Molecular definition of the endogenous Toll-like receptor signalling pathways.

Innate immune pattern recognition receptors, such as the Toll-like receptors (TLRs), are key mediators of the immune response to infection and central to our understanding of health and disease1. After microbial detection, these receptors activate inflammatory signal transduction pathways that involve IκB kinases, mitogen-activated protein kinases, ubiquitin ligases and other adaptor proteins. The mechanisms that connect the proteins in the TLR pathways are poorly defined. To delineate TLR pathway activities, we engineered macrophages to enable microscopy and proteomic analysis of the endogenous myddosome constituent MyD88. We found that myddosomes form transient contacts with activated TLRs and that TLR-free myddosomes are dynamic in size, number and composition over the course of 24 h. Analysis using super-resolution microscopy revealed that, within most myddosomes, MyD88 forms barrel-like structures that function as scaffolds for effector protein recruitment. Proteomic analysis demonstrated that myddosomes contain proteins that act at all stages and regulate all effector responses of the TLR pathways, and genetic analysis defined the epistatic relationship between these effector modules. Myddosome assembly was evident in cells infected with Listeria monocytogenes, but these bacteria evaded myddosome assembly and TLR signalling during cell-to-cell spread. On the basis of these findings, we propose that the entire TLR signalling pathway is executed from within the myddosome.

Auxetic piezoelectric effect in heterostructures.

Inherent symmetry breaking at the interface has been fundamental to a myriad of physical effects and functionalities, such as efficient spin-charge interconversion, exotic magnetic structures and an emergent bulk photovoltaic effect. It has recently been demonstrated that interface asymmetry can induce sizable piezoelectric effects in heterostructures, even those consisting of centrosymmetric semiconductors, which provides flexibility to develop and optimize electromechanical coupling phenomena. Here, by targeted engineering of the interface symmetry, we achieve piezoelectric phenomena behaving as the electrical analogue of the negative Poisson's ratio. This effect, termed the auxetic piezoelectric effect, exhibits the same sign for the longitudinal (d33) and transverse (d31, d32) piezoelectric coefficients, enabling a simultaneous contraction or expansion in all directions under an external electrical stimulus. The signs of the transverse coefficients can be further tuned via in-plane symmetry anisotropy. The effects exist in a wide range of material systems and exhibit substantial coefficients, indicating potential implications for all-semiconductor actuator, sensor and filter applications.

High-Precision Measurements of 44Ca/40Ca Using Multiple-Collector Inductively Coupled Plasma Mass Spectrometry without Collision-Cell Technology.

Herein, we present a new method for determining the Ca isotopic composition of geological samples. To eliminate matrix elements from Ca, a column chromatography method was developed using a N,N,N'N' tetraoctyl-1,5-diglycolamide (TODGA) resin. The Ca isotopic compositions were measured by a multiple collector inductively coupled plasma mass spectrometry (MC-ICP-MS) without collision cell equipment, especially that direct measurement to 44Ca/40Ca can be achieved. To mitigate the interference from 40Ar during 40Ca measurement, the cold plasma technique was used to suppress the Ar+ generation, resulting in a background Ar+ intensity of <300 mV, in contrast to the conventional hot plasma conditions, which typically yield thousands of volts for Ar+ intensities. Given the potential for a concentration mismatch between the sample and bracketed standard solutions to cause an intensive shift in measured Ca isotopic compositions, a correction for the [Ca] match is needed. To avoid matrix effects arising from residue matrix elements, it is crucial to limit the concentrations below 1% of Ca for most matrix elements (including Al, Mg, K, Na, and Sr) and below 1‰ for Fe. Notably, the tolerance of residue Sr is effectively improved compared to measurements with CC-MC-ICP-MS and traditional Hot-plasma-SSB-MC-ICP-MS methods with the conventional hot plasma technique, thereby lowering the complexity of column chemistry. The measured δ44/40Ca, δ44/42Ca, and ε40Ca values for eight reference materials agree well with previously reported values within analytical uncertainties. This method demonstrates long-term precision is better than 0.10‰ (two standard deviations) for both δ values (i.e., δ44/40Ca and δ44/42Ca). We anticipate that the proposed method will benefit the growth of the Ca isotope data set and foster an increase in the application of Ca isotope in Earth science studies.

