Approximate message passing from random initialization with applications to Z2 synchronization.

This paper is concerned with the problem of reconstructing an unknown rank-one matrix with prior structural information from noisy observations. While computing the Bayes optimal estimator is intractable in general due to the requirement of computing high-dimensional integrations/summations, Approximate Message Passing (AMP) emerges as an efficient first-order method to approximate the Bayes optimal estimator. However, the theoretical underpinnings of AMP remain largely unavailable when it starts from random initialization, a scheme of critical practical utility. Focusing on a prototypical model called [Formula: see text] synchronization, we characterize the finite-sample dynamics of AMP from random initialization, uncovering its rapid global convergence. Our theory-which is nonasymptotic in nature-in this model unveils the non-necessity of a careful initialization for the success of AMP.

Sugar status in preexisting leaves determines systemic stomatal development within newly developing leaves.

Stomata are pores found in the epidermis of stems or leaves that modulate both plant gas exchange and water/nutrient uptake. The development and function of plant stomata are regulated by a diverse range of environmental cues. However, how carbohydrate status in preexisting leaves might determine systemic stomatal formation within newly developing leaves has remained obscure. The glucose (Glc) sensor HEXOKINASE1 (HXK1) has been reported to decrease the stability of an ethylene/Glc signaling transcriptional regulator, EIN3 (ETHYLENE INSENSITIVE3). EIN3 in turn directly represses the expression of SUC2 (sucrose transporter 2), encoding a master transporter of sucrose (Suc). Further, KIN10, a nuclear regulator involved in energy homeostasis, has been reported to repress the transcription factor SPCH (SPEECHLESS), a master regulator of stomatal development. Here, we demonstrate that the Glc status of preexisting leaves determines systemic stomatal development within newly developing leaves by the HXK1-¦EIN3-¦SUC2 module. Further, increasing Glc levels in preexisting leaves results in a HXK1-dependent decrease of EIN3 and increase of SUC2, triggering the perception, amplification and relay of HXK1-dependent Glc signaling and thereby triggering Suc transport from mature to newly developing leaves. The HXK1-¦EIN3-¦SUC2 molecular module thereby drives systemic Suc transport from preexisting leaves to newly developing leaves. Subsequently, increasing Suc levels within newly developing leaves promotes stomatal formation through the established KIN10⟶ SPCH module. Our findings thus show how a carbohydrate signal in preexisting leaves is sensed, amplified and relayed to determine the extent of systemic stomatal development within newly developing leaves.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Glucose status within dark-grown etiolated cotyledons determines seedling de-etiolation upon light irradiation.

Exposure of dark-grown etiolated seedlings to light triggers the transition from skotomorphogenesis/etiolation to photomorphogenesis/de-etiolation. In the life cycle of plants, de-etiolation is essential for seedling development and plant survival. The mobilization of soluble sugars (glucose [Glc], sucrose, and fructose) derived from stored carbohydrates and lipids to target organs, including cotyledons, hypocotyls, and radicles, underpins de-etiolation. Therefore, dynamic carbohydrate biochemistry is a key feature of this phase transition. However, the molecular mechanisms coordinating carbohydrate status with the cellular machinery orchestrating de-etiolation remain largely opaque. Here, we show that the Glc sensor HEXOKINASE 1 (HXK1) interacts with GROWTH REGULATOR FACTOR5 (GRF5), a transcriptional activator and key plant growth regulator, in Arabidopsis (Arabidopsis thaliana). Subsequently, GRF5 directly binds to the promoter of phytochrome A (phyA), encoding a far-red light (FR) sensor/cotyledon greening inhibitor. We demonstrate that the status of Glc within dark-grown etiolated cotyledons determines the de-etiolation of seedlings when exposed to light irradiation by the HXK1-GRF5-phyA molecular module. Thus, following seed germination, accumulating Glc within dark-grown etiolated cotyledons stimulates a HXK1-dependent increase of GRF5 and an associated decrease of phyA, triggering the perception, amplification, and relay of HXK1-dependent Glc signaling, thereby facilitating the de-etiolation of seedlings following light irradiation. Our findings, therefore, establish how cotyledon carbohydrate signaling under subterranean darkness is sensed, amplified, and relayed, determining the phase transition from skotomorphogenesis to photomorphogenesis on exposure to light irradiation.

