4-octyl itaconate ameliorates ventilator-induced lung injury.

Ventilator-induced lung injury (VILI) disturbs the disordered immune system and causes persistent inflammatory damage. 4-octyl itaconate (OI) is a synthetic cell-permeable itaconate derivative with antioxidant and anti-inflammatory effects. In this study, we assessed whether OI protects against VILI. OI was intraperitoneally injected for three days before mechanical ventilation (MV; 20 ml/kg at 70 breaths/min) for 2 h. Mouse lung vascular endothelial cells (MLVECs) were pretreated with OI (62.5, 125, and 250 µM) prior to cyclic stretch for 4 h. We found that OI attenuated VILI and inflammatory response. OI also increased superoxide dismutase, nuclear factor E2-related factor 2, and heme oxygenase-1 levels, and decreased reactive oxygen species and malondialdehyde levels. Furthermore, OI inhibited the expression of NLR family pyrin domain-containing 3 (NLRP3), caspase-1 p20, apoptosis-associated speck-like protein containing a CARD, and N-terminal fragment of gasdermin D. Therefore, OI attenuates VILI, potentially by suppressing oxidative stress and NLRP3 activation.

Floristic changes and environmental drivers of soil fungi and archaea in different salt-tolerant plant communities in the intertidal habitat of coastal wetlands.

Microorganisms are crucial elements of terrestrial ecosystems, which play significant roles in improving soil physicochemical properties, providing plant growth nutrients, degrading toxic and harmful chemicals, and biogeochemical cycling. Variations in the types and quantities of root exudates among different plants greatly alter soil physicochemical properties and result in variations in the diversity, structure, and function of soil microorganisms. Not much is understood about the differences of soil fungi and archaea communities for different plant communities in coastal wetlands, and their response mechanisms to environmental changes. In this study, fungal and archaea communities in soils of Suaeda salsa, Phragmites australis, and Spartina alterniflora in the intertidal habitat of coastal wetlands were selected for research. Soil fungi and archaea were analyzed for diversity, community structure, and function using high throughput ITS and 16S rRNA gene sequencing. The study revealed significant differences in fungi and archaea's diversity and community structure in the rhizosphere soil of three plant communities. At the same time, there is no significant difference in the functional groups. SOM, TP, AP, MC, EC and SOM, TN, TP, AP, MC, EC are the primary environmental determinants affecting changes in soil fungal and archaeal communities, respectively. Variations in the diversity, community structure, and ecological functions of fungi and archaea can be used as indicators characterizing the impact of external disturbances on the soil environment, providing a theoretical foundation for the effective utilization of soil microbial resources, thereby achieving the goal of environmental protection and health promotion.

Global Epidemiology of Gaucher Disease: an Updated Systematic Review and Meta-analysis.

BACKGROUND: Gaucher disease [GD], an autosomal recessive lysosomal storage disorder, is characterized by progressive lysosomal storage of glucocerebroside in macrophages predominantly in bone, bone marrow, liver, and spleen. Meta-analysis of global GD epidemiology was not available before this study. METHODS: To provide a systematic review and meta-analysis of birth prevalence and prevalence of GD in multiple countries. MEDLINE and EMBASE databases were searched for original research articles on the epidemiology of GD from inception until July 21, 2021. Meta-analysis, adopting a random-effects logistic model, was performed to estimate the birth prevalence and prevalence of GD. RESULTS: Eighteen studies that were screened of 1874 records were included for data extraction. The studies that fulfilled the criteria for inclusion involved 15 areas/countries. The global birth prevalence of GD was 1.5 cases [95% confidence interval: 1.0 to 2.0] per 100,000 live births. The global prevalence of GD was 0.9 cases [95% confidence interval: 0.7 to 1.1] per 100,000 inhabitants. CONCLUSIONS: This is the first comprehensive systematic review that presented quantitative data of GD global epidemiology. Quantitative data on global epidemiology of GD could be the fundamental to evaluate the global efforts on building a better world for GD patients.

