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Pathological cardiac hypertrophy serves as a significant foundation for cardiac dysfunction and heart failure. Recently, growing evidence has revealed that microRNAs (miRNAs) play multiple roles in biological processes and participate in cardiovascular diseases. In the present research, we investigate the impact of miRNA-34c-5p on cardiac hypertrophy and the mechanism involved. The expression of miR-34c-5p was proved to be elevated in heart tissues from isoprenaline (ISO)-infused mice. ISO also promoted miR-34c-5p level in primary cultures of neonatal rat cardiomyocytes (NRCMs). Transfection with miR-34c-5p mimic enhanced cell surface area and expression levels of foetal-type genes atrial natriuretic factor (Anf) and β-myosin heavy chain (β-Mhc) in NRCMs. In contrast, treatment with miR-34c-5p inhibitor attenuated ISO-induced hypertrophic responses. Enforced expression of miR-34c-5p by tail intravenous injection of its agomir led to cardiac dysfunction and hypertrophy in mice, whereas inhibiting miR-34c-5p by specific antagomir could protect the animals against ISO-triggered hypertrophic abnormalities. Mechanistically, miR-34c-5p suppressed autophagic flux in cardiomyocytes, which contributed to the development of hypertrophy. Furthermore, the autophagy-related gene 4B (ATG4B) was identified as a direct target of miR-34c-5p, and miR-34c-5p was certified to interact with 3′ untranslated region of Atg4b mRNA by dual-luciferase reporter assay. miR-34c-5p reduced the expression of ATG4B, thereby resulting in decreased autophagy activity and induction of hypertrophy. Inhibition of miR-34c-5p abolished the detrimental effects of ISO by restoring ATG4B and increasing autophagy. In conclusion, our findings illuminate that miR-34c-5p participates in ISO-induced cardiac hypertrophy, at least partly through suppressing ATG4B and autophagy. It suggests that regulation of miR-34c-5p may offer a new way for handling hypertrophy-related cardiac dysfunction.

Switchable dielectric materials are attracting tremendous interest due to their low cost of manufacture, environment protection and structural flexibility. However, most of them have a single function. Here, we report one switchable dielectric material with high phase transition temperature based on 4-Ethylmorpholine. [4-Ethylmorpholine]2MnCl4 with the phase transition temperature of 425 K. What is more interesting is that this compound also has photoluminescence characteristic. Owing to the excellent switchable dielectric transition and efficacious Photoluminescence, this work may extend the application of switchable dielectric materials in the field of luminescence and multifunctional devices.

MicroRNAs (miRNAs) regulate multiple biological processes and participate in various cardiovascular diseases. This study aims to investigate the role of miR-339-5p in cardiomyocyte hypertrophy and the involved mechanism. Neonatal rat cardiomyocytes (NRCMs) were cultured and stimulated with isoproterenol (ISO). The hypertrophic responses were monitored by measuring the cell surface area and expression of hypertrophic markers including β-myosin heavy chain (β-MHC) and atrial natriuretic factor (ANF). Bioinformatic prediction tools and dual-luciferase reporter assay were performed to identify the target gene of miR-339-5p. Quantitative real-time polymerase chain reaction and Western blot analysis were used to determine the levels of miR-339-5p and its downstream effectors. Our data showed that miR-339-5p was up-regulated during cardiomyocyte hypertrophy triggered by ISO. MiR-339-5p overexpression resulted in enlargement of cell size and increased the levels of hypertrophic markers. In contrast, inhibition of miR-339-5p significantly attenuated ISO-induced hypertrophic responses of NRCMs. Valosin-containing protein (VCP), a suppressor of cardiac hypertrophy via inhibiting mechanistic target of rapamycin (mTOR) signaling, was validated as a target of miR-339-5p. MiR-339-5p suppressed VCP protein expression, leading to elevated phosphorylation of mTOR and ribosomal protein S6 kinase (S6K). VCP depletion activated the mTOR/S6K cascade and could compromise the anti-hypertrophic effects of miR-339-5p inhibitor. Additionally, the hypertrophic responses caused by miR-339-5p was alleviated in the presence of mTOR inhibitor rapamycin. In conclusion, our research revealed that miR-339-5p promoted ISO-induced cardiomyocyte hypertrophy by targeting VCP to activate the mTOR signaling, suggesting a promising therapeutic intervention by interfering miR-339-5p. This article is protected by copyright. All rights reserved.

