Design and synthesis of sulfonamide phenothiazine derivatives as novel ferroptosis inhibitors and their therapeutic effects in spinal cord injury.

Ferroptosis is a novel style of cell death, and studies have shown that ferroptosis is strongly associated with spinal cord injury (SCI). A large number of ferroptosis inhibitors have been reported, but so far no ferroptosis inhibitor has been used clinically. Therefore there is an urgent need to discover a better inhibitor of ferroptosis. In this study, 24 novel sulfonamide phenothiazine ferroptosis inhibitors were designed and synthesized, followed by structure-activity relationship studies on these compounds. Among them, compound 23b exhibited the best activity in Erastin-induced PC12 cells (EC50 = 0.001 µM) and demonstrated a low hERG inhibition activity (IC50 > 30 µM). Additionally, compound 23b was identified as a ROS scavenger and showed promising therapeutic effects in an SD rat model of SCI. Importantly, 23b did not display significant toxicity in both in vivo and in vitro experiments and show good pharmacokinetic properties. These findings suggest that compound 23b, a novel ferroptosis inhibitor, holds potential as a therapeutic agent for spinal cord injury and warrants further investigation.

Methane removal efficiencies of biochar-mediated landfill soil cover with reduced depth.

Biochar amendment for landfill soil cover has the potential to enhance methane removal efficiency while minimizing the soil depth. However, there is a lack of information on the response of biochar-mediated soil cover to the changes in configuration and operational parameters during the methane transport and transformation processes. This study constructed three biochar-amended landfill soil covers, with reduced soil depths from 75 cm (C2) to 55 cm (C3) and 45 cm (C4), and the control group (C1) with 75 cm and no biochar. Two operation phases were conducted under two soil moisture contents and three inlet methane fluxes in each phase. The methane removal efficiency increased for all columns along with the increase in methane flux. However, increasing moisture content from 10% to 20% negatively influenced the methane removal efficiency due to mass transfer limitation when at a low inlet methane flux, especially for C1; while this adverse effect could be alleviated by a high flux. Except for the condition with low moisture content and flux combination, C3 showed comparable methane removal efficiency to C2, both dominating over C1. As for C4 with only 45 cm, a high moisture content combined with a high methane flux enabled its methane removal efficiency to be competitive with other soil depths. In addition to the geotechnical reasons for gas transport processes, the evolution in methanotroph community structure (mainly type I methanotrophs) induced by biochar amendment and variations in soil properties supplemented the biological reasons for the varying methane removal efficiencies.

Research progress of microRNA in spinal cord injury.

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.

FifBase: a comprehensive fertility-associated indicators factor database for domestic animals.

Fertility refers to the ability of animals to maintain reproductive function and give birth to offspring, which is an important indicator to measure the productivity of animals. Fertility is affected by many factors, among which environmental factors may also play key roles. During the past years, substantial research studies have been conducted to detect the factors related to fecundity, including genetic factors and environmental factors. However, the identified genes associated with fertility from countless previous studies are randomly dispersed in the literature, whereas some other novel fertility-related genes are needed to detect from omics-based datasets. Here, we constructed a fertility index factor database FifBase based on manually curated published literature and RNA-Seq datasets. During the construction of the literature group, we obtained 3301 articles related to fecundity for 13 species from PubMed, involving 2823 genes, which are related to 75 fecundity indicators or 47 environmental factors. Eventually, 1558 genes associated with fertility were filtered in 10 species, of which 1088 and 470 were from RNA-Seq datasets and text mining data, respectively, involving 2910 fertility-gene pairs and 58 fertility-environmental factors. All these data were cataloged into FifBase (http://www.nwsuaflmz.com/FifBase/), where the fertility-related factor information, including gene annotation and environmental factors, can be browsed, retrieved and downloaded with the user-friendly interface.

Impacts of digestate-based compost on soil property and nutrient availability.