Polyoxovanadate-Based Metal-Organic Frameworks with Dual Active Sites for the Synthesis of p-Benzoquinones.

p-Benzoquinones are important organic intermediates in the synthesis of biopharmaceuticals and fine chemicals. In this study, two crystalline 3D polyoxovanadate-based metal-organic frameworks, H[Cu(tpi)2]{Cu2V7O21}·H2O (1, tpi = C18N5H13) and [Co(Htpi)2]{V4O12} (2, Htpi = C18N5H14), were synthesized, which as heterogeneous catalysts showed excellent catalytic activities for the synthesis of p-benzoquinones. Both compounds were characterized by IR, UV-vis diffuse reflectance spectroscopy, TG, XPS, X-ray diffraction, etc. In 1, {Cu2V7} clusters are connected together by copper cations and 1D Cu-organic coordination chains to yield a 3D polyoxometalate-based metal-organic framework (POMOF); in 2, adjacent 2D bimetallic oxide layers, constructed from 1D polyoxovanadate chains and cobalt ions, are further connected by 1D Co-organic coordination chains to form a 3D POMOF. Noteworthily, in the synthesis of trimethyl-p-benzoquinone, the key intermediate of vitamin E, using 2,3,6-trimethylphenol as the model substrate, the turnover frequency values for compounds 1 and 2 can, respectively, reach 607 and 380 h-1 in 8 min. Furthermore, both compounds demonstrated excellent recyclability and structural stability, characterized by PXRD and IR. The catalytic mechanism reveals that both the homolytic radical mechanism and heterolytic oxygen atom transfer mechanism are involved.

Application of Hemoperfusion in the Treatment of Acute Poisoning.

Rescue of acute poisoning is a race against time, and it is particularly important to remove toxic substances in time. Traditional methods include gastric lavage, promoting elimination, chelating agents, and other treatments. Hemoperfusion is a common blood purification technique. In the clinical practice of acute poisoning, hemoperfusion can directly remove toxic substances through its unique adsorption effect, showing its excellent efficacy. This paper reviews the experience of hemoperfusion in the treatment of various drug overdoses, pesticides, biological toxins, and industrial poisons, even drug addiction. It is hoped to provide a reference for clinicians in acute poisoning rescue.

Metformin attenuates lung ischemia-reperfusion injury and necroptosis through AMPK pathway in type 2 diabetic recipient rats.

BACKGROUND: Diabetes mellitus (DM) can aggravate lung ischemia-reperfusion (I/R) injury and is a significant risk factor for recipient mortality after lung transplantation. Metformin protects against I/R injury in a variety of organs. However, the effect of metformin on diabetic lung I/R injury remains unclear. Therefore, this study aimed to observe the effect and mechanism of metformin on lung I/R injury following lung transplantation in type 2 diabetic rats. METHODS: Sprague-Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion. RESULTS: Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C. CONCLUSIONS: Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.

Integration and transfer learning of single-cell transcriptomes via cFIT.

Large, comprehensive collections of single-cell RNA sequencing (scRNA-seq) datasets have been generated that allow for the full transcriptional characterization of cell types across a wide variety of biological and clinical conditions. As new methods arise to measure distinct cellular modalities, a key analytical challenge is to integrate these datasets or transfer knowledge from one to the other to better understand cellular identity and functions. Here, we present a simple yet surprisingly effective method named common factor integration and transfer learning (cFIT) for capturing various batch effects across experiments, technologies, subjects, and even species. The proposed method models the shared information between various datasets by a common factor space while allowing for unique distortions and shifts in genewise expression in each batch. The model parameters are learned under an iterative nonnegative matrix factorization (NMF) framework and then used for synchronized integration from across-domain assays. In addition, the model enables transferring via low-rank matrix from more informative data to allow for precise identification in data of lower quality. Compared with existing approaches, our method imposes weaker assumptions on the cell composition of each individual dataset; however, it is shown to be more reliable in preserving biological variations. We apply cFIT to multiple scRNA-seq datasets of developing brain from human and mouse, varying by technologies and developmental stages. The successful integration and transfer uncover the transcriptional resemblance across systems. The study helps establish a comprehensive landscape of brain cell-type diversity and provides insights into brain development.

Dose-response relationships between body-mass index and pressure injuries occurrence in hospitalized patients: A multi-center prospective study.

