Rosmarinic Acid Liposomes Downregulate Hepcidin Expression via BMP6-SMAD1/5/8 Pathway in Mice with Iron Overload.

The objective of this study is to examine the potential protective effect of rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on hepatic damage induced by iron overload. The characteristics, stability, and release of RosA-LIP in vitro were identified. The mice were randomly assigned to five groups: Control, Model, Model+DFO (DFO), Model+RosA (RosA), and Model+RosA-LIP (RosA-LIP). The iron overload model was induced by administering iron dextran (i.p.). The DFO, RosA, and RosA-LIP groups received iron dextran and were subsequently treated with DFO, RosA, and RosA-LIP for 14 days. We developed a novel formulation of RosA-LIP that exhibited stability and controlled release properties. Firstly, RosA-LIP improved liver function and ameliorated pathological changes in a mouse model of iron overload. Secondly, RosA-LIP demonstrated the ability to enhance the activities of T-SOD, GSH-Px, and CAT, while reducing the levels of MDA and 4-HNE, thereby effectively mitigating oxidative stress damage induced by iron overload. Thirdly, RosA-LIP reduced hepatic iron levels by downregulating FTL, FTH, and TfR1 levels. Additionally, RosA-LIP exerted a suppressive effect on hepcidin expression through the BMP6-SMAD1/5/8 signaling pathway. Furthermore, RosA-LIP upregulated FPN1 expression in both the liver and duodenum, thereby alleviating iron accumulation in these organs in mice with iron overload. Notably, RosA exhibited a comparable iron chelation effect, and RosA-LIP demonstrated superior efficacy in mitigating liver damage induced by excessive iron overload. RosA-LIP exhibited favorable sustained release properties, targeted delivery, and efficient protection against iron overload-induced liver damage. A schematic representation of the proposed protective mechanism of rosmarinic acid liposome during iron overload. Once RosA-LIP is transported into cells, RosA is released. On the one hand, RosA attenuates the BMP6-SMAD1/5/8-SMAD4 signaling pathway activation, leading to inhibiting hepcidin transcription. Then, the declined hepcidin contacted the inhibitory effect of FPN1 in hepatocytes and duodenum, increasing iron mobilization. On the other hand, RosA inhibits TfR1 and ferritin expression, which decreases excessive iron and oxidative damage.

Ionic Hyperbranched Poly(amido-amine)-Incorporated Nanofiltration Membranes for High-Efficiency Dye Desalination.

High-efficiency dye desalination is crucial in the textile industry, considering its importance for human health, safe aquatic ecological systems, and resource recovery. In order to solve the problem of effective separation of univalent salt and ionic dye under the condition of high salt, ionic hyperbranched poly(amido-amine) (HBPs) were synthesized based on a simple and scalable one-step polycondensation method and then incorporated into the polyamide (PA) selective layers to construct charged nanochannels through interfacial polymerization (IP) on the surface of a polyvinyl chloride ultrafiltration (PVC-UF) hollow fiber membrane. Both the internal nanopores of HBPs (internal nanochannels) and the interfacial voids between HBPs and the PA matrix (external nanochannels) can be regarded as a fast water molecule transport pathway, while the terminal ionic groups of ionic HBPs endow the nanochannels with charge characteristics for improving ionic dye/salt selectivities. The permeate fluxes and dye/salt selectivities of HBP-TAC/PIP (57.3 L m-2 h-1 and rhodamine B (RB)/NaCl selectivity of 224.0) and HBP-PS/PIP (63.7 L m-2 h-1 and lemon yellow (LY)/NaCl selectivity of 664.0) membranes under 0.4 MPa operation pressure are much higher than PIP-only and HBP-NH2/PIP membranes. At the same time, this project also studied the membrane desalination process in a simulated high-salinity dye/salt mixture system to provide a theoretical basis and technical support for the actual dye desalination process.

Self-Reconstructed Two-Dimensional Cluster-Based Co-Organic Layer Heterojunctions for Enhanced Oxygen Evolution Reactions.

