Effects of walking on epigenetic age acceleration: a Mendelian randomization study.

INTRODUCTION: Walking stands as the most prevalent physical activity in the daily lives of individuals and is closely associated with physical functioning and the aging process. Nonetheless, the precise cause-and-effect connection between walking and aging remains unexplored. The epigenetic clock emerges as the most promising biological indicator of aging, capable of mirroring the biological age of the human body and facilitating an investigation into the association between walking and aging. Our primary objective is to investigate the causal impact of walking with epigenetic age acceleration (EAA). METHODS: We conducted a two-sample two-way Mendelian randomization (MR) study to investigate the causal relationship between walking and EAA. Walking and Leisure sedentary behavior data were sourced from UK Biobank, while EAA data were gathered from a total of 28 cohorts. The MR analysis was carried out using several methods, including the inverse variance weighted (IVW), weighted median, MR-Egger, and robust adjusted profile score (RAPS). To ensure the robustness of our findings, we conducted sensitivity analyses, which involved the MR-Egger intercept test, Cochran's Q test, and MR-PRESSO, to account for and mitigate potential pleiotropy. RESULTS: The IVW MR results indicate a significant impact of usual walking pace on GrimAge (BETA = - 1.84, 95% CI (- 2.94, - 0.75)), PhenoAge (BETA = - 1.57, 95% CI (- 3.05, - 0.08)), Horvath (BETA = - 1.09 (- 2.14, - 0.04)), and Hannum (BETA = - 1.63, 95% CI (- 2.70, - 0.56)). Usual walking pace is significantly associated with a delay in epigenetic aging acceleration (EAA) (P < 0.05). Moreover, the direction of effect predicted by the gene remained consistent across RAPS outcomes and sensitivity MR analyses. There is a lack of robust causal relationships between other walking conditions, such as walking duration and walking frequency, on EAA (P > 0.05). CONCLUSION: Our evidence demonstrates that a higher usual walking pace is associated with a deceleration of the acceleration of all four classical epigenetic clocks acceleration.

Gut commensal metabolite rhamnose promotes macrophages phagocytosis by activating SLC12A4 and protects against sepsis in mice.

Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model. Cecal ligation and puncture (CLP) surgery was used to establish polymicrobial sepsis in mice. Mice depleted of gut microbiota by an antibiotic cocktail (ABX) exhibited a significantly higher level of mortality than controls. As determined by metabolomics analysis, ABX treatment has depleted many metabolites, and subsequent supplementation with l-rhamnose (rhamnose, Rha), a bacterial carbohydrate metabolite, exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis, which in turn improved organ damage and mortality. Mechanistically, rhamnose binds directly to and activates the solute carrier family 12 (potassium-chloride symporter), member 4 (SLC12A4) in macrophages and promotes phagocytosis by activating the small G-proteins, Ras-related C3 botulinum toxin substrate1 (Rac1) and cell division control protein 42 homolog (Cdc42). Interestingly, rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients. In conclusion, by identifying SLC12A4 as the host interacting protein, we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.

Resilient Output Control of Multiagent Systems With DoS Attacks and Actuator Faults: Fully Distributed Event-Triggered Approach.

This article investigates the fully distributed resilient practical leader-follower bipartite output consensus (LFBOC) problem for heterogeneous linear multiagent systems (MASs) with denial-of-service (DoS) attacks and actuator faults. To estimate the leader matrix and state in the presence of DoS attacks, two novel adaptive event-triggered observers are proposed based on newly developed lemmas, and then the adaptive event-triggered fault-tolerant controller without chattering behavior is developed to solve the LFBOC problem. Different from most existing resilient practical LFBOC working with DoS attacks and actuator faults, our method does not rely on any global information, event-triggered communication between neighbors and discrete update controllers are implemented simultaneously. Finally, an example is presented to well illustrate the effectiveness of developed method.

[Effect of Low-density Polyethylene Microplastics on Natural Attenuation of Oxygenated Polycyclic Aromatic Hydrocarbons in Soil].

