Assessment of Human Exposure to Traditional and Novel Organophosphate Esters via Multiple Personal Matrices.

Herein, 16 traditional and 13 novel organophosphate esters (OPEs) in skin wipes, personal PM2.5, sputum, and nails (fingernails and toenails) and 7 OPE metabolites in urine synchronously obtained from 64 college students were analyzed. Similar compositional profiles of the OPEs were found in skin wipes and nails and in personal PM2.5 and induced sputum. Significant correlations were observed between the concentrations of high-lipophilicity low-volatility OPEs in skin wipes and nails and between the concentrations of high-volatility low-lipophilicity OPEs in personal PM2.5 and sputum. These results imply that OPEs in fingernails and toenails may mainly come from external sources rather than internal exposure, and human nails and sputum can be used as indicators of human exposure to OPEs. A comparison between the daily exposure doses of the OPEs in personal PM2.5 and sputum shows that more volatile compounds may have higher inhalation bioavailability, which should be considered to improve the accuracy of inhalation exposure assessments. According to comprehensive external and internal exposure assessment, dermal absorption may be a more dominant pathway than inhalation, and skin wipes may be the best representative environmental matrix of human exposure to OPEs.

Br-Doped BiOCl Nanosheet Exposed (001) Facet: Surface Oxygen Vacancy and Directed Electron Flow Boosting the Photocatalytic Performance.

The defective BiOCl nanosheet exposed (001) facet with favorable photocatalytic performance was designed. The surface microstructure analysis and theoretical calculation certified the dominant exposed (001) facet and rich surface oxygen defects of Br--doped BiOCl (B-6) nanosheets. The energy level structure analysis indicates that the band gap can be narrowed and the light absorption range can be widened by introducing Br- to BiOCl, and the presence of defective energy levels increases the photogenerated carrier transfer efficiency. Moreover, the doping of Br- in BiOCl promotes the directional flow of electrons to the surface of B-6, which improves the photocatalytic performance of the sample. Thus, the Br--doped BiOCl can degrade 96.5% RhB within 6 min under visible-light irradiation with high apparent reaction rate constants of 0.51 min-1, exhibiting the strongest photocatalytic degradation performance. This work provides guidance for the preparation of Bi-based photocatalysts with excellent performance.

A Multivariable Model Based on Ultrasound Imaging Features of Gastrocnemius Muscle to Identify Patients With Sarcopenia.

OBJECTIVES: Low skeletal muscle mass, strength, or somatic function are used to diagnose sarcopenia; however, effective assessment methods are still lacking. Therefore, we evaluated the effectiveness of ultrasound in identifying patients with sarcopenia. METHODS: This study included 167 patients, 78 with sarcopenia and 89 healthy participants, from two hospitals. We evaluated clinical factors and five ultrasound imaging features, of which three ultrasound imaging features were used to create the model. In both the training and validation datasets, the sarcopenia detection performances of chosen ultrasonic characteristics and the constructed model were evaluated using receiver operating characteristic (ROC) curves. The predictive performance was evaluated by area under the ROC (AUROC), calibration, and decision curves. RESULTS: There were statistically significant differences in muscle thickness (MT) of gastrocnemius medialis muscle (GM), flaky myosteatosis echo (FE), pennation angle (PA), average shear wave velocity (SWV) in the relaxed state (RASWV), and average SWV in the passive stretched state (PASWV) between sarcopenic and normal subjects. PA, RASWV, and PASWV were effective predictors of sarcopenia. The AUROC (95% confidence interval) for these three parameters were 0.930 (0.882-0.978), 0.865 (0.791-0.940), and 0.849 (0.770-0.928), respectively, in the training set, and 0.873 (0.777-0.969), 0.936 (0.878-0.993), and 0.826 (0.716-0.935), respectively, in the validation set. The combined model had better detection power. Finally, the calibration curve showed that the combined model had good prediction accuracy. CONCLUSION: Our model can be used to identify sarcopenia in primary medical institutions, which is valuable for the early recognition and management of sarcopenia patients.

