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Fungal extraction is a promising approach for reclaiming phosphorus (P) from sewage sludge ash (SSA). However, this approach faces notable technical and economic challenges, including an unknown P speciation evolution and the addition of expensive chemical organic carbon. In this study, the use of an organic-rich effluent produced in sludge dewatering as nutrient source is proposed to initiate the fungal extraction of SSA-borne P with Aspergillus niger. The changes in P speciation in the ash during fungal treatment was analyzed by combined sequential extraction, solid-state

Corneal nerve wounding often causes abnormalities in the cornea and even blindness in severe cases. In this study, we construct a dorsal root ganglion-corneal stromal cell (DRG-CSC, DS) co-culture 3D model to explore the mechanism of corneal nerve regeneration. Firstly, this model consists of DRG collagen grafts sandwiched by orthogonally stacked and orderly arranged CSC-laden plastic compressed collagen. Nerve bundles extend into the entire corneal stroma within 14 days, and they also have orthogonal patterns. This nerve prevents CSCs from apoptosis in the serum withdrawal medium. The conditioned medium (CM) for CSCs in collagen scaffolds contains NT-3, IL-6, and other factors. Among them, NT-3 notably promotes the activation of ERK-CREB in the DRG, leading to the growth of nerve bundles, and IL-6 induces the upregulation of anti-apoptotic genes. Then, LM22B-10, an activator of the NT-3 receptor TrkB/TrkC, can also activate ERK-CREB to enhance nerve growth. After administering LM22B-10 eye drops to regular and diabetic mice with corneal wounding, LM22B-10 significantly improves the healing speed of the corneal epithelium, corneal sensitivity, and corneal nerve density. Overall, the DS co-culture model provides a promising platform and tools for the exploration of corneal physiological and pathological mechanisms, as well as the verification of drug effects in vitro. Meanwhile, we confirm that LM22B-10, as a non-peptide small molecule, has future potential in nerve wound repair. STATEMENT OF SIGNIFICANCE: The cornea accounts for most of the refractive power of the eye. Corneal nerves play an important role in maintaining corneal homeostasis. Once the corneal nerves are damaged, the corneal epithelium and stroma develop lesions. However, the mechanism of the interaction between corneal nerves and corneal cells is still not fully understood. Here, we construct a corneal stroma-nerve co-culture in vitro model and reveal that NT-3 expressed by stromal cells promotes nerve growth by activating the ERK-CREB pathway in nerves. LM22B-10, an activator of NT-3 receptors, can also induce nerve growth in vitro. Moreover, it is used as eye drops to enhance corneal epithelial wound healing, corneal nerve sensitivity and density of nerve plexus in corneal nerve wounding model in vivo.

In this study, a polyimide gel material with a high spatial network structure was synthesized. The pyrolysis process increased the material’s porous structure and specific surface area to improve the specific capacitance. The effects of pyrolysis temperature on morphology, structure, thermal, mechanical, and electrochemical properties were studied. The gel material is in the frozen state of the molecular chain from the frozen state to the moving state before 400°C. At the same time, pore structure formation with a weight loss rate of 11.9% in the decomposition state at 400°C–600°C, showing the breakage of the molecular chain and the decomposition of the polymer. With the increase of carbonized temperature, the pore structure becomes more compact while the pore size becomes smaller due to the reconstruction of the polymer structure. Meanwhile, due to the stable formation of carbon skeleton and the increase of carbon amount, the PI gel carbonized material’s thermal conductivity was improved to 1.458 [Formula: see text], which was 330% higher than that of pure PI gel (0.339 [Formula: see text]). Furthermore, the carbonized materials exhibit a specific capacitance of 66.17 [Formula: see text] and show good redox reversibility, apparent concentration polarization and good ion diffusion effect during charging and discharging, suggesting it is a promising electrode material for supercapacitors.