A method for fast and highly sensitive detection of antibodies in serum would greatly facilitate the early diagnosis of disease and infection and dose optimization of therapeutic antibody. Bioluminescence detection with LUMABS (renamed mNeonG-LUMABS, where mNeonG is short for mNeonGreen) sensors based on bioluminescence resonance energy transfer (BRET) between blue-emitting luciferase Nluc and green fluorescent protein (FP) mNeonGreen has been demonstrated to enable fast detection of antibodies directly in serum with reasonable sensitivity. However, some mNeonG-LUMABS sensors exhibit low sensitivity, and thus, sensitivity improvement remains imperative. Here, we report a bright green FP, Clover4, obtained by structure-guided mutagenesis of green FP Clover. Despite similar brightness and fluorescence spectra of Clover and mNeonGreen, Clover4-LUMABS sensors exhibit a largely increased dynamic range (maximum 20-fold) and much lower limit of detection (LOD) (maximum 5.6-fold), most likely because Clover4 is positioned in a more parallel orientation to Nluc in LUMABS. Due to modular design, Clover4-LUMABS offers a general BRET system for fast and highly sensitive antibody detection in serum.

Controlling the interaction of wetting surface with biomaterials is one of the key challenges in nanostructures to promote non-toxic and one-step fabrication technology. Here, a range spectrum of surface wettability characteristics and nanostructure modalities were demonstrated with a single treatment of glutaraldehyde (GA) on polyvinyl alcohol, poly (3,4-ethylene dioxythiophene)-poly (styrene sulfonate) (PVA/PEDOT:PSS) nanofiber mats. By modulating the density of coral-like dendritic nanostructure formation functionalized on PVA and PVA/PEDOT:PSS composite nanofibers and the degree of cross-linking between PVA/PEDOT:PSS and GA, the normally super hydrophilic behavior can be modified to show increasing hydrophobic characteristics correlating with an increased concentration of GA. The results of this study indicated the possibility and applicability of wettability effects available to a single application process alone, where the unique anti-dust wetting behavior can be predicted by estimating the adhesion force (~ maximum value of 24.20 μN) of water droplet. As a result of these nanostructure formations, the water droplet can exhibit hysteresis (CAr = 38 ± 0.5°, CAa = 106 ± 0.5°) and adhere to the nanofiber surface of glass substrate. This task may contribute to its potential optimization for use in a large range of future surface treatment for bio-coating and bio-sensing applications.

Background Alcohol consumption and smoking are the leading risk factors for laryngeal cancer (LC). Understanding the variations in disease burden of LC attributable to alcohol use and smoking is critical for LC prevention. Methods Disease burden data of LC were retrieved from the Global Burden of Disease Study 2019. We used estimated average percentage change (EAPC) to measure the temporal trends of the age-standardized mortality rate (ASMR) of LC. Results Globally, while the ASMR of LC decreased by 1.49% (95% CI, 1.41–1.57%) per year between 1990 and 2019, the number of deaths from LC has increased 41.0% to 123.4 thousand in 2019. In 2019, 19.4 and 63.5% of total LC-related deaths were attributable to alcohol use and smoking worldwide, respectively. The ASMR of alcohol- and smoking-related LC decreased by 1.78 and 1.93% per year, whereas the corresponding death number has increased 29.2 and 25.1% during this period, respectively. The decreasing trend was more pronounced in developed countries. In some developing countries, such as Guinea and Mongolia, the LC mortality has shown an unfavorable trend. Conclusion The ubiquitous decrease in LC mortality was largely attributed to the smoking control and highlighted the importance of smoking control policies. However, the disease burden of LC remained in increase and more effective strategies are needed to combat the global increase of alcohol consumption.

In this study, the acid sites on the surface of the catalyst were quantitatively analyzed by pyridine adsorption infrared spectroscopy. When the molar ratio of V/P is 5, the molar ratio of HCl/V is 3, and the calcination temperature is 450 °C, the selective catalytic reduction effect of NO over VPO/TiO2 catalyst is the best (up to 99% at 200 °C), and the acidity of the catalyst is the highest, which is 5600 μmol·g−1. The results showed that the SCR activity of VPO/TiO2 catalyst increased with the increase of acidity at low temperature. Furthermore, the correlation between the denitration activity and the surface acid level was established by means of data fitting. The results showed that the low temperature denitrification activities of all VPO/TiO2 catalysts were positively correlated with the content of weak Lewis acid center (correlation coefficient > 0.9). In conclusion, this study provides a new method for analyzing the structure–activity relationship of the catalyst and provides some theoretical basis for the design of NH3-SCR catalyst.

