Identification of COQ2 as a regulator of proliferation and lipid peroxidation through genome-scale CRISPR-Cas9 screening in myeloma cells.

Multiple myeloma (MM) is the second most common malignant haematological disease with a poor prognosis. The limit therapeutic progress has been made in MM patients with cancer relapse, necessitating deeper research into the molecular mechanisms underlying its occurrence and development. A genome-wide CRISPR-Cas9 loss-of-function screening was utilized to identify potential therapeutic targets in our research. We revealed that COQ2 plays a crucial role in regulating MM cell proliferation and lipid peroxidation (LPO). Knockout of COQ2 inhibited cell proliferation, induced cell cycle arrest and reduced tumour growth in vivo. Mechanistically, COQ2 promoted the activation of the MEK/ERK cascade, which in turn stabilized and activated MYC protein. Moreover, we found that COQ2-deficient MM cells increased sensitivity to the LPO activator, RSL3. Using an inhibitor targeting COQ2 by 4-CBA enhanced the sensitivity to RSL3 in primary CD138+ myeloma cells and in a xenograft mouse model. Nevertheless, co-treatment of 4-CBA and RSL3 induced cell death in bortezomib-resistant MM cells. Together, our findings suggest that COQ2 promotes cell proliferation and tumour growth through the activation of the MEK/ERK/MYC axis and targeting COQ2 could enhance the sensitivity to ferroptosis in MM cells, which may be a promising therapeutic strategy for the treatment of MM patients.

Retinoic acid released from self-assembling peptide activates cardiomyocyte proliferation and enhances repair of infarcted myocardium.

The limited cardiomyocyte proliferation is insufficient for repair of the myocardium. Therefore, activating cardiomyocyte proliferation might be a reasonable option for myocardial regeneration. Here, we investigated effect of retinoic acid (RA) on inducing adult cardiomyocyte proliferation and assessed efficacy of self-assembling peptide (SAP)-released RA in activating regeneration of the infarcted myocardium. Effect of RA on inducing cardiomyocyte proliferation was examined with the isolated cardiomyocytes. Expression of the cell cycle-associated genes and paracrine factors in the infarcted myocardium was examined at one week after treatment with SAP-carried RA. Cardiomyocyte proliferation, myocardial regeneration and improvement of cardiac function were assessed at four weeks after treatment. In the adult rat myocardium, expression of RA synthetase gene Raldh2 and RA concentration were decreased significantly. After treatment with RA, the proliferated cardiomyocytes were increased. The formulated SAP could sustainedly release RA. After treatment with SAP-carried RA, expression of the pro-proliferative genes in cell cycle and paracrine factors in the infarcted myocardium were up-regulated. Myocardial regeneration was enhanced, and cardiac function was improved significantly. These results demonstrate that RA can induce adult cardiomyocytes to proliferate effectively. The sustained release of RA with SAP is a promise strategy to enhance repair of the infarcted myocardium.

A Fetus with Maternal Uniparental Disomy on Chromosome 20: Case Report with Genetic Analysis and Prenatal Diagnosis.

BACKGROUND: A fetus with increased copy number of chromosome 20 was identified by NIPT. Here we utilize several genetic tests and analyses to illuminate the etiology of such aneuploidy. METHODS: Amniotic fluid cells were extracted from pregnant woman and sent for karyotype and chromosomal microarray analysis (CMA). Trio pedigree analysis was conducted with Chromosome Analysis Suite and uniparental disomy (UPD)-tool software. RESULTS: CMA identified consistent results, which were 2 regions of homozygosity: arr[GRCh37]20p12.2q11.1 (11265096_26266313)hmz and arr[GRCh37]20q11.21q13.2(29510306_54430467)hmz. The trio pedigree analysis discovered that the fetal chromosome 20 was the entire maternal UPD mosaic with isodisomy and heterodisomy. CONCLUSIONS: When a large segment of chromosome is homozygous, appropriate genetic tests are required to find the potential mechanisms for UPD formation.

Promoting CO2 Electroreduction to Hydrocarbon Products via Sulfur-Enhanced Proton Feeding in Atomically Precise Thiolate-Protected Cu Clusters.