Aging, a common risk factor for multiple retinal degeneration diseases, is susceptible to the tissue immune state. Our previous study suggested that a gamma-flicker light (γFL) improves retinal aging features. However, it remains unclear whether γFL could affect the retinal immune function under aging. In this study, we first explored the effects of γFL on astrocyte and microglia morphologies in different inner-retinal layers for mice of 8 w, 9 m, and 18 m. Unfortunately, these morphologies appeared to change only with age independent of 6-d γFL treatment. The immune transcriptomic analysis was then carried out for the whole retina tissue of 20-m mice, and we found that the major histocompatibility complex II (MHC-II) mediated antigen processing and presentation was most affected by γFL. The MHC-II related markers in the retina were then assessed, and the staining of all-age retina flat-mount showed that MHC-II+ cells were ionized calcium-binding adaptor molecule 1 (IBA-1) positive, the cells distributed along the retinal veins. The para-venous MHC-II+ microglia cells were increased with aging and further increased with γFL treatment in 18-m mice. Meanwhile, we found that γFL significantly activated subretinal microglia, whose MHC-II+ subpopulation was significantly increased. Echoing these results, γFL significantly elevated neural-retinal CD74 expression level in the western blotting. Furthermore, amyloid β (Aβ) oligomer solution was injected into the vitreous of 8-w and 9-m mice to mimic retina aging. Expression levels of CD68 and CD74 were increased in these mice after Aβ injection and further increased following 3-d γFL treatment. Similarly, we found that the Aβ-γFL treatment resulted in a linear distribution of MHC-II+ microglia along the retinal veins and brought about a co-staining of Aβ with other activated microglia distant from the veins. Overall, γFL treatment inspires the function of retinal microglia in MHC-II-mediated antigen phagocytosis and presentation under aging, thus being a potential immunomodulatory tool for the treatment of retinal aging or aging-related diseases.

N,N-dimethylformamide (DMF) as synthetic precursors contributing especially the methyl, acyl, and amino groups has played a significant role in heterocycle syntheses and functionalization. In this protocol, a wide range of pyrrolo/indolo[1,2-a]quinoxalines and quinazolin-4-ones were obtained in moderate to good yields by using elemental iodine without any metal or peroxides. We considered that N-methyl and N-acyl of DMF participate and complete the reaction separately through different mechanisms, which displayed potential still to be explored of DMF.

The three-dimensional (3D) retinal organoids (ROs) derived from human induced pluripotent stem cells (hiPSCs), mimicking the growth and development of the human retina, is a promising model for investigating inherited retinal diseases in vitro. However, the efficient generation of homogenous ROs remains a challenge. Here we introduce a novel polydimethylsiloxane (PDMS) microwell platform containing 62 V-bottom micro-cavities for the ROs differentiation from hiPSCs. The uniform adherent 3D ROs could spontaneously form using neural retina (NR) induction. Our results showed that the complex of NR (expressing VSX2), ciliary margin (CM) (expressing RDH10), and retinal pigment epithelium (RPE) (expressing ZO-1, MITF, and RPE65) developed in the PDMS microwell after the differentiation. It is important to note that ROs in PDMS microwell platforms not only enable one-stop assembly but also maintain homogeneity and mature differentiation over a period of more than 25 weeks without the use of BMP4 and Matrigel. Retinal ganglion cells (expressing BRN3a), amacrine cells (expressing AP2a), horizontal cells (expressing PROX1 and AP2α), photoreceptor cells for cone (expressing S-opsin and L/M-opsin) and rod (expressing Rod opsin), bipolar cells (expressing VSX2 and PKCα), and Müller glial cells (expressing GS and Sox9) gradually emerged. Furthermore, we replaced fetal bovine serum with human platelet lysate and established a xeno-free culture workflow that facilitates clinical application. Thus, our PDMS microwell platform for one-stop assembly and long-term culture of ROs using a xeno-free workflow is favorable for retinal disease modeling, drug screening, and manufacturing ROs for clinical translation.

A metal-free, peroxide-free, and efficient procedure for the highly selective synthesis of quinolines and methylquinolines was reported. The main feature of this method was that the same substrate can produce quinolines and methylquinolines, respectively, under different reaction conditions. PEG-400 was used as both a reactant and solvent in this reaction. The utility of the designed procedure was also demonstrated by the derivatization of the products to bioactive compounds.

Antimony (Sb) pollution in the water environment caused by the large-scale mining of Sb ore and the wide use of Sb-containing products seriously endangers human health and poses a great threat to the ecological environment. Coagulation is one of the most cost-effective technologies for Sb pollution control in water/wastewater treatment and has been widely used. However, a comprehensive understanding of Sb pollution control by coagulation, from fundamental research to practical applications, is lacking. In this work, based on the current status of Sb pollution in the water environment, a critical review of the Sb removal performance and mechanism by coagulation and related combined processes was carried out. The influencing factors of Sb removal performance by coagulation are introduced in detail. The internal mechanisms and improvement strategies of Sb removal by oxidation/reduction-coagulation and coagulation-membrane filtration technologies are emphasized. Moreover, given the development of Sb-removing coagulants and the resource utilization of Sb-containing sludge, future perspectives of coagulation for Sb removal are discussed. As the first review in this field, this work will illuminate avenues of basic research and practical applications for Sb and Sb-like pollution control in water/wastewater treatment.