BACKGROUND: Pressure injuries (PIs) are one of the leading potentially preventable hospital-acquired complications associated with prolonged hospital length, poor quality of life and financial burden. The relationship between body mass index (BMI) and PIs occurrence is controversial. OBJECTIVE: The aim of this study was to further examine relationships between BMI and PIs occurrence in hospitalized patients. DESIGN: A multi-center prospective study. SETTING: 39 hospitals located in northwest China from April 2021 to July 2023. PARTICIPANTS: 175,960 hospitalized patients aged over 18 years were enrolled, and 170,800 patients were included in the final analysis. METHODS: BMI and clinical characteristics were assessed at baseline. PIs assessment were performed by trained nurses, with data recorded for the presence, the location and stage of each PI. For staging PIs, the National Pressure Ulcer Advisory Panel（NPUAP） staging system were used. The multivariate logistic regressions analysis and restricted cubic splines (RCS) models were used to explore associations between BMI and PIs, adjusting for potential confounders. RESULTS: Of 175,960 participants, 5160 were excluded from analyses. The multivariate logistic regression model identified a positive relationship between under-weight BMI and risk of PIs occurrence (OR = 1.60, 95% CI:1.18-2.17). We also found U shaped association between BMI and PIs occurrence (non-linear P < 0.001). BMI less than 23 kg/m2 significantly increased risk of PIs, and there was a tendency to increase risk of PIs at BMI higher than 30 kg/m2. We stratified participants by sex to further investigate their association and found the risk of PIs increases substantially in women at BMI below 17 kg/m2 and in men at BMI below 23 kg/m2. CONCLUSIONS: The present study indicated that there was an approximate U shaped relationship between BMI and PIs occurrence, and this association was potentially different between men and women.

Visible-Light-Responsive 2D Photocatalysts Assembled by Evans-Showell-Type POMs and Metalloviologen Frameworks for Sulfide-Sulfoxide Transformation.

Sulfide-sulfoxide aerobic photo-oxidation is of great interest in organic and medicinal chemistry; however, developing efficient and facile heterogeneous photocatalytic systems without additional additives remains challenging. Herein, we intentionally designed and synthesized two polyoxometalate (POM)-based metalloviologen frameworks, formulated as [MII(4-PBPY)2(H2O)][MII(H2O)4][CoIII2MoVI10H4O38]·nH2O (M = Cu, n = 10 for 1; M = Co, n = 11 for 2), prepared by the mild one-step synthesis strategy and characterized in detail. X-ray single-crystal diffraction analysis shows that they present a two-dimensional layered structure formed by two parallel metalloviologen layers pillared by dimeric Evans-Showell-type POMs. The connection of POM to the metalloviologen framework enables easier flow of electrons to the POM port, which can theoretically further induce O2 to generate reactive oxygen species (O2•-) to oxidize substrates to form target products. As expected, both 1 and 2 exhibit outstanding photocatalytic activity in the oxidation of sulfides. Within 6 h, methyl phenyl sulfide can be quantitatively converted into methyl phenyl sulfoxide. The in-depth mechanism reveals that there is also a synergistic energy-transfer pathway in the catalytic system in addition to the electron-transfer pathway. In addition, the corresponding catalytic activity and structure can be well maintained after at least 10 cycle experiments.

Differences in the luminal and mucosal gut microbiomes and metabolomes of oriental rat snake (Ptyas mucosus).

Previous studies regarding the gastrointestinal biogeography of microbiomes generally focused on longitudinal comparisons, whereas few studies have compared luminal and mucosal microbiomes. Investigations of the snake gut microbiome have attracted interest because of the unique digestive physiology and hibernation behavior, but adequate sampling methods must be developed. Here, we used an omics approach combining 16S rRNA gene sequencing with untargeted metabolomics to profile the luminal and mucosal gut microbiomes and metabolomes in oriental rat snakes, with the goal of revealing the heterogeneity and co-occurrence at these sites. The α-diversity of the gut microbiome was significantly higher at mucosal sites than at luminal sites. Microbial composition also differed according to sampling site, with significant differences in the abundances of dominant phyla and genera, as well as ß-diversity clustering and distribution. Metabolome profiling revealed differences that were mainly related to cholinergic substances and nucleic acids. Analysis of variations in Kyoto Encyclopedia of Genes and Genomes functions of microbes and metabolites showed that the mucosal microbiome was more frequently involved in genetic information processing and cellular processes, whereas the luminal microbiome generally participated in metabolic regulation. Notably, we found a greater abundance of the opportunistic pathogen genus Escherichia-Shigella at luminal sites and higher levels of the lipid-regulator metabolite fenfluramine at mucosal sites. Despite the extensive differences between the two sampling sites, the results revealed similarities in terms of amplicon sequence variant composition and dominant core microbes. This pilot exploration of luminal and mucosal microbiomes and metabolites provides key insights to guide future research. KEY POINTS: • Snake luminal and mucosal microbiota was distinct in composition and function. • Metabolome profiling revealed differences related to different metabolites. • The pathogenic microbes are more likely to colonize the gut lumina.

