Effectively Reinforced α-Bi2O3 MPs/PDA-RGO Sensor for Selective Modality Sensing of a Hazardous Phenolic Compound.

The phenolic compound trichlorophenol (TCP) is an ingredient in fungicides and herbicides. This compound's high stability, bioaccumulation, toxicity, and poor biodegradability result in severe environmental and biological health issues. Consequently, it is crucial to have an affordable and sensitive method for detecting TCP in environmental samples. In this study, α-phase bismuth oxide microplates and polydopamine-functionalized reduced graphene oxide (α-Bi2O3 MPs/PDA-RGO) were synthesized using a simple ultrasonic method and characterized with various analytical and physical characterizations. The conversion of the catechol moieties present in the resulting PDA-RGO material into quinones facilitates productive interactions with diverse functional groups, such as hydroxyl, amine, and imine. Consequently, the compounds 2,4,6-trichlorophenol (TCP) engages in electrochemical interactions with the aforementioned functional groups. As a result, TCP shows more excellent selectivity on the designed α-Bi2O3 MPs/PDA-RGO/SPCE sensor. Under the optimized conditions, the sensor demonstrated a lower detection limit (0.0042 µM), a limit of quantification (0.0078 µM), good sensitivity (2.24 µA µM-1 cm2), a wide linear range (0.019-190.7 and 212.7-1649 µM), and pinpoint specificity. The efficacy of the sensor is additionally validated through the accurate identification of TCP residues in water, soil, and food samples.

Iron-Catalyzed Synthesis of Peroxylpyrrolo[2,1-a]isoquinolines through Oxidative Dearomatization.

A mild late-stage modification of pyrrolo[2,1-a]isoquinolines was established through iron-catalyzed oxidative dearomatization and peroxidation. Peroxylated pyrroloisoquinolines have been prepared readily with hydroperoxide in low to good yields (up to 72%) at room temperature. Interestingly, the treatment of fully aromatized pyrrolo[1,2-a]quinolines under the current reaction system resulted in the formation of ring-opening products.

Stress and safety of maternal and newborn healthcare workers early in the COVID-19 pandemic: a repeat cross-sectional analysis from a global online survey from March 2020 to March 2021.

OBJECTIVES: This study aims to characterise the physical and psychological well-being of maternal and newborn healthcare workers (MNHCWs) during the COVID-19 pandemic. DESIGN: Observational repeated cross-sectional study. SETTING: An online questionnaire was distributed to MNHCWs around the globe in three separate rounds from March 2020 to March 2021. PARTICIPANTS: Total samples of N=1357 (round 1) and N=420 (round 3) primarily consisted of doctors, midwives and nurses in maternal and newborn specialties. Samples represented all WHO regions, with 33% (round 1) and 42% (round 3) from low- or middle-income countries (LMICs). PRIMARY AND SECONDARY OUTCOME MEASURES: Responses from rounds 1 (March-June 2020) and 3 (December 2020-March 2021) were analysed to measure self-reported levels of relative stress and workplace protection from COVID-19, while associated factors were determined through multivariable ordinal logistic regression. RESULTS: In round 1, 90% of MNHCWs reported increased stress levels and 45% reported insufficient personal protective equipment (PPE) access. Nurses and physicians were less likely to report increased stress than midwives at the pandemic onset. Factors associated with increased stress included being female, being from an LMIC and insufficient PPE. In round 3, 75% reported similar or increased stress while 10% reported insufficient PPE. In both rounds, over 50% of MNHCWs felt relatively or completely unprotected from COVID-19 in the workplace. Those from LMICs were more likely to report feeling unprotected, while receiving organisational information that valued safety was associated with better feelings of protection in the workplace. CONCLUSIONS: Among our international sample of MNHCWs, we observed high rates of self-reported stress increase at the start of the pandemic with persistence or increase up to a year later. High rates of feeling unprotected persisted even as PPE became more available. These results may inform interventions needed to support and protect MNHCWs during this and future pandemics.

