Human Placenta Decellularized Extracellular Matrix Hydrogel Promotes the Generation of Human Spinal Cord Organoids with Dorsoventral Organization from Human Induced Pluripotent Stem Cells.

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.

Decellularized Brain Extracellular Matrix Hydrogel Aids the Formation of Human Spinal-Cord Organoids Recapitulating the Complex Three-Dimensional Organization.

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.

Real-time demonstration of two-aperture coherent digital combining free-space optical transmission with a real-valued MIMO adaptive equalizer.

Compared with the single-aperture system, the multi-aperture coherent digital combining system has the technical advantage of the effective mitigation of deep fading under strong turbulence, ease of scalability, and potential higher collected optical power. However, the tricky problem of a multi-aperture system is to efficiently combine multiple branch signals with a static skew mismatch and with time-varying characteristics of received power scintillation. In this Letter, a real-valued massive array multiple-input multiple-output (MIMO) adaptive equalizer is proposed for the first time to our knowledge to realize multi-aperture channel equalization and combining, simultaneously. In the proof-of-principle system, the feasibility of the combining technique is verified based on a MIMO 4 × 2 equalizer in a 2.5-GBaud data rate QPSK modulation FPGA-based two-aperture coherent receiver with a dynamic turbulence simulator. The results show that no reduction in combining efficiency is observed under static turbulence conditions at the hard-decision forward error correction (HD-FEC) limit of 3.8 × 0-3, and combining efficiencies of 95% and 88% are obtained for the dynamic moderate and strong turbulence.

Photobiomodulation Increases M2-Type Polarization of Macrophages by Inhibiting Versican Production After Spinal Cord Injury.

Spinal cord injury (SCI) is a catastrophic accidence with little effective treatment, and inflammation played an important role in that. Previous studies showed photobiomodulation (PBM) could effectively downregulate the process of inflammation with modification of macrophage polarization after SCI; however, the potential mechanism behind that is still unclear. In the presented study, we aimed to investigate the effect of PBM on the expression level of versican, a matrix molecular believed to be associated with inflammation, and tried to find the mechanism on how that could regulate the inflammation process. Using immunofluorescence technique and western blot, we found the expression level of versican is increased after injury and markedly downregulated by irradiation treatment. Using virus intrathecal injection, we found the knock-down of versican could produce the effect similar to that of PBM and might have an effect on inflammation and macrophage polarization after SCI. To further verify the deduction, we peptide the supernatant of astrocytes to induce M0, M1, and M2 macrophages. We found that the versican produced by astrocytes might have a role on the promotion of M2 macrophages to inflammatory polarization. Finally, we investigated the potential pathway in the regulation of M2 polarization with the induction of versican. This study tried to give an interpretation on the mechanism of inflammation inhibition for PBM in the perspective of matrix regulation. Our results might provide light on the inflammation regulation after SCI.

Accurate Electronic and Optical Properties of Organic Doublet Radicals Using Machine Learned Range-Separated Functionals.

Luminescent organic semiconducting doublet-spin radicals are unique and emergent optical materials because their fluorescent quantum yields (Φfl) are not compromised by the spin-flipping intersystem crossing (ISC) into a dark high-spin state. The multiconfigurational nature of these radicals challenges their electronic structure calculations in the framework of single-reference density functional theory (DFT) and introduces room for method improvement. In the present study, we extended our earlier development of ML-ωPBE [J. Phys. Chem. Lett., 2021, 12, 9516-9524], a range-separated hybrid (RSH) exchange-correlation (XC) functional constructed using the stacked ensemble machine learning (SEML) algorithm, from closed-shell organic semiconducting molecules to doublet-spin organic semiconducting radicals. We assessed its performance for a new test set of 64 doublet-spin radicals from five categories while placing all previously compiled 3926 closed-shell molecules in the new training set. Interestingly, ML-ωPBE agrees with the nonempirical OT-ωPBE functional regarding the prediction of the molecule-dependent range-separation parameter (ω), with a small mean absolute error (MAE) of 0.0197 a0-1, but saves the computational cost by 2.46 orders of magnitude. This result demonstrates an outstanding domain adaptation capacity of ML-ωPBE for diverse organic semiconducting species. To further assess the predictive power of ML-ωPBE in experimental observables, we also applied it to evaluate absorption and fluorescence energies (Eabs and Efl) using linear-response time-dependent DFT (TDDFT), and we compared its behavior with nine popular XC functionals. For most radicals, ML-ωPBE reproduces experimental measurements of Eabs and Efl with small MAEs of 0.299 and 0.254 eV, only marginally different from those of OT-ωPBE. Our work illustrates a successful extension of the SEML framework from closed-shell molecules to doublet-spin radicals and will open the venue for calculating optical properties for organic semiconductors using single-reference TDDFT.

