Insights Into the Role of Copper in Neurodegenerative Diseases and the Therapeutic Potential of Natural Compounds.

Neurodegenerative diseases encompass a collection of neurological disorders originating from the progressive degeneration of neurons, resulting in the dysfunction of neurons. Unfortunately, effective therapeutic interventions for these diseases are presently lacking. Copper (Cu), a crucial trace element within the human body, assumes a pivotal role in various biological metabolic processes, including energy metabolism, antioxidant defense, and neurotransmission. These processes are vital for the sustenance, growth, and development of organisms. Mounting evidence suggests that disrupted copper homeostasis contributes to numerous age-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), Menkes disease (MD), prion diseases, and multiple sclerosis (MS). This comprehensive review investigates the connection between the imbalance of copper homeostasis and neurodegenerative diseases, summarizing pertinent drugs and therapies that ameliorate neuropathological changes, motor deficits, and cognitive impairments in these conditions through the modulation of copper metabolism. These interventions include Metal-Protein Attenuating Compounds (MPACs), copper chelators, copper supplements, and zinc salts. Moreover, this review highlights the potential of active compounds derived from natural plant medicines to enhance neurodegenerative disease outcomes by regulating copper homeostasis. Among these compounds, polyphenols are particularly abundant. Consequently, this review holds significant implications for the future development of innovative drugs targeting the treatment of neurodegenerative diseases.

Exploring the therapeutic potential of natural compounds for Alzheimer's disease: Mechanisms of action and pharmacological properties.

Alzheimer's Disease (AD) is a global public health priority characterized by high mortality rates in adults and an increasing prevalence in aging populations worldwide. Despite significant advancements in comprehending the pathogenesis of AD since its initial report in 1907, there remains a lack of effective curative or preventive measures for the disease. In recent years, natural compounds sourced from diverse origins have garnered considerable attention as potential therapeutic agents for AD, owing to their anti-inflammatory, antioxidant, and neuroprotective properties. This review aims to consolidate the therapeutic effects of natural compounds on AD, specifically targeting the reduction of ß-amyloid (Aß) overproduction, anti-apoptosis, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Notably, the identified compounds exhibiting these effects predominantly originate from plants. This review provides valuable insights into the potential of natural compounds as a reservoir of novel therapeutic agents for AD, thereby stimulating further research and contributing to the development of efficacious treatments for this devastating disease.

Harnessing the Therapeutic Potential of Ginsenoside Rd for Activating SIRT6 in Treating a Mouse Model of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent global condition and a common precursor to liver cancer, yet there is currently no specific medication available for its treatment. Ginseng, renowned for its medicinal and dietary properties, has been utilized in NAFLD management, although the precise underlying mechanism remains elusive. To investigate the effectiveness of ginsenoside Rd, we employed mouse and cell models to induce NAFLD using high-fat diets, oleic acid, and palmitic acid. We explored and confirmed the specific mechanism of ginsenoside Rd-induced hepatic steatosis through experiments involving mice with a liver-specific knockout of SIRT6, a crucial protein involved in metabolic regulation. Our findings revealed that administration of ginsenoside Rd significantly reduced the inflammatory response, reactive oxygen species (ROS) levels, lipid peroxide levels, and mitochondrial stress induced by oleic acid and palmitic acid in primary hepatocytes, thereby mitigating excessive lipid accumulation. Moreover, ginsenoside Rd administration effectively enhanced the mRNA content of key proteins involved in fatty acid oxidation, with a particular emphasis on SIRT6 and its target proteins. We further validated that ginsenoside Rd directly binds to SIRT6, augmenting its deacetylase activity. Notably, we made a significant observation that the protective effect of ginsenoside Rd against hepatic disorders induced by a fatty diet was almost entirely reversed in mice with a liver-specific SIRT6 knockout. Our findings highlight the potential therapeutic impact of Ginsenoside Rd in NAFLD treatment by activating SIRT6. These results warrant further investigation into the development of Ginsenoside Rd as a promising agent for managing this prevalent liver disease.

Natural Wood-Derived Macroporous Cellulose for Highly Efficient and Ultrafast Elimination of Double-Stranded RNA from In Vitro-Transcribed mRNA.