The continuous accumulation of microplastics in agricultural soils may affect the natural attenuation of oxygen-containing polycyclic aromatic hydrocarbons (OPAHs). The effects of low-density polyethylene (LDPE) microplastics with the spiking proportion of 1 % and 0.01 % in soils on the natural attenuation of OPAHs were investigated via soil microcosm experiments. The relation between the response of bacterial communities and OPAHs dissipation was also explored. The initial content of OPAHs in the soil was 34.6 mg·kg-1. The dissipation of OPAHs in the soil on day 14 was inhibited by LDPE. The contents of OPAHs in LDPE groups were higher than that in the control by 0.9-1.6 mg·kg-1, and the inhibition degree increased with the proportion of LDPE. The contents of OPAHs were not significantly different among groups on day 28, indicating that the inhibitory effect of LDPE disappeared. LDPE did not change the composition of the dominant taxa in the OPAHs-contaminated soil community but influenced the relative abundances of some dominant taxa. LDPE increased the relative abundance of Proteobacteria and Actinobacteria at the phylum level and decreased that of Bacillus and increased those of Micromonospora, Sphingomonas, and Nitrospira (potential degrading bacteria of LDPE and endogenous substances) at the genus level, all four of which were the main genera dominating intergroup community differences. LDPE changed the α and ß diversity of bacterial communities, but the extents were not significant. LDPE affected the function of the bacterial community, reducing the total abundance of PAHs-degrading genes and some degrading enzymes, inhibiting the growth of PAHs-degrading bacteria and thus interfering with the natural decay of OPAHs.

Atorvastatin improved ulcerative colitis in association with gut microbiota-derived tryptophan metabolism.

AIMS: Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear. MATERIALS AND METHODS: The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics. KEY FINDINGS: Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice. SIGNIFICANCE: These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.

Mechanistic study on the increase of Microcystin-LR synthesis and release in Microcystis aeruginosa by amino-modified nano-plastics.

Ecological risk of micro/nano-plastics (MPs/NPs) has become an important environmental issue. Microcystin-leucine-arginine (MC-LR) produced by Microcystis aeruginosa (M. aeruginosa) is the most common and toxic secondary metabolites (SM). However, the influencing mechanism of MPs and NPs exposure on MC-LR synthesis and release have still not been clearly evaluated. In this work, under both acute (4d) and long-term exposure (10d), only high-concentration (10 mg/L) exposure of amino-modified polystyrene NPs (PS-NH2-NPs) promoted MC-LR synthesis (32.94 % and 42.42 %) and release (27.35 % and 31.52 %), respectively. Mechanistically, PS-NH2-NPs inhibited algae cell density, interrupted pigment synthesis, weakened photosynthesis efficiency, and induced oxidative stress, with subsequent enhancing the MC-LR synthesis. Additionally, PS-NH2-NPs exposure up-regulated MC-LR synthesis pathway genes (mcyA, mcyB, mcyD, and mcyG) combined with significantly increased metabolomics (Leucine and Arginine), thereby enhancing MC-LR synthesis. PS-NH2-NPs exposure enhanced the MC-LR release from M. aeruginosa via up-regulated MC-LR transport pathway genes (mcyH) and the shrinkage of plasma membrane. Our results provide new insights into the long-time coexistence of NPs with algae in freshwater systems might pose a potential threat to aquatic environments and human health.

The immunosuppressive landscape in tumor microenvironment.

Recent advances in cancer immunotherapy, especially immune checkpoint inhibitors (ICIs), have revolutionized the clinical outcome of many cancer patients. Despite the fact that impressive progress has been made in recent decades, the response rate remains unsatisfactory, and many patients do not benefit from ICIs. Herein, we summarized advanced studies and the latest insights on immune inhibitory factors in the tumor microenvironment. Our in-depth discussion and updated landscape of tumor immunosuppressive microenvironment may provide new strategies for reversing tumor immune evasion, enhancing the efficacy of ICIs therapy, and ultimately achieving a better clinical outcome.

Optically pumped flexible GaN-based ultraviolet VCSELs.