Correction: Gardenia jasminoides J. Ellis extract alleviated white matter damage through promoting the differentiation of oligodendrocyte precursor cells via suppressing neuroinflammation.

Correction for 'Gardenia jasminoides J. Ellis extract alleviated white matter damage through promoting the differentiation of oligodendrocyte precursor cells via suppressing neuroinflammation' by Caixia Zang et al., Food Funct., 2022, 13, 2131-2141, https://doi.org/10.1039/D1FO02127C.

BID-seq for transcriptome-wide quantitative sequencing of mRNA pseudouridine at base resolution.

Pseudouridine (Ψ) is an abundant RNA modification that is present in and affects the functions of diverse non-coding RNA species, including rRNA, tRNA and small nuclear RNA. Ψ also exists in mammalian mRNA and probably exhibits functional roles; however, functional investigations of mRNA Ψ modifications in mammals have been hampered by the lack of a quantitative method that detects Ψ at base precision. We have recently developed bisulfite-induced deletion sequencing (BID-seq), which provides the community with a quantitative method to map RNA Ψ distribution transcriptome-wide at single-base resolution. Here, we describe an optimized BID-seq protocol for mapping Ψ distribution across cellular mRNAs, which includes fast steps in both library preparation and data analysis. This protocol generates highly reproducible results by inducing high deletion ratios at Ψ modification within diverse sequence contexts, and meanwhile displayed almost zero background deletions at unmodified uridines. When used for transcriptome-wide Ψ profiling in mouse embryonic stem cells, the current protocol uncovered 8,407 Ψ sites from as little as 10 ng of polyA+ RNA input. This optimized BID-seq workflow takes 5 days to complete and includes four main sections: RNA preparation, library construction, next-generation sequencing (NGS) and data analysis. Library construction can be completed by researchers who have basic knowledge and skills in molecular biology and genetics. In addition to the experimental protocol, we provide BID-pipe ( https://github.com/y9c/pseudoU-BIDseq ), a user-friendly data analysis pipeline for Ψ site detection and modification stoichiometry quantification, requiring only basic bioinformatic and computational skills to uncover Ψ signatures from BID-seq data.

Biological Activities of Sesquiterpenoids： A Review / 中国实验方剂学杂志

Sesquiterpenoids are natural compounds composed of 15 carbon atoms， which can be divided into sesquiterpene alcohols， ketones， lactones， aldehydes， and carboxylic acids according to oxygen groups. These compounds are widely distributed in nature， and their physiological activities are diverse. For example， many sesquiterpenes with potential anticancer effects have been found for anti-tumor effects， including cytotoxicity， antioxidant， immune regulation， cell proliferation， and so on. In addition， some sesquiterpenoids have good application prospects in antibacterial， anti-inflammatory， and anti-cardiovascular diseases. Malignant tumors， inflammation， bacterial diseases， and cardiovascular diseases are the main diseases that cause human death， and natural products have unique advantages in the treatment of these diseases. Therefore， the development of new drugs that are easy to promote has become a new research hotspot. In this paper， the sesquiterpenes extracted from the natural components of Chinese herbs and plants with anti-tumor， anti-inflammatory， antibacterial， and anti-cardiovascular activities， such as Xanthium， Atractylodes， Convolvulus， Acanthium， Ligularia， Artemisia， Ligularia， Ligularia， Labiaceae Mint， Acanthophyllum， Turmeria， Ginger， and other Chinese herbs and plants， were discussed. The biological activities and related mechanisms of this compound were reviewed， which provided a reference for further research and clinical application of sesquiterpenes.

Base-resolution quantitative DAMM-seq for mapping RNA methylations in tRNA and mitochondrial polycistronic RNA.