Bifunctional Hot Water Vapor Template-Mediated Synthesis of Nanostructured Polymeric Carbon Nitride for Efficient Hydrogen Evolution.

Regulating bulk polymeric carbon nitride (PCN) into nanostructured PCN has long been proven effective in enhancing its photocatalytic activity. However, simplifying the synthesis of nanostructured PCN remains a considerable challenge and has drawn widespread attention. This work reported the one-step green and sustainable synthesis of nanostructured PCN in the direct thermal polymerization of the guanidine thiocyanate precursor via the judicious introduction of hot water vapor's dual function as gas-bubble templates along with a green etching reagent. By optimizing the temperature of the water vapor and polymerization reaction time, the as-prepared nanostructured PCN exhibited a highly boosted visible-light-driven photocatalytic hydrogen evolution activity. The highest H2 evolution rate achieved was 4.81mmol∙g-1∙h-1, which is over four times larger than that of the bulk PCN (1.19 mmol∙g-1∙h-1) prepared only by thermal polymerization of the guanidine thiocyanate precursor without the assistance of bifunctional hot water vapor. The enhanced photocatalytic activity might be attributed to the enlarged BET specific surface area, increased active site quantity, and highly accelerated photo-excited charge-carrier transfer and separation. Moreover, the sustainability of this environmentally friendly hot water vapor dual-function mediated method was also shown to be versatile in preparing other nanostructured PCN photocatalysts derived from other precursors such as dicyandiamide and melamine. This work is expected to provide a novel pathway for exploring the rational design of nanostructured PCN for highly efficient solar energy conversion.

Quality indicators of colonoscopy care: a qualitative study from the perspectives of colonoscopy participants and nurses.

BACKGROUND: Quality of care in colonoscopy is closely related to colonoscopy participants and the nursing workforce in endoscopy-related settings. However, limited data are available on the evaluations and recommendations regarding quality indicators for nursing care by these two groups. Therefore, the aim of this study was to explore the standards and requirements of quality of care in colonoscopy from the perspectives of patients and nurses. METHOD: With a descriptive qualitative study, semi-structured interviews were conducted between November 2021 and January 2022 with colonoscopy participants (P = 11) and nursing workforce (N = 7) in the endoscopy unit in a tertiary hospital. The interviews were analyzed using a thematic analysis. RESULTS: Nine major themes emerged according to the structure, process, and outcome care quality model: workforce structure, quality requirements, unit facilities, nursing tools, nursing quality control systems, dynamic assessment and intervention, pre-examination care, strengthening education, and colonoscopy outcomes. CONCLUSION: The indicator of quality of colonoscopy care should be used to assess and improve current practices to ensure a more direct and sustained impact of colonoscopy care. This study highlights the importance of nurse managers valuing the opinions and reflections of people involved in colonoscopy to improve the quality of colonoscopy care.

A natural cuttlefish melanin nanoprobe for preoperative and intraoperative mapping of lymph nodes.

Lymphatic metastasis plays an important role in malignant tumor invasion. Efficient identification of sentinel lymph node (SLN) is extremely significant for designing therapeutic strategies and assessing prognosis. In this work, we developed a natural cuttlefish melanin nanoprobe for the preoperative and intraoperative evaluation of lymphatic metastasis. The cuttlefish melanin nanoparticle could improve the water-solubility and biocompatibility of the near-infrared-II (NIR-II) dye, and extend the retention time of small molecule dye. The NIR-II imaging results verified that the nanoparticles have a high accumulation, high sensitivity, and high signal-to-noise ratio in the lymphatic system. Moreover, the nanoparticles have obvious naked-eye identification potential due to their natural brownish-black color. Additionally, the nanoparticles can combine with Gd ions to achieve preoperative lymphatic magnetic resonance imaging (MRI). The results of this study provide a unique approach to effectively identify and accurately remove lymph nodes before operation and during surgery, exhibiting tremendous potential in clinical translation.

Hydrolytic transformation mechanism of tetracycline antibiotics: Reaction kinetics, products identification and determination in WWTPs.