Thiolate-protected Cu clusters with well-defined structures and stable low-coordinated Cu+ species exhibit remarkable potential for the CO2RR and are ideal model catalysts for establishing structure-electrocatalytic property relationships at the atomic level. However, extant Cu clusters employed in the CO2RR predominantly yield 2e- products. Herein, two model Cu4(MMI)4 and Cu8(MMI)4(tBuS)4 clusters (MMI = 2-mercapto-1-methylimidazole) are prepared to investigate the synergistic effect of Cu+ and adjacent S sites on the CO2RR. Cu4(MMI)4 can reduce CO2 to deep-reduced products with a 91.0% Faradaic efficiency (including 53.7% for CH4) while maintaining remarkable stability. Conversely, Cu8(MMI)4(tBuS)4 shows a remarkable preference for C2+ products, achieving a maximum FE of 58.5% with a C2+ current density of 152.1 mA∙cm-2. In situ XAS and ex situ XPS spectra reveal the preservation of Cu+ species in Cu clusters during CO2RR, extensively enhancing the adsorption capacity of *CO intermediates. Moreover, kinetic analysis and theoretical calculations confirm that S sites facilitate H2O dissociation into *H species, which directly participate in the protonation process on adjacent Cu sites for the protonation of *CO to *CHO. This study highlights the important role of Cu-S dual sites in Cu clusters and provides mechanistic insights into the CO2RR pathway at the atomic level.

E2F2 modulates cell adhesion through the transcriptional regulation of PECAM1 in multiple myeloma.

Multiple myeloma (MM) is the second most common haematological malignancy. Despite the development of new drugs and treatments in recent years, the therapeutic outcomes of patients are not satisfactory. It is necessary to further investigate the molecular mechanism underlying MM progression. Herein, we found that high E2F2 expression was correlated with poor overall survival and advanced clinical stages in MM patients. Gain- and loss-of-function studies showed that E2F2 inhibited cell adhesion and consequently activated cell epithelial-to-mesenchymal transition (EMT) and migration. Further experiments revealed that E2F2 interacted with the PECAM1 promoter to suppress its transcriptional activity. The E2F2-knockdown-mediated promotion of cell adhesion was significantly reversed by the repression of PECAM1 expression. Finally, we observed that silencing E2F2 significantly inhibited viability and tumour progression in MM cell models and xenograft mouse models respectively. This study demonstrates that E2F2 plays a vital role as a tumour accelerator by inhibiting PECAM1-dependent cell adhesion and accelerating MM cell proliferation. Therefore, E2F2 may serve as a potential independent prognostic marker and therapeutic target for MM.

Computational study of the photophysical properties and electronic structure of iridium(III) photosensitizer complexes with electron-withdrawing groups.

A series of novel [Ir(tpy)(btp)Cl]+ complexes (Ir1-Ir4) have been reported to show excellent performance as photosensitizers. The introduction of electron-withdrawing groups increases visible light absorption and the lifetime of triplet states. To improve the photophysical properties, we theoretically design Ir5-Ir9 with electron-withdrawing groups (Cl, F, COOH, CN and NO2). Surprisingly, our findings indicate that the photosensitizer performance does not strictly increase with the electron-withdrawing ability of the substituents. In this work, the geometric and electronic structures, transition features, and photophysical properties of Ir1-Ir9 are investigated. The natural transition orbital (NTO) analysis indicates that the T1 and T2 states play a role in the photochemical pathways. Ultraviolet-visible (UV-vis) absorption spectra and charge-transfer spectra (CTS) have been investigated to show that the introduction of electron-withdrawing groups not only improves the visible light absorbing ability, but also changes the nature of electron excitation, providing a future molecular design strategy for similar series of photosensitizers. The rates of (reverse) intersystem crossing and the Huang-Rhys factors are evaluated to interpret the experimental results within the framework of Marcus theory. For complexes Ir1-Ir7, the introduction of electron-withdrawing groups leads to a lower efficiency of reverse intersystem crossing and a strong non-radiative process T2 → T1, resulting in a long triplet lifetime and excellent performance as a photosensitizer. Furthermore, some newly designed complexes (Ir7-Ir9) show great potential as thermally activated delayed fluorescence emitters, contrary to our initial expectations.

Humanized cerebral organoids-based ischemic stroke model for discovering of potential anti-stroke agents.