The human AlkB family proteins, such as FTO and ALKBH5, are known to mediate RNA m6A demethylation. However, although ALKBH7 localizes in mitochondria and affects metabolism, the detailed biological function and mechanism have remained unknown for years. We developed Demethylation-Assisted Multiple Methylation sequencing (DAMM-seq) to simultaneously detect N1-methyladenosine (m1A), N3-methylcytidine (m3C), N1-methylguanosine (m1G) and N2,N2-dimethylguanosine (m22G) methylations in both steady-state RNA and nascent RNA, and discovered that human ALKBH7 demethylates m22G and m1A within mt-Ile and mt-Leu1 pre-tRNA regions, respectively, in mitochondrial polycistronic RNA. DAMM-seq quantitatively and sensitively monitors the methylation stoichiometry change at pre-tRNA junctions within nascent mt-RNA, revealing the target region where ALKBH7 regulates RNA processing and local structural switch of polycistronic mt-RNAs. A new RNA demethylase in human cells was characterized through the base-resolution quantification of multiple RNA methylations in nascent mt-RNA, resolving the long-standing question about the functional substrate of ALKBH7.

Evolution of organic phosphor through precision regulation of nonradiative decay.

Development of single-component organic phosphor attracts increasing interest due to its wide applications in optoelectronic technologies. Theoretically, activating efficient intersystem crossing (ISC) via 1(π, π*) to 3(π, π*) transitions, rather than 1(n, π*) → 3(π, π*) transitions, is an alternative access to purely organic phosphors but remains challenging. Herein, we designed and successfully synthesized the sila-8-membered ring fused biaryl benzoskeleton by transition metal catalysis, which served as a new organic phosphor with efficient 1(π, π*) to 3(π, π*) ISC. We first found that such a compound exhibits a record-long phosphorescence lifetime of 6.5 s at low temperature for single-component organic systems. Then, we developed two strategies to tune their decay channels to evolve such nonemissive molecules into bright phosphors with elongated lifetimes at room temperature: 1) Physic-based design, where quantitative analyses of electron-phonon coupling led us to reveal and hinder the major nonradiative channels, thus lighted up room temperature phosphorescence (RTP) with a lifetime of 480 ms at 298 K; 2) chemical geometry-driven molecular engineering, where a geometry-based descriptor ΔΘT1-S0/ΘS0 was developed for rational screening RTP candidates and further improved the RTP lifetime to 794 ms. This study clearly shows the power of interdiscipline among synthetic methodology, physics-based rational design, and computational modeling, which represents a paradigm for the development of an organic emitter.

Heck Migratory Insertion Catalyzed by a Single Pt Atom Site.

Single-atom catalysts (SACs) have generated excitement for their potential to downsize metal particles to the atomic limit with engineerable local environments and improved catalytic reactivities and selectivities. However, successes have been limited to small-molecule transformations with little progress toward targeting complex-building reactions, such as metal-catalyzed cross-coupling. Using a supercritical carbon-dioxide-assisted protocol, we report a heterogeneous single-atom Pt-catalyzed Heck reaction, which provides the first C-C bond-forming migratory insertion on SACs. Our quantum mechanical computations establish the reaction mechanism to involve a novel C-rich coordination site (i.e., PtC4) that demonstrates an unexpected base effect. Notably, the base was found to transiently modulate the coordination environment to allow migratory insertion into an M-C species, a process with a high steric impediment with no previous example on SACs. The studies showcase how SACs can introduce coordination structures that have remained underexplored in catalyst design. These findings offer immense potential for transferring the vast and highly versatile reaction manifold of migratory-insertion-based bond-forming protocols to heterogeneous SACs.

Blind skew compensation and digital combining with widely linear equalizer for multi-aperture coherent FSO communication.

Coherent digital combining technology using multiple small apertures has a lot of advantages over doing so with a single large aperture, including the effective mitigation of deep fading under strong turbulence, ease of scalability, and potential higher collected optical power. However, the in-phase/quadrature (I/Q) imbalance and I/Q skew induced by manufacturing imperfections of the coherent receiver front end, and the time mismatch caused by the unequal length of multi-aperture branches will induce a high OSNR penalty and reduce the digital combining efficiency, especially when the system scales to a larger number of apertures, such as massive aperture system. In this work, a complex-valued multiple-input multiple-output (MIMO) 4N×2 widely linear (WL) equalizer is designed to combine multi-aperture signals. Using WL complex analysis, a general analytical model is derived and it is indicated that multi-aperture channel equalization and combining operations can be achieved simultaneously using a MIMO equalizer as long as appropriate tap coefficients are selected. Moreover, the feasibility of the proposed WL equalizer is verified by a 10-Gbps PM-QPSK modulation and a 20-Gbps PM-16QAM modulation four-aperture offline simulated turbulence experiment. The four-aperture combining efficiency of PM-QPSK exceeds 96% even at a single-aperture extremely low OSNR of -6 dB, and 80% for PM-16QAM at a single-aperture OSNR of 0 dB.