ObjectiveAs the high proportion of underweight pregnant women, omission of their weight gain and blood lipids management during gestation might lead to adverse pregnancy outcomes. This study aimed to determine the relationship between lipid profile and risks for adverse pregnancy outcomes in pre-pregnancy underweight women.MethodsThis study was part of an ongoing cohort study including Chinese gravidas delivered from January 2015 to December 2016. Included subjects were grouped into underweight, normal-weight, and overweight by BMI before conception. Logistic regression was used to assess the association between lipid profiles during second trimester and adverse obstetric outcomes in each group. A subgroup analysis according to the gestational weight gain, in which subjects in each group were divided into above and within the Institute of Medicine (IOM) recommendations, was performed.ResultsA total of 6, 223 women were included. The proportion of underweight (19.3%) was similar to that of overweight women (19.4%) in South China. Peripheral total cholesterol (TC) level in underweight women was significantly higher than that in overweight women (P ConclusionUnderweight pregnant women with high TC levels had a higher risk for LGA, especially among women whose gestational weight gain were above the IOM recommendations. Therefore, clinical management of lipids and weight gain during gestation should also be recommended for underweight women.

Diabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes, and the leading cause of preventable blindness in working-aged people. Here, we generated an induced pluripotent stem (iPS) cell line using blood-derived cells from a patient with DR. Peripheral blood mononuclear cells (PBMCs) were reprogrammed with Sendai virus.

Adverse skin reactions are the most common side effects of epidermal growth factor receptor inhibitors (EGFRIs) in the treatment of cancer, significantly affecting the survival rate and quality of life of patients. Qi Yin San Liang San Decoction (QYSLS) comes from folk prescription and is currently used in the clinical treatment of adverse skin reactions caused by EGFRIs. However, its therapeutic mechanism remains unclear.To explore the potential mechanism of QYSLS in the treatment of adverse skin reactions caused by EGFR inhibition using network pharmacology and experimental research.First, we verified the effectiveness of QYSLSIn theThe results revealed that QYSLS effectively treats EGFRI-related adverse skin reactions through multi-target and multi-pathway mechanisms. Luteolin and quercetin may be the core active ingredients of QYSLS in the treatment of EGFRI-related adverse skin reactions, and their therapeutic effects are potentially mediated through PTGS2, CCL2, and MMP9 in the IL-17 and TNF signaling pathway.

In vitro generation of a functional retinal pigment epithelium (RPE) monolayer sheet is useful and promising for RPE cell therapy. Here, for the first time, we used induced pluripotent stem (iPS) supernatant as the conditioned medium (iPS-CM) and femtosecond laser intrastromal lenticule (FLI-lenticule) as a scaffold to construct an engineered RPE sheet. There are significant enhancements in RPE cell density, transepithelial electrical resistance (TER) and inhibitions of ultraviolet C (UVC)-irradiated apoptosis when RPE cells are cultured in iPS supernatant/Dulbecco’s modified Eagle’s medium (DMEM)-F12 of 1/2 (iPS-CM) compared with those in normal medium (NM, DMEM-F12). Using the assay of a panel of cytokines, combined with transcriptome and protein analyses, we discover that iPS-CM contains high levels of platelet-derived growth factor AA (PDGF-AA), insulin-like growth factor binding protein (IGFBP)-2, transforming growth factor (TGF)-α and IGFBP-6, which are responsible for the upregulation of gene and protein markers with RPE phenotypes and downregulation of gene and protein markers with epithelial-mesenchymal transition (EMT) phenotypes for RPE cells in iPS-CM when compared to those in NM. Moreover, compared to cultures on tissue culture plates (TCP), RPE cells on FLI-lenticule display more microvilli and cilium in accordance with the results in terms of RNA-Seq data, quantitative polymerase chain reaction (qPCR) expression, immunofluorescence staining, and western blot assays. Furthermore, acellular FLI-lenticule exhibits biocompatibility after rabbit subretinal implantation by 30 days through electroretinography and histological examination. Thus, we determined that engineered RPE sheets treated by iPS-CM in conjunction with FLI-lenticule scaffold aid in enhanced RPE characteristics and cilium assembly. Such a strategy to construct RPE sheets is a promising avenue for developing RPE cell therapy, disease models and drug screening tools. Statement of Significance In vitro generation of a functional RPE monolayer sheet is useful and promising for RPE cell therapy. Here, we constructed engineered RPE sheets treated by iPS-CM in conjunction with FLI-lenticule scaffolds to help in enhanced RPE characteristics and cilium assembly. Such a strategy to generate RPE sheets is a promising avenue for developing RPE cell therapy, disease models and drug screening tools.