Effects of harvest time and desalination of feedstock on Spartina alterniflora biochar and its efficiency for Cd2+ removal from aqueous solution.

Cadmium (Cd2+), as the primary contaminant in Chinese soils, is dangerous to human health and ecological security. Invasive plant Spartina alterniflora in Chinese coastal wetlands presents a promising feedstock for biochar, which is an efficient adsorbent for heavy metal removal. S. alterniflora harvested in summer, autumn and winter were pyrolyzed to produce biochars. We analyzed the effects of harvest time and desalination of feedstock on biochar properties and Cd2+ adsorption capacity in aqueous solution. Biochars were characterized by pH probe, elemental analyzer, SEM, BJH, BET, and FTIR, and the Cd2+ concentrations were measured using AAS. Except pH (9.85-10.95) and nitrogen contents (0.71-1.59%), other biochar properties had no linear correlations with harvest time. Biochars produced from feedstock harvested in autumn had the highest carbon contents (73.25%) and lowest functional groups diversity (CC and -CHx). The pH and carbon contents (64.44-73.25%) were increased by desalination treatment. The surface area (0.48-2.27 m2/g), total pore volume (0.0015-0.0055 mL/g), mesopore volume (0.0015-0.0052 mL/g), and Cd2+ adsorption capacities (16.29-32.34 mg/g) were affected by desalination treatment, and the effects varied with harvest time. Biochars produced from desalted feedstock harvested in summer and untreated feedstock harvested in winter showed higher surface area, porosity, and Cd2+ adsorption capacity. Moderate salt contents (1.5-3.0% in chloride content) in feedstock promote the formation of biochars with higher surface area and porosity.

Remediation of cadmium-contaminated coastal saline-alkaline soil by Spartina alterniflora derived biochar.

Following oil extraction in the wetland of the Yellow River Delta, heavy metal contamination of coastal saline-alkaline soil, especially with cadmium (Cd), has become a serious environmental problem in some regions. Biochar application has been proposed to remedy Cd-contaminated soil, but the remediation effect is related to preparation conditions of biochar (e.g., pyrolysis temperature and raw material) and soil properties. The invasive plant, Spartina alterniflora, produces a high amount of biomass, making it suitable for biochar production in coastal China. We investigated the effect of S. alterniflora-derived biochar (SDB) pyrolyzed at four temperatures (350, 450, 550, and 650 °C) crossed with three addition ratios (1, 5, and 10%) and control on Cd contamination of coastal saline-alkaline soil. Pyrolysis temperature affected pH, surface area, and functional groups of SDB. SDB markedly improved soil pH and soil organic matter, but the degree of improvement was affected by pyrolysis temperature and addition ratio. SDB significantly altered available Cd content in soil, but reduced it only at low pyrolysis temperatures (350 and 450 °C). Available Cd content had a positive correlation with soil pH (R2 = 0.298, P < 0.01), but was not related to salinity and soil organic matter content. Thus, SDB pyrolyzed at 350 °C with 5% addition was optimal for passivating Cd in coastal saline-alkaline soil, since available Cd content in soil decreased mostly (by 26.9%). These findings act as a reference for the development of an application strategy for SDB to ameliorate Cd-contaminated coastal saline-alkaline soil.

Polarimetric-Phase-Enhanced Intensity Interrogation Scheme for Surface Wave Optical Sensors with Low Optical Loss.

A polarimetric-phase-enhanced intensity interrogation scheme leveraging the polarization-dependent sharp phase change induced by the surface wave excitation at a low-optical-loss sensor's surface is proposed and experimentally demonstrated. Based on a simple setup with no moving parts during interrogation, a polarimetric-phase-enhanced intensity can be obtained by subtracting the reflected intensities of two beam polarization states. Our results show a ~4-fold sensitivity increase compared to traditional intensity detection schemes for similar sensors. As novel surface wave optical sensors are designed and engineered with optimized phase responses, this scheme offers a low-complexity solution for such devices instead of traditional phase interrogation schemes.

SCN8A mutations in Chinese children with early onset epilepsy and intellectual disability.