Cell type hierarchy reconstruction via reconciliation of multi-resolution cluster tree.

A wealth of clustering algorithms are available for single-cell RNA sequencing (scRNA-seq) data to enable the identification of functionally distinct subpopulations that each possess a different pattern of gene expression activity. Implementation of these methods requires a choice of resolution parameter to determine the number of clusters, and critical judgment from the researchers is required to determine the desired resolution. This supervised process takes significant time and effort. Moreover, it can be difficult to compare and characterize the evolution of cell clusters from results obtained at one single resolution. To overcome these challenges, we built Multi-resolution Reconciled Tree (MRtree), a highly flexible tree-construction algorithm that generates a cluster hierarchy from flat clustering results attained for a range of resolutions. Because MRtree can be coupled with most scRNA-seq clustering algorithms, it inherits the robustness and versatility of a flat clustering approach, while maintaining the hierarchical structure of cells. The constructed trees from multiple scRNA-seq datasets effectively reflect the extent of transcriptional distinctions among cell groups and align well with levels of functional specializations among cells. Importantly, application to fetal brain cells identified subtypes of cells determined mainly by maturation states, spatial location and terminal specification.

The promoting effects of pyriproxyfen on autophagy and apoptosis in silk glands of non-target insect silkworm, Bombyx mori.

Pyriproxyfen is a juvenile hormone analogue. The physiological effects of its low-concentration drift during the process of controlling agricultural and forestry pests on non-target organisms in the ecological environment are unpredictable, especially the effects on organs that play a key role in biological function are worthy of attention. The silk gland is an important organ for silk-secreting insects. Herein, we studied the effects of trace pyriproxyfen on autophagy and apoptosis of the silk gland in the lepidopteran model insect, Bombyx mori (silkworm). After treating fifth instar silkworm larvae with pyriproxyfen for 24 h, we found significant shrinkage, vacuolization, and fragmentation in the posterior silk gland (PSG). In addition, the results of autophagy-related genes of ATG8 and TUNEL assay also demonstrated that autophagy and apoptosis in the PSG of the silkworm was induced by pyriproxyfen. RNA-Seq results showed that pyriproxyfen treatment resulted in the activation of juvenile hormone signaling pathway genes and inhibition of 20-hydroxyecdysone (20E) signaling pathway genes. Among the 1808 significantly differentially expressed genes, 796 were upregulated and 1012 were downregulated. Among them, 30 genes were identified for autophagy-related signaling pathways, such as NOD-like receptor signaling pathway and mTOR signaling pathway, and 30 genes were identified for apoptosis-related signaling pathways, such as P53 signaling pathway and TNF signaling pathway. Further qRT-PCR and in vitro gland culture studies showed that the autophagy-related genes Atg5, Atg6, Atg12, Atg16 and the apoptosis-related genes Aif, Dronc, Dredd, and Caspase1 were responsive to the treatment of pyriproxyfen, with transcription levels up-regulated from 24 to 72 h. In addition, ATG5, ATG6, and Dronc genes had a more direct response to pyriproxyfen treatment. These results suggested that pyriproxyfen treatment could disrupt the hormone regulation in silkworms, promoting autophagy and apoptosis in the PSG. This study provides more evidence for the research on the damage of juvenile hormone analogues to non-target organisms or organs in the environment, and provides reference information for the scientific and rational use of juvenile hormone pesticides.

Machine learning-based prediction models for pressure injury: A systematic review and meta-analysis.