Flexible optoelectronic platforms, which integrate optoelectronic devices on a flexible substrate, are promising in more complex working environments benefiting from the mechanical flexibility. Herein, for the first time to the best of our knowledge, a flexible GaN-based vertical cavity surface-emitting laser (VCSEL) in the ultraviolet A (UVA) range was demonstrated by using a thin-film transfer process based on laser lift-off (LLO) and spin-coating of a flexible substrate. The lasing wavelength is 376.5 nm with a linewidth of 0.6 nm and threshold energy of 98.4 nJ/pulse, corresponding to a threshold energy density of 13.9 mJ/cm2. The flexible substrate in this study is directly formed by spin-coating of photosensitive epoxy resin, which is much simplified and cost-effective, and a 2-in. wafer scale GaN-based membrane can be successfully transferred to a flexible substrate through this method. Such flexible UVA VCSELs are promising for the development of next-generation flexible and wearable technologies.

Bacteria from nodules of Abrus mollis Hance: genetic diversity and screening of highly efficient growth-promoting strains.

Introduction: Abrus mollis Hance. (AM) is an important species used in southern Chinese medicine. It is mainly found in Guangdong and Guangxi provinces in China, and it is effective in the treatment of hepatitis. Endophytic bacteria are known to affect the growth and quality of medicinal plants. However, there are limited reports describing endophytic bacteria related to AM. Methods: In the present study, Illumina-based 16S rRNA gene sequencing was used to investigate the endophytic bacterial communities of root nodules of AM at five sampling sites in Guangxi. In addition, 179 strains of endophytic bacteria were isolated and categorized into 13 haplotypes based on recA sequence analysis. Results: The phylogeny of the 16S rRNA gene sequences revealed a predominance of nonrhizobial endophytes. Microbial diversity analysis showed that Proteobacteria was the dominant phylum in all samples, while Bradyrhizobium was the dominant genus in different samples. An efficient strain, Rhizobium tropici FM-19, was screened and obtained through greenhouse experiments. The AM plants inoculated with this strain showed the best growth performance and high nitrogen fixation and nodulation capacity. Notably, total phenols and total flavonoids, important active components in AM, increased by 30.9 and 42.7%, respectively, after inoculation with Rhizobium tropici FM-19. Discussion: This study provides insights into the complex microbial diversity of AM nodules and provides strain information for the efficient cultivation of AM.

Cyanobacterial blooms control with CaO2 in different stages: Inhibition efficiency, water quality optimization and microbial community changes.

This study explored the feasibility of calcium peroxide (CaO2) to inhibit cyanobacterial blooms of the outbreak and dormancy stages. Our previous studies have found that CaO2 has a high inhibitory effect on cyanobacteria. In order to explore the application effect of CaO2 in actual cyanobacteria lake water, we conducted this study to clarify the effect of CaO2 on inhibiting cyanobacteria in outbreak and dormancy stages. The results showed that CaO2 inhibited the growth of cyanobacteria in the outbreak and dormancy stages by 98.7% and 97.6%, respectively. The main inhibitory mechanism is: (1) destroy the cell structure and make the cells undergo programmed cell death by stimulating the oxidation balance of cyanobacteria cells; (2) EPS released by cyanobacteria resist stimulation and combine calcium to form colonies, and accelerate cell settlement. In addition to causing direct damage to cyanobacteria, CaO2 can also improve water quality and sediment microbial diversity, and reduce the release of sediment to phosphorus, so as to further contribute to cyanobacterial inhibition. Finally, the results of qRT-PCR analysis confirmed the promoting effect of CaO2 on the downregulation of photosynthesis-related genes (rbcL and psaB), microcystn (mcyA and mcyD) and peroxiredoxin (prx), and verified the mechanism of CaO2 inhibition of cyanobacteria. In conclusion, this study provides new findings for the future suppression of cyanobacterial bloom, by combining water quality, cyanobacterial inhibition mechanisms, and sediment microbial diversity.

Trading strategies of energy storage participation in day-ahead joint market based on Stackelberg game.

The goal of "carbon peak, carbon neutral" and the increasing expansion of new energy have helped to advance the development of energy storage. However, since the operating cost of energy storage is high, carbon emission trading and power market trading have emerged, effectively improving the efficiency. In this paper, a trading strategy and bidding framework of energy storage participation in the day-ahead joint market are studied. A market bidding model has been established in a framework based on the Stackelberg game. Finally, the "Day-Ahead and Intra-Day and Carbon Emission Trading (CET)" market clearing model has been constructed. It has been simplified to solve the equivalent mixed-integer linear programming (MILP) problem with equilibrium constraints through the use of the Karush-Kuhn-Tucker (KKT) optimality criterion and duality principle. The proposed model is validated through improved examples to obtain thermal unit output cuts of up to 32.2% during load trough periods, and up to 16.75% increase in clearing prices during peak load periods. The storage life is extended and the storage output variation is minimized.