Photobiomodulation reduces neuropathic pain after spinal cord injury by downregulating CXCL10 expression.

BACKGROUND: Many studies have recently highlighted the role of photobiomodulation (PBM) in neuropathic pain (NP) relief after spinal cord injury (SCI), suggesting that it may be an effective way to relieve NP after SCI. However, the underlying mechanisms remain unclear. This study aimed to determine the potential mechanisms of PBM in NP relief after SCI. METHODS: We performed systematic observations and investigated the mechanism of PBM intervention in NP in rats after SCI. Using transcriptome sequencing, we screened CXCL10 as a possible target molecule for PBM intervention and validated the results in rat tissues using reverse transcription-polymerase chain reaction and western blotting. Using immunofluorescence co-labeling, astrocytes and microglia were identified as the cells responsible for CXCL10 expression. The involvement of the NF-κB pathway in CXCL10 expression was verified using inhibitor pyrrolidine dithiocarbamate (PDTC) and agonist phorbol-12-myristate-13-acetate (PMA), which were further validated by an in vivo injection experiment. RESULTS: Here, we demonstrated that PBM therapy led to an improvement in NP relative behaviors post-SCI, inhibited the activation of microglia and astrocytes, and decreased the expression level of CXCL10 in glial cells, which was accompanied by mediation of the NF-κB signaling pathway. Photobiomodulation inhibit the activation of the NF-κB pathway and reduce downstream CXCL10 expression. The NF-κB pathway inhibitor PDTC had the same effect as PBM on improving pain in animals with SCI, and the NF-κB pathway promoter PMA could reverse the beneficial effect of PBM. CONCLUSIONS: Our results provide new insights into the mechanisms by which PBM alleviates NP after SCI. We demonstrated that PBM significantly inhibited the activation of microglia and astrocytes and decreased the expression level of CXCL10. These effects appear to be related to the NF-κB signaling pathway. Taken together, our study provides evidence that PBM could be a potentially effective therapy for NP after SCI, CXCL10 and NF-kB signaling pathways might be critical factors in pain relief mediated by PBM after SCI.

m 6 A mRNA Methylation in Brown Adipose Tissue Regulates Systemic Insulin Sensitivity via an Inter-Organ Prostaglandin Signaling Axis.

Brown adipose tissue (BAT) has the capacity to regulate systemic metabolism through the secretion of signaling lipids. N6-methyladenosine (m 6 A) is the most prevalent and abundant post-transcriptional mRNA modification and has been reported to regulate BAT adipogenesis and energy expenditure. In this study, we demonstrate that the absence of m 6 A methyltransferase-like 14 (METTL14), modifies the BAT secretome to initiate inter-organ communication to improve systemic insulin sensitivity. Importantly, these phenotypes are independent of UCP1-mediated energy expenditure and thermogenesis. Using lipidomics, we identified prostaglandin E2 (PGE2) and prostaglandin F2a (PGF2a) as M14 KO -BAT-secreted insulin sensitizers. Notably, circulatory PGE2 and PGF2a levels are inversely correlated with insulin sensitivity in humans. Furthermore, in vivo administration of PGE2 and PGF2a in high-fat diet-induced insulin-resistant obese mice recapitulates the phenotypes of METTL14 deficient animals. PGE2 or PGF2a improves insulin signaling by suppressing the expression of specific AKT phosphatases. Mechanistically, METTL14-mediated m 6 A installation promotes decay of transcripts encoding prostaglandin synthases and their regulators in human and mouse brown adipocytes in a YTHDF2/3-dependent manner. Taken together, these findings reveal a novel biological mechanism through which m 6 A-dependent regulation of BAT secretome regulates systemic insulin sensitivity in mice and humans. Highlights: Mettl14 KO -BAT improves systemic insulin sensitivity via inter-organ communication; PGE2 and PGF2a are BAT-secreted insulin sensitizers and browning inducers;PGE2 and PGF2a sensitize insulin responses through PGE2-EP-pAKT and PGF2a-FP-AKT axis; METTL14-mediated m 6 A installation selectively destabilizes prostaglandin synthases and their regulator transcripts; Targeting METTL14 in BAT has therapeutic potential to enhance systemic insulin sensitivity.

