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This study evaluated the effects of feeding a microbial-derived antioxidant diet (MA) for 56 days on the growth performance of Eriocheir sinensis, as well as on digestive and metabolic enzyme activity and antioxidant capacity under ammonia stress (400 mg/L ammonia nitrogen for 48 h). The weight gain at 28d and the specific growth rate at 56ds for crabs in the MA group were significantly higher than those in the control diet (C) group (p

Abstract Objectives This study aimed to compare and evaluate different transverse width indices for diagnosing maxillary transverse deficiency (MTD), a common malocclusion characterized by uncoordinated dental arches, crossbites, and tooth crowding. Materials and methods Sixty patients aged 7–12 years were included in the study, with 20 patients diagnosed with MTD and 40 normal controls. Transverse width indices, including maxillary width at the buccal alveolar crest and lingual midroot level, as well as at the jugal process width, were measured. Differences between these indices and their corresponding mandibular indices were used as standardized transverse width indices. The reference range of these indices was determined and evaluated. Receiver operating characteristic (ROC) analysis was performed to evaluate their diagnostic ability. Results The transverse width indices and standardized transverse width indices of the MTD group were significantly smaller than those of the control group, except for the jugal process width. The evaluation of the reference range and ROC analysis revealed that the difference of the maxillomandibular width at buccal alveolar crest was the most accurate diagnostic method. Conclusions The jugal point analysis method may not be suitable for diagnosing MTD. Instead, measuring the difference in maxillomandibular width at the buccal alveolar crest proves to be a more reliable and accurate diagnostic method for MTD.

Abstract Profibrotic proximal tubules (PT) were identified as a unique phenotype of proximal tubule cells (PTCs) in renal fibrosis by single-cell RNA sequencing (scRNA-seq). Controlling the process of renal fibrosis requires understanding how to manage the S1 subset’s branch to the S3 subset rather than to the profibrotic PT subset. Insulin-induced gene 1 (Insig1) is one of the branch-dependent genes involved in controlling this process, although its role in renal fibrosis is unknown. Here, we discovered that tubular Insig1 deficiency, rather than fibroblast Insig1 deficiency, plays a detrimental role in the pathogenesis of renal fibrosis in vivo and in vitro. Overexpression of Insig1 profoundly inhibited renal fibrosis. Mechanistically, Insig1 deletion in PTCs boosted SREBP1 nuclear localization, increasing Aldh1a1 transcriptional activity, causing excessive NAD+ consumption and ER enlargement, as well as accelerating renal fibrosis. We also identified nicardipine as a selective inhibitor of Aldh1a1, which could restore NAD+ and maintain ER homeostasis, as well as improve renal fibrosis. Together, our findings support tubular Insig1 as a new therapeutic target for chronic kidney disease (CKD).

Abstract In higher plants, mature male gametophytes have distinct apertures. After pollination, pollen grains germinate, and a pollen tube grows from the aperture to deliver sperm cells to the embryo sac, completing fertilization. In rice, the pollen aperture has a single-pore structure with a collar-like annulus and a plug-like operculum. A crucial step in aperture development is the formation of aperture plasma membrane protrusion (APMP) at the distal polar region of the microspore during the late tetrad stage. Previous studies identified OsINP1 and OsDAF1 as essential regulators of APMP and pollen aperture formation in rice, but their precise molecular mechanisms remain unclear. We demonstrate that the Poaceae-specific OsSRF8 gene, encoding a STRUBBELIG-receptor family 8 protein, is essential for pollen aperture formation in Oryza sativa. Mutants lacking functional OsSRF8 exhibit defects in APMP and pollen aperture formation, like loss-of-function OsINP1 mutants. OsSRF8 is specifically expressed during early anther development and initially diffusely distributed in the microsporocytes. At the tetrad stage, OsSRF8 is recruited by OsINP1 to the pre-aperture region through direct protein-protein interaction, promoting APMP formation. The OsSRF8-OsINP1 complex then recruits OsDAF1 to the APMP site to co-regulate annulus formation. Our findings provide insights into the mechanisms controlling pollen aperture formation in cereal species.

