Advancing Electrically Conductive Metal-Organic Frameworks for Photocatalytic Energy Conversion.

ConspectusPhotocatalytic energy conversion is a pivotal process for harnessing solar energy to produce chemicals and presents a sustainable alternative to fossil fuels. Key strategies to enhance photocatalytic efficiency include facilitating mass transport and reactant adsorption, improving light absorption, and promoting electron and hole separation to suppress electron-hole recombination. This Account delves into the potential advantages of electrically conductive metal-organic frameworks (EC-MOFs) in photocatalytic energy conversion and examines how manipulating electronic structures and controlling morphology and defects affect their unique properties, potentially impacting photocatalytic efficiency and selectivity. Moreover, with a proof-of-concept study of photocatalytic hydrogen peroxide production by manipulating the EC-MOF's electronic structure, we highlight the potential of the strategies outlined in this Account.EC-MOFs not only possess porosity and surface areas like conventional MOFs, but exhibit electronic conductivity through d-p conjugation between ligands and metal nodes, enabling effective charge transport. Their narrow band gaps also allow for visible light absorption, making them promising candidates for efficient photocatalysts. In EC-MOFs, the modular design of metal nodes and ligands allows fine-tuning of both the electronic structure and physical properties, including controlling the particle morphology, which is essential for optimizing band positions and improving charge transport to achieve efficient and selective photocatalytic energy conversion.Despite their potential as photocatalysts, modulating the electronic structure or controlling the morphology of EC-MOFs is nontrivial, as their fast growth kinetics make them prone to defect formation, impacting mass and charge transport. To fully leverage the photocatalytic potential of EC-MOFs, we discuss our group's efforts to manipulate their electronic structures and develop effective synthetic strategies for morphology control and defect healing. For tuning electronic structures, diversifying the combinations of metals and linkers available for EC-MOF synthesis has been explored. Next, we suggest that synthesizing ligand-based solid solutions will enable continuous tuning of the band positions, demonstrating the potential to distinguish between photocatalytic reactions with similar redox potentials. Lastly, we present incorporating a donor-acceptor system in an EC-MOF to spatially separate photogenerated carriers, which could suppress electron-hole recombination. As a synthetic strategy for morphology control, we demonstrated that electrosynthesis can modify particle morphology, enhancing electrochemical surface area, which will be beneficial for reactant adsorption. Finally, we suggest a defect healing strategy that will enhance charge transport by reducing charge traps on defects, potentially improving the photocatalytic efficiency.Our vision in this Account is to introduce EC-MOFs as an efficient platform for photocatalytic energy conversion. Although EC-MOFs are a new class of semiconductor materials and have not been extensively studied for photocatalytic energy conversion, their inherent light absorption and electron transport properties indicate significant photocatalytic potential. We envision that employing modular molecular design to control electronic structures and applying effective synthetic strategies to customize morphology and defect repair can promote charge separation, electron transfer to potential reactants, and mass transport to realize high selectivity and efficiency in EC-MOF-based photocatalysts. This effort not only lays the foundation for the rational design and synthesis of EC-MOFs, but has the potential to advance their use in photocatalytic energy conversion.

Photocatalytic Hydrogen Peroxide Production through Functionalized Semiconductive Metal-Organic Frameworks.

Hydrogen peroxide (H2O2) holds significance as a vital chemical with the potential to serve as an energy carrier. Compared with the conventional anthraquinone process, photocatalytic H2O2 production has emerged as an appealing alternative because of its energy efficiency and environmental sustainability. However, the existing photocatalysts suffer from low catalytic efficiency, limited tunability of optical properties, and reliance on sacrificial agents due to high energy loss caused by inefficient charge separation. Therefore, developing catalysts with tunable optical properties and efficient charge separation is desirable. In this work, we introduce postsynthetic functionalization into an electrically conductive metal-organic framework, namely, DPT-MOF. Leveraging DPT (3,6-di(4-pyridyl)-1,2,4,5-tetrazine) as a pillar ligand, we exploited click-type chemistry to manipulate band position and charge separation efficiency, allowing for photocatalytic nonsacrificial H2O2 production. Notably, the fluorine-functionalized MOF exhibited the highest H2O2 production rate of 1676 µmol g-1 h-1 under visible light in O2-saturated water among our other samples. This high production rate is attributed to the tuned electronic structure and prolonged charge lifetime facilitated by the fluorine groups. This work highlights the effectiveness of postsynthetic methodology in tuning optical properties, opening a promising avenue for advancing the field of semiconductive MOF-based photocatalysis.