Choroidal thickness, myopia, and myopia control interventions in children: a Meta-analysis and systemic review.

AIM: To investigate changes of choroidal thickness (ChT) in children with myopia and the effect of current myopia control interventions on ChT. METHODS: Major literature databases were searched for studies relevant to myopia in children. All studies used swept-source optical coherence tomography (SS-OCT) or enhanced depth imaging optical coherence tomography (EDI-OCT) to measure the ChT value. The weighted mean difference (WMD) and 95% confidence interval (CI) were pooled to evaluate ChT in myopia children. RESULTS: A total of 11 eligible articles, including 1693 myopic and 1132 non-myopic eyes, were included in the first Meta-analysis. The sub-foveal choroidal thickness (SFCT; WMD=-40.06, 95%CI, -59.36 to -20.75, P<0.001) and ChT at other sectors were significantly thinner in myopic eyes compared with the non-myopic eyes. The Meta-analysis revealed that the ChT decreased horizontally from the temporal sector toward the nasal sector in the pediatric myopia population. Another 11 studies reporting the effect of myopia control interventions were included in the second Meta-analysis for the relationship between myopia control treatments and ChT. SFCT significantly increased after orthokeratology (OK) treatment and OK combined with 0.01% atropine (OKA) treatment (WMD=19.47, 95%CI, 15.96 to 22.98, P<0.001; WMD=21.81, 95%CI, 12.92 to 29.70, P<0.001, respectively). The forest plots showed that SFCT changed little in myopic children receiving 0.01% atropine (P=0.30). Furthermore, the Meta-analysis showed that OK treatment had a stronger effect on the value of SFCT in myopic children as compared with 0.01% atropine (WMD=9.86; 95%CI, -0.21 to 19.93, P=0.05). There is no difference between the treatment with OK and OKA treatment in ChT in myopic children (P=0.37). CONCLUSION: The ChT in myopic eyes is thinner than that in non-myopic eyes in pediatric population. Myopia control interventions including OK and OKA lead to ChT thickening, but other treatments such as 0.01% atropine did not show an increase in ChT.

Research Progress on the SERPINE1 Protein and Chronic Inflammatory Diseases of the Upper Respiratory Tract: A Literature Review.

SERPINE1 protein is one important member of the serine proteinase inhibitor E superfamily that plays a crucial role in the fibrinolytic system. It has been identified which is related to chronic inflammatory lung diseases like allergic asthma and lung fibrosis. Recently, researchers have focused on the impact of SERPINE1 and its genetic polymorphisms on inflammatory diseases of the upper respiratory tract. In this review, we conclude that SERPINE1 is widely involved in the pathological process of chronic rhinosinusitis and allergic rhinitis (AR) and may play a pivotal role in tissue remodelling in chronic rhinosinusitis without nasal polyps. It is also found that the 4G allele of SERPINE1 gene is associated with the risk of upper respiratory diseases. More studies are needed to further clarify how SERPINE1 influences chronic rhinosinusitis and AR, which would be conducive to improving the therapeutic efficacy of treatments for upper respiratory diseases.

Progress, Mechanisms and Applications of Liquid-Metal Catalyst Systems.

Among the significant growths of liquid metal (LM) research achieved over the past few years, the field of LM as catalysts offers promising opportunities for material scientists to exploit, and thus, burgeoning progress has been made. This article presents an overview of recent progress in developing LM catalysis, which spans from liquid-phase catalysts, photocatalysts, heterogeneous catalysts, and bimetallic catalysts, to catalysts based on liquid-metal/metal-oxide (LM/MO) frameworks. The different types, preparation methods, and typical applications of LM catalysts are classified and reviewed. Typical catalytic applications of LM systems discussed include the growth of graphene films/nanoribbons/carbon nanotube, photocatalytic degradation of CR or PFOA/splitting of H2 O/reduction of CO2 , and catalytic reactions like butane or acetylene dehydrogenation, methanol steam reforming, and reduction of potassium ferricyanide. The prospects, future trends, and challenges of LM catalysts are also mentioned.