Baicalein is a biologically important flavonoid in extracted from the Scutellaria baicalensis Georgi, which can effectively inhibit the influenza virus. This study aimed to analyze the safety and pharmacokinetic (PK) characteristics of baicalein tablets in healthy Chinese subjects and provide more information for phase II clinical trials. In this multiple‐ascending‐dose placebo‐controlled trial, 36 healthy subjects were randomized to receive 200, 400, and 600 mg of baicalein tablet or placebo once daily on day 1 and day 10, 3 times daily on days 4–9. All groups were intended to produce safety and tolerability outcomes (lowest dose first). Blood and urine samples were collected from subjects in the 600 mg group for baicalein PK analysis. Our study had shown that Baicalein tablet was generally safe and well‐tolerated. All adverse events were mild and resolved without any intervention except one case of fever reported in the 600 mg group, which was considered as moderate but not related with baicalein as judged by the investigator. Oral baicalein tablets were rapidly absorbed with peak plasma levels being reached within 2 h after multiple administration. The highest urinary excretion of baicalein and its metabolites peaked in 2 h, followed by 12 h, with a double peak trend.

This study aimed to investigate the therapeutic potential of human umbilical cord mesenchymal stem cells derived exosomes (hUCMSC-Exo) in acute liver failure (ALF) in mice as well as its underlying mechanism. We found that a single tail vein administration of hucMSC-Exo effectively enhanced the survival rate, inhibited apoptosis in hepatocytes, and improved liver function in APAP-induced mouse model of ALF. Furthermore, the deletion of glutathione (GSH) and superoxide dismutase (SOD), generation of malondialdehyde (MDA), and the over production of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP were also inhibited by hucMSC-Exo, indicating that hucMSC-Exo inhibited APAP-induced apoptosis of hepatocytes by reducing oxidative stress. Moreover, hucMSC-Exo significantly down-regulated the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in APAP-treated livers. Western blot showed that hucMSC-Exo significantly promoted the activation of ERK1/2 and IGF-1R/PI3K/AKT signaling pathways in APAP-injured LO2 cells, resulting in the inhibition of apoptosis of LO2 cells. Importantly, PI3K inhibitor LY294002 and ERK1/2 inhibitor PD98059 could reverse the function of hucMSC-Exo on APAP-injured LO2 cells in some extent. Our results suggest that hucMSC-Exo offer antioxidant hepatoprotection against APAP in vitro and in vivo by inhibitiing oxidative stress-induced apoptosis via upregulation of ERK1/2 and PI3K/AKT signaling pathways.

It is unclear how Toll-like receptor (TLR) 4 signaling affects protein succinylation in the brain after intracerebral hemorrhage (ICH). Here, we constructed a mouse ICH model to investigate the changes in ICH-associated brain protein succinylation, following a treatment with a TLR4 antagonist, TAK242, using a high-resolution mass spectrometry-based, quantitative succinyllysine proteomics approach. We characterized the prevalence of approximately 6700 succinylation events and quantified approximately 3500 sites, highlighting 139 succinyllysine site changes in 40 pathways. Further analysis showed that TAK242 treatment induced an increase of 29 succinyllysine sites on 28 succinylated proteins and a reduction of 24 succinyllysine sites on 23 succinylated proteins in the ICH brains. TAK242 treatment induced both protein hypersuccinylations and hyposuccinylations, which were mainly located in the mitochondria and cytoplasm. GO analysis showed that TAK242 treatment-induced changes in the ICH-associated succinylated proteins were mostly located in synapses, membranes and vesicles, and enriched in many cellular functions/compartments, such as metabolism, synapse, and myelin. KEGG analysis showed that TAK242-induced hyposuccinylation was mainly linked to fatty acid metabolism, including elongation and degradation. Moreover, a combined analysis of the succinylproteomic data with previously published transcriptome data revealed that most of the differentially succinylated proteins induced by TAK242 treatment were mainly distributed throughout neurons, astrocytes, and endothelial cells, and the mRNAs of seven and three succinylated proteins were highly expressed in neurons and astrocytes, respectively. In conclusion, we revealed that several TLR4 signaling pathways affect the succinylation processes and pathways in mouse ICH brains, providing new insights on the ICH pathophysiological processes. Data are available via ProteomeXchange with identifier PXD025622.