Anal fistula is a common anal and intestinal disease. The wound of anal fistula surgery is open and polluting, which is the most difficult to heal among all surgical incisions. To investigate the mechanism of Huanglian ointment (HLO) on wound healing after anal fistula incision. The S. aureus infected wound in SD rats were used to imitate poor healing wound after anal fistula surgery. SD rats with wound sites (n = 24) were randomly divided into four groups (Control group, Model group, Potassium permanganate (PP) treatment group, and HLO treatment group). The wound healing rate was evaluated, HE staining was used to evaluate the pathological changes of each group, ELISA was used to detect the secretion of inflammatory factors in each group, and the mechanism was explored through metabolomics and proteomics in plasma rat. Compared to other groups, the rate of wound healing in the HLO group was higher on days 7 and 14. Histological analysis showed that collagen and fibroblast in HLO rats were significantly increased, inflammatory cells were reduced, and vascular endothelial permeability was increased. ELISA results showed that the secretion of inflammatory factors in HLO rats was significantly lower. Significant proteins and metabolites were identified in the wound tissues of the infected rats and HLO-treated rats, which were mainly attributed to Cdc42, Ctnnb1, Actr2, Actr3, Arpc1b, Itgam, Itgb2, Cttn, Linoleic acid metabolism, d-Glutamine and d-glutamate metabolism, Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, alpha-Linolenic acid metabolism, and Ascorbate and aldarate metabolism. In conclusion, this study showed that HLO can promote S. aureus infected wound healing, and the data provide a theoretical basis for the treatment of wounds after anal fistula surgery with HLO.

Abstract Cisplatin‐containing combination chemotherapy has been used as the standard treatment for bladder cancer patients at advanced stage. However, nearly 50% of patients are nonresponders. To guide the selection of more effective chemotherapeutic agents, a bladder cancer spheroids microfluidic drug sensitivity analysis system was established in this study. Bladder cancer spheroids were established and successfully cultured in a customized microfluidic device to assess their response to different chemotherapeutic agents. The in vitro drug sensitivity results were also compared to patient‐derived xenograft (PDX) models and clinical responses of patients. As a result, bladder cancer spheroids faithfully recapitulate the histopathological and genetic features of their corresponding parental tumors. Furthermore, the in vitro drug sensitivity outcomes of spheroids (n = 8) demonstrated a high level of correlation with the PDX (n = 2) and clinical response in patients (n = 2). Our study highlights the potential of combining bladder cancer spheroids and microfluidic devices as an efficient and accurate platform for personalized selection of chemotherapeutic agents.

Abstract Breakdown of reproductive isolation facilitates flow of useful trait genes into crop plants from their wild relatives. Hybrid sterility, a major form of reproductive isolation exists between cultivated rice (Oryza sativa) and wild rice (O. meridionalis, Mer). Here, we report the cloning of qHMS1, a quantitative trait locus controlling hybrid male sterility between these two species. Like qHMS7, another locus we cloned previously, qHMS1 encodes a toxin-antidote system, but differs in the encoded proteins, their evolutionary origin, and action time point during pollen development. In plants heterozygous at qHMS1, ~ 50% of pollens carrying qHMS1-D (an allele from cultivated rice) are selectively killed. In plants heterozygous at both qHMS1 and qHMS7, ~ 75% pollens without co-presence of qHMS1-Mer and qHMS7-D are selectively killed, indicating that the antidotes function in a toxin-dependent manner. Our results indicate that different toxin-antidote systems provide stacked reproductive isolation for maintaining species identity and shed light on breakdown of hybrid male sterility.