Antibiotic residues and antibiotic resistance have been widely reported in aquatic environments. Hydrolysis of antibiotics is one of the important environmental processes. Here we investigated the hydrolytic transformation of four tetracycline antibiotics i.e. tetracycline (TC), chlortetracycline (CTC), oxytetracycline (OTC) and doxycycline (DC) under different environmental conditions, and determined their parents and transformation products in the wastewater treatment plants (WWTPs). The results showed that the hydrolysis of the four tetracyclines followed first-order reaction kinetics, and the acid-catalyzed hydrolysis rates were significantly lower than the base-catalyzed and neutral pH hydrolysis rates. The effect of temperature on tetracycline hydrolysis was quantified by Arrhenius equation, with Ea values ranged from 42.0 kJ mol-1 to 77.0 kJ mol-1 at pH 7.0. In total, nine, six, eight and nine transformation products at three different pH conditions were identified for TC, CTC, OTC and DC, respectively. The main hydrolysis pathways involved the epimerization/isomerization, and dehydration. According to the mass balance analysis, 4-epi-tetracycline and iso-chlortetracycline were the main hydrolytic products for TC and CTC, respectively. The 2 tetracyclines and 4 hydrolysis products were found in the sludge samples in two WWTPs, with concentrations from 15.8 ng/g to 1418 ng/g. Preliminary toxicity evaluation for the tetracyclines and their hydrolysis products showed that some hydrolysis products had higher predicted toxicity than their parent compounds. These results suggest that the hydrolysis products of tetracycline antibiotics should also be included in environmental monitoring and risk assessment.

Abnormal neurobehavior in fish early life stages after exposure to cyanobacterial exudates.

Cyanobacterial harmful algal blooms (cHABs) pose a risk to exposed aquatic and terrestrial species. Numerous studies have addressed effects of single toxins while much less attention has been devoted to mixtures of cHAB metabolites that are continually released by living cyanobacteria. Neuro-impairment associated with cHABs has been reported in fish, though the mechanism remains unclear. Here we exposed embryos of Sinocyclocheilus grahami, an endangered fish, to Microcystis aeruginosa exudates (MaE) to evaluate neurotoxicity and the toxicity mechanism(s). We found that MaE affected embryonic development by increasing malformation and mortality rates and decreasing the fertilization rate. MaE also inhibited fish neurobehavior including touch response, social frequency, swimming distance, and aggravated light-stimulation response. Neurobehavior suppression resulted from a decrease in excitatory neurotransmitters acetylcholine and dopamine, even though receptors increased. MaE also affected gene and protein expression of neurotransmitters, synthetic and/or degrading enzymes, and receptors. Our findings shed light on specific mechanisms by which MaE induces neurotoxicity in early life stages in fish and contributes to improvement of the conservation strategy for this species.

Trends of cervical cancer at global, regional, and national level: data from the Global Burden of Disease study 2019.

BACKGROUND: Cervical cancer is an important global health problem. In this study we aimed to analyze trends in cervical cancer at the global, regional, and national levels from 1990 to 2019, to inform health service decision-making. METHODS: Data on cervical cancer was extracted from the Global Burden of Disease study, 2019. Trends in cervical cancer burden were assessed based on estimated annual percentage change (EAPC) and age-standardized rate (ASR). RESULTS: Globally, decreasing trends were observed in incidence, death, and disability adjusted life years (DALYs) of cervical cancer from 1990 to 2019, with respective EAPCs of - 0.38 (95% confidence interval [CI]: - 0.41 to - 0.34), - 0.93 (95%CI: - 0.98 to - 0.88), and - 0.95 (95 CI%: - 1.00 to - 0.90). Meanwhile, decreasing trends were detected in most sociodemographic index (SDI) areas and geographic regions, particularly death and DALYs in Central Latin America, with respective EAPCs of - 2.61 (95% CI: - 2.76 to - 2.46) and - 2.48 (95% CI: - 2.63 to - 2.32); hhowever, a pronounced increasing trend in incidence occurred in East Asia (EAPC = 1.33; 95% CI: 1.12 to 1.55). At the national level, decreasing trends in cervical cancer were observed in most countries/territories, particularly DALYs in the Maldives (EAPC = - 5.06; 95% CI: - 5.40 to - 4.72), Whereas increasing trends were detected in Lesotho, Zimbabwe, and Bulgaria. CONCLUSIONS: Slowly decreasing trends in cervical cancer were detected worldwide from 1990 to 2019. Cervical cancer remains a substantial health problem for women globally, requiring more effective prevention and control strategies.