Oxygen homeostasis disturbances play a critical role in the pathogenesis of acute kidney injury (AKI). The transcription factor hypoxia-inducible factor-1 (HIF-1) is a master regulator of adaptive responses to hypoxia. Aside from posttranslational hydroxylation, the mechanism of HIF-1 regulation in AKI remains largely unclear. In this study, the mechanism of HIF-α regulation in AKI was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level in ischemia-reperfusion-, unilateral ureteral obstruction-, and sepsis-induced AKI models, which was closely associated with macrophage-dependent inflammation. Meanwhile, NF-κB, which plays a central role in the inflammation response, was involved in the increasing expression of HIF-1α in AKI, as evidenced by pharmacological modulation (NF-κB inhibitor BAY11-7082). Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription, which occurred not only under hypoxic conditions but also under normoxic conditions. Moreover, the induced HIF-1α by inflammation protected against tubular injury in AKI. Thus, our findings not only provide novel insights into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases.NEW & NOTEWORTHY Here, the mechanism of hypoxia-inducible factor-α (HIF-α) regulation in acute kidney injury (AKI) was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level, which was closely associated with macrophage-dependent inflammation. Meanwhile, NF-κB was involved in the increasing expression of HIF-1α in AKI. Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription. Our findings not only provide novel insights into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases.

ATG4D, a member of autophagy-related protein 4 (ATG4) family, plays an interplay role between autophagy and apoptosis in cancers. However, the role of ATG4D in hepatocellular carcinoma (HCC) has not been defined. Herein, this study aimed to investigate the role and the underlying mechanism of ATG4D in regulating HCC cell apoptosis. ATG4D was silenced in MHCC-97L HCC cells, and then cell proliferation and apoptosis were examined. ATG4D expression was significantly upregulated in HCC tissues when compared with paired non-tumor tissues. In vitro assays revealed that silencing of ATG4D significantly suppressed cell proliferation, promoted cell apoptosis, and enhanced sensitivity to cisplatin of MHCC-97L cells. Furthermore, silencing of ATG4D decreased the phosphorylation of Akt and increased the protein level of caspase-3. Taken together, ATG4D may play an oncogenic role in HCC progression. These findings suggest that ATG4D may serve as a therapeutic target for HCC therapy.

RNA modifications, such as N6-methyladenosine (m6A), modulate functions of cellular RNA species. However, quantifying differences in RNA modifications has been challenging. Here we develop a computational method, xPore, to identify differential RNA modifications from nanopore direct RNA sequencing (RNA-seq) data. We evaluate our method on transcriptome-wide m6A profiling data, demonstrating that xPore identifies positions of m6A sites at single-base resolution, estimates the fraction of modified RNA species in the cell and quantifies the differential modification rate across conditions. We apply xPore to direct RNA-seq data from six cell lines and multiple myeloma patient samples without a matched control sample and find that many m6A sites are preserved across cell types, whereas a subset exhibit significant differences in their modification rates. Our results show that RNA modifications can be identified from direct RNA-seq data with high accuracy, enabling analysis of differential modifications and expression from a single high-throughput experiment.

Despite the robust mechanical properties of bamboo, interaction with water can result in the instability of these properties. Hygroscopicity is closely related to the chemical content of bamboo. Here, we explored the influence of the chemical composition of bamboo on moisture content from both the equilibrium state and dynamic aspects. We used a simple manufacturing separation process to obtain bamboo fibers (C). A chemical treatment was then used to remove the lignin and hemicellulose, thus altering the chemical content and exposing a greater number of functional groups. We obtained the RL (partial lignin removal) sample via the removal of lignin and the RLH (partial lignin and hemicellulose removal) sample via the removal of lignin and hemicellulose, respectively. The characteristics of the samples were tested using scanning electron microscope, infrared spectrometer and X-ray. And then the hygroscopicity was tested. At 90% relative humidity, the removal of the lignin reduced the weight by 13.30 wt% and increased RL moisture content by 2.99%, while the removal of lignin and hemicellulose reduced the RLH moisture content by 1.94%. At low humidity, RL and RLH have similar hygroscopicity. The RLH sample exhibited the lowest hysteresis out of all the samples. The lignin exhibited an obvious inhibitory effect on the hygroscopicity, while the presence of hemicellulose increased the moisture content of the materials, which is not conducive to their dimensional stability. Moreover, the hygroscopicity of cellulose and hemicellulose is similar. In particular, the chemical-treated samples responded more sensitively and quickly to water through dynamic changes in the weight of the water.