A wheelset bearing is one of the crucial mechanical parts in a high-speed train. Its fault detection is of great significance, as it ensures the safety of a high-speed train service. To resolve the boundary changeability of the sidebands and false segments caused by measured noises and vibrational interferences, a novel automatic fault detection method of the wheelset bearing, named AFDMLEWT, is proposed based on the proposed multi-level empirical wavelet transform (MLEWT) and the developed segment selection method, named SSESKDB. MLEWT provides a complete framework for extracting the sidebands with different bandwidths distributed throughout different frequency positions. A novel index for evaluating the fault information capacity contained in different decomposition bandwidths, named ESKDB, is proposed. The segment selection method based on ESKDB, named SSESKDB, is proposed to select those segments of MLEWT containing the fruitful fault information in the full frequency range of wheelset bearing fault detection. Finally, the proposed method is then validated using two simulated signals and bench tests.

A simple, efficient, and practical protocol is reported, allowing quick access to diverse 2-arylquinolines from 2-vinylanilines and benzyl halides. This reaction is additive and metal catalyst-free with only solvent needed. A preliminary mechanistic investigation discloses the driving force comes from the in situ released HBr, which catalyzes the subsequent cyclization. The present synthetic route featured high functional group tolerance and simple post-processing. A variety of 2-arylquinolines were obtained up to 96% yield.

Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by the progressive photoreceptors and pigment epithelial cells dysfunction. Here, we report the human induced pluripotent stem cell line (iPSC) CSUASOi006-A, generated from urine-derived cells (UCs) of a 17-year-old male patient with clinically diagnosed RP carrying point mutation (c.C5792T) in the pre-mRNA processing factor 8 gene (PRPF8). The newly derived CSUASOi006-A cell line has the patient's same mutation (c.C5792T) and could provide useful resources for studying the pathogenic mechanism of PRPF8-related RP.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, erlotinib, and afatinib, are widely used in clinical practice and remarkably effective in treatment of advanced non-small cell lung cancer. However, there are some adverse effects while taking EGFR-TKIs, among which skin adverse reactions (SAR) are the most common events. At present, the poor outcome of SAR and insufficient research on SAR models need to be addressed. In this study we focused on the SAR models to lay a foundation for mechanism researches. Gefitinib, one of the EGFR-TKIs, was used as SAR inducing agents. We chose C57BL/6 and FVB/N mice as experimental model and they were divided into four groups. The weight and skin moisture of mice were detected every 7 days, itching behavior and abnormal eyelids were tested at 35th day after gavage, and survival rate was also recorded. The weight of unit area hair, length of whiskers and inflammatory cells were evaluated after mice sacrificed. C57BL/6 animals treated with gefitinib showed significant differences in survival rate, weight of unit area hair, skin moisture changes, skin dryness, itching behavior, whisker irregular growth, abnormal eyelids, and inflammatory cells; FVB/N animals treated with gefitinib only showed significant differences in survival rate, whisker irregular growth and abnormal eyelids, compared with the control group, respectively. In this study, we compared the similarities and differences of gefitinib-induced SAR between C57BL/6 and FVB/N mice, which illustrated different patients probably showing different symptoms clinically and provided experimental basis for researching mechanism of EGFR-TKIs induced SAR.