The simultaneous adsorption of Cu(II) and dyes (MB and MO) on LDH@GO-SH was investigated in single, MB–Cu, and MO–Cu binary systems. The coexistence of dye enhanced the adsorption of Cu(II) by LDH@GO-SH, while the presence of Cu(II) differently affected the adsorption of MB and MO. The adsorption capacity of MO remarkably increased due to the presence of Cu(II). The presence of Cu(II) had a negative effect on MB adsorption for lower MB initial concentration systems (2–10 mg·L−1), while it had a positive effect for higher MB concentration systems (25 mg·L−1 and 50 mg·L−1). The adsorption of Cu(II) in binary systems was satisfactorily fitted by a Langmuir model and pseudo-first-order kinetic model. Surface complex interaction was supposed to be a potential mechanism for the enhancement of Cu(II) adsorption in both MB–Cu and MO–Cu binary systems. The electrostatic interactions between MO and Cu(II) were another reason for the enhancement of Cu(II) adsorption in the MO–Cu binary system. LDH@GO-SH maintained a high adsorption capacity after three adsorption–desorption cycles, indicating that it can be repeatedly used for the treatment of heavy-metal-ion-containing wastewater.

Live fish transportation is crucial for managing aquaculture but can pose health risks to fish due to stressors encountered during transportation. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a crucial role in the central nervous system and is considered to exhibit anti-stress effects. This study aims to investigate the effects of GABA on the transport water quality, plasma biochemical indices, energy metabolism, and antioxidant capacity of tawny puffer (Takifugu flavidus) under transport stress. Tawny puffer were pretreated by immersing in aquariums containing GABA (final concentrations at 0, 5, 50, and 150 mg/L) seawater for 3 days; then, simulated transport was conducted using oxygen-filled polyethylene bags containing the same concentration of GABA seawater as the pretreatment period. Water samples, plasma, and liver were collected after 0, 6, and 12 h of transport. The results revealed that with the prolongation of transportation time, the control group’s water quality deteriorated, stress-related plasma biochemical indices increased, glycolytic substrate contents decreased, glycolytic enzyme activities and product contents increased, and aerobic metabolic enzyme activities exhibited initial increases followed by declines, ATPase activities decreased, antioxidant enzyme activities decreased, and the lipid peroxidation marker contents increased. It is noteworthy that GABA treatment could avoid water quality deterioration during transportation, inhibit an elevation in stress-related biochemical indicators, regulate energy metabolism, and reduce oxidative damage in tawny puffer, especially at 50 and 150 mg/L concentrations. In summary, GABA treatment can effectively alleviate the transport stress of tawny puffer.

Objectives Antibody-mediated rejection (AMR) is a large obstacle to the long-term survival of allograft kidneys. It is urgent to find novel strategies for its prevention and treatment. Bibliometric analysis is helpful in understanding the directions of one field. Hence, this study aims to analyze the state and emerging trends of AMR in kidney transplantation.Methods Literature on AMR in kidney transplantation from 1999 to 2022 was collected from the Web of Science Core Collection. HistCite (version 12.03.17), CiteSpace (version 6.2.R2), Bibliometrix 4.1.0 Package from R language, and Gephi (https://gephi.org) were applied to the bibliometric analysis of the annual publications, leading countries/regions, core journals, references, keywords, and trend topics.Results A total of 2522 articles related to AMR in kidney transplantation were included in the analysis and the annual publications increased year by year. There were 10874 authors from 118 institutions located in 70 countries/regions contributing to AMR studies, and the United States took the leading position in both articles and citation scores. Halloran PF from Canada made the most contribution to AMR in kidney transplantation. The top 3 productive journals, American Journal of Transplantation, Transplantation, and Transplantation Proceedings, were associated with transplantation. Moreover, the recent trend topics mainly focused on transplant outcomes, survival, and clinical research.Conclusions North American and European countries/regions played central roles in AMR of kidney transplantation. Importantly, the prognosis of AMR is the hotspot in the future. Noninvasive strategies like plasma and urine dd-cfDNA may be the most potential direction in the AMR field.