Bay41-4109-induced aberrant polymers of hepatitis b capsid proteins are removed via STUB1-promoted p62-mediated macroautophagy.

The hepatitis B virus (HBV) core protein (HBc) functions in multiple steps of the viral life cycle. Heteroaryldihydropyrimidine compounds (HAPs) such as Bay41-4109 are capsid protein allosteric modulators that accelerate HBc degradation and inhibit the virion secretion of HBV, specifically by misleading HBc assembly into aberrant non-capsid polymers. However, the subsequent cellular fates of these HAP-induced aberrant non-capsid polymers are not well understood. Here, we discovered that that the chaperone-binding E3 ubiquitin ligase protein STUB1 is required for the removal of Bay41-4109-induced aberrant non-capsid polymers from HepAD38 cells. Specifically, STUB1 recruits BAG3 to transport Bay41-4109-induced aberrant non-capsid polymers to the perinuclear region of cells, thereby initiating p62-mediated macroautophagy and lysosomal degradation. We also demonstrate that elevating the STUB1 level enhances the inhibitory effect of Bay41-4109 on the production of HBeAg and HBV virions in HepAD38 cells, in HBV-infected HepG2-NTCP cells, and in HBV transgenic mice. STUB1 overexpression also facilitates the inhibition of Bay41-4109 on the cccDNA formation in de novo infection of HBV. Understanding these molecular details paves the way for applying HAPs as a potentially curative regimen (or a component of a combination treatment) for eradicating HBV from hepatocytes of chronic infection patients.

Sub-50†fs, 0.5†W average power Nd-doped fiber amplifier at 920†nm.

We develop an all polarization-maintaining (PM) 920 nm Nd-doped fiber amplifier delivering a train of pulses with ∼0.53 W average power and sub-50 fs duration. The sub-50 fs pulse benefits from the pre-chirping management method that allows for over 60 nm broadening spectrum without pulse breaking in the amplification stage. By virtue of the short pulse duration, the pulse peak power can reach to ∼0.31 MW in spite of the moderate average power. These results represent a key step in developing high-peak-power pulse Nd-doped fiber laser systems at 920 nm, which will find important applications in fields such as biomedical imaging, ultrafast optical spectroscopy, and excitation of quantum-dot single photon sources.

Comprehensive metabolome characterization and comparison between two sources of Dragon's blood by integrating liquid chromatography/mass spectrometry and chemometrics.

Dragon's Blood (DB) serves as a precious Chinese medicine facilitating blood circulation and stasis dispersion. Daemonorops draco (D. draco; Qi-Lin-Jie) and Dracaena cochinchinensis (D. cochinchinenesis; Long-Xue-Jie) are two reputable plant sources for preparing DB. This work was designed to comprehensively characterize and compare the metabolome differences between D. draco and D. cochinchinenesis, by integrating liquid chromatography/mass spectrometry and untargeted metabolomics analysis. Offline two-dimensional liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS), by utilizing a powerful hybrid scan approach, was elaborated for multicomponent characterization. Configuration of an XBridge Amide column and an HSS T3 column in offline mode exhibited high orthogonality (A0 0.80) in separating the complex components in DB. Particularly, the hybrid high-definition MSE-high definition data-dependent acquisition (HDMSE-HDDDA) in both positive and negative ion modes was applied for data acquisition. Streamlined intelligent data processing facilitated by the UNIFI™ (Waters) bioinformatics platform and searching against an in-house chemical library (recording 223 known compounds) enabled efficient structural elucidation. We could characterize 285 components, including 143 from D. draco and 174 from D. cochinchinensis. Holistic comparison of the metabolomes among 21 batches of DB samples by the untargeted metabolomics workflows unveiled 43 significantly differential components. Separately, four and three components were considered as the marker compounds for identifying D. draco and D. cochinchinenesis, respectively. Conclusively, the chemical composition and metabolomic differences of two DB resources were investigated by a dimension-enhanced analytical approach, with the results being beneficial to quality control and the differentiated clinical application of DB.