Hepatocellular carcinoma (HCC), with its high recurrence and metastasis rates, is a leading cause of cancer-related mortality, and available treatments include surgical resection and liver transplantation. TOGA is a novel conjugate combining 18β-glycyrrhetinic acid (GA), an active component of licorice, and tetramethylpyrazine, an effective component of Chuanxiong, with a small-molecule amino acid. This study examined the anti-hepatoma effects of TOGA and its specific mechanisms of action. We found that TOGA significantly prevented tumor growth in both nude mice carrying liver cancer xenograftsand mice carrying orthotopic tumors with little toxicity. NanoString analysis screening illustrated that TOGA may exert its anti-tumor effects by targeting interleukin (IL)-1R receptor 1 (IL-1R1). Further, TOGA significantly prevented the invasion and migration of HepG2 cells induced by tumor-associated macrophages (TAMs) or IL-1β, as confirmed by the reduced expression of the epithelial-mesenchymal transition (EMT)-related proteins Snail and Vimentin. Furthermore, IL-1β-induced activation of the IL-1R1/IκB/IKK/NF-κB signaling pathway in HepG2 cells was proved to be inhibited by TOGA. Taken together, TOGA effectively prevents the support of TAMs from fueling tumorigenesis through a mechanism related to the NF-κB pathway, and it may be a promising GA-modified drug for the treatment of HCC.

X-linked retinoschisis (XLRS) is a one of most common retinal genetic diseases of juvenile progressive vitreoretinal degeneration in males, which caused by the mutation of RS1 gene. In this study, an induced pluripotent stem cell (iPSC) line was generated from human peripheral blood mononuclear cells (PBMC) of a 13-year-old male patient with X-linked juvenile retinoschisis carrying a novel mutation in RS1 gene. The iPSCs exhibited iPSC morphology, expression of the pluripotency markers and in vitro differentiation potential, and the CSUASOi005-A iPSC line retained the original mutation (c.527T > A) of RS1 with a normal karyotype.

X-linked juvenile retinoschisis (XLRS) is one of the most severely affected genetic causes of irreversible retinal degeneration diseases in young males, especially school-age boys. Here, we generated induced pluripotent stem cells (iPSCs) from a Chinese 11-year-old male with clinically diagnosed XLRS. Urine sample was collected with appropriate cooperation, then isolated cells were expanded for subsequent reprogramming procedure using integration-free Sendai virus. The newly derived CSUASOi001-A iPS cell line harboring the c.304C > T mutation in the RS1 gene (p.R102W) provides a useful resource to investigate pathogenic mechanisms in XLRS.

Aquaculture has attracted significant attention as an environmental gateway to the development of antibiotic resistance. The industry of Chinese mitten crab Eriocheir sinensis contributes significantly to the freshwater aquaculture industry in China. However, the situation of antibiotic resistance in the E. sinensis aquaculture environment is not known. In this study, high-throughput sequencing based metagenomic approaches were used to comprehensively investigate the structure of bacterial communities, the abundance and diversity of antibiotic resistance genes (ARGs), as well as mobile genetic elements (MGEs) in three E. sinensis aquaculture ponds in Jiangsu Province, China. The dominant phyla were Proteobacteria, Actinobacteria, and Bacteroidetes in water samples and Proteobacteria, Chloroflexi, Verrucomicrobia, and Bacteroidetes in sediment samples. Bacitracin and multidrug were predominant ARG types in water and sediment samples, respectively. There was a significant correlation between MGEs and ARGs. In particular, plasmids were the most abundant MGEs and strongly correlated with ARGs. This is the first study of antibiotic resistome that uses metagenomic approaches in the E. sinensis aquaculture environment. The results indicate that the opportunistic pathogens may acquire ARGs via horizontal gene transfer, intensifying the potential risk to human health.

Non-point source nutrient release from land to water, which leads to the eutrophication and toxic algal blooms in natural water, is not easy to control effectively because in-situ injection of suspended particles is often failed to reach deep soils due to nanoparticles tending to agglomerate into micro particles. In this work, we found that particle sizes of synthetic magnetite nanoparticles (Fe3O4) and sorption capacity of phosphate were controllable by manipulating the surface coverage of stabilizer (starch). The sorption density and starch stabilized particle sizes were positive correlation. In order to enhance the stability and dispersibility of the nanoparticles, the particle sizes were reduced to nano-scale with high dosage of starch, which weakened the phosphate sorption capability. To recover the activity of the nanoparticles, alpha-amylase was employed to degrade the surface coating. The phosphate sorption capacity was almost doubled when alpha-amylase was applied comparing with that without alpha-amylase. Column testes indicated that highly stabilized nanoparticles could be delivered to the targeted depth of soil column, and the sorption activity was recovered by the in-situ biodegradation of starch. The technology provides methods for in situ immobilization of phosphorus in over fertilized soils, which is significant in controlling the eutrophication of aquatic environments.