Short-Wavelength Infrared Organic Light-Emitting Diodes from A-D-A'-D-A Type Small Molecules with Emission beyond 1100 nm.

Short-wavelength infrared (SWIR) organic light-emitting diodes (OLEDs) have attracted great interest due to their potential applications in biological imaging, infrared lighting, optical communication, environmental monitoring, and surveillance. Due to an intrinsic limitation posed by the energy-gap law, achieving high-brightness in SWIR OLEDs remains a challenge. Herein, the study reports the use of novel A-D-A'-D-A type small molecules NTQ and BTQ for high-performance SWIR OLEDs. Benefiting from multiple D-A effect in conjugated skeleton, the small molecules NTQ and BTQ exhibit narrow optical gaps of 1.23 and 1.13 eV, respectively. SWIR electroluminescence (EL) emission from OLEDs based on NTQ and BTQ is achieved, with emission peaks at 1140 and 1175 nm, respectively. Not only owing to a negligible efficiency roll-off across the full range of applied current density but also the ability to afford a high operation current density of 5200 mA cm-2 , the resultant SWIR OLEDs based on NTQ exhibit a maximal radiant exitance of =1.12 mW cm-2 . Furthermore, the NTQ-based OLEDs also possess sub-gap turn-on voltage of 0.85 V, which is close to the physical limits derived from the generalized Kirchhoff and Planck equation. This work demonstrates that A-D-A'-D-A type small molecules offer significant promise for NIR/SWIR emitting material innovations.

Photobiomodulation augments the effects of mitochondrial transplantation in the treatment of spinal cord injury in rats by facilitating mitochondrial transfer to neurons via Connexin 36.

Mitochondrial transplantation is a promising treatment for spinal cord injury (SCI), but it has the disadvantage of low efficiency of mitochondrial transfer to targeted cells. Here, we demonstrated that Photobiomodulation (PBM) could promote the transfer process, thus augmenting the therapeutic effect of mitochondrial transplantation. In vivo experiments, motor function recovery, tissue repair, and neuronal apoptosis were evaluated in different treatment groups. Under the premise of mitochondrial transplantation, the expression of Connex36 (Cx36), the trend of mitochondria transferred to neurons, and its downstream effects, such as ATP production and antioxidant capacity, were evaluated after PBM intervention. In in vitro experiments, dorsal root ganglia (DRG) were cotreated with PBM and 18ß-GA (a Cx36 inhibitor). In vivo experiments showed that PBM combined with mitochondrial transplantation could increase ATP production and reduce oxidative stress and neuronal apoptosis levels, thereby promoting tissue repair and motor function recovery. In vitro experiments further verified that Cx36 mediated the transfer of mitochondria into neurons. PBM could facilitate this progress via Cx36 both in vivo and in vitro. The present study reports a potential method of using PBM to facilitate the transfer of mitochondria to neurons for the treatment of SCI.

Photobiomodulation provides neuroprotection through regulating mitochondrial fission imbalance in the subacute phase of spinal cord injury.

Increasing evidence indicates that mitochondrial fission imbalance plays an important role in delayed neuronal cell death. Our previous study found that photobiomodulation improved the motor function of rats with spinal cord injury. However, the precise mechanism remains unclear. To investigate the effect of photobiomodulation on mitochondrial fission imbalance after spinal cord injury, in this study, we treated rat models of spinal cord injury with 60-minute photobiomodulation (810 nm, 150 mW) every day for 14 consecutive days. Transmission electron microscopy results confirmed the swollen and fragmented alterations of mitochondrial morphology in neurons in acute (1 day) and subacute (7 and 14 days) phases. Photobiomodulation alleviated mitochondrial fission imbalance in spinal cord tissue in the subacute phase, reduced neuronal cell death, and improved rat posterior limb motor function in a time-dependent manner. These findings suggest that photobiomodulation targets neuronal mitochondria, alleviates mitochondrial fission imbalance-induced neuronal apoptosis, and thereby promotes the motor function recovery of rats with spinal cord injury.

Characteristics and comparisons of the aerobic and anaerobic denitrification of a Klebsiella oxytoca strain: Performance, electron transfer pathway, and mechanism.