Comprehensive understanding of electron mobility and superior performance in sub-10 nm DG ML tetrahex-GeC2 n-type MOSFETs.

In this study, we have investigated the electron mobility of monolayered (ML) tetrahex-GeC2 by solving the linearized Boltzmann transport equation (BTE) with the normalized full-band relaxation time approximation (RTA) using density functional theory (DFT). Contrary to what the deformation potential theory (DPT) suggested, the ZA acoustic mode was determined to be the most restrictive for electron mobility, not the LA mode. The electron mobility at 300 K is 803 cm2 (V s)-1, exceeding the 400 cm2 (V s)-1 of MoS2 which was calculated using the same method and measured experimentally. The ab initio quantum transport simulations were performed to assess the performance limits of sub-10 nm DG ML tetrahex-GeC2 n-type MOSFETs, including gate lengths (Lg) of 3 nm, 5 nm, 7 nm, and 9 nm, with the underlap (UL) effect considered for the first two. For both high-performance (HP) and low-power (LP) applications, their on-state currents (Ion) can meet the requirements of similar nodes in the ITRS 2013. In particular, the Ion is more remarkable for HP applications than that of the extensively studied MoS2. For LP applications, the Ion values at Lg of 7 and 9 nm surpass those of arsenene, known for having the largest Ion among 2D semiconductors. Subthreshold swings (SSs) as low as 69/53 mV dec-1 at an Lg of 9 nm were observed for HP/LP applications, and 73 mV dec-1 at an Lg of 5 nm for LP applications, indicating the excellent gate control capability. Moreover, the delay time τ and power dissipation (PDP) at Lg values of 3 nm, 5 nm, 7 nm, and 9 nm are all below the upper limits of the ITRS 2013 HP/LP proximity nodes and are comparable to or lower than those of typical 2D semiconductors. The sub-10 nm DG ML tetrahex-GeC2 n-type MOSFETs can be down-scaled to 9 nm and 5 nm for HP and LP applications, respectively, displaying desirable Ion, delay time τ, and PDP in the ballistic limit, making them a potential choice for sub-10 nm transistors.

THBru attenuates diabetic cardiomyopathy by inhibiting RAGE-dependent inflammation.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

Pain trajectories and their associations with cognition among older adults: a 10-year cohort study from network perspective.

BACKGROUND: Few studies have examined the associations between pain trajectories and cognitive function in older adults. This study explored the associations between pain trajectories and different cognitive domains in older adults from a network perspective. METHODS: Data on pain trajectories were derived from the Health and Retirement Study between 2010 and 2020 using latent class growth analyses. Measurements of key cognition domains, including memory, attention, calculation, orientation and language, were included. Linear regression and network analysis were performed to evaluate the associations between different pain trajectories and cognition. RESULTS: A total of 9,551 older adults were included in this study and three trajectories of pain were identified. After controlling for the covariates, persistent severe pain trajectory was associated with poorer overall cognition, memory and calculation ability when compared to mild or non-persistent pain trajectory. In the pain and cognition network model, memory (expected influence (EI) = 0.62), language (EI = 0.58) and calculation (EI = 0.41) were the most central domains. CONCLUSIONS: Pain trajectories appeared stable over time among older adults in this study. Severity of persistent pain was an important risk factor for poor cognition, especially in relation to memory and calculation domains. Interventions targeting memory, language and calculation domains might be useful in addressing cognitive decline in older adults with persistent pain.

COVID-19 and Sleep Problems: A Perspective from Bibliometric Analysis.

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic and the containment measures for COVID-19 have affected sleep quality in the population. This study explored sleep-related research from a bibliometric perspective to provide an overview of the research outputs in this field. METHODS: Original and review articles were retrieved from the Web of Science Core Collection (WOSCC) database from December 2019 to 7 Aug 2023. R package "bibliometrix" was used to summarize the number of articles of authors, institutions, and countries; count the citations of the articles, and generate a Three-Fields Plot. VOSviewer software was applied to visualize the collaboration network among authors and institutions, and to conduct a co-occurrence analysis of keywords. RESULTS: A total of 4,499 articles on COVID-19 and sleep, and 25,883 articles on non-COVID-19 and sleep were included. Sleep related articles were mainly published by authors from China, the USA, and Italy. For COVID-19 and sleep research, Huazhong University of Science was the most productive institution. The Psychiatry Research was the most influential journal across the different subject categories of this field. "Mental health", "anxiety", and "depression" were the most common keywords, while "sleep quality" and "quality of life" were the likely topic areas in terms of future research directions. CONCLUSIONS: Our findings provide a comprehensive perspective for researchers to understand the wider landscape of both COVID-19 and non-COVID-19 sleep-related research area.