Establishing a stoke experimental model, which is better in line with the physiology and function of human brain, is the bottleneck for the development of effective anti-stroke drugs. A three-dimensional cerebral organoids (COs) from human pluripotent stem cells can mimic cell composition, cortical structure, brain neural connectivity and epigenetic genomics of in-vivo human brain, which provides a promising application in establishing humanized ischemic stroke model. COs have been used for modeling low oxygen condition-induced hypoxic injury, but there is no report on the changes of COs in response to in vitro oxygen-glucose deprivation (OGD)-induced damage of ischemic stroke as well as its application in testing anti-stroke drugs. In this study we compared the cell composition of COs at different culture time and explored the cell types, cell ratios and volume size of COs at 85 days (85 d-CO). The 85 d-CO with diameter more than 2 mm was chosen for establishing humanized ischemic stroke model of OGD. By determining the time-injury relationship of the model, we observed aggravated ischemic injury of COs with OGD exposure time, obtaining first-hand evidence for the damage degree of COs under different OGD condition. The sensitivity of the model to ischemic injury and related treatment was validated by the proven pan-Caspase inhibitor Z-VAD-FMK (20 µM) and Bcl-2 inhibitor navitoclax (0.5 µM). Neuroprotective agents edaravone, butylphthalide, P7C3-A20 and ZL006 (10 µM for each) exerted similar beneficial effects in this model. Taken together, this study establishes a humanized ischemic stroke model based on COs, and provides evidence as a new research platform for anti-stroke drug development.

Metrnl regulates cognitive dysfunction and hippocampal BDNF levels in D-galactose-induced aging mice.

Aging is one of the main risk factors for cognitive dysfunction. During aging process, the decrease of brain-derived neurotrophic factor (BDNF) and the impairment of astrocyte function contribute to the cognitive impairment. Metrnl, a neurotrophic factor, promotes neural growth, migration and survival, and supports neural function. In this study, we investigated the role of Metrnl in cognitive functions. D-galactose (D-gal)-induced aging model was used to simulate the process of aging. Cognitive impairment was assessed by the Morris water maze test. We showed that Metrnl expression levels were significantly increased in the hippocampus of D-gal-induced aging mice. Metrnl knockout did not affect the cognitive functions in the baseline state, but aggravated the cognitive impairment in the D-gal-induced aging mice. Furthermore, Metrnl knockout significantly reduced hippocampal BDNF, TrkB, and glial fibrillary acidic protein (GFAP) levels in the D-gal-induced aging mice. In the D-gal-induced aging cell model in vitro, Metrnl levels in the hippocampal astrocytes were significantly increased, and Metrnl knockdown and overexpression regulated the BDNF levels in primary hippocampal astrocytes rather than in neurons. We conclude that Metrnl regulates cognitive functions and hippocampal BDNF levels during aging process. As a neurotrophic factor and an endogenous protein, Metrnl is expected to become a new candidate for the treatment or alleviation of aging-related cognitive dysfunction.

Metrnl deficiency retards skin wound healing in mice by inhibiting AKT/eNOS signaling and angiogenesis.

Meteorin-like (Metrnl) is a novel secreted protein with various biological activities. In this study, we investigated whether and how Metrnl regulated skin wound healing in mice. Global Metrnl gene knockout mice (Metrnl-/-) and endothelial cell-specific Metrnl gene knockout mice (EC-Metrnl-/-) were generated. Eight-mm-diameter full-thickness excisional wound was made on the dorsum of each mouse. The skin wounds were photographed and analyzed. In C57BL/6 mice, we observed that Metrnl expression levels were markedly increased in skin wound tissues. We found that both global and endothelial cell-specific Metrnl gene knockout significantly retarded mouse skin wound healing, and endothelial Metrnl was the key factor affecting wound healing and angiogenesis. The proliferation, migration and tube formation ability of primary human umbilical vein endothelial cells (HUVECs) were inhibited by Metrnl knockdown, but significantly promoted by addition of recombinant Metrnl (10 ng/mL). Metrnl knockdown abolished the proliferation of endothelial cells stimulated by recombinant VEGFA (10 ng/mL) but not by recombinant bFGF (10 ng/mL). We further revealed that Metrnl deficiency impaired VEGFA downstream AKT/eNOS activation in vitro and in vivo. The damaged angiogenetic activity in Metrnl knockdown HUVECs was partly rescued by addition of AKT activator SC79 (10 µM). In conclusion, Metrnl deficiency retards skin wound healing in mice, which is related to impaired endothelial Metrnl-mediated angiogenesis. Metrnl deficiency impairs angiogenesis by inhibiting AKT/eNOS signaling pathway.