In recent years, the widespread application of Mg alloy casting and Mg alloy products has generated a large amount of Mg alloy waste. This experiment used a single factor experimental analysis method to study the optimal process for removing Fe from Mg alloy AM50A waste, and developed an efficient Fe removal and regeneration process for Mg alloy AM50A. It was found that the optimal refining temperature for removing Fe ions was 670 °C, the optimal refining (RJ-2) agent mass ratio was 1.5%, and the optimal refining time was 40 min. Regenerated J40-1.5-AM50A Mg alloy was prepared using the best refining process, and its composition and mechanical properties were tested and analyzed. The experimental results show that the composition of the regenerated J40-1.5-AM50A Mg alloy prepared by this method is consistent with AM50A, with an Fe removal rate of 96.2%. The mechanical properties were improved compared to the original AM50A sample, with a maximum tensile strength increase of 1.611 KN and a tensile strength increase of 26.333 MPa. The elongation after fracture is 2.25 times that of the original sample. Research has shown that the RJ-2 refining agent can provide mechanical properties of magnesium alloys during the refining process. By analyzing the composition, XRD, SEM, and EDS of AM50A (Fe) and J40-1.5-AM50A, it was found that the refining process accelerates the removal of Fe in the form of Fe deposition.

The important parameters affecting the nutritional properties of lipids were analyzed and compared between human milk (HM), infant formulas (IFs), mammalian milk, and substitute fat, including molecular species, fatty acid composition, glyceride content, and important structural triacylglycerols (TAGs). The molecular species of triacylglycerols with functional fatty acids were significantly different between HM and IFs, and their contents in HM were significantly higher than those in IFs. Accordingly, the evaluation scores of fatty acid composition and glyceride content in IFs were less than 50 compared to HM. Although the introduction of vegetable oils effectively improved the unsaturation of IF lipid, the excessive addition of TAGs rich in oleic and linoleic acid resulted in an imbalance of TAG composition and structure. Only 36.84 % of IFs were supplemented with structured lipids, but those still lacked sn-2 palmitate TAGs. The adoption of multiple lipids and novel processing technologies is required for novel IFs to match the composition, content, positional structure and spherical membrane structure of HM as closely as possible.

IntroductionSoil salinization poses a worldwide challenge that hampers agricultural productivity.MethodsEmploying high-throughput sequencing technology, we conducted an investigation to examine the impact of compost on the diversity of bacterial communities in saline soils. Our study focused on exploring the diversity of bacterial communities in the inter-root soil of plants following composting and the subsequent addition of compost to saline soils.ResultsCompared to the initial composting stage, Alpha diversity results showed a greater diversity of bacteria during the rot stage. The germination index reaches 90% and the compost reaches maturity. The main bacterial genera in compost maturation stage are Flavobacterium, Saccharomonospora, Luteimonas and Streptomyces. Proteobacteria, Firmicutes, and Actinobacteria were the dominant phyla in the soil after the addition of compost. The application of compost has increased the abundance of Actinobacteria and Chloroflexi by 7.6 and 6.6%, respectively, but decreased the abundance of Firmicutes from 25.12 to 18.77%. Redundancy analysis revealed that soil factors pH, solid urease, organic matter, and total nitrogen were closely related to bacterial communities.DiscussionThe addition of compost effectively reduced soil pH and increased soil enzyme activity and organic matter content. An analysis of this study provides theoretical support for compost’s use as a saline soil amendment.