Polyhexamethylene guanidine accelerates the macrophage foamy formation mediated pulmonary fibrosis.

Polyhexamethylene guanidine (PHMG) is manufactured and applied extensively due to its superior disinfectant capabilities. However, the inhalatory exposure to PHMG aerosols is increasingly recognized as a potential instigator of pulmonary fibrosis, prompting an urgent call for elucidation of the underlying pathophysiological mechanisms. Within this context, alveolar macrophages play a pivotal role in the primary immune defense in the respiratory tract. Dysregulated lipid metabolism within alveolar macrophages leads to the accumulation of foam cells, a process that is intimately linked with the pathogenesis of pulmonary fibrosis. Therefore, this study examines PHMG's effects on alveolar macrophage foaminess and its underlying mechanisms. We conducted a 3-week inhalation exposure followed by a 3-week recovery period in C57BL/6 J mice using a whole-body exposure system equipped with a disinfection aerosol generator (WESDAG). The presence of lipid-laden alveolar macrophages and downregulation of pulmonary tissue lipid transport proteins ABCA1 and ABCG1 were observed in mice. In cell culture models involving lipid-loaded macrophages, we demonstrated that PHMG promotes foam cell formation by inhibiting lipid efflux in mouse alveolar macrophages. Furthermore, PHMG-induced foam cells were found to promote an increase in the release of TGF-ß1, fibronectin deposition, and collagen remodeling. In vivo interventions were subsequently implemented on mice exposed to PHMG aerosols, aiming to restore macrophage lipid efflux function. Remarkably, this intervention demonstrated the potential to retard the progression of pulmonary fibrosis. In conclusion, this study underscores the pivotal role of macrophage foaming in the pathogenesis of PHMG disinfectants-induced pulmonary fibrosis. Moreover, it provides compelling evidence to suggest that the regulation of macrophage efflux function holds promise for mitigating the progression of pulmonary fibrosis, thereby offering novel insights into the mechanisms underlying inhaled PHMG disinfectants-induced pulmonary fibrosis.

The counteractive effects of interventions addressing mental fatigue on sport-specific performance among athletes: A systematic review with a meta-analysis.

The deleterious consequences of mental fatigue (MF) on athletes in diverse sporting domains have been subject to extensive inquiry. However, the efficacy of interventions to counteract the effects of MF remains largely elusive. This review aims to evaluate the effects of counteractive interventions on the sport-specific performance of mentally fatigued athletes. Moreover, synthesizes the current evidence on which sports effectively counter the detrimental effects of MF with interventions, highlighting potential avenues for upcoming research. A systematic search was executed via Web of Science, Scopus, PubMed, and EBSCOhost, in addition to Google Scholar and references for grey literature. A meta-analysis was executed to compute effect sizes for different interventions with 13 qualified papers. Interventions include transcranial direct current stimulation, person-fit, mindfulness, glucose supplementation, caffeine mouth rinsing, and nature exposure showed potential to mitigate the detrimental effects on sport-specific performance, particularly in shooting accuracy (ES = 0.591; p = 0.001), decision-making accuracy (ES = 0.553; p = 0.006), and reaction time (ES = -0.871; p < 0.001), however, not in completion time (ES = -0.302; p = 0.182). This review underscores the unique roles of self-regulatory resources and directed attention. Nonetheless, a cautious interpretation of the findings is warranted given the paucity of investigations involving potential interventions in numerous other sports, such as volleyball, Australian football, cricket, and boxing.

Self-Assembled Molecules with Asymmetric Backbone for Highly Stable Binary Organic Solar Cells with 19.7 % Efficiency.