Double-stranded RNA (dsRNA) is a major impurity that can induce innate immune responses and cause adverse drug reactions. Removing dsRNA is an essential and non-trivial process in manufacturing mRNA. Current methods for dsRNA elimination use either high-performance liquid chromatography or microcrystalline cellulose, rendering the process complex, expensive, toxic, and/or time-consuming. This study introduces a highly efficient and ultrafast method for dsRNA elimination using natural wood-derived macroporous cellulose (WMC). With a naturally formed large total pore area and low tortuosity, WMC removes up to 98% dsRNA within 5 min. This significantly shortens the time for mRNA purification and improves purification efficiency. WMC can also be filled into chromatographic columns of different sizes and integrates with fast-protein liquid chromatography for large-scale mRNA purification to meet the requirements of mRNA manufacture. This study further shows that WMC purification improves the enhanced green fluorescent protein mRNA expression efficiency by over 28% and significantly reduces cytokine secretion and innate immune responses in the cells. Successfully applying WMC provides an ultrafast and efficient platform for mRNA purification, enabling large-scale production with significant cost reduction.

Heavy metals and Pb isotopes in sediment cores from the Bering and Chukchi seas: Implications for environmental changes and human activities over the past century.

The Bering Sea and the Chukchi Sea are important regions for marine ecosystems and climate change. However, the historical deposition and sources of metals in these regions are poorly understood. In this study, we utilized Pb isotopes and multi-element concentrations (Ni, Cu, Fe, Mn, Zn, Cd, Pb) coupled with Pb-210 dating to investigate the historical deposition and source identification of metals in sediment cores collected from the Bering Sea and the Chukchi Sea. Our findings reveal that the transport of organic matter was mainly transported by marine and terrestrial sources in the Bering and Chukchi Sea, respectively. Historical variations of metals were similar in both seas, showing an increasing trend of metals (excluding Mn) from the 1960s to the 1990s, followed by a gradual decrease after the 1990s, which can be attributed to the development of industrial and gasoline emission. The results of the geo-accumulation index indicated that sediment in both seas was relatively unpolluted with metals. Additionally, Pb isotopic ratios suggested that natural weathering was the primary source of Pb in the area, but the use and phase-out of gasoline were also well-reconstructed. This study provides valuable information for assessing environmental changes and human activities over the past century in the Arctic and subarctic Ocean.

Effects of High Temperature Stress on the Physiological and Biochemical Characteristics of Paeonia ostii.

In order to explore the effects of high temperature stress on the physiological characteristics of Paeonia ostii, the Paeonia ostii were subjected to 25 °C, 35 °C, 38 °C, and 40 °C for 7 days. Meanwhile, the physiological indicators of oxidative stress (hydrogen peroxide, H2O2; malondialdehyde, MDA; relative electrical conductivity, REC), antioxidant enzyme activity (superoxide dismutase, SOD; ascorbate peroxidase, APX; catalase, CAT; peroxidase, POD), photosynthetic pigment content (chlorophyll a, Chla; chlorophyll b, Chlb), photosynthetic characteristics (net photosynthetic rate, Pn; intercellular CO2 concentration, Ci; stomatal conductance, Gs; transpiration rate, Tr), and osmoregulatory substances content (soluble protein, SP; soluble sugar, SS) were determined. The results showed that, with the increase in temperature and stress time, the H2O2 content, MDA content, REC value, CAT activity, and APX activity increased, while Chla content, Chlb content, SS content, and SP content decreased. With the extension of stress time, the SOD activity, POD activity, and Tr value of each high temperature stress group first increased and then decreased; Ci first decreased, then increased, and then decreased; meanwhile, Pn and Gs showed an overall downward trend. PLS-DA (partial least squares discriminant analysis) was used to analyze the changes in physiological and biochemical indexes of peony leaves under 40 °C stress for different days. SOD was found to be the biggest factor affecting the changes in physiological and biochemical indexes of peony leaves treated with different days of stress.

Hepatic ZBTB22 promotes hyperglycemia and insulin resistance via PEPCK1-driven gluconeogenesis.