Abstract Mitochondria comprise the central metabolic hub of cells and their imbalance plays a pathogenic role in chronic kidney disease (CKD). Here, we studied Lon protease 1 (LONP1), a major mitochondrial protease, as its role in CKD pathogenesis is unclear. LONP1 expression was decreased in human patients and mice with CKD, and tubular‐specific Lonp1 overexpression mitigated renal injury and mitochondrial dysfunction in two different models of CKD, but these outcomes were aggravated by Lonp1 deletion. These results were confirmed in renal tubular epithelial cells in vitro. Mechanistically, LONP1 downregulation caused mitochondrial accumulation of the LONP1 substrate, 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (HMGCS2), which disrupted mitochondrial function and further accelerated CKD progression. Finally, computer‐aided virtual screening was performed, which identified a novel LONP1 activator. Pharmacologically, the LONP1 activator attenuated renal fibrosis and mitochondrial dysfunction. Collectively, these results imply that LONP1 is a promising therapeutic target for treating CKD.

Milk exosomes are a newly discovered functional vesicles secreted by animal mammary epithelial cells, small vesicles with membrane structure in the diameter of about 30~200 nm, which contain many bioactive substances such as proteins, lipids, and nucleic acids on the surface and inside the membrane. Recent studies have found exosomes with biological functions such as mediating cell communication, promoting cell proliferation, and participating in immune responses. Exosomes can be isolated from the emulsion by centrifugation, chemical, immunoaffinity and identified their morphology, size, specific substances. This article reviews the biological function, three omics studies, separation and identification methods, and aims to provide scientific reference for the research and development of milk source exosomes.

ABSTRACT The microbial network of the soil-root continuum plays a key role in plant growth. To date, limited information is available about the microbial assemblages in the rhizosphere and endosphere of endangered plants. We suspect that unknown microorganisms in roots and soil play an important role in the survival strategies of endangered plants. To address this research gap, we investigated the diversity and composition of the microbial communities of the soil-root continuum of the endangered shrub Helianthemum songaricum and observed that the microbial communities and structures of the rhizosphere and endosphere samples were distinguishable. The dominant rhizosphere bacteria were Actinobacteria (36.98%) and Acidobacteria (18.15%), whereas most endophytes were Alphaproteobacteria (23.17%) as well as Actinobacteria (29.94%). The relative abundance of rhizosphere bacteria was higher than that in endosphere samples. Fungal rhizosphere and endophyte samples had approximately equal abundances of the Sordariomycetes (23%), while the Pezizomycetes were more abundant in the soil (31.95%) than in the roots (5.70%). The phylogenetic relationships of the abundances of microbes in root and soil samples also showed that the most abundant bacterial and fungal reads tended to be dominant in either the soil or root samples but not both. Additionally, Pearson correlation heatmap analysis showed that the diversity and composition of soil bacteria and fungi were closely related to pH, total nitrogen, total phosphorus, and organic matter, of which pH and organic matter were the main drivers. These results clarify the different patterns of microbial communities of the soil-root continuum, in support of the better conservation and utilization of endangered desert plants in Inner Mongolia. IMPORTANCE Microbial assemblages play significant roles in plant survival, health, and ecological services. The symbiosis between soil microorganisms and these plants and their interactions with soil factors are important features of the adaptation of desert plants to an arid and barren environment. Therefore, the profound study of the microbial diversity of rare desert plants can provide important data to support the protection and utilization of rare desert plants. Accordingly, in this study, high-throughput sequencing technology was applied to study the microbial diversity in plant roots and rhizosphere soils. We expect that research on the relationship between soil and root microbial diversity and the environment will improve the survival of endangered plants in this environment. In summary, this study is the first to study the microbial diversity and community structure of Helianthemum songaricum Schrenk and compare the diversity and composition of the root and soil microbiomes.

