Pharmacological approaches for targeting lysosomes to induce ferroptotic cell death in cancer.

Lysosomes are crucial organelles responsible for the degradation of cytosolic materials and bulky organelles, thereby facilitating nutrient recycling and cell survival. However, lysosome also acts as an executioner of cell death, including ferroptosis, a distinctive form of regulated cell death that hinges on iron-dependent phospholipid peroxidation. The initiation of ferroptosis necessitates three key components: substrates (membrane phospholipids enriched with polyunsaturated fatty acids), triggers (redox-active irons), and compromised defence mechanisms (GPX4-dependent and -independent antioxidant systems). Notably, iron assumes a pivotal role in ferroptotic cell death, particularly in the context of cancer, where iron and oncogenic signaling pathways reciprocally reinforce each other. Given the lysosomes' central role in iron metabolism, various strategies have been devised to harness lysosome-mediated iron metabolism to induce ferroptosis. These include the re-mobilization of iron from intracellular storage sites such as ferritin complex and mitochondria through ferritinophagy and mitophagy, respectively. Additionally, transcriptional regulation of lysosomal and autophagy genes by TFEB enhances lysosomal function. Moreover, the induction of lysosomal iron overload can lead to lysosomal membrane permeabilization and subsequent cell death. Extensive screening and individually studies have explored pharmacological interventions using clinically available drugs and phytochemical agents. Furthermore, a drug delivery system involving ferritin-coated nanoparticles has been specifically tailored to target cancer cells overexpressing TFRC. With the rapid advancements in understandings the mechanistic underpinnings of ferroptosis and iron metabolism, it is increasingly evident that lysosomes represent a promising target for inducing ferroptosis and combating cancer.

Influence of continuous light and benzene exposure on erythrocyte parameters and expression of miRNA-144/451 in mice / 中国职业医学

@#Abstract: Objective To explore the effects of continuous light and benzene exposure on peripheral blood erythrocyte - Methods parameters and expression of miR 144/451 in the bone marrow of mice. This was a 2×2 factorial design. Photoperiod ， ， factor was set as normal and continuous light levels and mice were treated for 12 hours/12 hours light/dark or 24 hours light - respectively. The benzene exposure factor was set as non exposure and exposure levels. Mice were exposed to benzene by static 3 ， inhalation with a mass concentration of 0.0 and 32.5 mg/m for three hours per day five days per week for a total of four weeks. ， ， Specific pathogen free male C57BL/6 J mice were randomly divided into negative control group simple continuous light group - - ， ， simple benzene exposure group and combined exposure group with 12 mice per group. After benzene exposure peripheral ， blood was collected for the detection of erythrocyte parameters in four periods. After the mice were sacrificed the expression of - - - - miR 451a and miR 144 5p was detected by real time fluorescence quantitative polymerase chain reaction in bone marrow Results （ ）， ， tissues. The hematocrit volume HCT mean corpuscular volume mean corpuscular hemoglobin concentration （ ） - MCHC and mean corpuscular hemoglobin in peripheral blood and the relative expression of miR 451a in bone marrow tissue （ P< ） ， were statistically significant only in mice with benzene exposure all 0.05 . Among them the MCHC of benzene exposed （P< ）， （ P< ） - mice increased 0.05 but the other four indexes decreased all 0.05 compared with non benzene exposed mice. In thenegative control group the change of red blood cells count hemoglobin level and HCT in peripheral blood were rhythmical all P < ） ， （ P > ） rhythmical 0.05 . However the indexes above were out of rhythm all rhythmical 0.05 in the simple continuous light group and the - （ P > combined exposure group. The change of hemoglobin level and HCT of peripheral blood were also out of rhythm all rhythmical ） - - 0.05 in the simple benzene exposure group. The relative expression of miR 451a in bone marrow tissues of negative control （ P < ）， - group and simple continuous light group was rhythmical all rhythmical 0.05 while the relative expression of miR 451a in simple - - （ P > ）Conclusion benzene exposure group and combined exposure group was out of rhythm all rhythmical 0.05 . Benzene exposure ， induced changes in erythrocyte parameters of mice are independent effect and its mechanism may be related to the rhythmic - ， expression disorder of miR 451a in bone marrow tissues. Continuous light exposure benzene exposure and their interactions can ， interfere with the circadian rhythm of erythrocyte parameters such as red blood cell count hemoglobin and HCT to some extent.

