Nanofiber-based wound dressing in wound healing of elderly patients.

Introduction: With the aging of the population, it has become a serious problem that the wounds of elderly patients are not easy to heal. Aim: To explore the application of nanofiber wound dressing in wound healing of elderly patients. Material and methods: In this article, 86 elderly patients with chronic wounds admitted to the Affiliated Hospital of Shaanxi University of Chinese Medicine from January 2023 to September 2023 were enrolled, and they were randomly divided into control and experimental groups, with 43 cases in each group. Controls used traditional wound dressings in care. The experimental group used nanofiber wound dressings. The wound healing efficacy, inflammatory factors, side effects, wound infection degree, healing time, and pain were compared between the two groups. Results: The total effective rate of the experimental group (97.67%) was higher as against controls (86.04%). Wound germiculture positive (7.14 ±2.76%) was lower in the experimental group as against controls (22.13 ±3.27%. The wound healing time of the experimental group (18.68 ±5.78 d) was shorter as against controls (30.24 ±6.19 d). The visual analogue scale (VAS) score of the experimental group (2.68 ±0.41 s) was lower as against controls (3.57 ±0.89 s) after 16 days of care (p < 0.05). Conclusions: The use of nanofiber dressings is an effective means to promote wound healing in elderly patients, which is worthy of application in practical care.

Characteristics, treatment patterns and burden of illness in US patients with asthma newly initiating multiple-inhaler triple therapy.

INTRODUCTION: For patients with asthma who remain symptomatic on medium-dose inhaled corticosteroid/long-acting ß2-agonist, add-on long-acting muscarinic antagonist is a treatment option, which can be administered as multiple-inhaler triple therapy (MITT). A high proportion of patients (61.5%-88.2%) discontinue MITT use within 1 year postinitiation; however, which patients discontinue and their treatment patterns at initiation are unknown. This study aimed to understand the demographic, clinical and treatment-related characteristics of patients with asthma who newly initiated MITT, by discontinuation status. METHODS: This retrospective cohort study used administrative data from IBM Truven MarketScan Commercial Claims and Encounters Database with Medicare supplement between 1 January 2016 and 31 December 2019. Adult patients with asthma who initiated MITT between 1 January 2017 and 31 March 2019 were included and were classified based on their discontinuation status. 'Continuous users' had continuous use of MITT and 'discontinuers' discontinued treatment within the 6-month period postinitiation. Demographics and clinical characteristics, asthma treatment use prior to MITT initiation (12-month baseline period), mode of MITT initiation and complexity of regimen were described. RESULTS: Of 4132 patients (mean age: 49.0 years, 67.9% female), 78.0% (n=3224) were discontinuers; 22.0% (n=908) were continuous users. Demographic and other clinical and treatment-related characteristics during baseline were broadly similar between cohorts. A significantly higher proportion of continuous users versus discontinuers had ≥6 dispensed claims for short-acting ß2-agonist canisters (16.0% vs 12.5%; p=0.006) during baseline and initiated a once-daily MITT regimen (35.2% vs 26.2%; p<0.001). Fewer continuous MITT users used a mix of once-daily and twice-daily regimens than those who discontinued MITT (64.3% vs 72.3%; p<0.001). CONCLUSIONS: Most patients with asthma discontinued MITT within 6 months. Results indicate that patients with a history of uncontrolled, symptomatic asthma and those using less complex triple therapy regimens at initiation are less likely to discontinue MITT than patients with controlled asthma and those using a complex MITT regimen.

Improving linolenic acid content in rapeseed oil by overexpression of CsFAD2 and CsFAD3 genes.

With the increasing public attention to the health benefit of polyunsaturated fatty acids (PUFAs) and demand for linolenic acid (C18:3), it is of great significance to increase the C18:3 content in our meal. As an oil crop with high content of C18:3, Camelina sativa has three homologous copies of FAD2 and three homologous copies FAD3. In this study, we seed-specifically overexpressed two Camelina sativa fatty acid desaturase genes, CsFAD2 and CsFAD3, in rapeseed cultivar Zhongshuang 9. The results show that C18:3 content in CsFAD2 and CsFAD3 overexpressed seeds is increased from 8.62% in wild-type (WT) to 10.62-12.95% and 14.54-26.16%, respectively. We crossed CsFAD2 and CsFAD3 overexpression lines, and stable homozygous digenic crossed lines were obtained. The C18:3 content was increased from 8.62% in WT to 28.46-53.57% in crossed overexpression lines. In addition, we found that the overexpression of CsFAD2 and CsFAD3 had no effect on rapeseed growth, development, and other agronomic traits. In conclusion, we successfully generated rapeseed germplasms with high C18:3 content by simultaneously overexpressing CsFAD2 and CsFAD3, which provides a feasible way for breeding high C18:3 rapeseed cultivars. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01445-0.