Studies showed that the increase of myeloid‐derived suppressor cells (MDSCs) in tumour microenvironment is closely related to the resistant treatment and poor prognosis of metastatic breast cancer. However, the effect of tumour‐derived exosomes on MDSCs and its mechanism are not clear. Here, we reported that breast cancer cells (4T1)‐secreted exosomes (BCC‐Ex) were able to differentiate bone marrow cells into MDSCs and significantly inhibited the proliferation of T lymphocytes to provide an immunosuppressive microenvironment for cancer cells in vivo and in vitro. The number of MDSCs in bone marrow and spleen of 4T1 tumour‐bearing mice and BCC‐Ex infused mice was significantly higher than that of normal mice, whereas the number of T lymphocytes in spleen was significantly decreased. In addition, BCC‐Ex markedly promoted the differentiation of MDSCs from bone marrow cells or bone marrow cells derived macrophages, seen as the increased expressions of MDSCs‐related functional proteins Arginase‐1 (Arg‐1) and inducible nitric oxide synthase (iNOS). Furthermore, BCC‐Ex significantly down‐regulated the expressions of chemokine receptor CXCR4 and markedly up‐regulated the levels of inflammatory cytokines IL‐6 and IL‐10 in bone marrow cells and macrophages and remarkably inhibited the division and proliferation of T cells. Importantly, CXCR4 agonist, CXCL12, could reverse the function of BCC‐Ex, indicating that BCC‐Ex‐induced MDSCs might be dependent on the down‐regulation of CXCR4. Western blot showed that BCC‐Ex significantly promoted the phosphorylation of STAT3 in bone marrow cells, resulting in the inhibitions of the proliferation and apoptosis of bone marrow cells, and the aggravation of the differentiation of bone marrow cells into MDSCs.

In this paper, overcharge behaviors and thermal runaway (TR) features of large format lithium-ion (Li-ion) cells with different cathode materials (LiFePO4 (LFP), Li[Ni1/3Co1/3Mn1/3]O2 (NCM111), Li[Ni0.6Co0.2Mn0.2]O2 (NCM622) and Li[Ni0.8Co0.1Mn0.1]O2 (NCM811)) were investigated. The results showed that, under the same overcharge condition, the TR of LFP Li-ion cell occurred earlier compared with the NCM Li-ion cells, indicating its poor overcharge tolerance and high TR risk. However, when TR occurred, LFP Li-ion cell exhibited lower maximum temperature and mild TR response. All NCM Li-ion cells caught fire or exploded during TR, while the LFP Li-ion cell only released a large amount of smoke without fire. According to the overcharge behaviors and TR features, a safety assessment score system was proposed to evaluate the safety of the cells. In short, NCM Li-ion cells have better performance in energy density and overcharge tolerance (or low TR risk), while LFP Li-ion cell showed less severe response to overcharging (or less TR hazards). For NCM Li-ion cells, as the ratio of nickel in cathode material increases, the thermal stability of the cathode materials becomes poorer, and the TR hazards increase. Such a comparison study on large format Li-ion cells with different cathode materials can provide deeper insights into the overcharge behaviors and TR features, and provide guidance for engineers to reasonably choose battery materials in automotive applications.

A new transformation pattern for enantioselective intramolecular hydroacylation has been developed involving an alkene isomerization strategy. Proceeding through a five-membered rhodacycle intermediate, 3-enals were converted to C3 - or C3 ,C5 -chirogenic cyclopentanones with satisfactory yields, diastereoselectivities, and enantioselectivities. A catalytic cycle has been theoretically calculated and the origin of the stereoselection is rationally explained.