ACSL4 is a predictive biomarker of sorafenib sensitivity in hepatocellular carcinoma.

Sorafenib is the first-line treatment of advanced hepatocellular carcinoma (HCC). However, there is a lack of validated biomarkers to predict sorafenib sensitivity. In this study we investigated the role of ACSL4, a positive-activating enzyme of ferroptosis, in sorafenib-induced cell death and HCC patient outcome. We showed that ACSL4 protein expression was negatively associated with IC50 values of sorafenib in a panel of HCC cell lines (R = -0.952, P < 0.001). Knockdown of ACSL4 expression by specific siRNA/sgRNA significantly attenuated sorafenib-induced lipid peroxidation and ferroptosis in Huh7 cells, and also rescued sorafenib-induced inhibition of xenograft tumor growth in vivo. We selected 29 HCC patients with surgery as primary treatment and sorafenib as postoperative adjunct therapy from a hospital-based cohort. A high proportion (66.7%) of HCC patients who had complete or partial responses to sorafenib treatment (according to the revised RECIST guideline) had higher ACSL4 expression in the pretreated HCC tissues, compared with those who had stable or progressed tumor growth (23.5%, P = 0.029). Since ACSL4 expression was independent of sorafenib treatment, it could serve as a useful predictive biomarker. Taken together, this study demonstrates that ACSL4 is essential for sorafenib-induced ferroptosis and useful for predicting sorafenib sensitivity in HCC. This study may have important translational impacts in precise treatment of HCC.

Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma.

Sorafenib is the first-line medication for advanced hepatocellular carcinoma (HCC), but it can only extend limited survival. It is imperative to find a combination strategy to increase sorafenib efficacy. Artesunate is such a preferred candidate, because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms. In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms. We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7, SNU-449, and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice. The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic. Compared with the treatment with artesunate or sorafenib alone, combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis, which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate, but not by inhibitors of other types of cell death (z-VAD, necrostatin-1 and belnacasan). In Huh7 cells, we demonstrated that the combined treatment induced oxidative stress and lysosome-mediated ferritinophagy, two essential aspects of ferroptosis. Sorafenib at low dose mainly caused oxidative stress through mitochondrial impairments and SLC7A11-invovled glutathione depletion. Artesunate-induced lysosome activation synergized with sorafenib-mediated pro-oxidative effects by promoting sequential reactions including lysosomal cathepsin B/L activation, ferritin degradation, lipid peroxidation, and consequent ferroptosis. Taken together, artesunate could be repurposed to sensitize sorafenib in HCC treatment. The combined treatment can be easily translated into clinical applications.

Quercetin Induces Apoptosis via Downregulation of Vascular Endothelial Growth Factor/Akt Signaling Pathway in Acute Myeloid Leukemia Cells.

Acute myeloid leukemia (AML) is an aggressive haematological malignancy characterized by highly proliferative accumulation of immature and dysfunctional myeloid cells. Quercetin (Qu), one kind of flavonoid, exhibits anti-cancer property in multiple types of solid tumor, but its effect on acute myeloid leukemia is less studied, and the underlying mechanisms still largely unknown. This study aimed to explore the specific target and potential mechanism of quercetin-induced cell death in AML. First, we found that quercetin induces cell death in the form of apoptosis, which was caspase dependent. Second, we found that quercetin-induced apoptosis depends on the decrease of mitochondria membrane potential (MMP) and Bcl-2 proteins. With quantitative chemical proteomics, we observed the downregulation of VEGFR2 and PI3K/Akt signaling in quercetin-treated cells. Consistently, cell studies also identified that VEGFR2 and PI3K/Akt signaling pathways are involved in the action of quercetin on mitochondria and Bcl-2 proteins. The decrease of MMP and cell death could be rescued when PI3K/Akt signaling is activated, suggesting that VEGFR2 and PI3K/Akt exert as upstream regulators for quercetin effect on apoptosis induction in AML cells. In conclusion, our findings from this study provide convincing evidence that quercetin induces cell death via downregulation of VEGF/Akt signaling pathways and mitochondria-mediated apoptosis in AML cells.