Enhanced mechanical properties and antibacterial activities of chitosan films through incorporating zein-gallic acid conjugate stabilized cinnamon essential oil Pickering emulsion.

In this study, zein-gallic acid covalent complex prepared by alkali treatment was utilized as an emulsifier to stabilize cinnamon essential oil (CEO) Pickering emulsion, and the chitosan-based (CZGE) films loaded with CEO Pickering emulsion were prepared by blending. The influences of different contents of CEO Pickering emulsion on the physical properties and biological activities of CZGE films were investigated. The results showed that Pickering emulsion had good compatibility with chitosan matrix and enhanced the interaction between film-forming matrix polymer. In addition, incorporating with CEO Pickering emulsion (15 %, v/v) significantly improved the mechanical and barrier properties of the films, and also enhanced the light transmittance and thermal stability of the films. Furthermore, the loading of emulsion also improved the antioxidant activities of the films and led to the formation of high antimicrobial property against food pathogens, and the slow-release behavior of CEO could effectively extend the biological activity of the films. These results suggested that Pickering emulsion has potential as a loading system and a plasticizer in active packaging, and the feasibility of CZGE film in food packaging.

Highly efficient adsorption of ciprofloxacin from aqueous solutions by waste cation exchange resin-based activated carbons: Performance, mechanism, and theoretical calculation.

This study focused on the preparation of a highly efficient activated carbon adsorbent from waste cation exchange resins through one-step carbonization to remove ciprofloxacin (CIP) from aqueous solutions. Scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectrometry, and X-ray photoelectron spectroscopy were used to characterize the physicochemical properties of the carbonized materials. The CIP removal efficiency, influencing factors, and adsorption mechanisms of CIP on the carbonized resins were investigated. Density functional theory (DFT) computations were performed to elucidate the adsorption mechanisms. The CIP removal reached 93 % when the adsorbent dosage was 300 mg/L at 25 °C. The adsorption capacity of the carbonized resins to CIP gradually decreased with an increasing pH from 3.0 to 7.0 and sharply declined with a pH from 7.0 to 11.0. The adsorption process better fitted by the pseudo second-order kinetic and Langmuir models, indicating that the interaction between CIP and the carbonized resins was monolayer adsorption. The maximum adsorption capacity fitted by the Langmuir model was 384.4 mg/g at 25 °C. Microstructural analysis showed that the adsorption of CIP on the carbonized resins was a joint effect of H-bonding, ion exchange, and graphite-N adsorption. Computational results signified the strong H-bonding and ion exchange interactions existed between CIP and carbonized resins. The high adsorption and reusability suggest that waste cation exchange resin-based activated carbons can be used as an effective and reusable adsorbent for removing CIP from aqueous solutions.

[KEAP1/PGAM5/AIFM1 mediated oxeiptosis pathway in TDCIPP-induced reduction of TM4 cell viability].