Tight Junction Protein 1 Suppresses Kidney Renal Clear Cell Carcinoma Cells Proliferation by Inducing Autophagy.

TJP1, an adaptor protein of the adhesive barrier, has been found to exhibit distinct oncogenic or tumor suppressor functions in a cell-type dependent manner. However, the role of TJP1 in kidney renal clear cell carcinoma (KIRC) remains to be explored. The results showed a marked down-regulation of TJP1 in KIRC tissues compared to normal tissues. Low expression of TJP1 was significantly associated with high grade and poor prognosis in KIRC. Autophagosome aggregation and LC3 II conversion demonstrated that TJP1 may induce autophagy signaling in 786-O and OS-RC-2 cells. Knockdown of TJP1 led to a decrease in the expression of autophagy-related genes, such as BECN1, ATG3, and ATG7. Consistently, TJP1 expression showed a significant positive correlation with these autophagy-related genes in KIRC patients. Furthermore, the overall survival analysis of KIRC patients based on the expression of autophagy-related genes revealed that most of these genes were associated with a good prognosis. TJP1 overexpression significantly suppressed cell proliferation and tumor growth in 786-O cells, whereas the addition of an autophagy inhibitor diminished its inhibitory function. Taken together, these results suggest that TJP1 serves as a favorable prognostic marker and induces autophagy to suppress cell proliferation and tumor growth in KIRC.

The clinical effect evaluation of multidisciplinary collaborative team combined with palliative care model in patients with terminal cancer: a randomised controlled study.

OBJECTIVE: To evaluate the clinical effect of a multidisciplinary collaboration team combined with a palliative care model in patients with terminal cancer. METHOD: A total of 84 patients diagnosed with terminal cancer in our hospital were included and randomly divided into an intervention group and a control group, with 42 cases in each group. Patients in the intervention group were treated by a multidisciplinary collaborative team combined with the palliative care model, and patients in the control group were treated by routine nursing intervention. The Self-rating Anxiety Scale (SAS) and the Self-rating Depression Scale (SDS) were used to evaluate negative emotions and anxiety and depression of patients before and after intervention. The Quality of Life Scale (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30) and Social Support Scale (SSRS) were used to evaluate the quality of life and social support of patients. This study has been registered in 13/01/2023 (ClinicalTrials.gov Identifier: NCT05683236). RESULT: The general data of the two groups were comparable. After intervention, the SAS (43.7 ± 7.4 vs. 54.2 ± 9.3) and SDS scores (38.4 ± 6.5 vs. 53.1 ± 8.4) of the intervention group were significantly lower than those of the control group. The total SSRS score, subjective support score, objective support score and utilisation of support of the intervention group were significantly higher than those of the control group (P < 0.05). The overall quality of life score of the intervention group was higher than that of the control group, and the difference was statistically significant (79.5 ± 4.5 vs. 73.2 ± 3.6, P < 0.05). The scores of each functional scale were significantly higher than those of the control group (P < 0.05). CONCLUSION: Compared with conventional nursing, the application of the multidisciplinary collaborative team combined with tranquilisation therapy in patients with terminal cancer can significantly reduce the anxiety and depression of patients, enable patients to obtain comprehensive social support, and effectively improve the quality of life of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05683236, 13/01/2023, Retrospectively registered.

In Situ Photoisomerization of an Azobenzene-Based Triple Helicate with a Prolonged Thermal Relaxation Time.

The phosphate-coordination triple helicates A2 L3 (A=anion) with azobenzene-spaced bis-bis(urea) ligands (L) have proven to undergo a rare in situ photoisomerization (without disassembly of the structure) rather than the typically known, stepwise "disassembly-isomerization-reassembly" process. This is enabled by the structural self-adaptability of the "aniono" assembly arising from multiple relatively weak and flexible hydrogen bonds between the phosphate anion and bis(urea) units. Notably, the Z→E thermal relaxation rate of the isomerized azobenzene unit is significantly decreased (up to 20-fold) for the triple helicates compared to the free ligands. Moreover, the binding of chiral guest cations inside the cavity of the Z-isomerized triple helicate can induce optically pure diastereomers, thus demonstrating a new strategy for making light-activated chiroptical materials.

[Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis]. / 基于HMGB1/NF-κB/NLRP3è½´æŽ¢è®¨è¤ªé»‘ç´ å¯¹æ°§è¯±å¯¼è§†ç½‘è†œç— å˜çš„ä¿æŠ¤ä½œç”¨.

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS: Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

Cooperative Catalysis between Dual Copper Centers in a Metal-Organic Framework for Efficient Detoxification of Chemical Warfare Agent Simulants.

Chemical warfare agents (CWAs) are among the most lethal chemicals known to humans. Thus, developing multifunctional catalysts for highly efficient detoxification of various CWAs is of great importance. In this work, we developed a robust copper tetrazolate metal-organic framework (MOF) catalyst containing a dicopper unit similar to the coordination geometry of the active sites of natural phosphatase and tyrosinase enzymes. This catalyst aided in phosphate ester bond hydrolysis and hydrogen peroxide decomposition, ultimately achieving high detoxification efficiency against both a nerve agent simulant (diethoxy-phosphoryl cyanide (DECP)) with a half-life of 3.5 min and a sulfur mustard simulant (2-chloroethyl ethyl sulfide (CEES)) with a half-life of 4.5 min, making it competitive with other reported materials. The dicopper sites in ZZU-282 provide versatile binding modes with the substrates, thereby promoting the activation of substrates and enhancing the catalytic efficiency. A combination of postmodified metal exchange control experiments, density functional theory calculations, and catalytic evaluations confirmed that dual Cu sites are the active centers promoting the catalytic reaction. This study offers a new design perspective to achieve advanced catalysts for CWA detoxification.

Recent Developments of Microscopic Study for Lanthanide and Manganese Doped Luminescent Materials.

Luminescent materials are indispensable for applications in lighting, displays and photovoltaics, which can transfer, absorb, store and utilize light energy. Their performance is closely related with their size and morphologies, exact atomic arrangement, and local configuration about photofunctional centers. Advanced electron microscopy-based techniques have enabled the possibility to study nanostructures with atomic resolution. Especially, with the advanced micro-electro-mechanical systems, it is able to characterize the luminescent materials at the atomic scale under various environments, providing a deep understanding of the luminescent mechanism. Accordingly, this review summarizes the recent achievements of microscopic study to directly image the microstructure and local environment of activators in lanthanide and manganese (Ln/Mn2+ )-doped luminescent materials, including: 1) bulk materials, the typical systems are nitride/oxynitride phosphors; and 2) nanomaterials, such as nanocrystals (hexagonal-phase NaLnF4 and perovskite) and 2D nanosheets (Ca2 Ta3 O10 and MoS2 ). Finally, the challenges and limitations are highlighted, and some possible solutions to facilitate the developments of advanced luminescent materials are provided.

Global prevalence of occult hepatitis B: A systematic review and meta-analysis.

The study aimed to investigate the prevalence and risk factors associated with occult hepatitis B virus (HBV) infection (OBI) in the global population. We searched PubMed, Embase, CINAHL, Cochrane and Web of Science from database inception through 27 Dec, 2018. Studies reporting HBV-DNA serological data in previously undiagnosed hepatitis B patients were included. The data were further categorized according to the presence of risk factors. After an initial screening of 2,325 records, we finally included 98 articles about the prevalence of OBI from 34 countries and regions. The OBI prevalence was 0.82% (95% CI:0.69-0.96) in the general population, 16.26% (95% CI:10.97-22.34) in HIV patients, 13.99% (95% CI:8.33-20.79) in patients with other liver diseases, 4.25% (95% CI:1.64-7.87) in haemodialysis patients and 5.14% (95% CI:2.26-9.01) patients with other risk factors. In conclusion, OBI prevalence varies significantly across different populations and nations, which deserve attention from the public health authorities. Our results generate further epidemiological data to identify the population with OBI, which has important clinical implications in finding these high-risk populations to design preventive and management strategies.

Erratum: Stronger Interlayer Interactions Contribute to Faster Hot Carrier Cooling of Bilayer Graphene under Pressure [Phys. Rev. Lett. 126, 027402 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.126.027402.

Dietary inflammatory index, inflammation biomarkers and preeclampsia risk: a hospital-based case-control study.