The treatment of digestate from food waste (DFW) has emerged as the bottleneck for food waste anaerobic digestion. DFW generally contains abundant nutrients that can be recycled by composting. However, the effect of DFW-based compost on soil improvement has not been extensively explored. In this study, soil properties were improved by adding various amounts of DFW-based compost, and the growth conditions of Pak choi were monitored. The results indicated that the DFW-based compost could provide nitrogen, calcium, magnesium, and organic matter, thereby enhancing the growth of Pak choi, accumulating chlorophyll, and improving photosynthesis efficiency. As the amount of added DFW-based compost increased from 0% to 20%, the fresh biomass, leaf weight, and root weight of Pak choi increased by 242%, 262%, and 99%, respectively. The total chlorophyll content was 2.62 mg g-1 in control and increased to 12.45 mg g-1 in the group with 20% DFW-based compost, benefiting the photochemical efficiency of Pak choi. However, the growth was inhibited when the addition amount exceeded 20%, potentially due to excessive nutrient supplementation. Overall, the addition of 20% of DFW-based compost was suggested to promote the growth of Pak choi by providing proper nutrients.

Isolation and characterization of quorum quenching bacteria from municipal solid waste and bottom ash co-disposal landfills.

Co-landfilling of bottom ash (BA) accelerates the clogging of leachate collection systems (LCSs) and increases the risk of landfill failure. The clogging was mainly associated with bio-clogging, which may be reduced by quorum quenching (QQ) strategies. This communication reports on a study of how isolated facultative QQ bacterial strains from municipal solid waste (MSW) landfills and BA co-disposal landfills. In MSW landfills, two novel QQ strains (Brevibacillus agri and Lysinibacillus sp. YS11) can degrade the signal molecule hexanoyl-l-homoserine lactone (C6-HSL) and octanoyl-l-homoserine lactone (C8-HSL), respectively. Pseudomonas aeruginosa could degrade C6-HSL and C8-HSL in BA co-disposal landfills. Moreover, P. aeruginosa (0.98) was observed with a higher growth rate (OD600) compared to that of B. agri (0.27) and Lysinibacillus sp. YS11 (0.53). These results indicated that the QQ bacterial strains were associated with leachate characteristics and signal molecules and could be used for controlling bio-clogging in landfills.

Multimodal imaging features and genetic findings in Bietti crystalline dystrophy.

BACKGROUND: Bietti crystalline dystrophy (BCD) is a distinct entity of retinitis pigmentosa with a wide range of genotypic and phenotypic variabilities. The goal of the present study was to investigate the morphological, functional and genetic features of BCD. METHODS: A full series of multimodal imaging was performed in four Chinese patients with BCD, including fundus photography, fundus autofluorescence, fundus fluorescein angiography (FFA), indocyanine green (ICG) angiography, optical coherence tomography (OCT) and microperimetry. Electrophysiological tests including full-field electroretinography (ERG) and multifocal ERG were employed. CYP4V2 gene sequencing was performed. RESULTS: Intraretinal crystalline deposits were observed in fundus photographs in all patients. The crystals were better appreciated in infrared images. Autofluorescence imaging demonstrated multifocal patchy hypofluorescence, suggesting massive RPE atrophy. FFA and ICG angiography further confirmed atrophy of the RPE and the underlying choroidal vessels. OCT revealed disruption of the photoreceptors, RPE and the choroid. Outer retinal tubulations (ORTs) confining to the outer nuclear layer were detected in three out of four patients. Full-field ERG showed markedly diminished responses. Multifocal ERG displayed reduced central and peripheral responses in a patient with normal vision. Gene sequencing identified two deletion mutations in CYP4V2, c.802_807del and c.810delT. BCD complicated by choroidal neovascularization (CNV) was diagnosed in one patient, and intravitreal anti-vascular endothelial growth factor (VEGF) injection was given with favorable response. CONCLUSIONS: Multimodal imaging features and electrophysiological findings of BCD patients were comprehensively discussed. A novel deletion mutation, c.802_807del, in the CYP4V2 gene was reported. ORTs are important changes in the outer retina of BCD patients, further investigation of this structure may provide insights into pathology of BCD. Intravitreal anti-VEGF therapy was effective for treatment of BCD complicated by CNV.

Predicting maturity and identifying key factors in organic waste composting using machine learning models.

The measurement of germination index (GI) in composting is a time-consuming and laborious process. This study employed four machine learning (ML) models, namely Random Forest (RF), Artificial Neural Network (ANN), Support Vector Regression (SVR), and Decision Tree (DT), to predict GI based on key composting parameters. The prediction results showed that the coefficient of determination (R2) for RF (>0.9) and ANN (>0.9) was higher than SVR (<0.6) and DT (<0.8), suggesting that RF and ANN displayed superior predictive performance for GI. The SHapley additive exPlanations value result indicated that composting time, temperature, and pH were the important features contributing to GI. Composting time was found to have the most significant impact on GI. Overall, RF and ANN were suggested as effective tools for predicting GI in composting. This study offers the reliable approach of accurately predicting GI in composting processes, thereby enabling intelligent composting practices.