OBJECTIVE: To investigate the toxic effects and potential mechanisms of tri(1, 3-dichloro-2-propyl) phosphate(TDCIPP) exposure on the mouse testicular supporting cell line(TM4 cells). METHODS: TM4 cells were treated with different concentrations of TDCIPP(0, 12.5, 25 and 50 µmol/L), or 50 µmol/L TDCIPP combined with antioxidant N-acetylcysteine(NAC) for 24 h. Cell viability was assessed using the CCK8 assay, intracellular ROS levels were detected using the DCFH-DA probe, and the protein levels of oxeiptosis-related proteins, such as KEAP1, PGAM5, AIFM1 and phosphorylated AIFM1(p-AIFM1), were detected using Western blot. RESULTS: TDCIPP dose-dependently reduced TM4 cell viability(P<0.05). ROS levels in TM4 cells treated with 12.5, 25 and 50 µmol/L TDCIPP were 9.44±1.42, 17.25±1.81 and 18.38±2.66, respectively, significantly higher than the control group's 5.08±0.90(P<0.05). ROS levels in the 5 mmol/L NAC+50 µmol/L TDCIPP group were 14.70±0.50, significantly lower than the corresponding TDCIPP group's 26.44±0.73(P<0.05). The activity of TM4 cells in KEAP1siRNA+TDCIPP group and PGAM5siRNA+TDCIPP group were 77.00±1.73 and 76.67±1.53, respectively, significantly higher than TDCIPP group 68.67±1.53(P<0.05). The relative expression of KEAP1 protein in TM4 cells treated with 25 and 50 µmol/L TDCIPP were 0.77±0.04 and 0.82±0.02, respectively, significantly higher than the control group's 0.57±0.01(P<0.05). The relative expression of PGAM5 protein in TDCIPP-treated TM4 cells were 1.17±0.04, 1.38±0.03 and 1.41±0.03, respectively, significantly higher than the control group's 0.81±0.02(P<0.05). The relative expression of AIFM1 protein were 0.42±0.01, 0.63±0.01 and 0.68±0.02, respectively, significantly higher than the control group's 0.34±0.02(P<0.05). The relative expression of p-AIFM1 protein were 1.73±0.02, 1.52±0.02 and 0.73±0.01, respectively, significantly lower than the control group's 2.25±0.02(P<0.05). In the 5 mmol/L NAC+50 µmol/L TDCIPP group, the relative expression of KEAP1, PGAM5 and AIFM1 proteins in TM4 cells were 0.61±0.01, 0.58±0.01 and 0.48±0.03, respectively, significantly lower than the TDCIPP group's 0.86±0.12(P<0.05), 0.74±0.02(P<0.05) and 0.92±0.01(P<0.05). The relative expression of p-AIFM1 protein in the 5 mmol/L NAC+50 µmol/L TDCIPP group was 0.45±0.11, significantly higher than the TDCIPP group's 0.23±0.01(P<0.05). CONCLUSION: The reduction of TM4 cell viability induced by TDCIPP may be related to ROS-mediated regulation of the KEAP1/PGAM5/AIFM1 pathway, leading to oxeiptosis.

[Role of autophagy in cadmium-induced damage to the blood-testis barrier in mice].

OBJECTIVE: To investigate the role of autophagy in cadmium chloride (CdCl2)-induced damage to the blood-testis barrier (BTB) in mice. METHODS: Twenty four-week-old male C57BL/6 mice were randomly divided into four groups and intraperitoneally injected with CdCl2 at 0 mg/kg/d (the control), 0.5 mg/kg/d (low-dose), 1.0 mg/kg/d (medium-dose) and 2.0 mg/kg/d (high-dose) respectively for 28 consecutive days. Then the morphological changes of the testis tissue was observed by HE staining, the integrity of BTB measured with the biotracer, and the expressions of the BTB components ZO-1 and N-Cadherin proteins detected by Western blot. The TM4 Sertoli cells were treated with CdCl2at 0, 2.5, 5 and 10 µmol/L respectively for 24 hours, followed by determination of the expression levels of ZO-1 and N-Cadherin as well as the autophagy-related proteins LC3II and p62. Then the cells were again treated with CdCl2 in the presence of the autophagy inhibitor chloroquine (CQ) at 5 µmol/L or the autophagy inducer rapamycin (Rap) at 50 nmol/L for 24 hours, followed by measurement of the expressions of LC3II, p62, ZO-1 and N-Cadherin by Western blot. RESULTS: Compared with the control group, the cadmium-exposed mice showed increased interstitial space in the seminiferous tubules, formation of intracellular cavitation in the germ cells with decreased layers and disordered arrangement, and damaged integrity of the BTB. The expressions of the ZO-1 and N-Cadherin proteins were significantly down-regulated in the testis tissue of the mice in the medium- and high-dose CdCl2 groups (P < 0.05), and even more significantly in the CdCl2-exposed cells in comparison with those in the control mice (P < 0.01), while the expressions of the LC3II and p62 proteins were remarkably up-regulated (P < 0.05). The expressions of ZO-1, N-Cadherin, LC3II and p62 were also up-regulated in the cells co-treated with CQ and CdCl2 (P < 0.01), those of ZO-1, N-Cadherin and p62 down-regulated (P< 0.05) and that of LC3II up-regulated (P < 0.05) in the cells co-treated with Rap and CdCl2. CONCLUSION: CdCl2 can damage the integrity of the mouse BTB, which may be attributed to its ability to enhance the autophagy in Sertoli cells and regulate the expressions of BTB proteins.