Biodegradation of typical azole fungicides in activated sludge under aerobic conditions.

Widespread use of azole fungicides and low removal efficiency in wastewater treatment plants (WWTPs) have led to the elevated concentration of azole fungicides in receiving environment. However, there was limited research about the removal mechanism of azole fungicides in the biological treatment of WWTPs. Imidazole fungicide climbazole and triazole fungicide fluconazole were selected to investigate the biodegradation mechanism of azole fungicides in activated sludge under aerobic conditions. Climbazole was found to be adsorbed to solid sludge and resulted in quick biodegradation. The degradation of climbazole in the aerobic activated sludge system was fitted well by the first-order kinetic model with a half-life of 5.3 days, while fluconazole tended to stay in liquid and had only about 30% of loss within 77 days incubation. Ten biotransformation products of climbazole were identified by high resolution mass spectrometry using suspect and non-target screening method. But no biodegradation products of fluconazole were identified due to its limited removal. The possible biodegradation pathways for climbazole were proposed based on the products identification and pathway prediction system, and involves oxidative dehalogenation, side chain oxidation and azole ring loss. The findings from this study suggest that it should be a concern for the persistence of fluconazole in the environment.

Modulating Antibody-Drug Conjugate Payload Metabolism by Conjugation Site and Linker Modification.

Previous investigations on antibody-drug conjugate (ADC) stability have focused on drug release by linker-deconjugation due to the relatively stable payloads such as maytansines. Recent development of ADCs has been focused on exploring technologies to produce homogeneous ADCs and new classes of payloads to expand the mechanisms of action of the delivered drugs. Certain new ADC payloads could undergo metabolism in circulation while attached to antibodies and thus affect ADC stability, pharmacokinetics, and efficacy and toxicity profiles. Herein, we investigate payload stability specifically and seek general guidelines to address payload metabolism and therefore increase the overall ADC stability. Investigation was performed on various payloads with different functionalities (e.g., PNU-159682 analog, tubulysin, cryptophycin, and taxoid) using different conjugation sites (HC-A118C, LC-K149C, and HC-A140C) on THIOMAB antibodies. We were able to reduce metabolism and inactivation of a broad range of payloads of THIOMAB antibody-drug conjugates by employing optimal conjugation sites (LC-K149C and HC-A140C). Additionally, further payload stability was achieved by optimizing the linkers. Coupling relatively stable sites with optimized linkers provided optimal stability and reduction of payloads metabolism in circulation in vivo.

High-level production of Arthrobacter aurescens CYC705 nitrilase in Escherichia coli for biosynthesis of iminodiacetic acid.

Nitrilase from Arthrobacter aurescens CYC705 can hydrolyze the iminodiacetonitrile to iminodiacetic acid (IDA) efficiently, and its high-level production in Escherichia coli has not been established. In the present work, the production of this nitrilase expressed in E. coli BL21(DE3) with a recombinant plasmid pET28a-cyc705 was optimized. Various culture conditions and process parameters including medium components and concentrations, inducer types and concentrations, inducing temperature and time were systematically examined in a shake flask. After optimization, the OD600 , nitrilase activity, and productivity were obviously improved and achieved to 40.91 ± 1.341, 98.12 ± 1.248 U/mL, and 2,230 ± 28.36 U L(-1)  H(-1) , respectively, about 2.1-, 30-, and 33-fold increases as compared with those in the primary medium. Furthermore, four different fermentation strategies were adopted to scale up cultivation of the recombinant E. coli BL21(DE3)/pET28a-cyc705 in a 3.7-L fermenter. Substituting the peanut powder with fish peptone and accompanying with 1.0% glycerol feeding could significantly reduce the bubble production and shorten the fermentation time, which resulted in a nitrilase productivity of 4,653 ± 38.16 U L(-1) H(-1) that was about two times higher than that in a shake flask. The high-level production of A. aurescens CYC705 nitrilase established in this study will meet the need of industrial biosynthesis of IDA.