Despite the fact that machine learning (ML) algorithms to construct predictive models for pressure injury development are widely reported, the performance of the model remains unknown. The goal of the review was to systematically appraise the performance of ML models in predicting pressure injury. PubMed, Embase, Cochrane Library, Web of Science, CINAHL, Grey literature and other databases were systematically searched. Original journal papers were included which met the inclusion criteria. The methodological quality was assessed independently by two reviewers using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Meta-analysis was performed with Metadisc software, with the area under the receiver operating characteristic curve, sensitivity and specificity as effect measures. Chi-squared and I2 tests were used to assess the heterogeneity. A total of 18 studies were included for the narrative review, and 14 of them were eligible for meta-analysis. The models achieved excellent pooled AUC of 0.94, sensitivity of 0.79 (95% CI [0.78-0.80]) and specificity of 0.87 (95% CI [0.88-0.87]). Meta-regressions did not provide evidence that model performance varied by data or model types. The present findings indicate that ML models show an outstanding performance in predicting pressure injury. However, good-quality studies should be conducted to verify our results and confirm the clinical value of ML in pressure injury development.

The potential role of ferroptosis in the physiopathology of deep tissue injuries.

Deep tissue injuries (DTIs) are a serious type of pressure injuries that mainly occur at the bony prominences and can develop rapidly, making prevention and treatment more difficult. Although consistent research efforts have been made over the years, the cellular and molecular mechanisms contributing to the development of DTIs remain unclear. More recently, ferroptosis, a novel regulatory cell death (RCD) type, has been identified that is morphological, biochemical and genetic criteria distinct from apoptosis, autophagy and other known cell death pathways. Ferroptosis is characterized by iron overload, iron-dependent lipid peroxidation and shrunken mitochondria. We also note that some of the pathological features of DTI are known to be key features of the ferroptosis pathway. Numerous studies have confirmed that ferroptosis may be involved in chronic wounds, including DTIs. Here, we elaborate on the basic pathological features of ferroptosis. We also present the evidence that ferroptosis is involved in the pathology of DTIs and highlight a future perspective on this emerging field, desiring to provide more possibilities for the prevention and treatment of DTIs.

The prevalence and risk factors of facial pressure injuries related to adult non-invasive ventilation equipment: A systematic review and meta-analysis.

To systematically assess the prevalence of facial pressure injuries related to adult non-invasive ventilation equipment, and risk factors of facial pressure injuries. PubMed, Cochrane Library, Web of Science, Embase, China Knowledge Resource Integrated Database, Wanfang Database, Chinese Biomedical Database and Weipu Database were comprehensively searched for observational studies investigating the prevalence and risk factors of facial pressure injuries related to adult non-invasive ventilation equipment from inception to May 16th, 2022. Filter articles based on inclusion and exclusion criteria. The quality of the included studies was evaluated independently by two investigators. Meta-analysis was conducted using Stata 16.0 software package. In total, 2835 articles were screened and data from 12 studies were used in meta-analysis. The prevalence of facial pressure injuries related to adult non-invasive ventilation equipment was 25% (95% confidence interval, CI:15% to 37%, I2  = 97.34%, P < 0.0001). After controlling for confounding variables, the following risk factors of facial pressure injuries: use equipment form, with diabetes, fever, cumulative time of using equipment, facial skin oedema and Glasgow score. Understanding the risk factors of facial pressure injuries can provide the healthcare personnel with the theoretical basis for the management and treatment of the patients.

Gastrointestinal Biogeography of Luminal Microbiota and Short-Chain Fatty Acids in Sika Deer (Cervus nippon).

The gut microbiota of sika deer has been widely investigated, but the spatial distribution of symbiotic microbes among physical niches in the gastrointestinal tract remains to be established. While feces are the most commonly used biological samples in these studies, the accuracy of fecal matter as a proxy of the microbiome at other gastrointestinal sites is as yet unknown. In the present study, luminal contents obtained along the longitudinal axis of deer gastrointestinal tract (rumen, reticulum, omasum, abomasum, small intestine, cecum, colon, and rectum) were subjected to 16S rRNA gene sequencing for profiling of the microbial composition, and samples from the rumen, small intestine, and cecum were subjected to metabolomic analysis to evaluate short-chain fatty acid (SCFA) profiles. Prevotella bacteria were the dominant gastric core microbes, while Christensenellaceae_R-7_group was predominantly observed in the intestine. While the eight gastrointestinal sites displayed variations in microbial diversity, abundance, and function, they could be clustered into stomach, small intestine, and large intestine segments, and the results further highlighted a specific microbial niche of the small intestine. SCFA levels in the rumen, small intestine, and cecum were significantly different, with Bacteroidetes and Spirochaetes were shown to play a critical role in SCFA production. Finally, the rectal microbial composition was significantly correlated with colonic and cecum communities but not those of the small intestine and four gastric sites. Quantification of the compositions and biogeographic relationships between gut microbes and SCFAs in sika deer should provide valuable insights into the interactions contributing to microbial functions and metabolites. IMPORTANCE Feces or specific segments of the gastrointestinal tract (in particular, the rumen) were sampled to explore the gut microbiome. The gastrointestinal biogeography of the luminal microbiota in ruminants, which is critical to guide accurate sampling for different purposes, is poorly understood at present. The microbial community of the rectal sample (as a proxy of fecal sample) showed higher correlation with those of other large intestinal sites relative to the small intestine or stomach, suggesting that the microbial composition is specifically shaped by the unique physiological characteristics of different gastrointestinal niches. In addition, significant differences in microbiomes and SCFAs were observed among the different gastrointestinal sites.