Cadmium induces apoptosis of mouse spermatocytes through JNK activation and disruption of autophagic flux.

Cadmium has been reported to accumulate primarily in spermatogonia and spermatocytes. Exposure to cadmium results in male reproductive toxicity via germ-cell apoptosis and impaired autophagy. Apoptosis and autophagy are two physiologically conserved events that maintain cellular homeostasis. However, the precise role of autophagy in cadmium-induced apoptosis of male germ cells has yet to be addressed. The present study aimed to investigate the impact of cadmium exposure on the cytotoxicity of GC-2 spd cells, a mouse spermatocyte cell line. The results showed that cadmium exposure caused apoptotic cell death and the accumulation of autophagosomes, along with the up-regulation of ATG proteins in GC-2 spd cells. It was demonstrated that the cadmium-induced accumulation of autophagosomes contributes to the apoptosis of GC-2 spd cells. This notion is supported by the findings that the autophagy inhibitor 3-MA reduced accumulation of autophagosomes and apoptotic cell death. Conversely, the apoptosis inhibitor Z-VAD-FMK inhibited apoptosis but had little effect on the accumulation of autophagosomes. Cadmium may impede the fusion of autophagosomes with lysosomes, leading to the autophagosome buildup. Additionally, we found that the JNK pathway mediates transcriptional induction of several autophagy-related (ATG) genes involved in autophagosome formation. The cadmium-activated JNK pathway regulates apoptosis by mediating the autophagosome formation. Treatment of cells with the JNK inhibitor SP600125 attenuated the accumulation of autophagosomes, the upregulated expression of autophagosome-associated proteins and apoptotic cell death induced by cadmium. Overall, these findings suggest that cadmium enhances apoptosis of GC-2 spd cells by activating the JNK pathway and inhibiting autophagic flux.

[The role of PERK-eIF2α-ATF4-CHOP pathway in the apoptosis of TM4 cells induced by bisphenol A].

OBJECTIVE: To investigate the effects of bisphenol A(BPA) on the proliferation and apoptosis of mouse testicular sertoli cells(TM4 cells) and the role of PERK-eIF2α-ATF4-CHOP pathway. METHODS: TM4 cells were treated with different concentrations of BPA(0, 25, 50, 100 µmol/L) and 100 µmol/L BPA combined with protein kinase R-like ER kinase(PERK) inhibitor GSK2656157 for 24 h, and the apoptosis of TM4 cells was observed by TUNEL staining. The expression levels of Bax, Bcl-2, cleaved Caspase-3, GRP78 and PERK-eIF2α-ATF4-CHOP pathway-related proteins were detected by Western blot. RESULTS: The apoptosis rate of TM4 cells in 25, 50 and 100 µmol/L BPA exposed groups was increased to 3.31%±0.34%, 7.51%±1.10% and 14.58%±0.91%, respectively, which was significantly higher than that in control group(0.73%±0.03%, P<0.05). Compared with the control group(1.00), cleaved Caspase-3 protein expression of TM4 cells in the 25, 50 and 100 µmol/L BPA exposed groups increased to 1.49±0.11, 1.59±0.12, 2.42±0.24, respectively; the ratio of Bax/Bcl-2 increased to 2.06±0.19, 3.94±0.034, 6.14±0.71, respectively; the protein expression of GRP78 increased to 1.29±0.06, 1.39±0.06, 1.92±0.17, respectively; the expression of p-PERK protein was increased to 1.64±0.03, 2.52±0.09, 2.80±0.11, respectively; the expression of p-eIF2α protein was increased to 1.79±0.05, 2.48±0.10, 4.77±0.32, respectively; ATF4 protein expression was increased to 2.51±0.03, 3.24±0.14 and 7.45±0.51, respectively; CHOP protein expression was increased to 1.44±0.01, 3.20±0.11 and 3.80±0.11, respectively, and all the differences were statistically significant(P<0.05). Compared to 100 µmol/L BPA group, the expression level of p-PERK, p-eIF2α, ATF4, CHOP, cleaved Caspase-3 protein and the ratio of Bax/Bcl-2 in 100 µmol/L BPA+10 µmol/L GSK2656157 group were decreased to 2.17±0.11, 1.81±0.13, 1.71±0.23, 2.18±0.22, 1.43±0.03, 2.22±0.13, respectively; the apoptosis rate of TM4 cells was also decreased to 7.28%±0.47%, all the differences were statistically significant(P<0.05). CONCLUSION: BPA can induce apoptosis of TM4 cells by activating endoplasmic reticulum stress and regulating PERK-eIF2α-ATF4-CHOP pathway.