Inactive bowel movement and stroke are associated with increased risks of mild cognitive impairment among community-living Singapore elderly.

Mild cognitive impairment (MCI), as a preclinical phase of dementia, provides an invaluable time window for intervention. Besides several proposed modifiable risk factors, the associations of MCI with dietary habits and bowel movement are not well clarified. We thus conducted a cross-sectional study of community-living Singapore elderly and focused on the relationship of clinically diagnosed MCI with dietary habits and bowel movement frequencies. The multiple logistic regression results showed that frequent (≥4 days per week) fruit consumption (P = 0.004), active (≥4 days per week) bowel movement within 10 minutes (P = 0.027), and years of schooling were negatively associated with MCI occurrence. In contrast, medical comorbidities including hypertension, stroke, and cataract/glaucoma were found to be risk factors. Furthermore, a Bayesian network model of causal inference detected five hypothesized causal-association paths leading to MCI, namely bowel movement, stroke, years of schooling via fruit consumption, hypertension via stroke and hypertension via cataract/glaucoma. The combination of the two direct factors (inactive bowel movement and stroke) reached a maximum conditional probability of 60.00% for MCI occurrence. Taken together, this study was the first to link bowel movement with MCI occurrence. In addition, it suggested five modifiable hypothesized causal-association paths to MCI.

Ursolic acid potentiated oxaliplatin to induce apoptosis in colorectal cancer RKO cells.

Ursolic acid (UA) is found in multiple anticancer herbs and has shown anticancer effects in colorectal cancer (CRC) cells. The present study aimed to observe the effects of a combination of UA and oxaliplatin (Oxa), a frequently used chemotherapeutic drug in CRC, on human CRC RKO cells. The results showed that UA and Oxa synergistically inhibited the proliferation of RKO cells. A combination of UA and Oxa induced apoptosis in RKO cells and increased the activities of caspase-3, caspase-8, and caspase-9. Z-VAD-FMK, a caspase inhibitor, significantly antagonized UA- and Oxa-activated caspase-3, caspase-8, and caspase-9 and induced apoptosis. In addition, UA and Oxa downregulated the expression of X-linked inhibitor of apoptosis (XIAP) and Survivin in RKO cells. These observations suggested that a combination of UA and Oxa elicited synergistically anticancer effects in RKO cells and provided new evidence for potential application of UA and Oxa for CRC treatment.

Performance of polyvinyl pyrrolidone-isatis root antibacterial wound dressings produced in situ by handheld electrospinner.

Antibacterial dressings are an increasingly important tool for the prevention and management of wound infections, particularly in light of concerns surrounding conventional drug-resistant antibiotics. Handheld electrospinning devices provide opportunities for the rapid application of antibacterial dressing materials to wounds, but spinning formulations need to be compatible with live biological surfaces. We report the development of a new antibacterial formulation compatible with handheld electrospinning, and its manufacture directly on a wound site. Nanofibrous dressing mats were produced from polyvinyl pyrrolidone (PVP) containing isatis root (Indigowoad root or Ban-Lan-Gen), a traditional Chinese medicine, commonly used for the treatment of infectious disease. The resulting wound dressing mats of PVP/isatis root exhibited well-defined fibrous structures and excellent surface wetting, and permeability characteristics. The presence of isatis root conferred antibacterial activity against gram negative and gram positive strains. Moreover, in a Kunming mouse skin injury model, direct electrospinning of PVP/isatis root formulations on to wound sites produced near complete wound closure after 11 days and epidermal repair in histological studies.