Generation of an induced pluripotent stem cell line (SJTUGHi001-A) from a patient with Retinitis Pigmentosa carrying c.77C > T mutation in RAX2 gene.

Retinitis pigmentosa (RP) is a group of genetically heterogeneous retinopathy resulting in irreversible loss of vision. Mutations in RAX2 gene has been related to RP with mechanisms unclear. Here, we generated a human induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a RP patient carrying c.77C > T mutation in RAX2 gene. This cell line was induced by integration-free episomal vectors and validated for pluripotency and differentiation capacity, which may serve as a model to study the role of RAX2 in RP pathogenesis.

Hydrothermal-enhanced pyrolysis for efficient NOX reduction and biochar valorization from food waste digestate.

Pyrolysis has emerged as a promising technology for valorizing digestate resulting from the anaerobic digestion of food waste. However, the high NOX emissions during pyrolysis limit its application. This study proposed a hydrothermal coupled pyrolysis process to control the element transfer in digestate during biochar production. The efficient reduction of NOX emissions and the improvement of biochar adsorbability were realized. The hydrothermal process reduced the nitrogen content in solid digestate by 49.10 %-81.79 %, thus reducing the NOX precursors in syngas and the N-containing substances in bio-oil. Additionally, the specific surface area and the total pore volume of biochar were enhanced from 25 m2/g to 60-73 m2/g and 0.06 cm3/g to 0.12-0.14 cm3/g, respectively. More defects, oxygen-containing functional groups, and doped Ca on the biochar resulted in a high phosphate removal efficiency of 94 %. The proposed technology provides an efficient and environmentally friendly way to utilize the digestate.

Manipulating soil microbial community assembly by the cooperation of exogenous bacteria and biochar for establishing an efficient and healthy CH4 biofiltration system.

Manipulating the methanotroph (MOB) composition and microbial diversity is a promising strategy to optimize the methane (CH4) biofiltration efficiency of an engineered landfill cover soil (LCS) system. Inoculating soil with exogenous MOB-rich bacteria and amending soil with biochar show strong manipulating potential, but how the two stimuli interactively shape the microbial community structure and diversity has not been clarified. Therefore, three types of soils with active CH4 activities, including paddy soil, river wetland soil, and LCS were selected for enriching MOB-dominated communities (abbreviated as B_PS, B_RWS, and B_LCS, respectively). They were then inoculated to LCS which was amended with two distinct biochar. Besides the aerobic CH4 oxidation efficiencies, the evolution of the three microbial communities during the MOB enrichment processes and their colonization in two-biochar amended LCS were obtained. During the MOB enriching, a lag phase in CH4 consumption was observed merely for B_LCS. Type II MOB Methylocystis was the primary MOB for both B_PS and B_LCS; while type I MOB dominated for B_RWS and the major species were altered by gas concentrations. Compared to biochar, a more critical role was demonstrated for the bacteria inoculation in determining the community diversity and function of LCS. Instead, biochar modified the community structures by mainly stimulating the dominant MOB but could induce stochastic processes in community assembly, possibly related to its inorganic nutrients. Particularly, combined with biochar advantages, the paddy soil-derived bacteria consortiums with diverse MOB species demonstrated the potent adaption to LCS niches, not only retaining the high CH4-oxidizing capacities but also shaping a community structure with more diverse soil function. The results provided new insights into the optimization of an engineered CH4-mitigation soil system by manipulating the soil microbiomes with the cooperation of exogenous bacteria and biochar.

Generation of an induced pluripotent stem cell line (SJTUGHi003-A) from a patient with Sorsby fundus dystrophy carrying c.484G>A mutation in TIMP3 gene.

Sorsby fundus dystrophy (SFD) is a rare autosomal dominant disorder with macular dystrophy and severe visual loss. Mutations in TIMP3 gene has been related to SFD with mechanisms unclear. We have successfully reprogrammed the peripheral blood mononuclear cells (PBMCs) from an SFD patient carrying c.484G>A mutation in TIMP3 gene to induced pluripotent stem cells (iPSCs) and characterized their pluripotency and genetic stability. This line may serve as a useful tool to explore the role of TIMP3 in SFD pathogenesis.

