratory studies. In this study, a natural lake ecosystem (Liangzi Lake) was used to determine the relationship between pesticide contamination and abundance decline of metazoan zooplankton. In August 2020, the comprehensive trophic level indexes and the abundance of phytoplankton in the 14 sampling sites of Liangzi Lake were comparable, but the abundance of metazoan zooplankton showed significant variations across two orders of magnitude. These results suggested that other factors, such as pesticide contamination, might be responsible for the variations of metazoan zooplankton community. Furthermore, the responsible pesticides were screened, and totally 29 pesticides were obtained. Finally, five pesticides were identified to provide more than 99.4% toxic contributions and chlorpyrifos and cypermethrin were two main causal agents. These results were further supported by laboratory exposure experiments using D. magna and field study in November 2020, where the concentrations of the 29 pesticides were strongly decreased and the abundance of metazoan zooplankton was comparable across the 14 sites of Liangzi Lake. Taken together, this work provided an evidence that the contamination of pesticides might be responsible for the abundance decline of metazoan zooplankton in a natural freshwater ecosystem.

Evaluation of the slow-release polylactic acid/polyhydroxyalkanoates active film containing oregano essential oil on the quality and flavor of chilled pufferfish (Takifugu obscurus) fillets.

Active packaging is an innovative and effective way to extend the shelf life of food, but few studies have focused on the effect of its active ingredients on food flavor. This study aimed to develop slow-release polylactic acid/polyhydroxyalkanoates (PLA/PHA) active packaging containing oregano essential oil (OEO) and investigate the effect of active composite packaging on the flavor and quality of pufferfish fillets. The plasticizing effect of OEO increased the elongation at break (EAB) of the films from 23.36% to 65.80%. The adsorption of montmorillonite (MMT) reduces the loss of OEO during processing. The amount of active substance (carvacrol) released from PLA/PHA/OEO/MMT film to pufferfish was 9.70 mg/kg. The pufferfish fillets packed in PLA/PHA/OEO/MMT film showed the slightest difference on the 8th day from the beginning of storage. The slow-release composite films could extend the shelf life of pufferfish fillets by 2-3 days at 4 °C ± 1 °C.

Low sink demand caused net photosynthetic rate decrease is closely related to the irrecoverable damage of oxygen-releasing complex and electron receptor in peach trees.

Source sink balance is one of the major determinants of carbon partitioning in plants. However, its effects on photosynthesis in fruit trees are largely unknown. In this work, the effects of low sink demand on net photosynthetic rate (Pn) and chlorophyll fluorescence after fruit removal (-fruit) in peach (Prunus persica (L.) Batsch cv. 'Zaojiubao') trees were investigated. The stepwise energy flow through photosystem II (PSII) at the reaction center (RC) was analyzed with quantitative analyses of fluorescence transient, also called JIP-test. We found that Pn was significantly lower and closely correlated to the leaf stomatal conductance (Gs) of -fruit trees than that of fruit retained (+fruit) trees. Leaf temperature (Tleaf) of -fruit trees was remarkably higher than that of +fruit trees. Day-time-period assays of chlorophyll (Chl) fluorescence revealed that, in the leaves of -fruit trees, the fluorescence parameters, such as NPQ (non-photochemical quenching coefficient) and ΦD0 (maximum quantum yield of non-photochemical de-excitation), decreased in the morning and recovered to the normal level in the afternoon, whereas other parameters, such as ΦE0 (quantum yield for electron transport at t = 0), Ψ0 (probability that a trapped exciton moves an electron to QA pool), F0 (minimum fluorescence, when all PSII RCs are open) and Wk (relative variable fluorescence at 300 µs of the chlorophyll fluorescence transient), did not. These results suggest that OEC complex and QA pool were irreversibly affected by low sink demand, whereas light harvest antenna and PSII potential efficiency retained a strong ability to recover.

Covalent Immobilization of Polypeptides on Polylactic Acid Films and Their Application to Fresh Beef Preservation.