Thiatruxene-Based Conductive MOF: Harnessing Sulfur Chemistry for Enhanced Proton Transport.

Functionalizing the organic building blocks of electrically conductive MOFs (EC-MOFs) can be a powerful method for adjusting the electronic structure and introducing a specific chemistry. However, designing EC-MOF linkers with reactive functional groups for postsynthetic modification is challenging due to the requirements of d-p conjugation. This work addresses such design limitations by synthesizing an EC-MOF, Cu-thiatruxene (Cu-thiaTRX). This conductive framework incorporated a truxene-based linker with heterocyclic sulfur, allowing for efficient conjugation and an electrical conductivity of 2.2 × 10-2 S cm-1. Harnessing sulfur chemistry in Cu-thiaTRX involves a two-step postsynthetic modification: oxidation and SNAr. The sulfinic groups introduced in the framework enabled tunable proton conductivity, leading to a 200-fold improvement. These results highlight the importance of a rational linker design for functionalization.

Effect of Antidiabetic Therapy on Clinical Outcomes of COVID-19 Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis.

BACKGROUND: No study has yet systematically evaluated the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with type 2 diabetes (T2D). OBJECTIVE: We aimed to evaluate the effect of different antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. METHODS: We comprehensively retrieved the published research which examined the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. The odds ratio (OR) and its 95% confidence interval (95% CI) for clinical outcomes were calculated using the random-effects model, and meta-regression was adopted to evaluate the potential sources of heterogeneity between studies. RESULTS: A total of 54 studies were included in this study. We found that the use of metformin (OR = 0.66, 95% CI: 0.58-0.75), SGLT-2i (OR = 0.80, 95% CI: 0.73-0.88), and GLP-1ra (OR = 0.83, 95% CI: 0.70-0.98) were significantly associated with lower mortality risk in COVID-19 patients with T2D, while insulin use might unexpectedly increase the ICU admission rate (OR = 2.32, 95% CI: 1.34-4.01) and risk of death (OR = 1.52, 95% CI: 1.32-1.75). No statistically significant associations were identified for DPP-4i, SUs, AGIs, and TZDs. CONCLUSION AND RELEVANCE: We demonstrated that the usage of metformin, SGLT-2i, and GLP-1ra could significantly decrease mortality in COVID-19 patients with T2D. The heterogeneity across the studies, baseline characteristics of the included patients, shortage of dosage and the duration of antidiabetic drugs and autonomy of drug selection might limit the objectivity and accuracy of results. Further adequately powered and high-quality randomized controlled trials are warranted for conclusive findings.

Interconnected versus unconnected microorganisms: Does it matter in anaerobic digestion functioning.

Microorganisms in anaerobic digestion (AD) are essential for wastes/pollutants treatment and energy recovery. Due to microbial enormous diversity, developing effective perspectives to understand microbial roles therein is urgent. This study conducted AD of swine manure, used an ensemble-based network analysis to distinguish interconnected, unconnected, copresence (positively interconnected) and mutual-exclusion (negatively interconnected) microorganisms within microbial communities, and explored their importance towards AD performances, using amplicon sequencing of 16S rRNA and 16S rRNA gene. Our analyses revealed greater importance of interconnected than unconnected microorganisms towards CH4 production and AD multifunctionality, which was attributed to higher niche breadth, deterministic community assembly, community stability and phylogenetic conservatism. The diversity was higher in unconnected than interconnected microorganisms, but was not linked to AD performances. Compared to copresence microorganisms, mutual-exclusion microorganisms showed greater and equal importance towards CH4 production and AD multifunctionality, which was attributed to their roles in stabilizing microbial communities. The increased feedstock biodegradability, by replacing part of manure with fructose or apple waste, hardly affected the relative importance of interconnected versus unconnected microorganisms towards CH4 production or AD multifunctionality. Our findings develop a new framework to understand microbial roles, and have important implications in targeted manipulation of critical microorganisms in waste-treatment systems.