Due to the personalized large defect and bone absorption of the alveolar cleft, its regeneration is still a great challenge. Conventional autologous bone repair leads to donor site adverse reactions and then bioactive materials with stable mechanical properties, suitable degradation rates, good osteogenic ability are required. In this study, the α-tricalcium phosphate (doping with and without 6% strontium; α-TCP-Sr6, α-TCP) bioceramic scaffolds with high-precision pore structure were developed to repair the alveolar cleft, and the physicochemical properties and bone repair performances were systematically compared with the pure β phase of tricalcium phosphate (β-TCP) bioceramic scaffolds. It was shown that Sr dopant could adjust the bio-dissolution of α-TCP scaffolds, and contributed to excellent mechanical stability. As for the osteogenic capability in the alveolar cleft of rabbits, the α-phase TCP scaffolds both exhibited appreciable new bone ingrowth compared to the β-TCP scaffolds. However, bone malformation and fibrous tissue invasion occurred in the control group (without filling scaffolds). This study suggests that the Sr dopant may adjust the biodegradation and mechanical stability of α-TCP, and such biodegradable Ca-phosphate bioceramics scaffolds prepared by digital light processing (DLP)-based 3D printing technique demonstrate significance in promoting the reconstruction of the alveolar cleft.

Endosperm as the storage organ of starch and protein in cereal crops largely determines grain yield and quality. Despite the fact that several pentatricopeptide repeat (PPR) proteins required for endosperm development have been identified in rice, the molecular mechanisms of many P-type PPR proteins in endosperm development remains unclear. Here, we isolated a rice floury endosperm mutant ppr5 that developed small starch grains and an abnormal aleurone layer, accompanied by decreased starch, protein, and amylose contents. Map-based cloning combined with a complementation test demonstrated that PPR5 encodes a P-type PPR protein that is localized to the mitochondria. The mutation in PPR5 caused reduced splicing efficiency of mitochondrial NADH dehydrogenase 4 (nad4) gene intron 3 and reduced complex I assembly and activity. Loss of PPR5 function greatly up-regulated expression of alternative oxidases (AOXs), reduced ATP production, and affected mitochondrial morphology. We demonstrate that PPR5, as a P-type PPR protein, is required for mitochondrial function and endosperm development by controlling the cis-splicing of mitochondrial nad4 intron 3.

Abstract Background T cell immunoglobulin and mucin domain-containing-3 (Tim-3) is a negative regulator expressed on T cells, and is also expressed on natural killer (NK) cells. The function of Tim-3 chiefly restricts IFNγ-production in T cells, however, the impact of Tim-3 on NK cell function has not been clearly elucidated. Results In this study, we demonstrated down-regulation of Tim-3 expression on NK cells while Tim-3 is upregulated on CD4+ T cells during HIV infection. Functional assays indicated that Tim-3 mediates suppression of CD107a degranulation in NK cells and CD4+ T cells, while it fails to inhibit the production of IFN-γ by NK cells. Analyses of downstream pathways using an antibody to block Tim-3 function demonstrated that Tim-3 can inhibit ERK and NFκB p65 signaling; however, it failed to suppress the NFAT pathway. Further, we found that the NFAT activity in NK cells was much higher than that in CD4+ T cells, indicating that NFAT pathway is important for promotion of IFN-γ production by NK cells. Conclusions Thus, our data show that the expression of Tim-3 on NK cells is insufficient to inhibit IFN-γ production. Collectively, our findings demonstrate a potential mechanism of Tim-3 regulation of NK cells and a target for HIV infection immunotherapy.