Patient Biochemistry and Treatment Need in Chronic Hepatitis B Virus Infection Across Three Continents: Retrospective Cross-Sectional Cohort Studies.

INTRODUCTION: Chronic hepatitis B virus (HBV) infection is associated with significant global morbidity and mortality. Low treatment rates are observed in patients living with HBV; the reasons for this are unclear. This study sought to describe patients' demographic, clinical and biochemical characteristics across three continents and their associated treatment need. METHODS: This retrospective cross-sectional post hoc analysis of real-world data used four large electronic databases from the United States, United Kingdom and China (specifically Hong Kong and Fuzhou). Patients were identified by first evidence of chronic HBV infection in a given year (their index date) and characterized. An algorithm was designed and applied, wherein patients were categorized as treated, untreated but indicated for treatment and untreated and not indicated for treatment based on treatment status and demographic, clinical, biochemical and virological characteristics (age; evidence of fibrosis/cirrhosis; alanine aminotransferase [ALT] levels, HCV/HIV coinfection and HBV virology markers). RESULTS: In total, 12,614 US patients, 503 UK patients, 34,135 patients from Hong Kong and 21,614 from Fuzhou were included. Adults (99.4%) and males (59.0%) predominated. Overall, 34.5% of patients were treated at index (range 15.9-49.6%), with nucleos(t)ide analogue monotherapy most commonly prescribed. The proportion of untreated-but-indicated patients ranged from 12.9% in Hong Kong to 18.2% in the UK; almost two-thirds of these patients (range 61.3-66.7%) had evidence of fibrosis/cirrhosis. A quarter (25.3%) of untreated-but-indicated patients were aged ≥ 65 years. CONCLUSION: This large real-world dataset demonstrates that chronic hepatitis B infection remains a global health concern; despite the availability of effective suppressive therapy, a considerable proportion of predominantly adult patients apparently indicated for treatment are currently untreated, including many patients with fibrosis/cirrhosis. Causes of disparity in treatment status warrant further investigation.

Preparation and characterization of functionalized chitosan/polyvinyl alcohol composite films incorporated with cinnamon essential oil as an active packaging material.

In this study, amphiphilic chitosan (NPCS-CA) was synthesized by grafting quaternary phosphonium salt and cholic acid onto the chain of chitosan, aiming to develop an active edible film based on NPCS-CA and polyvinyl alcohol (PVA) incorporated with cinnamon essential oil (CEO) by the casting method. The chemical structure of the chitosan derivative was characterized by FT-IR, 1H NMR and XRD. Through the characterization of FT-IR, TGA, mechanical and barrier properties of the composite films, the optimal proportion of NPCS-CA/PVA was determined as 5/5. And, the tensile strength and elongation at break of the NPCS-CA/PVA (5/5) film with 0.4 % CEO were 20.32 MPa and 65.73 %, respectively. The results revealed that the NPCS-CA/PVA-CEO composite films exhibited an excellent ultraviolet barrier property at 200-300 nm and significantly reduced oxygen permeability, carbon dioxide permeability and water vapor permeability. Furthermore, the antibacterial property of film-forming solutions against E. coli, S. aureus, and C. lagenarium was distinctly improved with the increase of NPCS-CA/PVA proportion. And, the multifunctional films effectively extended the shelf-life of mangoes at 25 °C based on the characterization of surface changes and quality indexes. The NPCS-CA/PVA-CEO films could be developed as biocomposite food packaging material.

Nutrient controlled release performance of bio-based coated fertilizer enhanced by synergistic effects of liquefied starch and siloxane.

The porous structure and hydrophilicity of coating shells affect the nutrient controlled-release performance of castor oil-based (CO) coated fertilizers. In order to solve these problems, in this study, the castor oil-based polyurethane (PCU) coating material was modified with liquefied starch polyol (LS) and siloxane, and a new coating material with cross-linked network structure and hydrophobic surface was synthesized, and used it to prepare the coated controlled-release urea (SSPCU). The results demonstrated that the cross-linked network formed by LS and CO improved the density and reduced the pores on the surface of the coating shells. The siloxane was grafted on the surface of coating shells to improve its hydrophobicity and thus delayed water entry. The nitrogen release experiment indicated that the synergistic effects of LS and siloxane improved the nitrogen controlled-release performance of bio-based coated fertilizers. Nutrient released longevity of SSPCU with 7 % coating percentage reached >63 days. Moreover, the nutrient release mechanism of coated fertilizer was further revealed by the analysis of the release kinetics analysis. Therefore, the results of this study provide a new idea and technical support for development of efficient and environment-friendly bio-based coated controlled-release fertilizers.