SIRT2 Acts as a Cardioprotective Deacetylase in Pathological Cardiac Hypertrophy.

BACKGROUND: Pathological cardiac hypertrophy induced by stresses such as aging and neurohumoral activation is an independent risk factor for heart failure and is considered a target for the treatment of heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. We aimed to investigate the roles of SIRT2 in aging-related and angiotensin II (Ang II)-induced pathological cardiac hypertrophy. METHODS: Male C57BL/6J wild-type and Sirt2 knockout mice were subjected to the investigation of aging-related cardiac hypertrophy. Cardiac hypertrophy was also induced by Ang II (1.3 mg/kg/d for 4 weeks) in male C57BL/6J Sirt2 knockout mice, cardiac-specific SIRT2 transgenic (SIRT2-Tg) mice, and their respective littermates (8 to ≈12 weeks old). Metformin (200 mg/kg/d) was used to treat wild-type and Sirt2 knockout mice infused with Ang II. Cardiac hypertrophy, fibrosis, and cardiac function were examined in these mice. RESULTS: SIRT2 protein expression levels were downregulated in hypertrophic hearts from mice. Sirt2 knockout markedly exaggerated cardiac hypertrophy and fibrosis and decreased cardiac ejection fraction and fractional shortening in aged (24-month-old) mice and Ang II-infused mice. Conversely, cardiac-specific SIRT2 overexpression protected the hearts against Ang II-induced cardiac hypertrophy and fibrosis and rescued cardiac function. Mechanistically, SIRT2 maintained the activity of AMP-activated protein kinase (AMPK) in aged and Ang II-induced hypertrophic hearts in vivo as well as in cardiomyocytes in vitro. We identified the liver kinase B1 (LKB1), the major upstream kinase of AMPK, as the direct target of SIRT2. SIRT2 bound to LKB1 and deacetylated it at lysine 48, which promoted the phosphorylation of LKB1 and the subsequent activation of LKB1-AMPK signaling. Remarkably, the loss of SIRT2 blunted the response of AMPK to metformin treatment in mice infused with Ang II and repressed the metformin-mediated reduction of cardiac hypertrophy and protection of cardiac function. CONCLUSIONS: SIRT2 promotes AMPK activation by deacetylating the kinase LKB1. Loss of SIRT2 reduces AMPK activation, promotes aging-related and Ang II-induced cardiac hypertrophy, and blunts metformin-mediated cardioprotective effects. These findings indicate that SIRT2 will be a potential target for therapeutic interventions in aging- and stress-induced cardiac hypertrophy.

SIRT1 deacetylates the cardiac transcription factor Nkx2.5 and inhibits its transcriptional activity.

The homeodomain transcription factor Nkx2.5/Csx is critically essential for heart specification, morphogenesis, and homeostasis. Acetylation/deacetylation is important for the localization, stability and activation of transcription factors. It remains unknown how Nkx2.5 is deacetylated and how Nkx2.5 acetylation determines its activity. In this study, we provide evidence that the NAD+-dependent class III protein deacetylase SIRT1 deacetylates Nkx2.5 in cardiomyocytes and represses the transcriptional activity of Nkx2.5. We show that SIRT1 interacts with the C-terminus of Nkx2.5 and deacetylates Nkx2.5 at lysine 182 in the homeodomain. The mutation of Nkx2.5 at lysine 182 reduces its transcriptional activity. Furthermore, SIRT1 inhibits the transcriptional activity of Nkx2.5 and represses the expression of its target genes partly by reducing Nkx2.5 binding to its co-factors, including SRF and TBX5. Taken together, these findings demonstrate that SIRT1 deacetylates Nkx2.5 and inhibits the transcriptional activity of Nkx2.5.

SIRT1 mediates the protective function of Nkx2.5 during stress in cardiomyocytes.