When it comes to an efficient catalytic oxygen evolution reaction (OER) in the production of renewable energy and chemicals, the construction of heterogeneous structures is crucial to break the linear scalar relationship of a single catalyst. This heterogeneous structure construction helps creatively achieve high activity and stability. However, the synthesis process of heterogeneous crystalline materials is often complex and challenging to capture and reproduce, which limits their application. Here, the dynamic process of structural changes in Co-MOFs in alkali was captured by in situ powder X-ray diffraction, FT-IR spectroscopy, and Raman spectroscopy, and several self-reconfigured MOF heterogeneous materials with different structures were stably isolated. The created ß-Co(OH)2/Co-MOF heterojunction structure facilitates rapid mass-charge transfer and exposure of active sites, which significantly enhanced OER activity. Experimental results show that this heterogeneous structure achieves a low overpotential of 333 mV at 10 mA cm-2. The findings provide new insights and directions for the search for highly reactive cobalt-based MOFs for sustainable energy technologies.

A torus source and its application for non-primary radiation evaluation.

Objective. Non-primary radiation doses to normal tissues from proton therapy may be associated with an increased risk of secondary malignancies, particularly in long-term survivors. Thus, a systematic method to evaluate if the dose level of non-primary radiation meets the IEC standard requirements is needed.Approach. Different from the traditional photon radiation therapy system, proton therapy systems are composed of several subsystems in a thick bunker. These subsystems are all possible sources of non-primary radiation threatening the patient. As a case study, 7 sources in the P-Cure synchrotron-based proton therapy system are modeled in Monte Carlo (MC) code: tandem injector, injection, synchrotron ring, extraction, beam transport line, scanning nozzle and concrete reflection/scattering. To accurately evaluate the synchrotron beam loss and non-primary dose, a new model called the torus source model is developed. Its parametric equations define the position and direction of the off-orbit particle bombardment on the torus pipe shell in the Cartesian coordinate system. Non-primary doses are finally calculated by several FLUKA simulations.Main results. The ratios of summarized non-primary doses from different sources to the planned dose of 2 Gy are all much smaller than the IEC requirements in both the 15-50 cm and 50-200 cm regions. Thus, the P-Cure synchrotron-based proton therapy system is clean and patient-friendly, and there is no need an inner shielding concrete between the accelerator and patient.Significance. Non-primary radiation dose level is a very important indicator to evaluate the quality of a PT system. This manuscript provides a feasible MC procedure for synchrotron-based proton therapy with new beam loss model. Which could help people figure out precisely whether this level complies with the IEC standard before the system put into clinical treatment. What' more, the torus source model could be widely used for bending magnets in gantries and synchrotrons to evaluate non-primary doses or other radiation doses.

Identification and characterization of a novel 5-hydroxytryptamine receptor in the sea cucumber Apostichopus japonicus (Selenka).

Serotonin (5-hydroxytryptamine [5-HT]) receptors (5-HTRs) mediate neuroendocrine signaling via interactions with the ligand serotonin (5-HT). The 5-HT signaling system has been well studied in vertebrates, but rarely known in invertebrate animals, especially in the marine invertebrates. In this study, we identified and characterized a novel 5-HTR from the sea cucumber Apostichopus japonicus (Aj5-HT4/6 ). The cloned Aj5-HT4/6 open reading frame comprised 1290 bp and encoded 429 amino acids. Bioinformatic analysis of the receptor indicated that it was a member of the class A of the G protein-coupled receptor family. Further experiments using Aj5-HT4/6 -transfected HEK293 cells demonstrated that treatment with 5-HT could induce rapid internalization of Aj5-HT4/6 fused with enhanced green fluorescent protein from the cell surface into the cytoplasm and triggered a significant increase in levels of the second messenger cAMP as well as mitogen-activated protein kinase phosphorylation in a 5-HT dose-dependent manner. Quantitative real time-polymerase chain reaction demonstrated that Aj5-HT4/6 was predominantly expressed in the muscle and respiratory tree, and its expression was significantly decreased during estivation. Taken together, these results imply that Aj5-HT4/6 is potentially involved in the movement and metabolism of the sea cucumber.

Two new CdII MOFs of 1,4-bis(1H-benzimidazol-1-yl)butane and flexible dicarboxylate ligands: luminescence sensing towards Fe3.