Non-Lethal Concentrations of CdCl2 Cause Marked Alternations in Cellular Stress Responses within Exposed Sertoli Cell Line.

Cadmium is a component of ambient metal pollution, which is linked to diverse health issues globally, including male reproductive impairment. Assessments of the acute effects of cadmium on male reproduction systems, such as testes, tend to be based on frank adverse effects, with particular molecular pathways also involved. The relationship between cytotoxicity potential and cellular stress response has been suggested to be one of the many possible drivers of the acute effects of cadmium, but the link remains uncertain. In consequence, there is still much to be learned about the cellular stress response induced by a non-lethal concentration of cadmium in male reproductive cells. The present study used temporal assays to evaluate cellular stress response upon exposure to non-lethal concentrations of Cadmium chloride (CdCl2) in the Sertoli cell line (TM4). The data showed alternations in the expression of genes intimated involved in various cellular stress responses, including endoplasmic reticulum (ER) stress, endoplasmic unfolded protein stress (UPRmt), endoplasmic dynamics, Nrf2-related antioxidative response, autophagy, and metallothionein (MT) expression. Furthermore, these cellular responses interacted and were tightly related to oxidative stress. Thus, the non-lethal concentration of cadmium perturbed the homeostasis of the Sertoli cell line by inducing pleiotropic cellular stresses.

[Effect of reactive oxygen species in cadmium chloride induced apoptosis of mouse Leydig cells].

OBJECTIVE: To study the effect of reactive oxygen species(ROS) in cadmium chloride-induced apoptosis of mouse Leydig cells(TM3 cells) and explore the underlying molecular mechanisms. METHODS: TM3 cells were used as an in vitro model for studying reproductive toxicity induced by cadmium exposure. The cells were treated with different concentrations of CdCl_2(0, 5 and 10 µmol/L) for 24 h. CCK-8 assay was used to detect the effect of CdCl_2 on TM3 cell activity. Hoechst33342 staining was performed to explore the formation of apoptotic bodies. DCFH-DA probe was used to detect the level of ROS in the cells. TM3 cells were pretreated with 1 mmol/L NAC for 1 h and then treated with 10 µmol/L CdCl_2 for 24 h. The protein expression levels of pro-apoptotic proteins Caspase-9 and cleaved Caspase-3 were detected by Western blot; RT-qPCR was used to measure the expression of anti-apoptotic gene Bcl-2 and pro-apoptotic genes Caspase-9 and Caspase-3. RESULTS: After exposure to CdCl_2 for 24 h, viability of TM3 cells decreased and the number of apoptotic bodies increased. Western blot result showed that the protein level of Caspase-9 in the 10 µmol/L CdCl_2 treatment group was increased to 0.86±0.10(P<0.05) compared with the control group(0.56±0.07). Compared with the control group(0.37±0.11), the protein level of cleaved Caspase-3 in the 5 and 10 µmol/L CdCl_2 treatment groups were increased to 0.65±0.03 and 1.05±0.13(P<0.05). Compared with the control group(46.80±1.24), the intracellular ROS content in the 5 and 10 µmol/L treatment groups increased to 60.47±1.39 and 80.63±1.34(P<0.05). Compared with the cadmium-treated group, NAC inhibited Caspase-9(CdCl_2 group: 0.89±0.07; CdCl_2+NAC group: 0.28±0.02)and cleaved Caspase-3(CdCl_2 group: 1.53±0.21; CdCl_2+NAC group: 0.66 ±0.07), the difference was statistically significant(P<0.05). At the same time, NAC decreased the ROS level(62.64±0.93) in the CdCl_2 exposure group(80.13±0.94)(P<0.05). In addition, RT-qPCR result showed that the Caspase-9 mRNA levels in the 5 and 10 µmol/L CdCl_2 treatment groups were 1.40±0.14 and 1.90±0.12(P<0.05), compared with the control group(0.97±0.10). Compared with the control group(0.88±0.08), the cleaved Caspase-3 mRNA levels in the 5 and 10 µmol/L CdCl_2 treatment groups were increased to 1.42±0.11 and 1.59±0.12(P<0.05). While in the 5 and 10 µmol/L CdCl_2-treated group, compared with the control group(0.94±0.02), the Bcl-2 mRNA level were decreased to 0.60±0.02 and 0.50±0.09(P<0.05). Compared with the cadmium treatment group(0.57±0.06), NAC could significantly improve the cadmium-induced Bcl-2 mRNA expression level(0.92±0.03), and Caspase-9(CdCl_2 group: 1.96±0.07; CdCl_2+NAC group: 1.04±0.02) and Caspase-3(CdCl_2 group: 1.65±0.02; CdCl_2+NAC group: 0.66±0.04) were decreased(P<0.05). CONCLUSION: The Caspase cascade in mouse Leydig cells can be activated by excessive ROS induced by CdCl_2, and inhibition of ROS production can significantly reduce the CdCl_2-induced apoptosis of TM3 cells.