Leveraging Crystalline and Amorphous States of a Metal-Organic Complex for Transformation of the Photosalient Effect and Positive-Negative Photochromism.

Uncovering differences between crystalline and amorphous states in molecular solids would both promote the understanding of their structure-property relationships, as well as inform development of multi-functional materials based on the same compound. Herein, for the first time, we report an approach to leverage crystalline and amorphous states of a zero-dimensional metal-organic complex, which exhibited negative and positive photochromism, due to the competitive chemical routes between photocycloaddition and photogenerated radicals. Furthermore, different polymorphs lead to the on/off toggling of photo-burst movement (photosalient effect), indicating the controllable light-mechanical conversion. Three demos were further constructed to support their application in information encryption and anti-counterfeiting. This work provides the proof-of-concept of a state- and polymorph-dependent photochemical route, paving an effective way for the design of new dynamically responsive systems.

Notch4 mediates vascular remodeling via ERK/JNK/P38 MAPK signaling pathways in hypoxic pulmonary hypertension.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling. METHODS: Lung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. RESULTS: In this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats. CONCLUSIONS: These findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.

Metal-Halide Coordination Polymers with Excitation Wavelength- and Time-Dependent Ultralong Room-Temperature Phosphorescence.

Metal-organic hybrids with ultralong room-temperature phosphorescence (RTP) have potential applications in many fields, including optical communications, anticounterfeiting, encryption, bioimaging, and so on. Herein, we report two isostructural one-dimensional zinc-organic halides as coordination polymers ZnX2(bpp) (X = Cl, 1; Br, 2; bpp = 1,3-di(4-pyridyl)propane) with excitation wavelength- and time-dependent ultralong RTP properties. The dynamic multicolor afterglow can be assigned to the emission of the pristine ligand bpp and its interactions with halogen atoms. Experiments and theoretical calculations both suggest that ZnX2 is crucial for ultralong RTP: (a) the metal coordination and X...π bonds in coordination polymers fix the bpp molecules and suppress the nonradiative transitions; (b) the spin-orbital coupling of coordination polymers is largely enhanced relative to the bpp because of the heavy atom effect; and (c) the charge transfer exists between halogens and bpp ligand. Therefore, this work not only presents metal-halide coordination polymers with excitation wavelength- and time-dependent RTP properties, but also provides a facile method for the new types of dynamic multicolor afterglow materials.

Application of attention-DnCNN for ESPI fringe patterns denoising.

Fringe patterns' denoising in electronic speckle pattern interferometry (ESPI) is an important step in phase extraction. In this study, we propose a new denoising method for ESPI fringe patterns based on a convolutional neural network (CNN). The proposed model which combines the attention mechanism and CNN is defined as attention-denoising CNN. In this model, owing to the attention mechanism, more attention will be paid to fringe information, and better filtering results will be achieved. The experimental results show that our proposed method can obtain excellent results, especially with high and large variation density ESPI fringe patterns.

Dynamic Manipulating Space-Resolved Persistent Luminescence in Core-Shell MOFs Heterostructures via Reversible Photochromism.

Photo-controllable persistent luminescence at the single crystal level can be achieved by the integration of long-lived room temperature phosphorescence (RTP) and photochromism within metal-organic frameworks (MOFs) for the first time. Moreover, the multiblock core-shell heterojunctions have been prepared utilizing the isostructural MOFs through an epitaxial growth process, in which the shell exhibits bright yellow afterglow emission that gradually disappears upon further irradiation, but the core does not show such property. Benefitting from combined persistent luminescence and photochromic behavior, a multiple encryption demo can be facilely designed based on the dynamic manipulating RTP via reversible photochromism. This work not only develops new types of dynamically photo-controllable afterglow switch, but also provides a method to obtain MOFs-based optical heterojunctions towards potential space/time-resolved information encryption and anti-counterfeiting applications.

CENPE contributes to pulmonary vascular remodeling in pulmonary hypertension.