Excessive gluconeogenesis can lead to hyperglycemia and diabetes through as yet incompletely understood mechanisms. Herein, we show that hepatic ZBTB22 expression is increased in both diabetic clinical samples and mice, being affected by nutritional status and hormones. Hepatic ZBTB22 overexpression increases the expression of gluconeogenic and lipogenic genes, heightening glucose output and lipids accumulation in mouse primary hepatocytes (MPHs), while ZBTB22 knockdown elicits opposite effects. Hepatic ZBTB22 overexpression induces glucose intolerance and insulin resistance, accompanied by moderate hepatosteatosis, while ZBTB22-deficient mice display improved energy expenditure, glucose tolerance, and insulin sensitivity, and reduced hepatic steatosis. Moreover, hepatic ZBTB22 knockout beneficially regulates gluconeogenic and lipogenic genes, thereby alleviating glucose intolerance, insulin resistance, and liver steatosis in db/db mice. ZBTB22 directly binds to the promoter region of PCK1 to enhance its expression and increase gluconeogenesis. PCK1 silencing markedly abolishes the effects of ZBTB22 overexpression on glucose and lipid metabolism in both MPHs and mice, along with the corresponding changes in gene expression. In conclusion, targeting hepatic ZBTB22/PEPCK1 provides a potential therapeutic approach for diabetes.

2,3-Butanediol from the leachates of pine needles induces the resistance of Panax notoginseng to the leaf pathogen Alternaria panax.

Compared with the use of monocultures in the field, cultivation of medicinal herbs in forests is an effective strategy to alleviate disease. Chemical interactions between herbs and trees play an important role in disease suppression in forests. We evaluated the ability of leachates from needles of Pinus armandii to induce resistance in Panax notoginseng leaves, identified the components via gas chromatography-mass spectrometry (GC-MS), and then deciphered the mechanism of 2,3-Butanediol as the main component in the leachates responsible for resistance induction via RNA sequencing (RNA-seq). Prespraying leachates and 2,3-Butanediol onto leaves could induce the resistance of P. notoginseng to Alternaria panax. The RNA-seq results showed that prespraying 2,3-Butanediol onto leaves with or without A. panax infection upregulated the expression of large number of genes, many of which are involved in transcription factor activity and the mitogen-activated protein kinase (MAPK) signaling pathway. Specifically, 2,3-Butanediol spraying resulted in jasmonic acid (JA) -mediated induced systemic resistance (ISR) by activating MYC2 and ERF1. Moreover, 2,3-Butanediol induced systemic acquired resistance (SAR) by upregulating pattern-triggered immunity (PTI)- and effector-triggered immunity (ETI)-related genes and activated camalexin biosynthesis through activation of WRKY33. Overall, 2,3-Butanediol from the leachates of pine needles could activate the resistance of P. notoginseng to leaf disease infection through ISR, SAR and camalexin biosynthesis. Thus, 2,3-Butanediol is worth developing as a chemical inducer for agricultural production.

Hepatic ZBTB22-mediated detoxification ameliorates acetaminophen-induced liver injury by inhibiting pregnane X receptor signaling.

Overdose acetaminophen (APAP) can cause acute liver injury (ALI), but the underlying mechanism remains undetermined. This study explored the role of hepatic Zinc Finger And BTB Domain Containing 22 (ZBTB22) in defense against APAP-mediated hepatotoxicity. The results showed that hepatic ZBTB22 expression was significantly reduced in patients with ALI and mice. In mouse primary hepatocytes (MPHs), ZBTB22 deletion aggravated APAP overdose-induced ALI, whereas ZBTB22 overexpression attenuated that pathological progression. The results were further verified in ZBTB22 over-express or knockout mice models. In parallel, hepatocyte-specific ZBTB22 knockout also enhanced ALI. Furthermore, ZBTB22 decreased pregnane X receptor (PXR) expression, and the PXR activator pregnane-16α-carbonitrile suppressed the protective effect of ZBTB22 in APAP-induced ZBTB22-overexpressing mice. Collectively, our findings highlight the protective effect of ZBTB22 against APAP-induced ALI and unravel PXR signaling as the potential mechanism. Strategies to increase hepatic ZBTB22 expression represent a promising therapeutic approach for APAP overdose-induced ALI.

Network Pharmacology and Mechanism Studies of the Protective Effect of Ginseng against Alzheimer's Disease Based on Aß Pathogenesis.