In Situ Electrospun Zein/Thyme Essential Oil-Based Membranes as an Effective Antibacterial Wound Dressing.

Wound dressings are an important element in promoting the healing of wounds. Electrospun fibrous materials have a highly porous structure and controllable antibacterial activity and are therefore popular as potential wound dressings. However, electrospun fibrous wound dressings are usually conveniently packaged for immediate use but cannot accommodate irregularly shaped wounds, and their misuse runs the risk of causing a secondary injury to the wound. To overcome these issues, in situ electrospun zein/thyme essential oil (TEO) nanofibrous membranes are proposed as a potential type of wound dressing and applied for wound management through an in situ electrospinning process, which uses a portable electrospinning device. The as-spun zein/TEO membranes show high gas permeability up to 154 ± 20.9 m2/s and superhydrophilicity with a 0° contact angle. With the addition of TEO, good antibacterial effects are also imparted onto the membrane to prevent infection. Moreover, the in situ electrospinning can directly deposit the zein/TEO membranes onto the site of the wound to accommodate the shape of the wound with increased convenience and perceived comfort. Experiments carried out on mice suggest that the in situ electrospun zein/TEO membrane greatly promotes the wound healing process within 11 days. The study results, therefore, suggest that wound dressings in the form of in situ electrospun zein/TEO membranes can be used to facilitate wound healing.

Corrigendum: Quercetin Induces Apoptosis Via Downregulation of VEGF/Akt Signaling Pathway in Acute Myeloid Leukemia Cells.

[This corrects the article DOI: 10.3389/fphar.2020.534171.].

Scutellarein suppresses Aß-induced memory impairment via inhibition of the NF-κB pathway in vivo and in vitro.

The flavonoid compound scutellarin (Scu) is a traditional Chinese medicine used to treat a variety of diseases; however, the use of scutellarein (Scue), the hydrolysate of Scu, and its mechanisms of action in Alzheimer's disease (AD) have not been fully elucidated. In the present study, the effects of Scue on amyloid ß (Aß)-induced AD-like pathology were investigated. An in vitro model of inflammation and an aged rat model were used to confirm the effects of Scue. In vitro MTT assays and flow cytometry were used to assess the effects of Scue on cell viability and apoptosis, respectively. A Morris water maze was used to evaluate spatial learning and memory, and the levels of Aß deposition, superoxide dismutase, malondialdehyde, apoptosis, neuro-inflammatory factors and nuclear factor-κB (NF-κB) activation in hippocampal tissues in vivo were measured to determine the effect of Scue in AD. Scue may be protective, as it decreased the apoptosis of hippocampal cells in vitro, inhibited Aß-induced cognitive impairment, suppressed hippocampal neuro-inflammation and suppressed activation of NF-κB in vivo. Therefore, Scue may be a useful agent for the treatment of Aß-associated pathology in the central nervous system through inhibition of the protein kinase B/NF-κB signaling pathway and thus, future studies are required to investigate the efficacy of Scue in patients with AD.

Histone deacetylases up-regulate C/EBPα expression through reduction of miR-124-3p and miR-25 in hepatocellular carcinoma.

BACKGROUND: CCAAT enhancer binding protein α (C/EBPα), as an important transcription factor involved in cell proliferation, differentiation and metabolism, was up-regulated in primary hepatocellular carcinoma (HCC) and predicted poorer prognosis. In this study, we explored how histone deacetylases (HDACs) up-regulated C/EBPα in HCC. METHODS: The protein expressions of HDAC1, HDAC2 were associated with C/EBPα by immunohistochemistry staining in a HCC tissue microarray. HCC cells were then treated with HDAC inhibitors or siRNAs to determine the roles of miR-124-3p and miR-25 in the regulation of C/EBPα mRNA expression. RESULTS: Both HDAC1 and HDAC2 proteins were significantly associated with C/EBPα. Inhibition of HDAC by either pharmacological inhibitors or siRNAs decreased C/EBPα mRNA expression in dose-dependent manners in HCC cells. HDAC inhibitors reduced C/EBPα mRNA stability as shown by pmiRGLO luciferase reporter assays. HDAC inhibition consistently induced miR-124-3p and miR-25 expression. Conversely, blockage of miR-124-3p and/or miR-25 by treatment with specific synthetic inhibitors abolished C/EBPα reduction. More importantly, C/EBPα mRNA stability could be rescued by site-directed mutations of miR-124-3p or miR-25 recognition sites in the C/EBPα 3'UTR sequence. In summary, HDAC may up-regulate C/EBPα expression through miR-124-3p and miR-25 in HCC.