Hypoxic pulmonary vascular remodeling is a pathological feature of pulmonary hypertension (PH). Our results showed that centromere-associated protein E (CENPE) expression in PH patients and hypoxia-induced PH rats was significantly higher than that in normal controls. In addition, CENPE deficiency significantly inhibited the development of pulmonary vascular remodeling and right ventricular hypertrophy. Moreover, knocking out CENPE effectively inhibited the proliferation and induced the apoptosis of primary pulmonary artery smooth muscle cells (PASMCs) in vivo. Furthermore, CENPE silencing by small interference significantly inhibited abnormal proliferation, apoptosis resistance, migration, and cell cycle arrest in hypoxia-induced PASMCs. Interestingly, we found that CENPE might exert its biological effect by targeting the transcription of CDK1 proteins.

TRB3 mediates vascular remodeling by activating the MAPK signaling pathway in hypoxic pulmonary hypertension.

BACKGROUND: Hypoxic pulmonary hypertension (PH) is a refractory pulmonary vascular remodeling disease, and the efficiency of current PH treatment strategies is unsatisfactory. Tribbles homolog 3 (TRB3), a member of the pseudokinase family, is upregulated in diverse types of cellular stresses and functions as either a pro-proliferative or pro-apoptotic factor depending on the specific microenvironment. The regulatory mechanisms of TRB3 in hypoxic PH are poorly understood. METHODS: We performed studies using TRB3-specific silencing and overexpressing lentiviral vectors to investigate the potential roles of TRB3 on hypoxic pulmonary artery smooth muscle cells (PASMCs). Adeno-associated virus type 1(AVV1) vectors encoding short-hairpin RNAs against rat TRB3 were used to assess the role of TRB3 on hypoxic PH. TRB3 protein expression in PH patients was explored in clinical samples by western blot analysis. RESULTS: The results of whole-rat genome oligo microarrays showed that the expression of TRB3 and endoplasmic reticulum stress (ERS)-related genes was upregulated in hypoxic PASMCs. TRB3 protein expression was significantly upregulated by hypoxia and thapsigargin. In addition, 4-PBA and 4µ8C, both inhibitors of ERS, decreased the expression of TRB3. TRB3 knockdown promoted apoptosis and damaged the proliferative and migratory abilities of hypoxic PASMCs as well as inhibited activation of the MAPK signaling pathway. TRB3 overexpression stimulated the proliferation and migration of PASMCs but decreased the apoptosis of PASMCs, which was partly reversed by specific inhibitors of ERK, JNK and p38 MAPK. The Co-IP results revealed that TRB3 directly interacts with ERK, JNK, and p38 MAPK. Knockdown of TRB3 in rat lung tissue reduced the right ventricular systolic pressure and decreased pulmonary medial wall thickness in hypoxic PH model rats. Further, the expression of TRB3 in lung tissues was higher in patients with PH compared with those who have normal pulmonary artery pressure. CONCLUSIONS: TRB3 was upregulated in hypoxic PASMCs and was affected by ERS. TRB3 plays a key role in the pathogenesis of hypoxia-induced PH by binding and activating the ERK, JNK, and p38 MAPK pathways. Thus, TRB3 might be a promising target for the treatment of hypoxic PH.

IL-1ß augments TGF-ß inducing epithelial-mesenchymal transition of epithelial cells and associates with poor pulmonary function improvement in neutrophilic asthmatics.