Amphiphilic chitosan/carboxymethyl gellan gum composite films enriched with mustard essential oil for mango preservation.

In this paper, amphiphilic chitosan and carboxymethyl modified gellan gum were synthesized to develop an active edible fresh-keeping material. The optimal weight ratio of CMCS-g-CA/CMGG was determined as 5:2 through the characterization of Fourier transform infrared (FT-IR), Thermogravimetric analysis (TGA), mechanical and barrier properties of the composite films. In addition, the water vapor permeability and oxygen permeability of CMCS-g-CA/CMGG composite films incorporated with mustard essential oil were all declined, and the antibacterial property of the composite film solutions against E. coli, S. aureus and Bacillus anthracis was distinctly improved with the increase of mustard essential oil (MEO) dosage. Furthermore, the CMCS-g-CA/CMGG + 2.0 µL/mL MEO composite film exhibited an effective preservation on mango fruits during 20 days of storage based on the characterization of surface appearance and quality indexes of fruits. Hence, the multifunctional CMCA-g-CA/CMGG/MEO composite films can be served as a prospective eco-friendly packaging material for fruit preservation.

Characteristics, Treatment Patterns, and Clinical Outcomes of Chronic Hepatitis B Across 3 Continents: Retrospective Database Study.

INTRODUCTION: The prevalence of chronic hepatitis B virus (HBV) infection is high in many countries; however, robust, real-world epidemiological data are lacking. This study describes the prevalence, characteristics, treatment patterns, and long-term clinical outcomes of patients with chronic HBV infection in the US, Germany, and Taiwan. METHODS: This was a retrospective cohort analysis of three healthcare/insurance claims databases. Individuals were identified as patients with chronic HBV infection if their records contained HBV diagnostic codes from 1 January 2010 to 31 December 2012 (Germany and Taiwan) or 1 January 2013 (USA). Included patients were indexed on 1 January 2013. Patients' demographics, clinical characteristics, and healthcare utilisation were described. Treatment patterns and long-term clinical outcomes over follow-up (to 31 December 2016 or loss to follow-up) were estimated. RESULTS: The prevalence of chronic HBV infection was 0.10%, 0.17%, and 2.39% in the US, Germany, and Taiwan respectively. Prevalence was very low in children, increased rapidly in adulthood, and peaked in 50- < 65 year olds before declining in the elderly. More US (16.6%) and German (15.4%) patients were HIV ± HCV coinfected than in Taiwan (4.1%). Baseline clinical characteristics and healthcare utilisation were broadly similar between countries. In total, 19.2%, 11.1%, and 5.9% of non-coinfected adult patients received treatment at index in the US, Germany, and Taiwan, respectively; most frequently with nucleos(t)ide analogue monotherapy (94.4%, 97.2%, 99.8% of treated patients, respectively) and rarely with interferons (0.27%, 1.63%, and 0.06%, respectively). Untreated Taiwanese patients were more likely to remain untreated than elsewhere, and treated Taiwanese patients were less likely to persist with therapy. Generally, the cumulative incidence of long-term clinical outcomes was lowest in Germany. CONCLUSION: This study provides a contemporary, real-world, intercontinental snapshot of chronic HBV infection. Long-term sequelae occurred in all populations, and treatment levels were low, suggesting an unmet need for (or access to) effective treatments.

Dual-grafted dextran based nanomicelles: Higher antioxidant, anti-inflammatory and cellular uptake efficiency for quercetin.