Two new CdII MOFs, namely, two-dimensional (2D) poly[[[µ2-1,4-bis(1H-benzimidazol-1-yl)butane](µ2-heptanedioato)cadmium(II)] tetrahydrate], {[Cd(C7H10O4)(C18H18N4)]·4H2O}n or {[Cd(Pim)(bbimb)]·4H2O}n (1), and 2D poly[diaqua[µ2-1,4-bis(1H-benzimidazol-1-yl)butane](µ4-decanedioato)(µ2-decanedioato)dicadmium(II)], [Cd2(C10H16O4)2(C18H18N4)(H2O)2]n or [Cd(Seb)(bbimb)0.5(H2O)]n (2), have been synthesized hydrothermally based on the 1,4-bis(1H-benzimidazol-1-yl)butane (bbimb) and pimelate (Pim2-, heptanedioate) or sebacate (Seb2-, decanedioate) ligands. Both MOFs were structurally characterized by single-crystal X-ray diffraction. In 1, the CdII centres are connected by bbimb and Pim2- ligands to generate a 2D sql layer structure with an octameric (H2O)8 water cluster. The 2D layers are further connected by O-H...O hydrogen bonds, resulting in a three-dimensional (3D) supramolecular structure. In 2, the CdII centres are coordinated by Seb2- ligands to form binuclear Cd2 units which are linked by bbimb and Seb2- ligands into a 2D hxl layer. The 2D layers are further connected by O-H...O hydrogen bonds, leading to an 8-connected 3D hex supramolecular network. IR and UV-Vis spectroscopy, thermogravimetric analysis and solid-state photoluminescence analysis were carried out on both MOFs. Luminescence sensing experiments reveal that both MOFs have good selective sensing towards Fe3+ in aqueous solution.

Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in a central Chinese urban population: a cross-sectional survey.

BACKGROUND: This study was conducted to evaluate and update the current prevalence of and risk factors for chronic kidney disease (CKD) and diabetic kidney disease (DKD) in a central Chinese urban population. METHODS: From December 2017 to June 2018, a total of 5231 subjects were randomly enrolled from 3 communities in 3 districts of Zhengzhou. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min.1.73m2 or urinary albumin to creatinine ratio ≥ 30 mg/g (albuminuria). Diabetic subjects with systolic blood pressure > 140 mmHg, albuminuria or an eGFR less than 60 mL/min/1.73 m2 were classified as having DKD. Participants completed a questionnaire assessing lifestyle and relevant medical history, and blood and urine specimens were taken. Serum creatinine, uric acid, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein and urinary albumin were assessed. The age- and sex-adjusted prevalences of CKD and DKD were calculated, and risk factors associated with the presence of reduced eGFR, albuminuria, DKD, severity of albuminuria and progression of reduced renal function were analyzed by binary and ordinal logistic regression. RESULTS: The overall adjusted prevalence of CKD was 16.8% (15.8-17.8%) and that of DKD was 3.5% (3.0-4.0%). Decreased renal function was detected in 132 participants (2.9, 95% confidence interval [CI]: 2.5-3.2%), whereas albuminuria was found in 858 participants (14.9, 95% CI: 13.9-15.9%). In all participants with diabetes, the prevalence of reduced eGFR was 6.3% (95% CI = 3.9-8.6%) and that of albuminuria was 45.3% (95% CI = 40.4-50.1%). The overall prevalence of CKD in participants with diabetes was 48.0% (95% CI = 43.1-52.9%). The results of the binary and ordinal logistic regression indicated that the factors independently associated with a higher risk of reduced eGFR and albuminuria were older age, sex, smoking, alcohol consumption, overweight, obesity, diabetes, hypertension, dyslipidemia and hyperuricemia. CONCLUSIONS: Our study shows the current prevalence of CKD and DKD in residents of Central China. The high prevalence suggests an urgent need to implement interventions to relieve the high burden of CKD and DKD in China.

Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1.

The number of patients with diabetic nephropathy (DN) is still on the rise worldwide, and this requires the development of new therapeutic strategies. Recent reports have highlighted genetic factors in the treatment of DN. Herein, we aimed to study the roles of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and histone 3 lysine 27 trimethylation (H3K27me3) in DN. A model of DN was established by inducing diabetes in mice with streptozotocin. Mouse podocyte clone 5 (MPC5) podocytes and primary podocytes were cultured in normal and high glucose media to observe cell morphology and to quantify PVT1 expression. The roles of PVT1 and enhancer of zeste homolog 2 (EZH2) were validated via loss-of-function and gain-of-function in vitro experiments to identify the interactions among PVT1, EZH2, and forkhead box A1 (FOXA1). The podocyte damage and apoptosis due to PVT1 and FOXA1 were verified with in vivo experiments. PVT1 was highly expressed in MPC5 and primary podocytes in DN patients and in cultures grown in high glucose medium. A large number of CpG (C-phosphate-G) island sites were predicted at the FOXA1 promoter region, where PVT1 recruited EZH2 to promote the recruitment of H3K27me3. The silencing of PVT1 or the overexpression of FOXA1 relieved the damage and inhibited the apoptosis of podocytes in DN, as was evidenced by the upregulated expression of synaptopodin and podocin, higher expression of Bcl-2, and lower expression of Bax and cleaved caspase-3. The key findings of this study collectively indicate that the suppression of lncRNA PVT1 exerts inhibitory effects on podocyte damage and apoptosis via FOXA1 in DN, which is of clinical significance.