BACKGROUND: Neutrophilic asthmatics (NA) have less response to inhaled corticosteroids. We aimed to find out the predictor of treatment response in NA. METHODS: Asthmatics (n = 115) and healthy controls (n = 28) underwent clinical assessment during 6-month follow-up with standardized therapy. Asthmatics were categorized by sputum differential cell count. The mRNA expressions were measured by RT-qPCR for sputum cytokines (IFN-γ, IL-1ß, IL-27, FOXP3, IL-17A, and IL-5). The protein of IL-1ß in sputum supernatant was detected by ELISA. Reticular basement membranes (RBM) were measured in the biopsy samples. The role and signaling pathways of IL-1ß mediating the epithelial-mesenchymal transition (EMT) process were explored through A549 cells. RESULTS: NA had increased baseline sputum cell IL-1ß expression compared to eosinophilic asthmatics (EA). After follow-up, NA had less improvement in FEV1 compared to EA. For all asthmatics, sputum IL-1ß mRNA was positively correlated with protein expression. Sputum IL-1ß mRNA and protein levels were negatively correlated to FEV1 improvement. After subgrouping, the correlation between IL-1ß mRNA and FEV1 improvement was significant in NA but not in EA. Thickness of RBM in asthmatics was greater than that of healthy controls and positively correlated with neutrophil percentage in bronchoalveolar lavage fluid. In vitro experiments, the process of IL-1ß augmenting TGF-ß1-induced EMT cannot be abrogated by glucocorticoid or montelukast sodium, but can be reversed by MAPK inhibitors. CONCLUSIONS: IL-1ß level in baseline sputum predicts the poor lung function improvement in NA. The potential mechanism may be related to IL-1ß augmenting TGF-ß1-induced steroid-resistant EMT through MAPK signaling pathways. TRIAL REGISTRATION: This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (IRB ID: 20150406).

Aspartic acid assisted one-step synthesis of stable CsPbX3@Asp-Cs4PbX6 by in situ growth in NH2-MIL-53 for ratiometric fluorescence detection of 4-bromophenoxybenzene.

A molecularly imprinted ratiometric fluorescent sensor was synthesized for the detection of 4-bromophenoxybenzene (BDE-3) based on perovskite quantum dots and metal organic framework. First, aspartic acid (Asp) was introduced during the synthesis of perovskite CsPbX3 for the formation of a core-shell structure of CsPbX3@Asp-Cs4PbX6. Due to the protection of the shell layer Cs4PbX6, the stability of the core CsPbX3 was improved significantly. Compared to CsPb(BrI)3, the ultraviolet and thermal stabilities of CsPb(BrI)3@Asp-Cs4Pb(BrI)6 were increased by 26 times and 32 times, respectively, and, compared to CsPbBr3, these stabilities of CsPbBr3@Asp-Cs4PbBr6 were increased by 3 times and 13 times, respectively. The water stabilities of CsPb(BrI)3@Asp-Cs4Pb(BrI)6 and CsPbBr3@Asp-Cs4PbBr6 were greatly improved too. Then, a ratiometric fluorescence sensor was constructed by in situ growth of CsPb(BrI)3@Asp-Cs4Pb(BrI)6 in metal organic framework (NH2-MIL-53) for the detection of BDE-3, in which the orange fluorescence of CsPb(BrI)3@Asp-Cs4Pb(BrI)6 (614 nm) was regarded as the reference signal and the cyan fluorescence of NH2-MIL-53 (494 nm) was used as the fluorescence response signal. To improve the selectivity of the sensor, the molecular imprinting polymer (MIP) was modified on the NH2-MIL-53 and an imprinting factor of 3.17 was obtained. Under 365 nm light excitation, the fluorescent response signal at 494 nm was quenched gradually by BDE-3 in the range 11.4 to 68.5 nmol/L, while the reference signal at 614 nm remained unchanged. The limit of detection and limit of quantification were 3.35 and 11.2 nmol/L, respectively, and the fluorescent color of the sensor changed gradually from cyan to green to orange, which illustrated that the developed sensor has an ability to recognize BDE-3 specifically, a good anti-interference ability, and a sensitively visual detection ability. Moreover, the sensor was successfully applied to the BDE-3 detection in polyethylene terephthalate plastic bottle, polyvinyl chloride plastic bag, and circuit board with satisfactory recoveries (96.3-108.1%) and low relative standard deviations (5%). The preparation processes of NH2-MIL-53, NH2-MIL-53-CsPb(BrI)3@Asp-Cs4Pb(BrI)6, and the MIP-NH2-MIL-53-CsPb(BrI)3@Asp-Cs4Pb(BrI)6 composites.

TRB3 interacts with ERK and JNK and contributes to the proliferation, apoptosis, and migration of lung adenocarcinoma cells.