Comparative anatomy of the mouse and human ankle joint using Micro-CT: Utility of a mouse model to study human ankle sprains.

The use of mouse models as a tool to study ankle sprain requires a basic understanding of the similarities and differences between human and mouse ankle joint anatomy. However, few studies have been conducted that address the merits and drawbacks of these differences in the functioning of joints. Twenty hindfoot specimens were obtained from 10 male C57BL/6J mice and scanned using micro-CT. The foot and ankle skeletal structures were reconstructed in three dimensions. Morphological parameters were then measured using a plane projection method and normalized data were compared with those of human ankles. There was no significant difference in the malleolar width, maximal tibial thickness, tibial arc length, trochlea tali arc length or trochlea tali width of the mouse specimens compared with the human model. However, a groove was observed on the talar dome in the mouse specimens which was not observed in humans, the talar dome being more symmetric. The mouse ankle was to a large extent able to mimic the mechanism of a human ankle and so a mouse model could be appropriate for expanding our understanding of ankle biomechanics in general. However, the structural differences in the talar dome in the mouse and human should not be ignored. Although there are some differences in the mouse and human ankle that cannot be ignored, compared to other animals, the human ankle is more similar to that of the mouse.

Preventive impacts of PAS-Na on the slow growth and activated inflammatory responses in Mn-exposed rats.

BACKGROUND: Sodium para-aminosalicylic acid (PAS-Na), an anti-tuberculosis drug, has been demonstrated its function in facilitating the Mn elimination in manganism patients and Mn-exposed models in vivo and improving the symptoms of Mn poisoning. But whether it can improve the growth retardation and inflammatory responses induced by Mn have not been reported. OBJECTIVES: This study was designed to investigate the preventive effects of PAS-Na on the development of retardation and inflammatory responses in Mn-exposed rats. METHODS: Male Sprague Dawley (SD) rats (8 weeks old, weighing 180 ± 20 g) were randomly divided into normal control group and Mn-exposed group in the 4 weeks experiment observation and normal control group, Mn-exposed group, PAS-Na preventive group and PAS-Na control group in the 8 weeks experiment observation. The Mn-exposed group received an intraperitoneal injection (i.p.) of 15 mg/kg MnCl2 and the normal control group i.p. physiological Saline in the same volume once a day for 4 or 8 weeks, 5 days per week. The PAS-Na preventive group i.p. 15 mg/kg MnCl2 along with back subcutaneous (s.c.) injection of 240 mg/kg PAS-Na once a day for 8 weeks, 5 days per week. PAS-Na control group received s.c. injection of 240 mg/kg PAS-Na along with i.p. injection of saline once daily. The body weight was determined once a week until the end of the experiment. The manganese contents in the blood were detected by graphite furnace atomic absorption spectrometry. The inflammatory factor levels (TNF-α, IL-1ß, IL-6, and PGE2) in the blood were detected by using enzyme-linked immunosorbent assay (Elisa) and each organ taking from rats were weighed and recorded. RESULTS: Mn exposure significantly suppressed the growth in rats and increased heart, liver, spleen and kidney coefficients as compared with the control group. The whole blood Mn level and serum levels of IL-1ß, IL-6, PGE2, and TNF-α in sub-chronic Mn-exposure group were markedly higher than those in the control group. However, preventive treatment with PAS-Na obviously reduced the whole blood Mn level, the spleen and liver coefficients of the Mn-exposed rats. And serum levels of IL-1ß and TNF-α were significantly reduced by 33.9% and 14.7% respectively in PAS-Na prevention group. CONCLUSIONS: PAS-Na could improve the growth retardation and alleviate inflammatory responses in Mn-exposed rats.