Alzheimer's disease (AD) is a critical neurodegenerative disease that manifests as progressive intellectual decline and is pathologically characterized by a progressive loss of neurons in the brain. Despite extensive research on this topic, the pathogenesis of AD is not fully understood, while the beta-amyloid (Aß) hypothesis remains the dominant one and only a few symptomatic drugs are approved for the treatment of AD. Ginseng has been widely reported as an effective herbal medicine for the treatment of neurodegenerative diseases such as dementia. Therefore, we explore the protective effects of ginseng in AD by a network pharmacological approach based on the pathogenesis of Aß. Twenty-one major ginsenosides are screened based on ultraperformance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) data. Among them, MAPK8, MAPK9, BACE1, FLT1, CDK2, and CCR5 are the core targets. By molecular docking and validation with the in vitro cell model APPswe-SH-SY5Y, we find that ginsenosides Rg3 and Ro have good neuroprotective effects and can reduce the expression of Aß 1 - 42 in APPswe-SH-SY5Y. Finally, through RT-qPCR experiment, we find that ginsenoside Rg3 targeted MAPK8, FLT1, and CCR5, while ginsenoside Ro targeted MAPK8, MAPK9, FLT1, and CCR5 for its potential anti-AD efficacy.

Ginsenoside Rc attenuates DSS-induced ulcerative colitis, intestinal inflammatory, and barrier function by activating the farnesoid X receptor.

Objectives: Farnesoid X receptor (FXR) activation is involved in ameliorating inflammatory bowel disease (IBD), such as ulcerative colitis (UC), and inflammatory regulation may be involved in its mechanism. Ginsenoside Rc (Rc) is a major component of Panax ginseng, and it plays an excellent role in the anti-inflammatory processes. Our aim is to explore the alleviative effect of Rc on dextran sulfate sodium (DSS)-induced inflammation and deficiencies in barrier function based on FXR signaling. Materials and Methods: In vitro, we treated human intestinal epithelial cell lines (LS174T) with LPS to explore the anti-inflammatory effect of Rc supplementation. In vivo, a DSS-induced IBD mice model was established, and the changes in inflammatory and barrier function in colons after Rc treatment were measured using the disease activity index (DAI), hematoxylin and eosin (H&E) staining, immunofluorescence, ELISA, and qPCR. Molecular docking analysis, luciferase reporter gene assay, and qPCR were then used to analyze the binding targets of Rc. DSS-induced FXR-knockout (FXR-/-) mice were used for further validation. Results: Rc significantly recovered the abnormal levels of inflammation indexes (TNF-α, IL-6, IL-1ß, and NF-KB) induced by LPS in LS174T. DSS-induced C57BL/6 mice exhibited a significantly decreased body weight and elevated DAI, as well as a decrease in colon weight and length. Increased inflammatory markers (TNF-α, IL-6, IL-1ß, ICAM1, NF-KB, F4/80, and CD11b displayed an increased expression) and damaged barrier function (Claudin-1, occludin, and ZO-1 displayed a decreased expression) were observed in DSS-induced C57BL/6 mice. Nevertheless, supplementation with Rc mitigated the increased inflammatory and damaged barrier function associated with DSS. Further evaluation revealed an activation of FXR signaling in Rc-treated LS174T, with FXR, BSEP, and SHP found to be upregulated. Furthermore, molecular docking indicated that there is a clear interaction between Rc and FXR, while Rc activated transcriptional expression of FXR in luciferase reporter gene assay. However, these reversal abilities of Rc were not observed in DSS-induced FXR-/- mice. Conclusion: Our findings suggest that Rc may ameliorate inflammation and barrier function in the intestine, which in turn leads to the attenuation of DSS-induced UC, in which Rc may potentially activate FXR signaling to protect the intestines from DSS-induced injury.

Photosynthetic and physiological responses of different peony cultivars to high temperature.