Tribbles homolog 3 (TRB3) has been accounted for regulation of a few cell processes through interaction with other significant proteins. The molecular mechanisms underlying TRB3 in tumorigenesis in lung adenocarcinoma have not been entirely elucidated. The present study is aimed at determining the function and fundamental mechanisms of TRB3 in lung adenocarcinoma progression. TRB3 was highly expressed in A549 and H1299 cells and lung adenocarcinoma tissues compared with human bronchial epithelial cells (HBEpC) and adjacent normal lung tissues. Hypoxia significantly upregulated the expression of TRB3 protein in A549 and H1299 cells in a time-dependent way. Gene expression profiling interactive analysis data analysis indicated that patients with lung adenocarcinoma with excessive expression of TRB3 mRNA had fundamentally shorter survival time. TRB3 knockdown in A549 cells can inhibit cell proliferation and migration, and promote cell apoptosis. TRB3 knockdown reduced the expression of p-ERK and p-JNK, but did not affect the expression of p-P38 MAPK. TRB3 overexpression enhances the malignant transformation abilities of HBEpC such as cell proliferation, migration and colony formation, which could be reversed by U0126 and SP600125. TRB3 overexpression promotes the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) but was not affected by U0126 and SP600125. The results of coimmunoprecipitation experiments indicated that TRB3 binds directly to ERK and JNK. This study suggests that TRB3 has a potentially carcinogenic role in lung adenocarcinoma by binding to ERK and JNK and promoting the phosphorylation of ERK and JNK. TRB3 can be a possible therapeutic focus for lung adenocarcinoma.

Manipulating Light-Induced Dynamic Macro-Movement and Static Photonic Properties within 1D Isostructural Hydrogen-Bonded Molecular Cocrystals.

Smart molecular crystals with light-driven mechanical responses have received interest owing to their potential uses in molecular machines, artificial muscles, and biomimetics. However, challenges remain in control over both the dynamic photo-mechanical behaviors and static photonic properties of molecular crystals based on the same molecule. Herein, we show the construction of isostructural co-crystals allows their light-induced cracking and jumping behaviors (photosalient effect) to be controlled. Hydrogen-bonded co-crystals from 4-(1-naphthylvinyl)pyridine (NVP) with co-formers (tetrafluoro-4-hydroxybenzoic acid (THA) and tetrafluorobenzoic acid (TA)) crystallize as isostructural crystals, but have different static and dynamic photo-mechanical behaviors. These differences are due to alternations in the orientation of NVP and hydrogen-bonding modes of the co-formers. After light activation, the 1D NVP-TA crystal splits and shears off within 1 s. For NVP-THA, its photostability and high quantum yield give novel photonic properties, including low optical waveguide loss, highly polarized anisotropy, and efficient up-conversion fluorescence.

Discovery and Biological evaluation of pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione derivatives as potent Bruton's tyrosine kinase inhibitors.

Aberrant activation of B cell receptor (BCR) signal transduction cascade contributes to the propagation and maintenance of B cell malignancies. The discovery of mall molecules with high potency and selectivity against Bruton's tyrosine kinase (BTK), a key signaling molecule in this cascade, is particularly urgent in modern treatment regimens. Herein, a series of pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione derivatives were reported as potent BTK inhibitors. Compounds 17 and 18 displayed strong BTK inhibitory activities in the enzymatic inhibition assay, with the IC50 values of 1.2 and 0.8 nM, respectively, which were comparable to that of ibrutinib (IC50 = 0.6 nM). Additionally, compound 17 had a more selective profile over EGFR than ibrutinib. According to the putative binding poses, the molecular basis of this series of compounds with respect to potency against BTK and selectivity over EGFR was elucidated. In further experiments at cellular level, compounds 17 and 18 significantly inhibited the proliferation of Ramos and TMD8 cells. And they arrested 75.4% and 75.2% of TMD8 cells in G1 phase, respectively, at the concentration of 1 µM.

Different substrate regimes determine transcriptional profiles and gene co-expression in Methanosarcina barkeri (DSM 800).