To enhance the advantage of a long-term stability and low-toxicity active packaging system, two biodegradable covalent immobilized antibacterial packaging films were developed and applied to fresh beef preservation in this study. A polylactic acid (PLA) film was prepared by the extrusion-casting method. The surface of the PLA film was modified with plasma treatment to generate carboxylic acid groups, and then antibacterial agent nisin or ε-poly lysine (ε-PL) was covalently attached to the modified film surface. Physical, chemical, and antimicrobial properties of films were then characterized. Scanning electron microscopy and water contact angle images confirmed that nisin or ε-PL was successfully grafted onto the film surface. The values of protein loading on the nisin-g-PLA film and ε-PL-g-PLA film were 5.34 ± 0.26 and 3.04 ± 0.25 µg of protein/cm2 on the surface. Microbial analysis indicated that the grafted films effectively inhibit the growth of bacteria. Finally, the effects of the nisin-g-PLA film or ε-PL-g-PLA film on physicochemical changes and microbiological counts of fresh beef during cold storage at 4 °C were investigated. The total viable count of the control sample exceeded 7 logarithms of the number of colony forming units per gram (log CFU/g) after 11 days of cold storage (7.01 ± 0.14 log CFU/g) versus 15 days for the ε-PL-g-PLA film (7.37 ± 0.06 log CFU/g) and the nisin-g-PLA film (6.83 ± 0.10 log CFU/g). The results showed that covalent immobilized antibacterial packaging films had positive impacts on the shelf life and quality of fresh beef. Therefore, a covalent immobilized antibacterial packaging system could be a novel preservative method for foods.

[Progress in genetic research on psoriatic arthritis].

Psoriatic arthritis is a form of inflammatory arthritis found among patients with psoriasis, which can lead to pain, swelling or stiffness in one or more joints and even movement disorders. Epidemiological studies have shown a higher heritability for psoriatic arthritis compared with psoriasis vulgaris. With the evolvement of DNA sequencing, many genes have been associated with psoriasis vulgaris and psoriatic arthritis, which included MHC, TNF, LCE, IL23R, IL12B, TRAF3IP2 and TNFAIP3, though some, such as MHC, IL-13 and PTPN22, have been specifically associated with psoriatic arthritis. These studies have laid a foundation for risk prediction, diagnosis and drug development for psoriatic arthritis.

Evaluation of volatile compounds from Chinese dwarf cherry (Cerasus humilis (Bge.) Sok.) germplasms by headspace solid-phase microextraction and gas chromatography-mass spectrometry.

The types and amounts of volatiles in denucleated fruit of 30 Chinese dwarf cherry germplasms were determined by headspace solid-phase microextraction and gas chromatography-mass spectrometry to assess the genotypic variation. Eighty-five volatiles were identified; hexyl acetate, 4-penten-1-yl acetate, prenyl acetate, (Z)-pent-2-enyl hexanoate, geranyl acetate, n-butyl acetate, (3Z)-3,7-dimethylocta-1,3,6-triene, geraniol, pent-2-enyl butanoate, ethyl caprylate, butyl hexanoate, and linalool were the main volatiles. The type and content of volatile varied with genotype. Red fruits had the most abundant aroma and vinicolor fruits exhibited the least. Principal component analysis clustered the 30 Chinese dwarf cherry germplasms into four groups: (1) 2 germplasms (NM2 and HN3) had high ester content, (2) 24 germplasms (BJ1-BJ6, HB1, HB2, HN1, HN2, NM1, NM3, SX1, SX2, SX4-SX6, SX8-SX10, SX12, SX13, SX15, and SX16) contained mainly esters, lactones, and terpenes, (3) 2 germplasms (SX11 and SX14) had high ester and lactone content, and (4) 2 germplasms (SX3 and SX7) had high ester and terpene content.

UNC-51-like kinase 1 blocks S6k1 phosphorylation contributes to neurodegeneration in Parkinson's disease model in vitro.