In order to investigate the causes of the differences in heat tolerance ('Lu He Hong' and 'Zhi Hong'), we studied the physiological changes, photosynthetic properties and regulatory mechanism of the two peony cultivars at high temperature. The results showed that the physiological changed of different peony cultivars varied significantly under high temperature stress. With the extension of high temperature stress time, MDA content of 'Lu He Hong' increased,while 'Zhi Hong' rised first and then decreased, SOD activity of 'Lu He Hong' rised first and then decreased, that of 'Zhi Hong' kept rising, POD activity of 'Lu He Hong' kept decreasing, while 'Zhi Hong' rised. The photosynthetic instrument records the change of peony photosynthesis parameters at high temperature; the chlorophyll A (Chla) fluorescence transient is recorded using the plant efficiency analyzer (PEA), analyzed according to the JIP test (O-J-I-P fluorescence transient analysis), and several parameters were derived to explain the photosynthetic efficiency difference between different peony cultivars. The tested cultivars responded differently to the survey conditions, and the PCA analysis showed that the 'Zhi Hong' was more well tolerated and showed better thermal stability of the PSII. The reduced efficiency of the 'Lu He Hong' PSII antenna leads to higher heat dissipation values to increase the light energy absorbed by unit reaction center (ABS/RC), the energy captured by unit reaction center (TR0/RC), and the energy dissipated by unit reaction center (DI0/RC), which significantly leads to its lower total photosynthetic performance (PItotal). The light capture complex of the variety 'Zhi Hong' has high connectivity with its reaction center, less damage to OEC activity, and better stability of the PSII system. The results show that 'Zhi Hong' improves heat resistance by stabilizing the cell membrane, a strong antioxidant system, as well as a more stable photosynthetic system. The results of this study provide a theoretical basis for the screening of heat-resistant peonies suitable for cultivation in Jiangnan area and for the selection and breeding of heat-resistant cultivars.

Ginsenoside Rc, as an FXR activator, alleviates acetaminophen-induced hepatotoxicity via relieving inflammation and oxidative stress.

Acetaminophen (APAP) intake leads to excessive NAPQI deposition, stimulating inflammatory and oxidative stress and causing fatal liver injury. However, the detailed molecular mechanism involved is unknown, and effective therapeutic approaches remain insufficient. In this study, we discovered that treatment with ginsenoside Rc can prevent the inflammatory response caused by APAP and oxidative stress in mouse primary hepatocytes (MPHs), along with the corresponding changes in related genes. Additionally, Ginsenoside Rc effectively alleviates APAP-induced cellular apoptosis and NAPQI accumulation in MPHs. In vivo, Ginsenoside Rc administration remarkably attenuates APAP-induced hepatotoxicity, repairing liver damage and improving survival. Moreover, Ginsenoside Rc treatment modulates genes involved in APAP metabolism, leading to a decrease in NAPQI and resulting in the alleviation of fatal oxidative stress and inflammatory response after APAP exposure, along with the expression of their related indicators. Furthermore, our RNA-seq and molecular docking analysis implies that FXR expression and FXR transcriptional activity are stimulated by Ginsenoside Rc treatment. Notably, due to the lack of FXR in mice and MPHs, ginsenoside Rc can no longer play its original protective role against hepatotoxicity and cell damage caused by APAP, and it is difficult to improve the corresponding survival rate and prevent hepatic apoptosis, NAPQI generation, fatal oxidative stress, and the inflammatory response induced by APAP and the expression of related genes. In summary, our results indicate that Ginsenoside Rc could act as an effective FXR activator and effectively regulate FXR-induced antioxidant stress and eliminate inflammation while also having an anti-apoptotic function.

Sensitive and Easy-Read CRISPR Strip for COVID-19 Rapid Point-of-Care Testing.

Rapid and clinically sensitive detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) play an important role in the contact tracing and containment of the COVID-19 pandemic. A recently developed field-deployable clustered regularly interspaced short palindromic repeats (CRISPR) detection assay with lateral flow strips shows promise for point-of-care detection of SARS-CoV-2. However, the limit of detection of paper strip-based assays (10-100 copies/µL) is much lower than that of fluorescence-based detection methods. In this study, we developed an easy-readout and sensitive enhanced (ERASE) strip to visualize the results of CRISPR detection and improve the sensitivity to 1 copy/µL with an unambiguous easy-read result. Using 649 clinical samples from blind specimens collected from patients in China, we validated our ERASE assay for SARS-CoV-2 RNA detection with 90.67% positive predictive agreement and 99.21% negative predictive agreement. In conclusion, our study provided a customized CRISPR strip for use in a simple, rapid, ultrasensitive, and highly specific assay for SARS-CoV-2 detection. (Clinical Trial Registration number: 2020-008-01; [2020]IEC(ZD01); PJ-NBEY-2020-009-01; 2020#34).