Quercetin (QCT) has antioxidant, anti-inflammatory, anti-tumor and other important pharmacological activities, but the poor water solubility limits its application. In this work, the amphiphilic dextran (ADEX) was prepared by grafting L-cysteine and octadecylamine onto carboxymethyl dextran with the grafting rate of 21.29 % and 19.35 %. Then, the QCT-loaded nanomicelles (QNMs) were prepared by using ADEX as wall material and the QCT as core material via ultrasonic self-assembly method. The particle size and zeta potential of QNMs were 372 nm and 31.4 mV. Under simulated gastric and simulated intestinal fluids, the cumulative release QNMs were 37.54 % and 52.13 % within 180 min, and the QNMs showed better stability in simulated gastric fluid. The QNMs showed significantly better PTIO, OH and O2- scavenging activities than QCT. In addition, QNMs could effectively down-regulate the expression of pro-inflammatory cytokines and promoted the expression of anti-inflammatory cytokine. The cellular uptake results proved that the QNMs were more easily absorbed by cells than free QCT, indicating that the nano-encapsulation procedure effectively improved the uptake efficiency of QCT by cells.

[HFD-induced obesity triggers testicular cell senescence and endoplasmic reticulum stress in male mice].

OBJECTIVE: To investigate high-fat diet-induced obesity-triggered testicular cell senescence and endoplasmic reticulum stress. METHODS: We randomly and equally divided 10 four-week-old male C57BL/6J mice into a control and a high-fat group, the former fed with a diet of 10% fat content while the latter with a diet of 60% fat content to establish an obesity model. After eight weeks of feeding, we observed the pathological changes in the testis tissue of the mice by HE staining, detected the serum T content by ELISA, measured the telomere length in the testis cells by RT-PCR, and examined the activity of senescence-associated ß-galactosidase (SA-ß-gal) by histochemical staining. Using RT-qPCR and Western blot, we determined the protein and mRNA expressions of the cell senescence markers p16 and p21 as well as the protein expressions of the endoplasmic reticulum stress markers GRP78 and CHOP in the testis tissue. RESULTS: Compared with the controls, the animals of the high-fat group showed a 45% increase in the body weight, disordered structure of the spermatogenic cells, reduced level of serum T and shortened telomere length of the testis cells (P < 0.01). The mRNA and protein expressions of p16 and p21 were dramatically higher in the high-fat than in the control group (P<0.01), so were the intracellular SA-ß-gal activity and the protein expressions of CHOP and GRP78 (P<0.01). CONCLUSION: High-fat diet-induced obesity triggers testicular cell senescence and endoplasmic reticulum stress in male mice.

Cadmium-induced apoptosis of Leydig cells is mediated by excessive mitochondrial fission and inhibition of mitophagy.

Cadmium is one of the environmental and occupational pollutants and its potential adverse effects on human health have given rise to substantial concern. Cadmium causes damage to the male reproductive system via induction of germ-cell apoptosis; however, the underlying mechanism of cadmium-induced reproductive toxicity in Leydig cells remains unclear. In this study, twenty mice were divided randomly into four groups and exposed to CdCl2 at concentrations of 0, 0.5, 1.0 and 2.0 mg/kg/day for four consecutive weeks. Testicular injury, abnormal spermatogenesis and apoptosis of Leydig cells were observed in mice. In order to investigate the mechanism of cadmium-induced apoptosis of Leydig cells, a model of mouse Leydig cell line (i.e. TM3 cells) was subjected to treatment with various concentrations of CdCl2. It was found that mitochondrial function was disrupted by cadmium, which also caused a significant elevation in levels of mitochondrial superoxide and cellular ROS. Furthermore, while cadmium increased the expression of mitochondrial fission proteins (DRP1 and FIS1), it reduced the expression of mitochondrial fusion proteins (OPA1 and MFN1). This led to excessive mitochondrial fission, the release of cytochrome c and apoptosis. Conversely, cadmium-induced accumulation of mitochondrial superoxide was decreased by the inhibition of mitochondrial fission through the use of Mdivi-1 (an inhibitor of DRP1). Mdivi-1 also partially prevented the release of cytochrome c from mitochondria to cytosol and attenuated cell apoptosis. Finally, given the accumulation of LC3II and SQSTM1/p62 and the obstruction of Parkin recruitment into damaged mitochondria in TM3 cells, the autophagosome-lysosome fusion was probably inhibited by cadmium. Overall, these findings suggest that cadmium induces apoptosis of mouse Leydig cells via the induction of excessive mitochondrial fission and inhibition of mitophagy.