Aldosterone exerts an enormous function on proximal tubular cells (PTC) senescence, which is a common pathomechanism contributing to renal dysfunction. Numerous studies have shown that oxidative stress is deeply involved in the pathophysiologic processes of chronic kidney diseases. The study aims to investigate whether autophagy could regulate the process of senescence through oxidative stress in PTC both in vivo and ex vivo. Our results suggested that aldosterone treatment increased the senescence and oxidative stress as evidenced by increased percent of SA-β-Gal positive cells, reactive oxygen species level, expression of NADPH oxidase 4 (NOX4) rather than NOX2, and the up-regulation of p21 in cultured PTC. Furthermore, the alternation of the expression of p62 and LC3-II/LC3-I demonstrated that aldosterone treatment remarkably influenced autophagic flux. NOX4 siRNA treatment or autophagy induction with rapamycin reduced the oxidative stress and senescence in aldosterone-induced PTC. On the contrary, inhibition of autophagy with chloroquine worsened these changes. Similar results were further confirmed in vivo. Our results suggested that autophagy may become a realistic therapeutic strategy against aldosterone-induced PTC injury via improving oxidative stress.

Reductive dechlorination is the most efficient way for depletion of chlorinated organic pollutants (COPs) in anaerobic environment, where the methanogenesis is usually mass-produced. Both processes...

NSD2 is the primary oncogenic driver in t(4;14) multiple myeloma. Using SILAC-based mass spectrometry, we demonstrate a novel role of NSD2 in chromatin remodeling through its interaction with the SWI/SNF ATPase subunit SMARCA2. SMARCA2 was primarily expressed in t(4;14) myeloma cells, and its interaction with NSD2 was noncanonical and independent of the SWI/SNF complex. RNA sequencing identified PTP4A3 as a downstream target of NSD2 and mapped NSD2–SMARCA2 complex on PTP4A3 promoter. This led to a focal increase in the permissive H3K36me2 mark and transcriptional activation of PTP4A3. High levels of PTP4A3 maintained MYC expression and correlated with a 54-gene MYC signature in t(4;14) multiple myeloma. Importantly, this mechanism was druggable by targeting the bromodomain of SMARCA2 using the specific BET inhibitor PFI-3, leading to the displacement of NSD2 from PTP4A3 promoter and inhibiting t(4;14) myeloma cell viability. In vivo, treatment with PFI-3 reduced the growth of t(4;14) xenograft tumors. Together, our study reveals an interplay between histone-modifying enzymes and chromatin remodelers in the regulation of myeloma-specific genes that can be clinically intervened. Significance: This study uncovers a novel, SWI/SNF–independent interaction between SMARCA2 and NSD2 that facilitates chromatin remodeling and transcriptional regulation of oncogenes in t(4;14) multiple myeloma, revealing a therapeutic vulnerability targetable by BET inhibition.

Calcium ions are crucial for the growth and development of photosynthetic organisms, whereas its eco-physiological significance on the edible cyanobacterium Nostoc sphaeroides remains unclear. The percentage of spherical microcolonies from N. sphaeroides vegetative filaments was up to 88–93% after 18 days at higher Ca2+ levels (0.25, 1, and 4 mM), but only about 51% at lower Ca2+ levels (0.01 and 0.06 mM). When cultured at higher Ca2+ levels, N. sphaeroides specific growth rates based on the chlorophyll a content and absolute growth rates based on the dry weight significantly increased by 13–18% and 23–30%, respectively, compared to those at lower Ca2+ levels. The colonies cultured at higher Ca2+ levels exhibited 13–20% increase in light-limited photosynthetic efficiency, 28–42% increase in the maximum electron transport rate and 57–95% increase in the light-saturated photosynthetic rate relative to those at lower Ca2+ levels. The higher Ca2+-treated colonies were more tolerant to high light than lower Ca2+-treated colonies and more rapid recovery of photoinhibited colonies induced by the subsequent dim light was also observed in higher Ca2+-treated colonies. We further found the photosynthetic recovery of photoinhibited colonies required the influx of apoplastic Ca2+ and the maintenance of photosynthetic activity for desiccated colonies during rehydration was also extracellular Ca2+-dependent. These results indicated that higher levels of Ca2+ promoted colony formation, growth, and photosynthesis of N. sphaeroides, suggesting available calcium ions in natural environment may be an important factor affecting its productivity and distribution.