Arbuscular mycorrhizal fungi (AMF) are considered to be an essential indicator of ecosystem biodiversity and can increase a plant’s ability to withstand arid conditions. Despite the obvious significance of AMF in the root and rhizosphere system, little is known about how the AMF variety varies between the soil and roots of endangered plants and how this varies depending on habitats in dry and semiarid regions. This study aimed to address this research gap by investigating the characteristics and diversity of AMF colonization in Zygophyllaceae. Using Illumina MiSeq high-throughput sequencing, indigenous AMF in the roots and rhizosphere soil of three endangered plants (Tetraena mongolica, Sarcozygium xanthoxylon, and Nitraria tangutorum Bobr) were investigated. The three threatened plants had different AMF populations in their root and rhizosphere soils, according to a hierarchical clustering analysis. AMF communities in rhizosphere soil were more sensitive to LDA than root AMF communities based on linear discriminant analysis effect size (LEfSe). Glomus, Septoglomus, and Rhizophagus were seen to function as dominant fungi as the soil and root AMF populations carried out their various tasks in the soil and roots as a cohesive collective. Distance-based redundancy analysis (db-RDA) showed that pH, total phosphorus, and accessible potassium were closely associated with AMF communities. The pH of the soil appears to be an important factor in determining AMF community stability. These findings can serve as a guide for the use of AM fungus in the rehabilitation of agricultural land in arid regions. In summary, our work contributed new knowledge for the scientific preservation of these endangered plant species and for the further investigation of the symbiotic link between AMF and endangered plant species.

BackgroundUrachal cancer is a rare neoplasm in the urological system. To our knowledge, no published study has explored to establish a model for predicting the prognosis of urachal cancer. The present study aims to develop and validate nomograms for predicting the prognosis of urachal cancer based on clinicopathological parameters.MethodsBased on the data from the Surveillance, Epidemiology, and End Results database, 445 patients diagnosed with urachal cancer between 1975 and 2018 were identified as training and internal validation cohort; 84 patients diagnosed as urachal cancer from 2001 to 2020 in two medical centers were collected as external validation cohort. Nomograms were developed using a multivariate Cox proportional hazards regression analysis in the training cohort, and their performance was evaluated in terms of its discriminative ability, calibration, and clinical usefulness by statistical analysis.ResultsThree nomograms based on tumor–node–metastasis (TNM), Sheldon and Mayo staging system were developed for predicting cancer-specific survival (CSS) of urachal cancer; these nomograms all showed similar calibration and discrimination ability. Further internal (c-index 0.78) and external (c-index 0.81) validation suggested that Sheldon model had superior discrimination and calibration ability in predicting CSS than the other two models. Moreover, we found that the Sheldon model was able to successfully classify patients into different risk of mortality both in internal and external validation cohorts. Decision curve analysis proved that the nomogram was clinically useful and applicable.ConclusionsThe nomogram model with Sheldon staging system was recommended for predicting the prognosis of urachal cancer. The proposed nomograms have promising clinical applicability to help clinicians on individualized patient counseling, decision-making, and clinical trial designing.

Neuropathic pain is mainly triggered after nerve injury and associated with plasticity of the nociceptive pathway in primary sensory neurons. Currently, the treatment remains a challenge. In order to identify specific therapeutic targets, it is necessary to clarify the underlying mechanisms of neuropathic pain. It is well established that primary sensory neuron sensitization (peripheral sensitization) is one of the main components of neuropathic pain. Calcium channels act as key mediators in peripheral sensitization. As the target of gabapentin, the calcium channel subunit α2δ1 (Cavα2δ1) is a potential entry point in neuropathic pain research. Numerous studies have demonstrated that the upstream and downstream targets of Cavα2δ1 of the peripheral primary neurons, including thrombospondins, N-methyl-D-aspartate receptors, transient receptor potential ankyrin 1 (TRPA1), transient receptor potential vanilloid family 1 (TRPV1), and protein kinase C (PKC), are involved in neuropathic pain. Thus, we reviewed and discussed the role of Cavα2δ1 and the associated signaling axis in neuropathic pain conditions.