Targeting Atmospheric Oxidants Can Better Reduce Sulfate Aerosol in China: H2O2 Aqueous Oxidation Pathway Dominates Sulfate Formation in Haze.

Particulate sulfate is one of the most important components in the atmosphere. The observation of rapid sulfate aerosol production during haze events provoked scientific interest in the multiphase oxidation of SO2 in aqueous aerosol particles. Diverse oxidation pathways can be enhanced or suppressed under different aerosol acidity levels and high ionic strength conditions of atmospheric aerosol. The importance of ionic strength to sulfate multiphase chemistry has been verified under laboratory conditions, though studies in the actual atmosphere are still limited. By utilizing online observations and developing an improved solute strength-dependent chemical thermodynamics and kinetics model (EF-T&K model, EF is the enhancement factor that represents the effect of ionic strength on an aerosol aqueous-phase reaction), we provided quantitative evidence that the H2O2 pathway was enhanced nearly 100 times and dominated sulfate formation for entire years (66%) in Tianjin (a northern city in China). TMI (oxygen catalyzed by transition-metal ions) (14%) and NO2 (14%) pathways got the second-highest contributions. Machine learning supported the result that aerosol sulfate production was more affected by the H2O2 pathway. The collaborative effects of atmospheric oxidants and SO2 on sulfate aerosol production were further investigated using the improved EF-T&K model. Our findings highlight the effectiveness of adopting target oxidant control as a new direction for sustainable mitigation of sulfate, given the already low SO2 concentrations in China.

TNF-α derived from arsenite-induced microglia activation mediated neuronal necroptosis.

Arsenic, an identified environmental toxicant, poses threats to the health of human beings through contaminated water and food. Recently, increasing reports focused on arsenic-induced nerve damage, however, the underlying mechanism remains elusive. Microglia are important immune cells in the nervous system, which produce a large number of inflammatory factors including TNF-α when activated. Recent reports indicated that TNF-α is involved in the process of necroptosis, a new type of programmed cell death discovered recently. Although there were evidences suggested that arsenic could induce both microglia activation and TNF-α production in the nervous system, the mechanism of arsenic-induced neurotoxicity due to microglia activation is rarely studied. In addition, the role of microglia-derived TNF-α in response to arsenic exposure in necroptosis has not been documented before. In this study, we found that arsenite induced microglial activation through p38 MAPK signaling pathway, leading to the production of TNF-α. Microglia-derived TNF-α further induced necroptosis in the neuronal cells. Our findings suggested that necroptosis induced by microglia-derived TNF-α upon arsenite exposure partially played a role in arsenic-induced cell death which underlie the fundamental event of arsenic-related neurotoxicity.

Advances in chondroitinase delivery for spinal cord repair.

Chondroitin sulfate proteoglycans (CSPGs) present a formidable barrier to regrowing axons following spinal cord injury. CSPGs are secreted in response to injury and their glycosaminoglycan (GAG) side chains present steric hindrance preventing the growth of axons through the lesion site. The enzyme chondroitinase has been proven effective at reducing the CSPG GAG chains, however, there are issues with direct administration of the enzyme specifically due to its limited timeframe of activity. In this perspective article, we discuss the evolution of chondroitinase-based therapy in spinal cord injury as well as up-to-date advances on this critical therapeutic. We describe the success and the limitations around use of the bacterial enzyme namely issues around thermostability. We then discuss current efforts to improve delivery of chondroitinase with a push towards gene therapy, namely through the use of lentiviral and adeno-associated viral vectors, including the temporal modulation of its expression and activity. As a chondroitinase therapy for spinal cord injury inches nearer to the clinic, the drive towards an optimised delivery platform is currently underway.