Methanosarcina barkeri (DSM 800) is a metabolically versatile methanogen and shows distinct metabolic status under different substrate regimes. However, the mechanisms underlying distinct transcriptional profiles under different substrate regimes remain elusive. In this study, based on transcriptional analysis, the growth performances and gene expressions of M. barkeri fed on acetate, H2 + CO2, and methanol, respectively, were investigated. M. barkeri showed higher growth performances under methanol, followed by H2 + CO2 and acetate, which corresponded well with the variations of gene expressions. The α diversity (evenness) of gene expressions was highest under the acetate regime, followed by H2 + CO2 and methanol, and significantly and negatively correlated with growth performances. The gene co-expression analysis showed that "Energy production and conversion," "Coenzyme transport and metabolism," and "Translation, ribosomal structure, and biogenesis" showed deterministic cooperation patterns of intra- and inter-functional classes. However, "Posttranslational modification, protein turnover, chaperones" showed exclusion with other functional classes. The gene expressions and especially the relationships among them potentially drove the shifts of metabolic status under different substrate regimes. Consequently, this study revealed the diversity-related ecological strategies that a high α diversity probably provided more fitness and tolerance under natural environments and oppositely a low α diversity strengthened some specific physiological functions, as well as the co-responses of gene expressions to different substrate regimes.

Microorganism-regulated mechanisms of temperature effects on the performance of anaerobic digestion.

BACKGROUND: Temperature is an important factor determining the performance and stability of the anaerobic digestion process. However, the microorganism-regulated mechanisms of temperature effects on the performance of anaerobic digestion systems remain further elusive. To address this issue, we investigated the changes in composition, diversity and activities of microbial communities under temperature gradient from 25 to 55 °C using 16S rRNA gene amplicon sequencing approach based on genomic DNA (refer to as "16S rDNA") and total RNA (refer to as "16S rRNA"). RESULTS: Microbial community structure and activities changed dramatically along the temperature gradient, which corresponded to the variations in digestion performance (e.g., daily CH4 production, total biogas production and volatile fatty acids concentration). The ratios of 16S rRNA to 16S rDNA of microbial taxa, as an indicator of the potentially relative activities in situ, and whole activities of microbial community assessed by the similarity between microbial community based on 16S rDNA and rRNA, varied strongly along the temperature gradient, reflecting different metabolic activities. The daily CH4 production increased with temperature from 25 to 50 °C and declined at 55 °C. Among all the examined microbial properties, the whole activities of microbial community and alpha-diversity indices of both microbial communities and potentially relative activities showed highest correlations to the performance. CONCLUSIONS: The whole activities of microbial community and alpha-diversity indices of both microbial communities and potentially relative activities were sensitive indicators for the performance of anaerobic digestion systems under temperature gradient, while beta-diversity could predict functional differences. Microorganism-regulated mechanisms of temperature effects on anaerobic digestion performance were likely realized through increasing alpha-diversity of both microbial communities and potentially relative activities to supply more functional pathways and activities for metabolic network, and increasing the whole activities of microbial community, especially methanogenesis, to improve the strength and efficiency in anaerobic digestion process.

Multiple serial correlations in global air temperature anomaly time series.

Serial correlations within temperature time series serve as indicators of the temporal consistency of climate events. This study delves into the serial correlations embedded in global surface air temperature (SAT) data. Initially, we preprocess the SAT time series to eradicate seasonal patterns and linear trends, resulting in the SAT anomaly time series, which encapsulates the inherent variability of Earth's climate system. Employing diverse statistical techniques, we identify three distinct types of serial correlations: short-term, long-term, and nonlinear. To identify short-term correlations, we utilize the first-order autoregressive model, AR(1), revealing a global pattern that can be partially attributed to atmospheric Rossby waves in extratropical regions and the Eastern Pacific warm pool. For long-term correlations, we adopt the standard detrended fluctuation analysis, finding that the global pattern aligns with long-term climate variability, such as the El Niño-Southern Oscillation (ENSO) over the Eastern Pacific. Furthermore, we apply the horizontal visibility graph (HVG) algorithm to transform the SAT anomaly time series into complex networks. The topological parameters of these networks aptly capture the long-term correlations present in the data. Additionally, we introduce a novel topological parameter, Δσ, to detect nonlinear correlations. The statistical significance of this parameter is rigorously tested using the Monte Carlo method, simulating fractional Brownian motion and fractional Gaussian noise processes with a predefined DFA exponent to estimate confidence intervals. In conclusion, serial correlations are universal in global SAT time series and the presence of these serial correlations should be considered carefully in climate sciences.