OBJECTIVE: Mutations in SCN8A, a voltage-gated sodium-channel type VIII alpha subunit gene, have recently been recognized as one of the pathogenic mechanisms leading to epilepsy and intellectual/developmental disabilities (IDDs). The aim of this study was to detect SCN8A mutations in Chinese patients with epilepsy of unknown etiology and ID/DD. METHODS: We used targeted next-generation sequencing to identify SCN8A mutations in Chinese patients with epilepsy of unknown etiology and IDDs. A filter process was performed to prioritize rare variants of potential functional significance. Sanger sequencing confirmed the variants and determined the parental origin. We followed all patients with SCN8A mutations in our cohort and analyzed their clinical data. RESULTS: Five de novo SCN8A mutations were identified, including four novel mutations (p.Ala890Thr, p.Leu407Phe, p.Arg850Gln, and p.Ser1596Cys) and one reported (p.Arg1617Gln). Polyphen2 and SIFT software predicted that all five mutations probably damaged Nav1.6 protein function; Mutation Taster indicated that all mutations were disease-causing. Three of these five patients were controlled well by sodium channel blockers (SCBs). Two of these three patients remained seizure free for 6 and 1.5 months, respectively. One patient had sudden unexpected death in epilepsy (SUDEP) at the age of 1 year and 4 months. SIGNIFICANCE: Five SCN8A mutations were first reported in Chinese patients with epilepsy and ID/DD, expanding the phenotype and mutation spectrum of SCN8A mutations. Although three of these patients were controlled well by SCBs in our study, the effectiveness of SCBs should be validated in more patients with epilepsy caused by SCN8A mutations in the future. One of our five patients had sudden unexpected death in epilepsy SUDEP, suggesting that we should pay more attention to SUDEP in epileptic patients with SCN8A mutations.

[Cases of hepatitis C virus infection with 2i/2a recombination genotype in the Lanzhou area and effects of related genetic variations on interferon alpha response].

OBJECTIVE: To investigate Lanzhou area cases of hepatitis C virus (H-CV) infection with a 5'-non coding region (NCR) 2i genotype and core (C), envelope protein (E) and non-structural protein (NS5) 2a genotype and the relationship with therapeutic response to interferon-alpha (IFNa). METHODS: Nine patients who received IFNa-based treatment for HCV between 2007 and 2009 at the Second People's Hospital of Gansu Province were selected for analysis.Restriction enzyme analysis was carried out for the 5'-NCR and sequencing was carried out for the other gene areas.The relationship between genetic variants and IFNaresponse was examined. RESULTS: Of the total nine HCV cases treated with IFNa-based therapies, five of the patients achieved sustained virological response (SVR), which included two cases with type 2 genotype and three cases with no MboI restriction enzyme point of tangency (i.e.type 1b). The remaining four patients that did not achieve SVR included one case of type 2a, with a 1b and 2a mixed state, and one case with 5'-NCR 2i genotype and C area, NS5 area 2a genotype; the other two cases had 5'-NCR and C area type 1b. Of the five cases with 5'-NCR 2i genotype, all had C 2a genotype and two had C/E 2a and NS5 2a genotypes.The seven patients that showed no response to ordinary IFNa were converted to long-term IFNa plus ribavirin combination antiviral treatment; five (71.4%) of the cases showed response in HCV RNA level and the patients treated with the pegylated form showed greater response. CONCLUSION: HCV genotyping can only provide information on the particular region of gene sequence examined, and it is important to sequence all gene regions where mutations related to antiviral drug response are located. Peg-IFNa-2a combined with ribavirin may achieve better therapeutic effect in patients infected with 2i/2a recombinant forms of HCV.