In Situ Synthesis of FeOCl in Hollow Dendritic Mesoporous Organosilicon for Ascorbic Acid-Enhanced and MR Imaging-Guided Chemodynamic Therapy in Neutral pH Conditions.

Chemodynamic therapy (CDT) based on the Fenton reaction is a promising strategy for nonlight cancer treatment. However, the traditional Fenton reaction is only efficient in strongly acidic conditions (pH = 2-4), resulting in the limited curative effect in a weakly acidic tumor microenvironment (TME). Herein, we first developed a simple in situ growth method to confine FeOCl nanosheets into hollow dendritic mesoporous organosilicon (H-DMOS) nanoparticles to obtain FeOCl@H-DMOS nanospheres. Ascorbic acid (AA) was then absorbed on the nanosystem as a H2O2 prodrug and, meanwhile, was used for the regeneration of Fentons reagent for Fe2+. Finally, poly(ethylene glycol) (PEG) was coated on FeOCl@H-DMOS-AA to enhance the permeability and retention (EPR) effect in tumor tissue. The as-fabricated FeOCl@H-DMOS-AA/PEG can generate a large amount of highly toxic hydroxyl radicals (•OH) by catalyzing H2O2 even in neutral pH conditions with the help of AA. As a result, the effect of CDT has been markedly enhanced by the increased amount of H2O2 and the efficient Fenton reaction in mild acidic TME, which can remove almost all of the tumors in mice. In addition, FeOCl also endows the nanosystem with T2-weighted MR imaging capability (r2 = 34.08 mM-1 s-1), thus realizing the imaging-guided cancer therapy. All in all, our study may contribute a new direction and may have a bright future for enhanced CDT with a neutral pH range.

Insight into the Luminescence Alternation of Sub-30 nm Upconversion Nanoparticles with a Small NaHoF4 Core and Multi-Gd3+ /Yb3+ Coexisting Shells.

It is absolutely imperative for development of material science to adjust upconversion luminescence (UCL) properties of highly doped upconversion nanoparticles (UCNPs) with special optical properties and prominent application prospects. In this work, featuring NaHoF4 @NaYbF4 (Ho@Yb) structures, sub-30 nm core-multishell UCNPs are synthesized with a small NaHoF4 core and varied Gd3+ /Yb3+ coexisting shells. X-ray diffraction, transmission electron microscopy, UCL spectrum, UCL lifetime, and pump power dependence are adhibited for characterization. Compared with the former work, except for a smaller total size, tunable emission in color from red to yellow to green, and intensity from low to stronger than that of traditional UCNPs is achieved for ≈10 nm NaHoF4 core size by means of changing number of layers and Gd3+ /Yb3+ concentration ratios in different layers. Besides, simultaneously doping Ho3+ into the shells will result in lowered UCL intensity and lifted green/red ratio. Surface energy loss and sensitizing energy supply, which can be modulated with inert shielding of Gd3+ and sensitization of Yb3+ , are proved to be the essential determinant. More UCL properties of these peculiar Ho@Yb UCNPs are uncovered and detailedly summarized, and the findings can help to expand the application scope of NaHoF4 into photoinduced therapy.

Rapid Decomposition and Catalytic Cascade Nanoplatforms Based on Enzymes and Mn-Etched Dendritic Mesoporous Silicon for MRI-Guided Synergistic Therapy.