Phase-Transition-Promoted Thermoelectric Textiles Based on Twin Surface-Modified CNT Fibers.

With the fast development of new science and technology, wearable devices are in great demand in modern human daily life. However, the energy problem is a long-lasting issue to achieve real smart, wearable, and portable devices. Flexible thermoelectric generators (TEGs) based on thermoelectric conversion systems can convert body waste heat into electricity with excellent flexibility and wearability, which shows a new direction to solving this issue. Here in this work, polyethylenimine (PEI) and gold nanoparticles (Au NPs) twin surface-modified carbon nanotube fibers (CNTFs) were designed and prepared to fabricate thermoelectric textiles (TET) with high performance, good air stability, and high-efficiency power generation. To better utilize the heat emitted by the human body, microencapsulated phase change materials (MPCM) were coated on the hot end of the TET to achieve the phase-transition-promoted TET. MPCM-coated TET device could generate 25.7% more energy than the untreated control device, which indicates the great potential of the phase-transition-promoted TET.

Optimization strategy of power purchase and sale for electricity retailers in a two-tier market.

Against the backdrop of the gradual advancement of China's electricity market reform, the number of Power Trading Companies in China has been increasing year by year, and as of October 2022, the number has reached more than 10,000. As an important hub connecting the electricity market and users, electricity retailers face double risks from downstream user load fluctuations and electricity market price fluctuations. Therefore, a reasonable power purchase and sale strategy is very important for an electricity retailer. In this study, a block bidding mechanism is adopted to optimize the clearing of the medium-to long-term market and a DA-RBF neural network is established for spot electricity price forecasting model based on numerical feature similarity to improve the accuracy of electricity price forecasting. Furthermore, the model considers the differences in user demand responses and investigates the optimal power purchase and sale strategy, guided by differentiated time-of-use electricity pricing. The case study analysis demonstrated that the proposed power purchase and sale optimization strategy yields favorable results, improving profitability and enhancing the stability of the power system.

Soft tissue infection and osteomyelitis caused by Mycobacterium farcinogenes after heart surgery: Case report and literature review of human cases.

Mycobacterium farcinogenes (M. farcinogenes) is rapidly growing mycobacterium, belonging to non-tuberculous mycobacterial (NTM). M. farcinogenes is an exceedingly rare causative agent of human infection. Only seven cases with M. farcinogenes infections in humans were reported. This is a case of soft tissue infection and osteomyelitis caused by M. farcinogenes after heart surgery. Microbial identification was achieved by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The clinical outcome was favorable after surgical debridement and 4-month antibiotics treatment. We also provide a comprehensive literature review on this disease.

PbrWRKY62-PbrADC1 module involves in superficial scald development of Pyrus bretschneideri Rehd.fruit via regulating putrescine biosynthesis.

Putrescine plays a role in superficial scald development during the cold storage of pear fruit. However, the molecular mechanism behind this phenomenon has not been un-fully clarified until recently. In this study, a conjoint analysis of metabolites and gene expression profiles in the putrescine-metabolic pathway of P. bretschneideri Rehd. fruit followed by experimental validation revealed that PbrADC1, forming a homodimer in the chloroplast, was involved in putrescine biosynthesis and thus fruit chilling resistance. Additionally, the substrate-binding residue Cys546 in PbrADC1, whose activity was modified by H2O2, played a crucial role in arginine decarboxylation into agmatine. Through a combined analysis of the distribution of cis-acting elements in the PbrADC1 promoter as well as the expression profiles of related transcription factors (TFs), several TFs were identified as upstream regulators of PbrADC1 gene. Further investigation revealed that the nuclear PbrWRKY62 could directly bind to the W-box elements in the PbrADC1 promoter, activate its expression, enhance putrescine accumulation, and thus increase fruit chilling tolerance. In conclusion, our results suggest that the PbrWRKY62-PbrADC1 module is involved in the development of superficial scald in P. bretschneideri Rehd. fruit via regulating putrescine biosynthesis. Consequently, these findings could serve as valuable genetic resources for breeding scald-resistant pear fruit.