Role of mitochondria in neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxic-ischemic encephalopathy, an important cause of death as well as long-term disability in survivors, is caused by oxygen and glucose deprivation, and limited blood flow. Following hypoxic-ischemic injury in the neonatal brain, three main biochemical damages (excitotoxicity, oxidative stress, and exacerbated inflammation) are triggered. Mitochondria are involved in all three cascades. Mitochondria are the nexus of metabolic pathways to offer most of the energy that our body needs. Hypoxic-ischemic injury affects the characteristics of mitochondria, including dynamics, permeability, and ATP production, which also feed back into the process of neonatal hypoxic-ischemic encephalopathy. Mitochondria can be a cellular hub in inflammation, which is another main response of the injured neonatal brain. Some treatments for neonatal hypoxic-ischemic encephalopathy affect the function of mitochondria or target mitochondria, including therapeutic hypothermia and erythropoietin. This review presents the main roles of mitochondria in neonatal hypoxic-ischemic encephalopathy and discusses some potential treatments directed at mitochondria, which may foster the development of new therapeutic strategies for this encephalopathy.

Clinical characteristics of BRAT1-related disease: a systematic literature review.

BACKGROUND: BRAT1 (BRCA1-associated ataxia telangiectasia mutated activator 1) is involved in many important biological processes, including DNA damage response and maintenance of mitochondrial homeostasis. Dysfunctional BRAT1 causes variable clinical phenotypes, which hinders BRAT1-related disease from recognition and diagnosis. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was the guideline for this systematic review. MEDLINE was searched by terms ("BAAT1" and "BRAT1") from inception until June 21, 2022. RESULTS: Twenty-eight studies, screened out of 49 records, were included for data extraction. The data from fifty patients with mutated BRAT1 were collected. There are 3 high relevant phenotypes, 4 medium relevant phenotypes and 3 low relevant phenotypes. Eye-related abnormal features were most frequently reported: 27 abnormal features were observed. Thirty-nine kinds of pathogenic nucleotide change in BRAT1 were reported. Top three common mutations of BRAT1 were c.638_639insA (16 cases), c.1395G > A (5 cases) and c.294dupA (4 cases). Homozygous mutations in BRAT1 presented a more severe phenotype than those who are compound heterozygotes. CONCLUSIONS: This is the first comprehensive systematic review to present quantitative data about clinical characteristics of BRAT1-related disease, which helps doctors to recognize and diagnose it easier.

Investigation on Wire Electrochemical Discharge Micro-Machining.

With the development of MEMS, the machining demand and requirements for difficult-to-machine metal micro parts are getting higher. Microelectric discharge machining is an effective method to process difficult-to-machine metals. However, the recast layer caused by high temperatures in microelectric discharge machining affects the properties of machined materials. Here, we propose the wire electrochemical discharge micro-machining (WECDMM) and develop a new electrolyte system, which removes the recast layer. In this study, the mechanism of WECDMM was elucidated. The electrolyte was optimized through a comparison experiment, and NaNO3-glycol solution was determined as the best electrolyte. The influences of key process parameters including the conductivity of the electrolyte, pulse voltage, pulse-on time and wire feed rate were analyzed on the slit width, standard deviation, the radius of fillet at the entrance of the slit and roughness. Typical microstructures were machined, which verified the machining ability of WECDMM.

Immunity and Immune Evasion Mechanisms of Epstein-Barr Virus.

Epstein-Barr virus (EBV) is the first human oncogenic virus to be identified, which evades the body's immune surveillance through multiple mechanisms that allow long-term latent infection. Under certain pathological conditions, EBVs undergo a transition from the latent phase to the lytic phase and cause targeted dysregulation of the host immune system, leading to the development of EBV-related diseases. Therefore, an in-depth understanding of the mechanism of developing an immune response to EBV and the evasion of immune recognition by EBV is important for the understanding of the pathogenesis of EBV, which is of great significance for finding strategies to prevent EBV infection, and developing a therapy to treat EBV-associated diseases. In this review, we will discuss the molecular mechanisms of host immunological responses to EBV infection and the mechanisms of EBV-mediated immune evasion during chronic active infection.

Performance of wetland applied to ecological remediation of abandoned fish ponds: A case study in Gonghu Bay, Tai lake.