OBJECTIVE: This study was aim to determine the role and underling mechanism of ribosomal protein S6 kinases 1 (S6k1) phosphorylation in Parkinson's disease (PD). METHODS: The dopaminergic neuron MN9D was employed and 1-methyl-4-phenylpyridium (MPP) iodide (MPP(+)) was used to generate PD model in vitro. The S6k1 phosphorylation and UNC-51-like kinase 1 (ULK1) protein levels were analyzed by western blot. The ULK1 mRNA level was evaluated by Real-time RT-PCR. The S6k1 threonine 389 (T389) site-directed mutagenesis, the phosphodeficit T389A (threonine to alanine) and the phosphomimetic T389D (threonine to aspartate) were generated to examine the phosphorylation site of S6k1. RESULTS: An increase in the ULK1 mRNA and protein levels were detected in the MPP(+)-treated MN9D cells compared to control. ULK1 knockdown increased neuronal cell viability, and enhanced S6k1 phosphorylation. Further investigation demonstrated ULK1 knockdown promoted the S6k1 T389 phosphorylation in particular. T389A enhanced the viability of MPP iodide-treated MN9D, whereas T389D decreased the cell viability. CONCLUSION: ULK1 acts to inhibit S6k1 phosphorylation at T389, leading to MN9D viability reduction under MPP(+) treatment. These results provide evidence for a novel mechanism by which the ULK1 inhibit S6k1 T389 phosphorylation contributes to neurodegeneration in MPP(+) treated-MN9D, and suggests a new therapeutic strategy for PD.

[Investigation of entecavir treatment in patients with LAM-refractory chronic hepatitis B].

OBJECTIVE: To evaluate the efficacy and safety of entecavir (ETV) as a long-term treatment in patients with lamivudine (LAM)-refractory chronic hepatitis B (CHB). METHODS: In this phase II study of ETV-056, 32 CHB patients with resistance to LAM monotherapy were administered ETV at 1.0 mg/day and monitored over a period of 8 years. The virologic, serologic and biochemical responses were measured throughout the treatment course. Outcomes analysis was conducted according to intention-to-treat principles. RESULTS: At baseline and treatment weeks 8, 12, 24, 48, 96, 144, 192, 240, and 420, the proportion of patients with HBV DNA less than 300 copies/ml was 0, 6.3% (2/32), 9.4% (3/32), 18.8% (6/32), 18.8%(6/32), 46.9% (15/32), 43.8% (14/32), 50.0% (16/32), 50.0% (16/32), and 62.5% (20/32). At treatment weeks 48, 96, 168, 192, 240, and 420, the proportion of patients experiencing virological breakthrough was 6.1% (2/32), 9.4% (3/32), 12.5% (4/32), 18.8%(6/32), 25.0%(8/32), and 28.1% (9/32). In the 8 year study period, 32.3% (10/31) of patients achieved HBs seroconversion and four patients achieved HBe seroconversion. CONCLUSION: While treatment with 1.0 mg/day ETV for up to 8 years resulted in mild HBV DNA suppression and increase of HBeAg seroconversion, the safety profile of this therapy was good but the economic cost was high and virological breakthrough rates were high.

Effects of bagging on volatiles and polyphenols in "Wanmi" peaches during endocarp hardening and final fruit rapid growth stages.

Fruits of the late-ripening peach cultivar "Wanmi" were bagged at the early period of fruit endocarp hardening, and the bags were removed 1 wk before maturity harvest. The effects of bagging on volatile compounds and polyphenols were studied. Total volatiles and the sum of C(6) compounds, esters from bagged fruits were significantly lower than from nonbagged fruits from the beginning of the final rapid fruit growth stage to maturity. As the most dominant compounds of C(6) compounds and esters, the lower contents of hexanal, trans-2-hexenal, hexyl acetate, cis-3-hexenyl acetate, and trans-2-hexenyl acetate attributed to the lower content of C(6) compounds and esters in bagged fruit. γ-Hexalactone and δ-decalactone were produced earlier in bagged fruits than in nonbagged ones, suggesting that bagging accelerates fruit maturity. Level of γ-decalactone in bagged fruits was significantly lower than in nonbagged fruits at 159 days after full blossom (DAFB), so did δ-decalactone at 166 DAFB. Bagging did not affect chlorogenic acid and catechol contents of either fruit peel or flesh, nor did it affect contents of keracyanin or quercetin-3-rutinoside in fruit flesh during fruit development. However, keracyanin and quercetin-3-rutinoside levels were significantly reduced in bagged fruit peels before ripening compared to nonbagged fruit peels. Considering the large changes in volatiles and polyphenols, the key stage for "Wanmi" fruit maturity was between 126 DAFB and 147 DAFB, about 1 mo ahead of maturity.