The endogenous tumor microenvironment (TME) can signally influence the therapeutic effects of cancer, so it is necessary to explore effective synergistic therapeutic strategies based on changing of the TME. Here, a catalytic cascade nanoplatform based on manganese (Mn)-etched dendritic mesoporous silicon nanoparticles (designated as DMMnSiO3 NPs) loaded with indocyanine green (ICG) and natural glucose oxidase (GOD) is established (designated as DIG nanocomposites). As the Mn-O bonds in DMMnSiO3 NPs are susceptive to mildly acidic and reducing environments, the DIG nanocomposites can be rapidly decomposed because of the biodegradation of DMMnSiO3 NPs once internalized into the tumor by the consumption of glutathione (GSH) in TME to weaken the antioxidant capability of the tumors. The released Mn2+ could catalyze endogenous hydrogen peroxide (H2O2) to generate oxygen (O2) to relieve the hypoxia in TME. The generation of O2 may promote the catalyzed oxidation of glucose by GOD, which will cut off nutrient supplies, accompanied by the regeneration of H2O2. The regenerated H2O2 could be sequentially catalyzed by Mn2+ to compensate for the consumed O2, and thus, the catalytic cascade process between Mn2+ and GOD was set up. As a result, a synergistic therapeutic strategy based on T1-weighted magnetic resonance imaging (MRI) of Mn2+, starvation therapy by O2-compensation enhanced catalyzing glucose, dual-model (GSH consumption and O2 compensation) enhanced photodynamic therapy, and effective photothermal therapy of ICG (η = 23.8%) under 808 nm laser irradiation has been successfully established.

Geochemical Assessment and Spatial Analysis of Heavy Metals in the Surface Sediments in the Eastern Beibu Gulf: A Reflection on the Industrial Development of the South China Coast.

The Beibu Gulf (also named the Gulf of Tonkin), located in the northwest of the South China Sea, is representative of a bay suffering from turbulence and contamination associated with rapid industrialization and urbanization. In this study, we aim to provide the novel baseline levels of heavy metals for the research area. Concentrations of five heavy metals (i.e., Cu, Pb, Zn, Cd and Cr) were determined in surface sediments from 35 sites in the eastern Beibu Gulf. The heavy metal content varied from 6.72 to 25.95 mg/kg for Cu, 16.99 to 57.98 mg/kg for Pb, 73.15 to 112.25 mg/kg for Zn, 0.03 to 0.12 mg/kg for Cd, and 20.69 to 56.47 mg/kg for Cr, respectively. With respect to the Chinese sediment quality criteria, sediments in the eastern Beibu Gulf have not been significantly affected by coastal metal pollutions. The results deduced from the geoaccumulation index (Igeo) showed that the study area has been slightly polluted by Pb, which might be caused by non-point sources. Relatively high concentrations of Cu, Pb and Cd were found around the coastal areas of Guangxi province, the Leizhou Peninsula and the northwest coast of Hainan Island, whereas the highest concentrations of Zn and Cr were found on the northwest coast of Hainan Island. Spatial distribution patterns of the heavy metals showed that bioavailable fractions of Pb were higher than in the residual fractions, while Cu and Cd concentrations in exchangeable and carbonate fractions were relatively higher than those in the bioavailable fractions. Hierarchical clustering analysis suggested that the sampling stations could be separated into three groups with different geographical distributions. Accompanying their similar spatial distribution in the study area, significant correlation coefficients among Cu, Cd and Pb were also found, indicating that these three metals might have had similar sources. Overall, the results indicated that the distribution of these heavy metals in the surface sediments collected from the Beibu Gulf was complex.

Metals in Fishes from Yongshu Island, Southern South China Sea: Human Health Risk Assessment.

In order to assess the bioaccumulation of metals associated with gender, tissues, and their potential ecological risk, four species of fish were collected from the Yongshu Island in the Southern South China Sea. Metals and stable Pb isotopes in their tissues (muscle, gill, liver, intestine, and ovary) were determined. The concentrations of metals (mg/kg, dry weight) in these species were ND-21.60 (Cd), 1.21-4.87 (Cr), 0.42-22.4 (Cu), 1.01-51.8 (Mn), 0.30-3.28 (Ni), 6.04-1.29 × 103 (Zn), 14.89-1.40 × 103 (Fe), and 0.22-3.36 (Pb). In general, the liver and intestine absorbed more metals than the other tissues. Metals accumulation can be influenced by gender and feeding behavior and in fact, female fish and dietary exposure are more prone to accumulate metals. In addition, Pb isotopic ratios indicated that all species had significant biological fractionation, which may not make them good tracers for source identification. The metal concentrations of most samples were lower than the national standard values of the FAO (USA), which suggested that human consumption of these species may not cause health risks. However, since the surrounding areas are developing rapidly, the potential environmental risk of metals will intensify and should receive more attention.