Endosonography Elastography and Magnetic Resonance Imaging in the Restaging and Response Assessment of Rectal Cancer After Neoadjuvant Therapy.

ABSTRACT: The objective of this academic research is to assess the efficacy of conventional endorectal ultrasound (ERUS), ultrasonic shear wave elastography (SWE), and magnetic resonance imaging (MRI) techniques in evaluating the impact of neoadjuvant therapy (nCRT). Forty-five patients with advanced low rectal cancer (T ≥ 3) were included. Before and after nCRT, ERUS, SWE, and MRI evaluations were conducted. The T staging of ultrasound (uT) and MRI (mT) were evaluated and compared with the pathological T staging (ypT). The accuracy of the 2 diagnostic methods for T staging, and T downstaging was evaluated. The ultrasound elasticity difference and relative elasticity before and after treatment and pathological T downstaging were compared, and its cutoff value and the area under the curve were assessed. In terms of T staging accuracy after chemoradiotherapy, the values for ERUS, ERUS combined with SWE, and MRI were 64.4%, 71.1%, and 62.2%, respectively. No significant difference was observed among these groups ( P > 0.05). The accuracy of uT downstaging was 84.4%, and that of mT downstaging was 88.9%. The receiver operating characteristic curve of uLD and elastic differences and relative elasticity of T downstaging after treatment were 0.754, 0.817, and 0.886, respectively (all P < 0.05). Both ERUS and MRI can evaluate ypT downstaging. The indicators for evaluating T downstaging are uLD, elasticity difference, and relative elasticity, providing more reference for clinical assessment of nCRT efficacy.

Corylifol A suppresses osteoclastogenesis and alleviates ovariectomy-induced bone loss via attenuating ROS production and impairing mitochondrial function.

Osteoporosis is a systemic disease characterized by an imbalance in bone homeostasis, where osteoblasts fail to fully compensate for the bone resorption induced by osteoclasts. Corylifol A, a flavonoid extracted from Fructus psoraleae, has been identified as a potential treatment for this condition. Predictions from network pharmacology and molecular docking studies suggest that Corylifol A exhibits strong binding affinity with NFATc1, Nrf2, PI3K, and AKT1. Empirical evidence from in vivo experiments indicates that Corylifol A significantly mitigates systemic bone loss induced by ovariectomy by suppressing both the generation and activation of osteoclasts. In vitro studies further showed that Corylifol A inhibited the activation of PI3K-AKT and MAPK pathways and calcium channels induced by RANKL in a time gradient manner, and specifically inhibited the phosphorylation of PI3K, AKT, GSK3 ß, ERK, CaMKII, CaMKIV, and Calmodulin. It also diminishes ROS production through Nrf2 activation, leading to a decrease in the expression of key regulators such as NFATcl, C-Fos, Acp5, Mmp9, and CTSK that are involved in osteoclastogenesis. Notably, our RNA-seq analysis suggests that Corylifol A primarily impacts mitochondrial energy metabolism by suppressing oxidative phosphorylation. Collectively, these findings demonstrate that Corylifol A is a novel inhibitor of osteoclastogenesis, offering potential therapeutic applications for diseases associated with excessive bone resorption.

Oral magnesium prevents acetaminophen-induced acute liver injury by modulating microbial metabolism.

Acetaminophen overuse is a common cause of acute liver failure (ALF). During ALF, toxins are metabolized by enzymes such as CYP2E1 and transformed into reactive species, leading to oxidative damage and liver failure. Here, we found that oral magnesium (Mg) alleviated acetaminophen-induced ALF through metabolic changes in gut microbiota that inhibit CYP2E1. The gut microbiota from Mg-supplemented humans prevented acetaminophen-induced ALF in mice. Mg exposure modulated Bifidobacterium metabolism and enriched indole-3-carboxylic acid (I3C) levels. Formate C-acetyltransferase (pflB) was identified as a key Bifidobacterium enzyme involved in I3C generation. Accordingly, a Bifidobacterium pflB knockout showed diminished I3C generation and reduced the beneficial effects of Mg. Conversely, treatment with I3C or an engineered bacteria overexpressing Bifidobacterium pflB protected against ALF. Mechanistically, I3C bound and inactivated CYP2E1, thus suppressing formation of harmful reactive intermediates and diminishing hepatocyte oxidative damage. These findings highlight how interactions between Mg and gut microbiota may help combat ALF.