Nkx2.5 plays protective roles in cardiac homeostasis and survival in the postnatal hearts. However, the underlying molecular mechanisms that mediate the protective functions of Nkx2.5 remain unknown. Here, we showed that Nkx2.5 was downregulated in response to various stresses and was required for protection against the stress-induced apoptosis of cardiomyocytes. SIRT1, a member of the sirtuin family of proteins, was found to be a direct transcriptional target of Nkx2.5 and was required for the Nkx2.5-mediated protection of cardiomyocytes from doxorubicin (DOX)-induced apoptosis. Moreover, using chromatin immunoprecipitation assays, we found that Nkx2.5 was able to bind to the SIRT1 promoter and that this binding was significantly decreased in DOX-treated mouse hearts. Furthermore, the cardiac-specific overexpression of SIRT1 decreased the DOX-induced apoptosis of cardiomyocytes in SIRT1 transgenic mouse hearts compared with the hearts of their wild-type littermates. These findings demonstrate that SIRT1 acts as a direct transcriptional target of Nkx2.5 that maintains cardiomyocyte homeostasis and survival.

Lysine-specific demethylase 1 represses THP-1 monocyte-to-macrophage differentiation.

OBJECTIVE: To investigate the role of lysine-specific demethylase 1 (LSD1) in the process of THP-1 monocyte-to-macrophage differentiation. METHODS: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting were performed to analyze the expression of LSD1 and interleukin-6 (IL-6) in THP-1 monocytes and THP-1-derived macrophages. Chromatin immunoprecipitation (ChIP) assay was applied to detect the occupancy of LSD1 and H3K4 methylation at IL-6 promoter during THP-1 monocyte-to-macrophage differentiation. IL-6 mRNA level and H3K4 methylation at IL-6 promoter were analyzed using qRT-PCR and ChIP assay in LSD1-knockdown THP-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) for 0, 4, 8, 12, and 24 hours. Fluorescence activated flow cytometry was performed to reveal the percentage of macrophages differentiated from THP-1 monocytes. RESULTS: The expression of LSD1 reduced during THP-1 monocyte-to-macrophage differentiation (P<0.01). LSD1 occupancy decreased and H3K4 methylation increased at IL-6 promoter during the differentiation. With knockdown of LSD1, H3K4 methylation at IL-6 promoter was found increased after TPA treatment at different times points (all P<0.05, except 24 hours). The percentage of macrophages increased significantly in the THP-1 cells with LSD1 knockdown (P<0.05). CONCLUSIONS: LSD1 is repressed during the monocyte-to-macrophage differentiation of THP-1 cells. Suppression of LSD1-mediated H3K4 demethylation may be required for THP-1 monocyte-to-macrophage differentiation.

Mitofilin regulates cytochrome c release during apoptosis by controlling mitochondrial cristae remodeling.

Mitochondria amplify caspase-dependent apoptosis by releasing proapoptotic proteins, especially cytochrome c. This process is accompanied by mitochondrial cristae remodeling. Our studies demonstrated that mitofilin, a mitochondrial inner membrane protein, acted as a cristae controller to regulate cytochrome c release during apoptosis. Knockdown of mitofilin in HeLa cells with RNAi led to fragmentation of the mitochondrial network and disorganization of the cristae. Mitofilin-deficient cells showed cytochrome c redistribution between mitochondrial cristae and the intermembrane space (IMS) upon intrinsic apoptotic stimuli. In vitro cytochrome c release experiments further confirmed that, compared with the control group, tBid treatment led to an increase in cytochrome c release from mitofilin-deficient mitochondria. Furthermore, the cells with mitofilin knockdown were more prone to apoptosis by accelerating cytochrome c release upon the intrinsic apoptotic stimuli than controls. Moreover, mitofilin deficiency did not interfere with the activation of proapoptotic member Bax upon intrinsic apoptotic stimuli. Thus, mitofilin distinctly functions in cristae remodeling and controls cytochrome c release during apoptosis.