The hole-transporting material (HTM), poly (3,4-ethylene dioxythiophene) poly(styrene sulfonate) (PEDOT : PSS), is the most widely used material in the realization of high-efficiency organic solar cells (OSCs). However, the stability of PEDOT : PSS-based OSCs is quite poor, arising from its strong acidity and hygroscopicity. In addition, PEDOT : PSS has an absorption in the infrared region and high highest occupied molecular orbital (HOMO) energy level, thus limiting the enhancement of short-circuit current density (Jsc) and open-circuit voltage (Voc), respectively. Herein, two asymmetric self-assembled molecules (SAMs), namely BrCz and BrBACz, were designed and synthesized as HTM in binary OSCs based on the well-known system of PM6 : Y6, PM6 : eC9, PM6 : L8-BO, and D18 : eC9. Compared with BrCz, BrBACz shows larger dipole moment, deeper work function and lower surface energy. Moreover, BrBACz not only enhances photon harvesting in the active layer, but also minimizes voltage losses as well as improves interface charge extraction/ transport. Consequently, the PM6 : eC9-based binary OSC using BrBACz as HTM exhibits a champion efficiency of 19.70 % with a remarkable Jsc of 29.20 mA cm-2 and a Voc of 0.856 V, which is a record efficiency for binary OSCs so far. In addition, the unencapsulated device maintains 95.0 % of its original efficiency after 1,000 hours of storage at air ambient, indicating excellent long-term stability.

Comparative physiological and transcriptomic analysis of two salt-tolerant soybean germplasms response to low phosphorus stress: role of phosphorus uptake and antioxidant capacity.

BACKGROUND: Phosphorus (P) and salt stress are common abiotic stressors that limit crop growth and development, but the response mechanism of soybean to low phosphorus (LP) and salt (S) combined stress remains unclear. RESULTS: In this study, two soybean germplasms with similar salt tolerance but contrasting P-efficiency, A74 (salt-tolerant and P-efficient) and A6 (salt-tolerant and P-inefficient), were selected as materials. By combining physiochemical and transcriptional analysis, we aimed to elucidate the mechanism by which soybean maintains high P-efficiency under salt stress. In total, 14,075 differentially expressed genes were identified through pairwise comparison. PageMan analysis subsequently revealed several significantly enriched categories in the LP vs. control (CK) or low phosphorus + salt (LPS) vs. S comparative combination when compared to A6, in the case of A74. These categories included genes involved in mitochondrial electron transport, secondary metabolism, stress, misc, transcription factors and transport. Additionally, weighted correlation network analysis identified two modules that were highly correlated with acid phosphatase and antioxidant enzyme activity. Citrate synthase gene (CS), acyl-coenzyme A oxidase4 gene (ACX), cytokinin dehydrogenase 7 gene (CKXs), and two-component response regulator ARR2 gene (ARR2) were identified as the most central hub genes in these two modules. CONCLUSION: In summary, we have pinpointed the gene categories responsible for the LP response variations between the two salt-tolerant germplasms, which are mainly related to antioxidant, and P uptake process. Further, the discovery of the hub genes layed the foundation for further exploration of the molecular mechanism of salt-tolerant and P-efficient in soybean.

Geographical distance, host evolutionary history and diet drive gut microbiome diversity of fish across the Yellow River.

Fish represent a large part of the taxonomic diversity of vertebrates and are of high commercial value. However, the factors influencing the gut microbiota composition of freshwater fish over large spatial scales remain unclear. Therefore, this study explored gut microbiome diversity in 24 fish species from the Yellow River, which spans over 1500 km across China. The results showed that geographical distance, host phylogeny and diet significantly influenced gut microbial community diversity, whereas sex, body length and body weight had minimal influence. Geographical distance was the primary factor shaping gut microbiota, and dissimilarity in microbial community structure increased with an increase in geographical distance, which was mainly driven by dispersal limitation. The microbial communities were more homogeneous at higher host taxonomic resolutions due to the dominant role of homogeneous selection in community convergence. Phylosymbiosis was observed across all host species, with a stronger pattern in Cypriniformes, which harbour host-specific microbial taxa. Host diet explained little variation in gut microbiome diversity, although it was significant for all diversity metrics tested. These findings collectively suggest that the geographical and host-based patterns of fish gut microbiota tend to be shaped by different ecological forces across the Yellow River. The present work provides a robust assessment of multiple factors driving fish gut microbial community assembly and offers insight into the mechanisms underlying shifts in fish gut microbiota in rivers across large spatial scales.