Progress in Research on Inhibitors Targeting SARS-CoV-2 Main Protease (Mpro).

Since 2019, the novel coronavirus (SARS-CoV-2) has caused significant morbidity and millions of deaths worldwide. The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2 and its variants, has further highlighted the urgent need for the development of effective therapeutic agents. Currently, the highly conserved and broad-spectrum nature of main proteases (Mpro) renders them of great importance in the field of inhibitor study. In this study, we categorize inhibitors targeting Mpro into three major groups: mimetic, nonmimetic, and natural inhibitors. We then present the research progress of these inhibitors in detail, including their mechanism of action, antiviral activity, pharmacokinetic properties, animal experiments, and clinical studies. This review aims to provide valuable insights and potential avenues for the development of more effective antiviral drugs against SARS-CoV-2.

Association between sleep duration and serum neurofilament light chain levels among adults in the United States.

Background: Neurofilaments are neuron specific skeleton proteins maintaining axon transduction speed, leaked into cerebrospinal fluid and serum after axonal injury or neuron death. Sleep duration change has long related to many health issues but lack laboratory examination. Methods: This study enrolled total 10,175 participants from 2013 to 2014 National Health and Nutrition Examination Survey and used a multi-variable linear model to analyze the relationship between sleep duration and serum neurofilament light chain (sNfL) level. Results: There was a fixed relationship between sleep duration and sNfL level (ß = 0.65, p = 0.0280). After adjusted for covariates, this relationship still (ß = 0.82, p = 0.0052). Segmented regression showed that the turning point of sleep duration was 7 h 1 h decrease in sleep duration was significantly associated with -1.26 higher sNfL level (95 % CI: 2.25, -0.28; p = 0.0115) when sleep duration <7 h; however, 1 h increase in sleep duration was significantly associated with 3.20 higher sNfL level (95 % CI: 2.13, 4.27; p < 0.0001) when sleep duration >7 h. Furthermore, the stratified analysis indicated that the associations between sleep duration and sNfL level were stronger among those normal body mass index and trouble sleeping (p-interaction <0.0001 and 0.0003). Conclusion: In summary, there was a J-shaped relationship between sleep duration and sNfL level in the United States of America representative group, these may suggest that extreme sleep duration can be deleterious judged by sNfL level. And still need large cohort study to determine the accurate relationship, and cluster analysis to infer the nervous disease connected with extreme sleep duration.

Insights into the influence of digestate-derived biochar upon the microbial community succession during the composting of digestate from food waste.

The by-product from the anaerobic digestion of food waste (FW) called the digestate (DFW) needs proper disposal because of its high environmental burden. Composting can transform DFW into a nutrient-containing soil improver via a series of microbial metabolic activities. However, the long composting time and high amount of ammonia emission are the key concerns of DFW composting. In the present study, the effect of DFW-derived biochar (BC-DFW) on microbial succession and its involvement in nitrogen transformation and humification during DFW composting were investigated. The results indicated that the BC-DFW accelerated bacterial and fungal evolution, and the bacterial diversity was augmented by increasing the amount of BC-DFW. In particular, Cryomorpha, Castellaniella, Aequorivita, and Moheibacter were enriched by the addition of BC-DFW, thereby enhancing the degradation of organic matter and nitrogen transformation and increasing the germination index. The group with 25% BC-DFW contained a higher relative abundance of Cryomorpha (2.08%, 2.47%) than the control (0.39%, 1.72%) on days 19 and 35 which benefited the degradation of organic matter. The group with 25% BC-DFW quickly enhanced the growth of Nitrosomonas, thereby accelerating the conversion of ammonium-nitrogen to nitrate-nitrogen and reducing the phytotoxicity of the composting product.

The Role of Widefield Optical Coherence Tomography Angiography in the Diagnosis and Management of Acute Vogt-Koyanagi-Harada Disease.