Immune response plays a vital role in the pathogenesis of neuropathic pain. Immune response-targeted therapy becomes an effective strategy for treating neuropathic pain. Licochalcone A (Lic-A) possesses anti-inflammatory and neuroprotective effects. However, the potential of Lic-A to attenuate neuropathic pain has not been well explored. To investigate the protective effect and evaluate the underlying mechanism of Lic-A against neuropathic pain in a rat model. Chronic constriction injury (CCI) surgery was employed in rats to establish neuropathic pain model. Rats were intraperitoneally administrated with Lic-A (1.25, 2.50 and 5.00 mg/kg) twice daily. Mechanical withdrawal threshold and thermal withdrawal latency were used to evaluate neuropathic pain. After administration, the lumbar spinal cord enlargement of rats was collected for ELISA, Western blot and immunofluorescence analysis. Mechanical withdrawal threshold and thermal withdrawal latency results showed that Lic-A significantly attenuated CCI-evoked neuropathic pain in dose-dependent manner. Lic-A administration also effectively blocked microglia activation. Moreover, Lic-A suppressed p38 phosphorylation and the release of inflammatory factors such as tumor necrosis factor-α, interleukin-1 and interleukin-6. Our findings provide evidence that Lic-A may have the potential to attenuate CCI-evoked neuropathic pain in rats by inhibiting microglia activation and inflammatory response.

In this work, a new α–γ-type [Mo8O26]4– anion was first synthesized and characterized by single-crystal X-ray diffraction analysis and was obtained by introducing molybdate to the synthesis of meta...

Background Myocardial infarction (MI), a common type of coronary heart disease, is the major cause of morbidity and mortality around the world. Chemokine-mediated inflammatory cell infiltration and local inflammatory damage response are recent research hotspots. Hence, we attempted to examine the role of C-X-C motif chemokine 16 (CXCL16) as a potential candidate in MI. Methods Human cardiomyocytes were treated with hypoxia/reoxygenation (H/R) to establish an in vitro cell model. GEO database provided the clinical data of MI patients and GSEA verified the relationship of chemokine and MI. CCK-8 and flow cytometry analyses were used to measure cell viability and apoptosis. Bioinformatics analysis and luciferase reporter assay were conducted to determine the correlation between CXCL16 and miR-545. qRT-PCR and western blot assays were performed to investigate the expression level of the indicated genes. The activity of lactate dehydrogenase (LDH) and the levels of TNF-α, IL-6, IL-1β, and IL-10 were explored using ELISA assay. Results CXCL16 was increased in MI. CXCL16 knockdown can reverse the inhibitory effect of H/R treatment on cell viability, while overexpression of CXCL16 showed the opposite trend. MiR-545 directly targeted CXCL16 and negatively regulated CXCL16 levels. MiR-545 promoted cell proliferation and inhibited apoptosis in the MI cell model, which attenuated the CXCL16-induced injury on cardiomyocytes. Conclusion These findings demonstrated that CXCL16 aggravated MI damage through being directly targeted by miR-545 and mediating inflammatory responses, thereby providing potential therapeutic targets for MI therapy.

Collagen is a major structural component of the extracellular matrix and connective tissue. The key structural feature of collagen is the collagen triple helix, with a Xaa-Yaa-Gly (glycine) repeating pattern. The most frequently occurring triplet is Pro (proline)-Hyp (hydroxyproline)-Gly. The reversible thermal folding and unfolding of a series of heterotrimeric collagen triple helices with varying number of Pro-Hyp-Gly triplets were monitored by circular dichroism spectroscopy to determine the unfolding thermodynamic parameters Tm (midpoint transition temperature), ΔHTm (unfolding enthalpy), and ΔGunfold (unfolding free energy). The Tm and ΔGunfold of the heterotrimeric collagen triple helices increased with increasing number of Pro-Hyp-Gly triplets. The ΔGunfold increased by 2.0 ± 0.2 kcal mol-1 upon inserting one Pro-Hyp-Gly triplet into all three chains. The Tm difference between the most stable ABC combination and the second most stable BCC combination decreased with increasing number of Pro-Hyp-Gly triplets, even though the ΔGunfold difference remained the same. These results should be useful for tuning the stability of collagen triple helical peptides for hydrogel formation, recognition of denatured collagen triple helices as diagnostics and therapeutics, and targeted drug delivery.