The performance and electron (e-) transfer mechanisms of anaerobic and aerobic denitrification by strain Klebsiella were investigated in this study. The RT-PCR results demonstrated that the membrane bound nitrate reductase gene (narG) and Cu-nitrite reductase gene (nirK) were responsible for both aerobic and anerobic denitrification. The extreme low gene relative abundance of nirK might be responsible for the severe accumulation of NO2--N (nitrogen in the form of NO2- ion) under anaerobic condition. Moreover, the nitrite reductase (Nir) activity was 0.31 µg NO2--N min-1 mg-1 protein under anaerobic conditions, which was lower than that under aerobic conditions (0.38 µg NO2--N min-1 mg-1 protein). By using respiration chain inhibitors, the e- transfer pathways of anaerobic and aerobic denitrification of Klebsiella strain were constructed. Fe-S protein and Complex III were the core components under anaerobic conditions, while Coenzyme Q (CoQ), Complexes I and III played a key role in aerobic denitrification. Nitrogen assimilation was found to be the main way to generate NH4+-N (nitrogen in the form of NH4+ ion) during anaerobic denitrification, and also served as the primary nitrogen removal way under aerobic condition. The results of this study may help to improve the understanding of the core components of strain Klebsiella during aerobic and anaerobic denitrifications, and may suggest potential applications of the strain for nitrogen-containing wastewater.

Yinma Jiedu Granule attenuates LPS-induced acute lung injury in rats via suppressing inflammation level.

ETHNOPHARMACOLOGICAL RELEVANCE: Yinma Jiedu Granule (YMJD) is a traditional Chinese patent medicine (CPM), which has been proved to have anti-inflammatory effects and therapeutical effects on obstructive pulmonary disease. AIM OF STUDY: The purpose of the current investigation is to find out if YMJD can alleviate acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats and its underlying mechanisms. MATERIALS AND METHODS: Rats were treated with either vehicle or YMJD for 14 consecutive days, and 2 h after the last administration, the rat model of ALI was induced by the intratracheal instillation of LPS. High performance liquid chromatography (HPLC) was applied for the fingerprint analysis of YMJD. The efficacy and molecular mechanisms were investigated. RESULTS: The results showed that treatment with YMJD improved the general state of rats, reduced weight loss and serum lactate (LA) levels, attenuated pulmonary edema and pathological damage of the lung tissue. Moreover, we found that YMJD effectively decreased the infiltration of white blood cells (WBC), lymphocytes (LYM), mononuclear cells (MON) and neutrophils (NEUT) in bronchoalveolar lavage fluid (BALF), reduced the concentration of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the lung tissue. Additionally, we found that YMJD could significantly increase the activity of superoxide dismutase (SOD) and reduce the malondialdehyde (MDA) level in the lung tissue. By employing RNA-sequencing, we have identified that JAK2/STAT1 is an important pathway that is involved in the lung protection of YMJD, and further Western blot assay verified that YMJD could effectively inhibit the activation of the JAK2/STAT1 pathway. CONCLUSIONS: YMJD could attenuate LPS-induced ALI through suppressing inflammation and oxidative stress in the lung tissue of rats, associating with the inhibition of JAK2/STAT1 activation. These findings provide evidence for the clinical use of YMJD for treatment of inflammatory pulmonary diseases like ALI.

The role of anthraquinone-2-sulfonate on intra/extracellular electron transfer of anaerobic nitrate reduction.

To improve the electron (e-) transfer efficiency, exogenous redox mediators (RMs) were usually employed to enhance the denitrification efficiency due to the electron shuttling. Previous studies were mainly focused on how to improve the extracellular electron transfer (EET) by exogenous RMs. However, the intracellular electron transfer (IET), another crucial e- transfer pathway, of biological denitrification was scarcely reported, especially for the relationship between the denitrification and IET. In this study, Coenzyme Q, Complexes I, II and III were determined as the core components in the IET chain of denitrification by using four specific respiration chain inhibitors (RCIs). Anthraquinone-2-sulfonate (AQS) partially recovered the IET of denitrification from NO3--N to N2 gas when the RCIs were added. Specifically, the generations of N2 gas were improved by 9.68%-18.25% in the experiments with RCIs and AQS, comparing to that with RCIs. nrfA gene was not detected by reverse transcription-polymerase chain reaction, suggesting that Klebsiella oxytoca strain could not conduct dissimilatory nitrate reduction to ammonium. Nitrate assimilation was considered as the main NH4+-N formation way of K. oxytoca strain. The two e- transfer pathways of denitrification were constructed and the roles of AQS on the IET and EET of denitrification were specifically discussed. The results of this study provided a better understanding of the e- transfer pathways of denitrification, and suggested a potential practical use of exogenous RM on bio-treatment of nitrate-containing wastewater.