An engineered Escherichia coli Nissle strain prevents lethal liver injury in a mouse model of tyrosinemia type 1.

BACKGROUND & AIMS: Hereditary tyrosinemia type 1 (HT1) results from the loss of fumarylacetoacetate hydrolase (FAH) activity and can lead to lethal liver injury. Therapeutic options for HT1 remain limited. In this study, we aimed to construct an engineered bacterium capable of reprogramming host metabolism and thereby provide a potential alternative approach for the treatment of HT1. METHODS: Escherichia coli Nissle 1917 (EcN) was engineered to express genes involved in tyrosine metabolism in the anoxic conditions that are characteristic of the intestine (EcN-HT). Bodyweight, survival rate, plasma (tyrosine/liver function), H&E staining and RNA sequencing were used to assess its ability to degrade tyrosine and protect against lethal liver injury in Fah-knockout (KO) mice, a well-accepted model of HT1. RESULTS: EcN-HT consumed tyrosine and produced L-DOPA (levodopa) in an in vitro system. Importantly, in Fah-KO mice, the oral administration of EcN-HT enhanced tyrosine degradation, reduced the accumulation of toxic metabolites, and protected against lethal liver injury. RNA sequencing analysis revealed that EcN-HT rescued the global gene expression pattern in the livers of Fah-KO mice, particularly of genes involved in metabolic signaling and liver homeostasis. Moreover, EcN-HT treatment was found to be safe and well-tolerated in the mouse intestine. CONCLUSIONS: This is the first report of an engineered live bacterium that can degrade tyrosine and alleviate lethal liver injury in mice with HT1. EcN-HT represents a novel engineered probiotic with the potential to treat this condition. IMPACT AND IMPLICATIONS: Patients with hereditary tyrosinemia type 1 (HT1) are characterized by an inability to metabolize tyrosine normally and suffer from liver failure, renal dysfunction, neurological impairments, and cancer. Given the overlap and complementarity between the host and microbial metabolic pathways, the gut microbiome provides a potential chance to regulate host metabolism through degradation of tyrosine and reduction of byproducts that might be toxic. Herein, we demonstrated that an engineered live bacterium, EcN-HT, could enhance tyrosine breakdown, reduce the accumulation of toxic tyrosine byproducts, and protect against lethal liver injury in Fah-knockout mice. These findings suggested that engineered live biotherapeutics that can degrade tyrosine in the gut may represent a viable and safe strategy for the prevention of lethal liver injury in HT1 as well as the mitigation of its associated pathologies.

Lessons learned from characteristics of extraordinarily severe traffic crashes in China, 2004-2019.

China has experienced remarkable achievements in terms of reducing the number of extraordinarily severe traffic crashes (ESTCs) that cause more than 10 deaths each crash. However, ESTCs still occur occasionally and result in extremely adverse social impacts. This study aims at investigating the common characteristics, characteristic patterns, and changes of characteristics of ESTCs in China with the expectation to learn from the past and act for the future. A total of 373 ESTCs occurred in 2004-2019 were collected, and characteristics of driver factors, road factors, vehicle factors, environment factors, and other factors were analyzed through the multiple correspondence analysis (MCA). The results show that run off road crashes, not qualified drivers, improper driving, large bus, overload, class II highway, and straight road sections are the most common categories of characteristics. In addition, four underlying characteristic patterns are identified through the MCA. Significant changes in characteristics and characteristic patterns are also found, and these changes are the results of various law enforcement, safety policies, educational interventions, and engineering interventions. It is also inferred that the specific law enforcement targeting to certain category of characteristics is more effective than the corresponding safety campaigns or policies in terms of ESTC prevention.