PURPOSE: We explore the choroid vasculature changes of acute Vogt-Koyanagi-Harada (VKH) disease using widefield optical coherence tomography angiography (OCTA). METHODS: In this retrospective, observational, longitudinal study, 16 patients with acute VKH disease (32 eyes, mean age: 42.19 ±13.66 years) were measured using widefield OCTA. RESULTS: In this study, we first described the multiple dark foci in choriocapillaris and Sattler's layer in the panoramic montage of the five 12x12mm images in 30 eyes (93.8%) of acute VKH disease. OCTA follow-up in these 30 eyes demonstrated the diminished size and number of these dark foci in choriocapillaris and Sattler's layer after the initiation of treatment. CONCLUSIONS: Widefield OCTA enables noninvasive identification of characteristics of flow void at the level of superficial choroidal vessels in the acute phase and may be a novel valuable tool for diagnosis and monitoring of disease progression in VKH disease in the future.

Exercise Rehabilitation and Chronic Respiratory Diseases: Effects, Mechanisms, and Therapeutic Benefits.

Chronic respiratory diseases (CRD), is a group of disorders, primarily chronic obstructive pulmonary disease and asthma, which are characterized by high prevalence and disability, recurrent acute exacerbations, and multiple comorbidities, resulting in exercise limitations and reduced health-related quality of life. Exercise training, an important tool in pulmonary rehabilitation, reduces adverse symptoms in patients by relieving respiratory limitations, increasing gas exchange, increasing central and peripheral hemodynamic forces, and enhancing skeletal muscle function. Aerobic, resistance, and high-intensity intermittent exercises, and other emerging forms such as aquatic exercise and Tai Chi effectively improve exercise capacity, physical fitness, and pulmonary function in patients with CRD. The underlying mechanisms include enhancement of the body's immune response, better control of the inflammatory response, and acceleration of the interaction between the vagus and sympathetic nerves to improve gas exchange. Here, we reviewed the new evidence of benefits and mechanisms of exercise intervention in the pulmonary rehabilitation of patients with chronic obstructive pulmonary disease, bronchial asthma, bronchiectasis, interstitial lung disease, and lung cancer.

Carbon dots/TiO2 enhanced visible light-assisted photocatalytic of leachate: Simultaneous effects and Mechanism insights.

The persistence and potential fouling risks associated with humic substances and bacteria present in leachate have gained increasing attention. Therefore, developing efficient and environmentally compatible technologies for their removal is essential. This study presented the hydrothermal synthesis of a photocatalyst by coupling carbon dots (CDs) and bulk TiO2 (P25). The incorporation of CDs increased the photocatalytic performance by enhancing visible light absorption and facilitating the separation of electrons/holes. Compared to P25, the CDs/P25 exhibited optimal photocatalytic activity for humic acid (HA), fulvic acid (FA), and leachate, with 1.64, 1.02, and 1.12 times higher activity, respectively. Remarkedly, the CDs/P25 accelerated the conversion of large HA molecules into small molecules at a faster rate and higher amount than the bulk P25, due to the increase of hydroxyl radicals, monoclinic oxygen radicals, and superoxide radicals. Additionally, the CDs/P25 demonstrated better bacterial-deactivation ability than the P25, with dead bacteria percentages of 83.3% and 34.6%, respectively. This study provides a promising strategy for efficiently applying CDs/P25 photocatalysis to leachate treatment.

Enhanced methane oxidation efficiency by digestate biochar in landfill cover soil: Microbial shifts and carbon metabolites insights.

The ability of biochar to enhance the oxidation of methane (CH4) in landfill cover soil by promoting the growth and activity of methane-oxidizing bacteria (MOB) has attracted significant attention. However, the optimal characteristics of digestate-derived biochar (DBC) for promoting the MOB community and CH4 removal performance remain unclear. This study examined how the CH4 oxidation capacity and respiratory metabolism of MOB life process are affected by the application of DBC compared with the most commonly used woody-derived biochar (WBC). The addition of both WBC and DBC enhanced CH4 oxidation, with DBC exhibiting a nearly twofold increase in cumulative CH4 oxidation mass (7.14 mg CH4 g-1) compared to WBC. The high ion-exchange capacity of DBC was found to be more favorable for the growth of Type I MOB, which have more efficient metabolic pathways for CH4 oxidation. Type I MOB which are abundant in DBC may prefer monovalent positive ions, while the charge-rich nature of DBC may also have hindered extracellular protein aggregation. The superiority of DBC in terms of CH4 oxidation thus highlights the underlying mechanisms of biochar-MOB interactions, offering potential biochar options for landfill cover soil.