To restore the abandoned fish ponds to "near natural" state, the wetland restoration was carried out in Gonghu Bay lakeside, and its long-term performance of controlling external load was studied for 5 years. The findings showed that water quality and biodiversity had been improved dramatically after the preliminary transformation. The concentrations of permanganate index (CODMn), total nitrogen (TN), and total phosphorus (TP) obviously decreased from 12.91 mg L-1 to 4.32 mg L-1, from 3.46 mg L-1 to 1.42 mg L-1, and from 0.27 mg L-1 to 0.04 mg L-1, respectively. The proportion of Cyanophyta was effectively reduced from 31.82% to 18.89%, and favored the growth of diatoms (31.82%-37.78%) to be the dominant algae species. Aquatic plant species and coverage gradually increased from 16 to 56 and from 5% to 60%, respectively. An in-deep monitoring done for 5 years (2013-2017) showed that the wetland achieved a satisfactory removal efficiency of 58.95% for TN, 64.60% for TP, and up to 77.83% for chlorophyll-a. Besides, three pollution scenarios, such as stormwater runoff, algal bloom, and continuous water transfer, were selected to explore the tolerance of the wetland to the suddenly increased pollution loads. The results dedicated that even if the inlet load was up to 1.0 × 105 m3 d-1, the removal rate coefficients of wetland for chlorophyll-a, TP, and TN were 0.135-0.239 d-1, 0.041-0.112 d-1, and 0.030-0.109 d-1, respectively, which were equivalent to the well-running wetlands. This study confirmed that the wetland was not only a promising ecological remediation technique to contaminated abandoned fish ponds, but also could withstand high pollution load, which had the prospect of sustainable utilization.

Fabrication of ACP-CCS-PVA composite membrane for a potential application in guided bone regeneration.

The barrier membranes of guided bone regeneration (GBR) have been widely used in clinical medicine to repair bone defects. However, the unmatched mechanical strength, unsuitable degradation rates, and insufficient regeneration potential limit the application of the current barrier membranes. Here, amorphous calcium phosphate-carboxylated chitosan-polyvinyl alcohol (ACP-CCS-PVA) composite membranes are fabricated by freeze-thaw cycles, in which the ATP-stabilized ACP nanoparticles are uniformly distributed throughout the membranes. The mechanical performance and osteogenic properties are significantly improved by the ACP incorporated into the CCS-PVA system, but excess ACP would suppress cell proliferation and osteogenic differentiation. Our work highlights the pivotal role of ACP in GBR and provides insight into the need for biomaterial fabrication to balance mechanical strength and mineral content.

Nearly three orders of magnitude enhancement of Goos-Hanchen shift by exciting Bloch surface wave.

Goos-Hanchen effect is experimentally studied when the Bloch surface wave is excited in the forbidden band of a one-dimensional photonic band-gap structure. By tuning the refractive index of the cladding covering the truncated photonic crystal structure, either a guided or a surface mode can be excited. In the latter case, strong enhancement of the Goos-Hanchen shift induced by the Bloch-surface-wave results in sub-millimeter shifts of the reflected beam position. Such giant Goos-Hanchen shift, ~750 times of the wavelength, could enable many intriguing applications that had been less than feasible to implement before.

Molecular environment and atypical function: What do we know about enzymes associated with Mucopolysaccharidoses?

Mucopolysaccharidoses are a group of lysosomal storage disorders caused by deficiency of enzymes involved in glycosaminoglycans degradation. Relationship between mucopolysaccharidoses and related enzymes has been clarified clearly. Based on such relationship, lots of therapies have been commercialized or are in the process of research and development. However, many potential treatments failed, because those treatments did not demonstrate expected efficacy or safety data. Molecular environment of enzyme, which is essential for their expression and activity, is fundamental for efficacy of therapy. In addition to enzyme activities, mucopolysaccharidoses-related enzymes have other atypical functions, such as regulation, which may cause side effects. This review tried to discuss molecular environment and atypical function of enzymes that are associated with mucopolysaccharidoses, which is very important for the efficacy and safety of potential therapies.