Risk of Second Primary Cancer in People with Non-melanoma Skin Cancer: A Nationwide Cohort Study.

PURPOSE: Previous western studies have found Caucasians with skin cancer, either melanoma or nonmelanoma skin cancer (NMSC), have an elevated risk of second primary cancer. Our objective was to assess the risk of second primary cancer in Taiwanese with NMSC. MATERIALS AND METHODS: By using data from Taiwan's National Health Insurance Research Database, we conducted a population-based cohort study to assess the risk of incident second primary cancer in Taiwanese affected by NMSC. RESULTS: We identified 505 subjects with NMSC and 2,020 matched controls. After adjustment for potential confounders including age, sex, urbanization, and Charlson Comorbidity Index, people who had NMSC had a 1.43-fold (95% confidence interval [CI], 1.05 to 1.96) risk for the development of second primary cancer as comparedwith control group. Menwith NMSC had a 2.99-fold (95% CI, 1.00 to 9.10) risk for second primary cancer involving the lip, oral cavity, and pharynx and a 3.51-fold (95% CI, 1.21 to 10.17) risk for second primary cancer involving the genitourinary organs when compared to the control group. By contrast, women with NMSC did not have an increased risk of second primary cancer. CONCLUSION: This study revealed Asians with NMSC have an increased risk of second primary cancer. Our findings can be a useful reference for health care for people diagnosed with NMSC.

Partial ablation of the pancreas of Sprague Dawley® rats by focused ultrasound reveals no significant adverse effects on glycometabolism function.

To investigate the safety of focused ultrasound (FUS) partial ablation on the pancreas of Sprague Dawley® (SD) rats by histopathological examination of the outcome and investigation of glycometabolism function changes after local ablation. A total of 135 healthy SD rats were randomly divided into three groups (n=45 of each): FUS ½ group, FUS » group, and control group. Levels of serum amylase was measured using the enzyme dynamics method, fasting blood glucose was measured by the glucose oxidase-peroxidase method, fasting serum insulin was measured by direct chemiluminescence assay, and an ELISA was used to measure fasting serum glucagon immediately after treatment, and at 2h, 3days, 1, 2, 3 and 4weeks, 3 and 6months after FUS ablation. Pancreatic tissue was stained with hematoxylin and eosin and the pathology of the ablation area was examined under an optical microscope; additionally, the expression of insulin and glucagon was investigated by immunohistochemistry. Compared with the control group, serum amylase and fasting blood glucose levels in the ablation groups rose significantly immediately after operation; fasting blood glucose, serum amylase, serum insulin and glucagon levels in the ablation groups were significantly different at 2h after treatment, and serum amylase levels in the ablation groups remained significantly different on day 3. Histological findings showed that the coagulation necrosis area gradually shrank, with formation of new blood vessels observed at week 3, and new ducts observable in the ablation area at the 3rd month after FUS ablation, but no formation of islets was observed. Expression of insulin and glucagon in the ablation groups were significantly higher than in the control group at 2h after FUS ablation. There were no significant adverse effects on the glycometabolic function of SD rats after FUS ablation, and the influence of FUS treatment on pancreatic functions were minimal.

Allergens, air pollutants, and childhood allergic diseases.