Traditional Chinese medicine formulation Yanggan Jiedu Sanjie inhibits TGF-ß1-induced epithelial-mesenchymal transition and metastatic potential in human hepatocarcinoma Bel-7402 cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a vital process in cancer progression and metastasis. Yanggan Jiedu Sanjie (YGJDSJ) is Traditional Chinese Medicine formulation for liver cancer treatment. In the present study, we evaluated the effects of YGJDSJ on TGF-ß1-induced EMT in hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were treated with TGF-ß1 and YGJDSJ. EMT was identified by morphological changes and expression of marker proteins. Cell morphology was observed under a microscope. Protein expression and phosphorylation was detected by western blotting. Cell migration was measured by the scratch assay. Cell adhesion and invasion was detected by a commercial kit. RESULTS: YGJDSJ reversed TGF-ß1-induced morphological changes, as well as the expression of the EMT markers E-cadherin and N-cadherin in Bel-7402 cells. YGJDSJ also inhibited TGF-ß1 up-regulated Smad3 phosphorylation and Snail expression in Bel-7402 cells. Moreover, YGJDSJ inhibited TGF-ß1-induced cell adhesion, migration and invasion in Bel-7402 cells. CONCLUSIONS: YGJDSJ inhibited TGF-ß1-induced EMT and mediated metastatic potential of Bel-7402 cells, which may be related to down-regulation of Smad3 phosphorylation and Snail expression. The present study provides a new basis for application of this herbal formula for prevention of liver cancer metastasis.

Midlife Long-Hour Working and Later-life Social Engagement Are Associated with Reduced Risks of Mild Cognitive Impairment among Community-Living Singapore Elderly.

Mild cognitive impairment (MCI), as a transitional stage between normal aging and dementia, causes cognitive decline among one-fifth of elders aged 65 years and older. Health-related lifestyles (HRL) are generally regarded as modifiable influencing factors of cognitive decline. The present study investigated how HRLs at two different life stages (one at midlife and the other at later life) affect MCI occurrence among community-dwelling elders, as part of the Diet and Healthy Aging (DaHA) study in Singapore. The frequencies of major HRL activities were compared between 119 clinical diagnosed MCI cases and 632 normal aging controls with functional cognition. The associations of HRLs with MCI were determined by multivariate logistic regression analysis and adjusted according to known factors including age, childhood education, and major chronic diseases (hypertension, stroke, diabetes, and cataracts or glaucoma). Long-hour working in midlife (adjusted OR = 0.418 with 95% CI 0.215-0.812) and social engagement in later-life (adjusted OR = 0.532 with 95% CI 0.329-0.859) were associated with reduced risks of MCI, respectively. It is important to note that those elders who had both midlife long-hour working and later-life social engagement were related to the lowest risk of MCI (adjusted OR = 0.285 with 95% CI 0.143-0.565), when compared to the least active subgroup who neither had worked long hours in midlife nor participate in social activities in later-life. Therefore, the present study demonstrated that midlife long-hour working and later-life social engagement were modifiable factors for the maintenance of cognitive functions.

Monte Carlo simulation on the dynamics of a semi-flexible polymer in the presence of nanoparticles.

The dynamics of a semi-flexible polymer chain in the presence of periodically distributed nanoparticles is simulated by using off-lattice Monte Carlo simulations. For repulsive or weak attractive nanoparticles, the dynamics are slowed down monotonically by increasing the chain stiffness kθ or decreasing the inter-particle distance d. For strong attractive nanoparticles, however, the dynamics show nonmonotonic behaviors with kθ and d. An interesting result is that a stiff polymer may move faster than a flexible one. The underlying mechanism is that the nanoparticle's attraction is weakened by the chain stiffness. The nonmonotonic behavior of the polymer's dynamics with kθ is explained by the competition between the weakening effect of the chain stiffness on the nanoparticle's attraction and the intrinsic effect of chain stiffness which reduces the dynamics of the polymer. In addition, the nonmonotonic behavior of the polymer's dynamics with d is explained by the competition between the nanoparticle-exchange motion of the polymer dominated at small d and the desorption-and-adsorption motion at large d. The excluded volume effect of the nanoparticles plays a more important role for stiffer polymers as the attraction of the nanoparticles is weakened by the chain stiffness.