Tea consumption and mortality of all cancers, CVD and all causes: a meta-analysis of eighteen prospective cohort studies.

Epidemiological studies have demonstrated inconsistent associations between tea consumption and mortality of all cancers, CVD and all causes. To obtain quantitative overall estimates, we conducted a dose-response meta-analysis of prospective cohort studies. A literature search in PubMed and Embase up to April 2015 was conducted for all relevant papers published. Random-effects models were used to calculate pooled relative risks (RR) with 95 % CI. In eighteen prospective studies, there were 12 221, 11 306 and 55 528 deaths from all cancers, CVD and all causes, respectively. For all cancer mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 1·06 (95 % CI 0·98, 1·15) and 0·79 (95 % CI 0·65, 0·97), respectively. For CVD mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·67 (95 % CI 0·46, 0·96) and 0·88 (95 % CI 0·77, 1·01), respectively. For all-cause mortality, the summary RR for the highest v. lowest category of green tea and black tea consumption were 0·80 (95 % CI 0·68, 0·93) and 0·90 (95 % CI 0·83, 0·98), respectively. The dose-response analysis indicated that one cup per d increment of green tea consumption was associated with 5 % lower risk of CVD mortality and with 4 % lower risk of all-cause mortality. Green tea consumption was significantly inversely associated with CVD and all-cause mortality, whereas black tea consumption was significantly inversely associated with all cancer and all-cause mortality.

Strong p-d Orbital Hybridization on Bismuth Nanosheets for High Performing CO2 Electroreduction.

Single-atom alloys (SAAs) show great potential for a variety of electrocatalytic reactions. However, the atomic orbital hybridization effect of SAAs on the electrochemical reactions is unclear yet. Herein, the in situ confinement of vanadium/molybdenum/tungsten atoms on bismuth nanosheet is shown to create SAAs with rich grain boundaries, respectively. With the detailed analysis of microstructure and composition, the strong p-d orbital hybridization between bismuth and vanadium enables the exceptional electrocatalytic performance for carbon dioxide (CO2 ) reduction with the Faradaic efficiency nearly 100% for C1 products in a wide potential range from -0.6 to -1.4 V, and a long-term electrolysis stability for 90 h. In-depth in situ investigations with theoretical computations reveal that the electron delocalization toward vanadium atoms via the p-d orbital hybridization evokes the bismuth active centers for efficient CO2 activation via the σ-donation of O-to-Bi, thus reduces protonation energy barriers for formate production. With such fundamental understanding, SAA electrocatalyst is employed to fabricated the solar-driven electrolytic cell of CO2 reduction and 5-hydroxymethylfurfural oxidation, achieving an outstanding 2,5-furandicarboxylic acid yield of 90.5%. This study demonstrates a feasible strategy to rationally design advanced SAA electrocatalysts via the basic principles of p-d orbital hybridization.

Automatic IMRT treatment planning through fluence prediction and plan fine-tuning for nasopharyngeal carcinoma.