Facile preparation of Ru nanoassemblies for electrochemical immunoassay of carcinoembryonic antigen in clinical serum.

Abnormal expression of carcinoembryonic antigen (CEA) can be used for early diagnosis of various cancers (e.g. colorectal cancer, cervical carcinomas, and breast cancer). In this work, using l-cysteine-ferrocene-ruthenium nanocomposites (L-Cys-Fc-Ru) to immobilize secondary antibody (Ab2) and Au nanoparticles (NPs) as the substrate to ensure accurate capture of primary antibody (Ab1), a signal-on sandwich-like biosensor was constructed in the presence of CEA. Specifically, Ru nanoassemblies (NAs) were first prepared by a facile one-step solvothermal approach as signal amplifiers for the electrical signal of Fc. Based on specific immune recognition, as the increase of CEA concentration, the content of L-Cys-Fc-Ru-Ab2 captured on the electrode surface also increased, thus the signal of Fc gradually increased. Therefore, the quantitative detection of CEA can be realized according to the peak current of Fc. After a series of experiments, it was found that the biosensor has a wide detection range from 1.0 pg mL-1 to 100.0 ng mL-1 and a low detection limit down to 0.5 pg mL-1, as well as good selectivity, repeatability and stability. Furthermore, satisfactory results were also obtained for the determination of CEA in serums, which were comparable to commercial electrochemiluminescence (ECL) method. The developed biosensor shows great potential in clinical applications.

METTL3 boosts mitochondrial fission and induces cardiac fibrosis by enhancing LncRNA GAS5 methylation.

Dysregulated mitochondrial metabolism occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the role of mitochondrial fission is not well appreciated in cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. We investigated the causes and consequences of mitochondrial fission in cardiac fibrosis using cultured cells, animal models, and clinical samples. Increased METTL3 expression caused excessive mitochondrial fission, resulting in the proliferation and migration of cardiac fibroblasts that lead to cardiac fibrosis. Knockdown of METTL3 suppressed mitochondrial fission, inhibiting fibroblast proliferation and migration for ameliorating cardiac fibrosis. Elevated METTL3 and N6-methyladenosine (m6A) levels were associated with low expression of long non-coding RNA GAS5. Mechanistically, METTL3-mediated m6A methylation of GAS5 induced its degradation, dependent of YTHDF2. GAS5 could interact with mitochondrial fission marker Drp1 directly; overexpression of GAS5 suppressed Drp1-mediated mitochondrial fission, inhibiting cardiac fibroblast proliferation and migration. Knockdown of GAS5 produced the opposite effect. Clinically, increased METTL3 and YTHDF2 levels corresponded with decreased GAS5 expression, increased m6A mRNA content and mitochondrial fission, and increased cardiac fibrosis in human heart tissue with atrial fibrillation. We describe a novel mechanism wherein METTL3 boosts mitochondrial fission, cardiac fibroblast proliferation, and fibroblast migration: METTL3 catalyzes m6A methylation of GAS5 methylation in a YTHDF2-dependent manner. Our findings provide insight into the development of preventative measures for cardiac fibrosis.

Soft, flexible pressure sensors for pressure monitoring under large hydrostatic pressure and harsh ocean environments.