Effect of manganese on neural endocrine hormones in serum of welders and smelters.

BACKGROUND: Although manganese (Mn)-induced neurotoxicity effects are well known among occupational Mn exposure, few reports have investigated the effects on endocrine systems among welders and smelters. OBJECTIVE: To determine the effect of high level occupational manganese (Mn) exposure on neuropsychological parameters and hormonal status. METHODS: We used a cross-sectional design with 52 welders, 48 smelters and 43 age-matched office workers from the same factory in China. We analyzed serum endocrine hormones level and airborne Mn concentrations. Erythrocyte and urine Mn levels were quantified using inductively-coupled plasma atomic emission spectroscopy. RESULTS: The geometric mean of air Mn concentrations for the welders and smelters were 19.7 and 273.1 µg/m3, respectively. Mn concentrations in erythrocytes of smelters were markedly greater than those in controls and welders, but there was no difference between the erythrocytes Mn levels of Control and welders. We also found an increase of Mn levels in the urine of both welders and smelters vs. controls; Mn levels in urine of smelters were higher than in welders. Self-reported neurobehavioral symptoms were higher in welders and smelters than in controls. Finally, thyroid-stimulating hormone (TSH) levels of welders were significantly lower than in controls, whereas smelters had lower prolactin (PRL), testosterone (TST) and follicle-stimulating hormone (FSH) concentrations than either controls or welders. CONCLUSIONS: These results show that smelters have higher Mn exposure than do welders, and that Mn levels in erythrocytes or urine can be a marker for exposure. Moreover, high level occupational Mn exposure increases adverse neurobehavioral effects, and also may disrupt endocrine systems.

Water-Based Black Phosphorus Hybrid Nanosheets as a Moldable Platform for Wound Healing Applications.

Black phosphorus (BP) nanosheets with unique biocompatibility and superior optical performance have attracted enormous attention in material science. However, their instability and poor solution-processability severely limit their clinical applications. In this work, we demonstrate the use of silk fibroin (SF) as an exfoliating agent to produce thin-layer BP nanosheets with long-term stability and facile solution-processability. Presence of SF prevents rapid oxidation and degradation of the resultant BP nanosheets, enhancing their performance in physiological environment. The SF-modified BP nanosheets exhibit subtle solution-processability and are fabricated into various BP-based material formats. As superior photothermal agents, BP-based wound dressings effectively prevent bacterial infection and promote wound repair. Therefore, this work opens new avenues for unlocking current challenges of BP nanosheet applications for practical biomedical purposes.

New secondary metabolites from an engineering mutant of endophytic Streptomyces sp. CS.

In previous work, a series of bioactive natural products had been isolated from the plant endophytic Streptomyces sp. CS, which was isolated from Maytenus hookeri. To mine new active metabolites, we describe introducing an alien carbamoyltransferase (asm21) gene into the strain CS by conjugal transfer. As a result, three recombinatorial mutants named CS/asm21-1, CS/asm21-2 and CS/asm21-4 were successfully constructed. Three mutants and wild type CS were cultured on solid medium, and the extracts were detected and analyzed by liquid chromatography-mass spectrometry (LC-MS). The LC-MS profiles showed several unknown peaks that were present in the spectra of extracts of the CS/asm21-4 cultured on oatmeal solid medium. Then, three new naphthomycins O-Q (1-3), a new macrolide hookerolide (4) as well as nine known compounds were obtained from the solid cultured medium. Their structures were identified by spectra data. These new compounds showed moderate antimicrobial activities.