BACKGROUND: At present, the implementation of intensity-modulated radiation therapy (IMRT) treatment planning for geometrically complex nasopharyngeal carcinoma (NPC) through manual trial-and-error fashion presents challenges to the improvement of planning efficiency and the obtaining of high-consistency plan quality. This paper aims to propose an automatic IMRT plan generation method through fluence prediction and further plan fine-tuning for patients with NPC and evaluates the planning efficiency and plan quality. METHODS: A total of 38 patients with NPC treated with nine-beam IMRT were enrolled in this study and automatically re-planned with the proposed method. A trained deep learning model was employed to generate static field fluence maps for each patient with 3D computed tomography images and structure contours as input. Automatic IMRT treatment planning was achieved by using its generated dose with slight tightening for further plan fine-tuning. Lastly, the plan quality was compared between automatic plans and clinical plans. RESULTS: The average time for automatic plan generation was less than 4 min, including fluence maps prediction with a python script and automated plan tuning with a C# script. Compared with clinical plans, automatic plans showed better conformity and homogeneity for planning target volumes (PTVs) except for the conformity of PTV-1. Meanwhile, the dosimetric metrics for most organs at risk (OARs) were ameliorated in the automatic plan, especially Dmax of the brainstem and spinal cord, and Dmean of the left and right parotid glands significantly decreased (P < 0.05). CONCLUSION: We have successfully implemented an automatic IMRT plan generation method for patients with NPC. This method shows high planning efficiency and comparable or superior plan quality than clinical plans. The qualitative results before and after the plan fine-tuning indicates that further optimization using dose objectives generated by predicted fluence maps is crucial to obtain high-quality automatic plans.

CD44-targeted melanin-based nanoplatform for alleviation of ischemia/reperfusion-induced acute kidney injury.

Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a serious kidney disease with high morbidity and mortality. However, there is no effective clinical treatment strategy. Herein, we developed a CD44 targeting nanoplatform based on HA-assembled melanin NPs covalently coupled with dexamethasone for I/R-induced AKI therapy by alleviating oxidative/inflammatory- induced damage. The constructed HA-MNP-DXM NPs had good dispersion, stability, and broad-spectrum scavenging capabilities against multiple reactive free radicals. Moreover, the NPs could be efficiently internalized and exhibited antioxidative, anti-inflammatory, and antiapoptotic effects in CoCl2-stimulated renal tubular epithelial NRK-52E cells. Furthermore, the I/R-induced AKI murine model was established to evaluate the in vivo performance of NPs. The results suggested the NPs could specifically target impaired kidneys upon intravenous administration according to NIR-II fluorescence imaging and showed high biosafety. Importantly, the NPs could improve renal function, alleviate oxidative stress and inflammatory reactions, inhibit apoptosis of tubular cells, and restore mitochondrial structure and function, exhibiting excellent therapeutic effects. Further therapeutic mechanism indicated the NPs maintained the cellular/mitochondrial redox balance by modulating the Nrf2 and HO-1 expression. Therefore, the NPs can be a promising therapeutic candidate for the treatment of I/R-induced AKI.

Acute exposure to tris(2,4-di-tert-butylphenyl)phosphate elicits cardiotoxicity in zebrafish (Danio rerio) larvae via inducing ferroptosis.

Tris(2,4-di-tert-butylphenyl)phosphate (AO168 =O), a novel organophosphate ester, is prevalent and abundant in the environment, posing great exposure risks to ecological and public health. Nevertheless, the toxicological effects of AO168 =O remain entirely unknown to date. The results in this study indicated that acute exposure to AO168 =O at 10 and 100 µg/L for 5 days obviously impaired cardiac morphology and function of zebrafish larvae, as proofed by decreased heartbeat, stroke volume, and cardiac output and the occurrence of pericardial edema and ventricular hypertrophy. Transcriptomics, polymerase chain reaction, and molecular docking revealed that the strong interaction of AO168 =O and transferrin receptor 1 activated the transportation of ferric iron into intracellular environment. The release of free ferrous ion to cytoplasmic iron pool also contributed to the iron overload in heart region, thus inducing ferroptosis in larvae via generation of excessive reactive oxygen species, glutathione peroxidase 4 inhibition, glutathione depletion and lipid peroxidation. Ferroptosis inhibitor (Fer-1) co-exposure effectively relieved the cardiac dysfunctions of zebrafish, verifying the dominant role of ferroptosis in the cardiotoxicity caused by AO168 =O. This research firstly reported the adverse impact and associated mechanisms of AO168 =O in cardiomyogenesis of vertebrates, underlining the urgency of concerning the health risks of AO168 =O.