A nickel-catalyzed strategy for the synthesis of 1,3-diaryl-6H-pyrazino[2,1-b]quinazolin-6-one was developed. This method enabled us to access valuable pyrazino-fused quinazolinones with tolerance of many functional groups even at room temperature. The desired pyrazino-fused quinazolinones emit strongly in both solution and solid states. Furthermore, the thermally-activated delayed fluorescence (TADF) of 3a was investigated. This study provides an efficient synthetic route for the development of TADF-active pyrazino-fused quinazolinones, thus expanding the application range of this versatile molecular scaffold in optoelectronics.

Heterocycle-fused quinazolinone derivatives have attracted great attention due to their diversified biological and optical activities. In this study, a novel one-pot palladium-catalyzed cascade C–C coupling/cyclization/aromatization of 2-(4-oxoquinazolin-3(4H)-yl)acetonitrile derivatives with arylboronic acids has been disclosed to synthesize 1,3-diaryl-6H-pyrazino[2,1-b]quinazolin-6-one in water. This protocol provides an efficient access to valuable pyrazino-fused quinazolinones in a green solvent (i.e., water) with yields ranging from moderate to excellent. Furthermore, the photophysical properties of these molecules were investigated. The resultant pyrazino-fused quinazolinones exhibit tunable fluorescence, and 3e displays the aggregation induced emission properties with a large Stokes shift. This study provides a useful approach to the development of pyrazino-fused quinazolinones, which have potential applications in chemistry, biology, and materials science.

By regulating different metal ions and polyoxometalates (POMs), four Anderson-type POM-based metal-pyrazolamide complexes, namely, {M2(L)2 [XMo6(OH)5O19](H2O)2} (M = Co, X = Cr (1), M = Ni, X = Al (2)) and {M3(L)2[XMo6O24](H2O)6} (X = Te, M = Co (3), M = Ni (4), (L = N,N-bis(3-pyrazolamide)-1,2-ethane)), were obtained under hydrothermal conditions. The results of characterization of IR spectra and powder X-ray diffraction patterns, as well as single-crystal X-ray diffraction analysis, are provided. Complexes 1 and 2 displayed isostructural 1D chains constructed from B-type [CrMo6(OH)5O19]4− anions and [M2(L)2]4+ loops. Complexes 3 and 4 exhibited 2D networks derived from A-type [TeMo6O24]6− anions and [M2(L)2]4+ loops. The effects of the POM types on their structures and properties were investigated. Complexes 1–4 showed electrocatalytic performance for bromate reduction. Only complexes 1 and 2 constructed from B-type Anderson polyoxoanions showed electrocatalytic activity towards the oxidation of dopamine. It is notable that complex 3 after potentiostatic treatment also shows electrocatalytic activity towards the oxidation of dopamine, which indicates that the –OH from the Anderson-type POM played a vital role in the electrocatalytic oxidation of dopamine. All the title complexes showed adsorption activity for gentian violet, and complexes 3 and 4 exhibited better adsorption capacities for methylene blue than 1 and 2.

Background Hyperhomocysteinemia (HHcy) plays an important role in the progression of many kidney diseases; however, the relationship between HHcy and ischemia-reperfusion injury (IRI)-induced acute kidney injury (IRI-induced AKI) is far from clear. In this study, we try to investigate the effect and possible mechanisms of HHcy on IRI-induced AKI. Methods Twenty C57/BL6 mice were reared with a regular diet or high methionine diet for 2 weeks (to generate HHcy mice); after that, mice were subgrouped to receive sham operation or ischemia-reperfusion surgery. Twenty four hour after reperfusion, serum creatinine, blood urea nitrogen, and Malondialdehyde (MDA) were measured. H&E staining for tubular injury, western blot for γH2AX, JNK, p-JNK, and cleaved caspase 3, and TUNEL assay for tubular cell apoptosis were also performed. Results Our results showed that HHcy did not influence the renal function and histological structure, as well as the levels of MDA, γH2AX, JNK, p-JNK, and tubular cell apoptosis in control mice. However, in IRI-induced AKI mice, HHcy caused severer renal dysfunction and tubular injury, higher levels of oxidative stress, DNA damage, JNK pathway activation, and tubular cell apoptosis. Conclusion Our results demonstrated that HHcy could exacerbate IRI-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, JNK pathway activation, and consequent apoptosis.