BACKGROUND: The synergistic effect of allergens and air pollutants on the risk of allergic diseases is unclear. OBJECTIVE: To evaluate the joint effect of outdoor pollutants and indoor allergens on the risk of allergic diseases. METHODS: We enrolled 2661 kindergarten children from the CEAS cohort. Data on allergic diseases and environmental exposure were collected. Skin prick tests were performed. Individual exposure to air pollution was estimated using a geographic information system with the mean concentration of air pollutants. Multiple logistic regression analysis was performed to estimate the association between air pollutants, allergen exposure and the risk of allergic diseases with adjustments for potential confounders. RESULTS: Overall, 12.6% of the children had asthma, 30.0% had allergic rhinitis (AR), and 14.4% had atopic dermatitis (AD). Mite sensitization significantly increased the risk of AD, AR, and asthma (OR (95%CI) 2.15 (1.53-3.03), 1.94 (1.46-2.58), and 2.31 (1.63-3.29), respectively). Exposure to PM10, PM(2.5), CO, and O(3) was associated with asthma (OR (95% CI) 1.39 (1.03-1.87), 1.45 (1.07-1.97), 1.36 (1.01-1.83), and 0.68 (0.51-0.92), respectively). PM(2.5) may have increased the risk of AR (OR (95% CI) 1.54 (1.03-2.32). Mite sensitization showed a synergistic effect with PM(2.5) on the development of asthma (p < 0.001). Moreover, mite allergens may modify the effect of air pollutants on allergic diseases. CONCLUSION: Dust mites and PM(2.5) play an important role on the risk of asthma and AR. Exposure to PM(2.5) and mite allergens had a synergistic effect on the development of asthma. Avoiding co-exposure to allergens and air pollutants is important.

Relationship between obesity, metabolic syndrome, and nonalcoholic fatty liver disease in the elderly agricultural and fishing population of Taiwan.

BACKGROUND: The purpose of this study was to explore the relationship between obesity, the metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD) in the elderly agricultural and fishing population of Taipei, Taiwan. METHODS: The study participants comprised 6,511 (3,971 male and 2,540 female) healthy elderly subjects voluntarily attending a teaching hospital for a physical check-up in 2010. Blood samples and real-time ultrasound-proven fatty liver sonography results were collected. RESULTS: The prevalence of NAFLD in this elderly population was 27.2%, including mild NAFLD (16.0%), moderate NAFLD (10.3%), and severe NAFLD (0.9%). The prevalence of moderate or severe NAFLD for metabolic syndrome proved to be substantially greater (P<0.0001, χ(2) test) for one or two metabolic factors. Using multinomial logistic regression analysis, age, sex, metabolic syndrome, and higher body mass index had a statistically significant association with mild NAFLD. Age, sex, metabolic syndrome, higher body mass index, and higher alanine aminotransferase were significantly related to moderate NAFLD. In addition, higher body mass index, higher uric acid, and higher alanine aminotransferase levels were significantly related to severe NAFLD. The sensitivity and specificity of body mass index and waist circumference as markers of NAFLD were estimated to be 81% and 84%, respectively, and 77% and 69%, respectively. CONCLUSION: The prevalence of mild or moderate NAFLD was related to obesity and metabolic syndrome. Higher body mass index was also related to severe NAFLD but not to metabolic syndrome. Targeting this population for control of obesity and improved metabolic function is important.

[Efficacy control observation on electroacupuncture with different waveforms combined with rehabilitation therapy for post-stroke shoulder subluxation].

OBJECTIVE: To compare the efficacy differences of electroacupuncture (EA) with intermittent wave, disperse-dense wave and continuous wave combined with rehabilitation therapy for post-stroke shoulder subluxation in order to provide clinical evidence for selection of electroacupuncture wave. METHODS: Seventy-five cases of shoulder subluxation were randomly divided into an intermittent wave (IW) group, a disperse-dense wave (DW) group and a continuous wave (CW) group, 25 cases in each one. Based on regular treatment including blood pressure and sugar control, EA and rehabilitation therapy were given in three groups. With EA at Jianqian (Extra), Taijian(Extra), Binao (LI 14), Jianzhong (Extra), Jianzhen (SI 9), Naoshu (SI 10), Jianwaishu (SI 14) and Bingfeng (SI 12), IW group was treated with intermittent wave with a frequency of 15 Hz, DW group was treated with disperse-dense wave with a frequency of 2 Hz/15 Hz and CW group was treated with continuous wave with a frequency of 15 Hz. The EA treatment was given for 20 min, once a day, six times a week and totally for 4 weeks. The Fugl-Meyer score and Barthel index score were used for assessment of function recovery before and after treatment respectively, also the efficacy of three groups was compared. RESULTS: The total effective rate was 96.0% (24/25) in the IW group, which was superior to 68.0% (17/ 25) in the DW group and 64.0% (16/25) in the CW group (both P < 0.05). After the treatment, Fugl-Meyer score and Barthel index score in the three groups were obviously improved (all P < 0.05), which was most significant in the IW group (all P < 0.01). CONCLUSION: Electroacupuncture with intermittent wave combined with rehabilitation therapy has superior effect to disperse-dense wave and continuous wave on the treatment of post-stroke shoulder subluxation, which could effectively improve shoulder subluxation and promote shoulder function recovery.