This study evaluated the association between inflammatory diets as measured by the Dietary Inflammatory index (DII), inflammation biomarkers and the development of preeclampsia among the Chinese population. We followed the reporting guidelines of the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies. A total of 466 preeclampsia cases aged over 18 years were recruited between March 2016 and June 2019, and 466 healthy controls were 1:1 ratio matched by age (±3 years), week of gestation (±1 week) and gestational diabetes mellitus. The energy-adjusted DII (E-DII) was computed based on dietary intake assessed using a seventy-nine item semiquantitative FFQ. Inflammatory biomarkers were analysed by ELISA kits. The mean E-DII scores were -0·65 ± 1·58 for cases and -1·19 ± 1·47 for controls (P value < 0·001). E-DII scores positively correlated with interferon-γ (r s = 0·194, P value = 0·001) and IL-4 (r s = 0·135, P value = 0·021). After multivariable adjustment, E-DII scores were positively related to preeclampsia risk (Ptrend < 0·001). The highest tertile of E-DII was 2·18 times the lowest tertiles (95 % CI = 1·52, 3·13). The odds of preeclampsia increased by 30 % (95 % CI = 18 %, 43 %, P value < 0·001) for each E-DII score increase. The preeclampsia risk was positively associated with IL-2 (OR = 1·07, 95 % CI = 1·03, 1·11), IL-4 (OR = 1·26, 95 % CI = 1·03, 1·54) and transforming growth factor beta (TGF-ß) (OR = 1·17, 95 % CI = 1·06, 1·29). Therefore, proinflammatory diets, corresponding to higher IL-2, IL-4 and TGF-ß levels, were associated with increased preeclampsia risk.

A highly selective and sensitive CdS fluorescent quantum dot for the simultaneous detection of multiple pesticides.

The abuse of pesticides has introduced a large number of residues in soil and drinking water, which can then enter the food chain and the human body. Monitoring pesticide residues and developing simple and fast detection systems for pesticide residues is urgently needed. In this study, we presented one-pot prepared CdS fluorescent quantum dots (QDs) and explored their sensing application for organic pesticides. The CdS QDs can sensitively and selectively detect three different pesticides, dichlorvos (DDVP), paraquat, and glufosinate-ammonium, through different fluorescence responses. Paraquat can effectively quench the fluorescence of the QDs and DDVP can cause remarkable fluorescent enhancement. Glufosinate-ammonium can induce both 150 nm fluorescent blueshifting and 30-fold fluorescent enhancement. The probe exhibited low detection limits for the three pesticides: 1.44 µM for paraquat, 0.23 mM for DDVP, and 49.8 µM for glufosinate-ammonium. Furthermore, based on the results, we utilized the powerful functions of smartphones to establish a concentration-gray value standard curve through RGB values and gray values to realize the qualitative detection and quantitative analysis of DDVP. It is believed that this work presents a new platform for the simultaneous detection of multiple pesticides using a single QDs probe. The present on-site method using a smartphone is of great potential for water monitoring in rural areas.

Reducing lipofuscin accumulation and cardiomyocytic senescence of aging heart by enhancing autophagy.

Cardiomyocytes are particularly prone to lipofuscin accumulation. In the aging heart, lipofuscin accumulation is augmented. This study examined distribution of lipofuscin and senescent cardiomyocytes and evaluated improvement of lipofuscin accumulation and cardiomyocytic senescence of the aging heart after treatment with rapamycin. The results of Schmorl staining, Sudan black staining and autofluorescence detection showed that there was more lipofuscin in the myocardium of the ventricles especially in the left ventricle. The conductive tissue contained less lipofuscin than the myocardium. In the aged hearts, lipofuscin accumulation and senescent cardiomyocytes were increased, and the level of autophagy was reduced. In double staining of Sudan black B and senescence-associated ß-galactosidase, 10%-20% lipofuscin-loaded cardiomyocytes became senescent. All senescent cardiomyocytes contained lipofuscin deposits. After enhancing autophagy with feed of rapamycin for six months, lipofuscin accumulation and senescence of cardiomyocytes were improved in old rats. Colocalization of autophagic structure and lipofuscin as well as electron micrographs showed that some lipofuscin-loaded lysosomes were sequestrated by autophagic structures. This study suggests that rapamycin-enhanced autopahgy is effective for reducing lipofuscinogenesis and promoting degradation of lipofuscin. Therefore, enhancing autophagy is a novel therapy for alleviating lipofuscin accumulation and myocardial senescence.