Silencing of immunoglobulin superfamily containing leucine-rich repeat inhibits gastric cancer cell growth and metastasis by regulating epithelial-mesenchymal transition.

This study aims to investigate the immunoglobulin superfamily containing leucine-rich repeat (ISLR) expression in gastric cancer (GC) and ISLR's underlying mechanisms regulation of GC progression. Through The Cancer Genome Atlas (TCGA) cohort datasets, we analyzed the ISLR expression in GC tumor tissues and normal tissues. ISLR expression in GC tissues and cells was determined using quantitative real-time polymerase chain reaction. Cell viability, proliferation, migration, and invasion assays were performed in GC cells transfected with sh-ISLR, ISLR plasmids, or controls. TCGA results showed that ISLR expression was higher in GC tumor tissues compared to normal tissues, and its expression levels were related to lymph node metastasis, tumor size, and clinical stage. ISLR was highly expressed in tumor cells. ISLR knockdown suppressed cell viability, proliferation, migration, and invasion in HGC-27 cells, whereas ISLR overexpression led to opposite effects in AGS cells. Gene Set Enrichment Analysis showed that ISLR could activate the epithelial-mesenchymal transition (EMT) signaling pathway. Silencing of ISLR suppressed EMT in HGC-27 cells and overexpression of ISLR promoted EMT in AGS cells. ISLR was overexpressed in both GC cell lines and tumor tissues, and our study first showed that silencing of ISLR inhibited GC cell growth and metastasis by reversing EMT.

Update of treatment for Gaucher disease.

Gaucher disease (GD), the most common lysosomal disorders, is a rare autosomal recessive hereditary disease that is caused by deficiency of glucosylceramidase. For now, there are five approved therapies for GD, which are used to treat thousands of patients with GD. Despite success of approved therapies, many unresolved issues attract academic institutions and industry to develop potential therapies to resolve them. This paper updated the latest information about approved therapies and potential curative therapies.

Tannic acid induces dentin biomineralization by crosslinking and surface modification.

It is currently known that crosslinking agents can effectively improve the mechanical properties of dentin by crosslinking type I collagen. However, few scholars have focused on the influence of crosslinking agents on the collagen-mineral interface after crosslinking. Analysis of the Fourier transform infrared spectroscopy (FTIR) results showed that hydrogen bonding occurs between the tannic acid (TA) molecule and the collagen. The crosslinking degree of TA to collagen reached a maximum 41.28 ± 1.52. This study used TA crosslinked collagen fibers to successfully induce dentin biomineralization, and the complete remineralization was achieved within 4 days. The crosslinking effect of TA can improve the mechanical properties and anti-enzyme properties of dentin. The elastic modulus (mean and standard deviation) and hardness values of the remineralized dentin pretreated with TA reached 19.1 ± 1.12 GPa and 0.68 ± 0.06 GPa, respectively, which were close to those of healthy dentin measurements, but significantly higher than those of dentin without crosslinking (8.91 ± 1.82 GPa and 0.16 ± 0.01 GPa). The interface energy between the surface of collagen fibers and minerals decreased from 10.59 mJ m-2 to 4.19 mJ m-2 with the influence of TA. The current work reveals the importance of tannic acid crosslinking for dentin remineralization while providing profound insights into the interfacial control of biomolecules in collagen mineralization.

Angiorganoid: vitalizing the organoid with blood vessels.

The emergence of the organoid simulates the native organs and this mini organ offers an excellent platform for probing multicellular interaction, disease modeling and drug discovery. Blood vessels constitute the instructive vascular niche which is indispensable for organ development, function and regeneration. Therefore, it is expected that the introduction of infiltrated blood vessels into the organoid might further pump vitality and credibility into the system. While the field is emerging and growing with new concepts and methodologies, this review aims at presenting various sources of vascular ingredients for constructing vascularized organoids and the paired methodology including de- and recellularization, bioprinting and microfluidics. Representative vascular organoids corresponding to specific tissues are also summarized and discussed to elaborate on the next generation of organoid development.