Traditional rigid ocean pressure sensors typically require protection from bulky pressure chambers and complex seals to survive the large hydrostatic pressure and harsh ocean environment. Here, we introduce soft, flexible pressure sensors that can eliminate such a need and measure a wide range of hydrostatic pressures (0.1 MPa to 15 MPa) in environments that mimic the ocean, achieving small size, high flexibility, and potentially low power consumption. The sensors are fabricated from lithographically patterned gold thin films (100 nm thick) encapsulated with a soft Parylene C film and tested in a customized pressure vessel under well-controlled pressure and temperature conditions. Using a rectangular pressure sensor as an example, the resistance of the sensor is found to decrease linearly with the increase of the hydrostatic pressure from 0.1 MPa to 15 MPa. Finite element analysis (FEA) reveals the strain distributions in the pressure sensor under hydrostatic pressures of up to 15 MPa. The effect of geometry on sensor performance is also studied, and radially symmetric pressure sensors (like circular and spike-shaped) are shown to have more uniform strain distributions under large hydrostatic pressures and, therefore, have a potentially enhanced pressure measurement range. Pressure sensors of all geometries show high consistency and negligible hysteresis over 15 cyclic tests. In addition, the sensors exhibit excellent flexibility and operate reliably under a hydrostatic pressure of 10 MPa for up to 70 days. The developed soft pressure sensors are promising for integration with many platforms including animal tags, diver equipment, and soft underwater robotics.

A B12-dependent radical SAM enzyme involved in oxetanocin A biosynthesis.

Oxetanocin A (OXT-A) is a potent antitumour, antiviral and antibacterial compound. Biosynthesis of OXT-A has been linked to a plasmid-borne Bacillus megaterium gene cluster that contains four genes: oxsA, oxsB, oxrA and oxrB. Here we show that both the oxsA and oxsB genes are required for the production of OXT-A. Biochemical analysis of the encoded proteins, a cobalamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohydrolase, OxsA, reveals that OXT-A is derived from a 2'-deoxyadenosine phosphate in an OxsB-catalysed ring contraction reaction initiated by hydrogen atom abstraction from C2'. Hence, OxsB represents the first biochemically characterized non-methylating Cbl-dependent AdoMet radical enzyme. X-ray analysis of OxsB reveals the fold of a Cbl-dependent AdoMet radical enzyme, a family of enzymes with an estimated 7,000 members. Overall, this work provides a framework for understanding the interplay of AdoMet and Cbl cofactors and expands the catalytic repertoire of Cbl-dependent AdoMet radical enzymes.

Characteristics of dissolved organic matter in point-source wastewaters at a petrochemical plant: Molecular constituents and contributions to the influent of wastewater treatment plant.

Dissolved organic matter (DOM) in point-source petrochemical wastewaters (PCWs) from different operating units is closely linked to the efficiency of wastewater treatment plant (WWTP). However, systematic studies on DOM characters of point-source PCWs and their influences on WWTP influents were seldom conducted. In this study, DOM in three low-salinity point-source PCWs and four high-salinity point-source PCWs at a typical petrochemical plant were comprehensively characterized at a molecular level. Orbitrap mass spectrometry results indicated that point-source PCWs had diverse DOM constituents tightly related to the corresponding petrochemical processes. Phenols in oily wastewaters (OW), phenols and N-containing compounds in coal partial oxidation wastewater (POXW), and naphthenic acids (NAs) and aromatic acids in crude oil electric desalting unit wastewater (EDW) were characteristic DOM constituents for low-salinity point-source PCWs. While S-containing compounds (mercaptans, thiophenes) and NAs in spent caustic liquors (SCL), alcohols and esters in butanol-octanol plant wastewater (BOW), high molecular weight aromatic ketones in phenol-acetone plant wastewater (PAW), and oxygenated NAs as well as short chain N-containing compounds in concentrate from reverse osmosis unit (ROC) were characteristic DOM constituents for high-salinity point-source PCWs. Spearman correlation analysis indicated that though with relative low pollutant contents (OW) and discharge volume (EDW), N/O/S-containing compounds of OW and EDW greatly contributed to the polar DOM constituents of low-salinity influent in WWTP (R > 0.5, P < 0.001). While N-containing compounds of ROC mainly contributed to the polar DOM of high-salinity influent (R > 0.5, P < 0.001). Though N-/S-containing species in PAW had low contents, they also posed obvious impacts on DOM constituents of high-salinity influent. Interestingly, some O-/S-containing species were newly formed during the confluent process of high-salinity point-source PCWs. The results strengthened the combined contributions of pollutants contents, discharge emission and DOM constituents of point-source PCWs to the water matrix of WWTP influents, which would provide reference for the management of PCW streams.