New Insights into Identification, Distribution, and Health Benefits of Polyamines and Their Derivatives.

Polyamines and their derivatives are ubiquitously present in free or conjugated forms in various foods from animal, plant, and microbial origins. The current knowledge of free polyamines in foods and their contents is readily available; furthermore, conjugated polyamines generate considerable recent research interest due to their potential health benefits. The structural diversity of conjugated polyamines results in challenging their qualitative and quantitative analysis in food. Herein, we review and summarize the knowledge published on polyamines and their derivatives in foods, including their identification, sources, quantities, and health benefits. Particularly, facing the inherent challenges of isomer identification in conjugated polyamines, this paper provides a comprehensive overview of conjugated polyamines' structural characteristics, including the cleavage patterns and characteristic ion fragments of MS/MS for isomer identification. Free polyamines are present in all types of food, while conjugated polyamines are limited to plant-derived foods. Spermidine is renowned for antiaging properties, acclaimed as antiaging vitamins. Conjugated polyamines highlight their anti-inflammatory properties and have emerged as the mainstream drugs for antiprostatitis. This paper will likely help us gain better insight into polyamines and their derivatives to further develop functional foods and personalized nutraceuticals.

Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast.

Tumor necrosis factor-alpha (TNFα) plays a crucial role in inflammatory diseases such as rheumatoid arthritis and postmenopausal osteoporosis. Recently, it has been demonstrated that hydrogen gas, known as a novel antioxidant, can exert therapeutic anti-inflammatory effect in many diseases. In this study, we investigated the effect of treatment with hydrogen molecule (H(2)) on TNFα-induced cell injury in osteoblast. The osteoblasts isolated from neonatal rat calvariae were cultured. It was found that TNFα suppressed cell viability, induced cell apoptosis, suppressed Runx2 mRNA expression, and inhibited alkaline phosphatase activity, which was reversed by co-incubation with H(2). Incubation with TNFα-enhanced intracellular reactive oxygen species (ROS) formation and malondialdehyde production increased NADPH oxidase activity, impaired mitochondrial function marked by increased mitochondrial ROS formation and decreased mitochondrial membrane potential and ATP synthesis, and suppressed activities of antioxidant enzymes including SOD and catalase, which were restored by co-incubation with H(2). Treatment with H(2) inhibited TNFα-induced activation of NFκB pathway. In addition, treatment with H(2) inhibited TNFα-induced nitric oxide (NO) formation through inhibiting iNOS activity. Treatment with H(2) inhibited TNFα-induced IL-6 and ICAM-1 mRNA expression. In conclusion, treatment with H(2) alleviates TNFα-induced cell injury in osteoblast through abating oxidative stress, preserving mitochondrial function, suppressing inflammation, and enhancing NO bioavailability.

Generating Retinas through Guided Pluripotent Stem Cell Differentiation and Direct Somatic Cell Reprogramming.

Retinal degeneration diseases affect millions of people worldwide but are among the most difficult eye diseases to cure. Studying the mechanisms and developing new therapies for these blinding diseases requires researchers to have access to many retinal cells. In recent years there has been substantial advances in the field of biotechnology in generating retinal cells and even tissues in vitro, either through programmed sequential stem cell differentiation or direct somatic cell lineage reprogramming. The resemblance of these in vitro-generated retinal cells to native cells has been increasingly utilized by researchers. With the help of these in vitro retinal models, we now have a better understanding of human retinas and retinal diseases. Furthermore, these in vitro-generated retinal cells can be used as donor cells which solves a major hurdle in the development of cell replacement therapy for retinal degeneration diseases, while providing a promising option for patients suffering from these diseases. In this review, we summarize the development of pluripotent stem cell-to-retinal cell differentiation methods, the recent advances in generating retinal cells through direct somatic cell reprogramming, and the translational applications of retinal cells generated in vitro. Finally, we discuss the limitations of the current protocols and possible future directions for improvement.