A major barrier to HIV eradication is the persistence of viral reservoirs. Resting CD4+ T cells are thought to be one of the major viral reservoirs, However, the underlying mechanism regulating HIV infection and the establishment of viral reservoir in T cells remain poorly understood. We have investigated the role of IP-10 in the establishment of HIV reservoirs in CD4+ T cells, and found that in HIV-infected individuals, plasma IP-10 was elevated, and positively correlated with HIV viral load and viral reservoir size. In addition, we found that binding of IP-10 to CXCR3 enhanced HIV latent infection of resting CD4+ T cells in vitro. Mechanistically, IP-10 stimulation promoted cofilin activity and actin dynamics, facilitating HIV entry and DNA integration. Moreover, treatment of resting CD4+ T cells with a LIM kinase inhibitor R10015 blocked cofilin phosphorylation and abrogated IP-10-mediated enhancement of HIV latent infection. These results suggest that IP-10 is a critical factor involved in HIV latent infection, and that therapeutic targeting of IP-10 may be a potential strategy for inhibiting HIV latent infection.

Abstract Natural extracellular matrices (ECMs) are three-dimensional (3D) and multi-scale hierarchical structure. However, coatings used as ECM-mimicking structures for osteogenesis are typically two-dimensional or single-scaled. Here, we design a distinct quasi-three-dimensional hierarchical topography integrated of density-controlled titania nanodots and nanorods. We find cellular pseudopods preferred to anchor deeply across the distinct 3D topography, dependently of the relative density of nanorods, which promote the osteogenic differentiation of osteoblast but not the viability of fibroblast. The in vivo experimental results further indicate that the new bone formation, the relative bone-implant contact as well as the push-put strength, are significantly enhanced on the 3D hierarchical topography. We also show that the exposures of HFN7.1 and mAb1937 critical functional motifs of fibronectin for cellular anchorage are up-regulated on the 3D hierarchical topography, which might synergistically promote the osteogenesis. Our findings suggest the multi-dimensions and multi-scales as vital characteristic of cell-ECM interactions and as an important design parameter for bone implant coatings.

Abstract Background The prognosis of bladder urothelial carcinoma (BLCA) varies greatly among patients, and conventional pathological predictors are generally inadequate and often inaccurate to predict the heterogeneous behavior of BLCA. This study aims to investigate the prognostic value and function of TOP2A in BLCA. Methods TOP2A expression level was examined by RNA-sequencing, quantitative real time polymerase chain reaction and immunohistochemistry from 10, 40 and 209 BLCA samples, respectively. Public databases were analyzed for validation. Cell proliferation, migration, invasion assays were performed to explore potential functions of TOP2A in BLCA. Flow cytometry was performed for cell cycle and apoptosis analysis. Univariable and multivariable Cox regression models were performed to identify independent risk factors for the prognosis of BLCA. Results We found TOP2A was significantly upregulated in BLCA samples, especially for high-grade and advanced stage tumors, compared with matched normal epithelial tissue. Univariable COX regression analysis revealed high TOP2A expression was significantly associated with poorer cancer-specific, progression-free and recurrence-free survival, but not independently of clinical characteristics in the multivariable models. Knockdown of TOP2A remarkably inhibited the proliferation of BLCA cells and non-cancerous urothelial cells. Furthermore, migration and invasion capacity of BLCA cells were strongly suppressed after TOP2A knockdown. Moreover, flow cytometry suggested TOP2A had anti-apoptotic function, and knockdown of TOP2A could induce resistance to doxorubicin in J82 cells. Conclusions In our study, TOP2A was overexpressed in BLCA and could serve as a prognostic biomarker for BLCA. Moreover, TOP2A is functionally important for the proliferation, invasion and survival of BLCA cells.

In this paper, the effects of CaO on the phase evolution mechanism of vanadium slag during slagging, direct roasting, and (NH4)2CO3 leaching processes are investigated. Results indicate that with the increase in CaO content, vanadium is always concentrated as (Fe, Mn, Mg)V2O4 in spinels, part of titanium is concentrated and transformed into CaTiO3, and phosphorus is concentrated in 3CaO·P2O5 (C3P) and transformed into n·2CaO·SiO2-3CaO·P2O5 (nC2S-C3P). During the direct roasting process, a part of the vanadium-containing spinel phase oxidizes and reacts with Ca2SiO4 to produce calcium vanadate (Ca3V2O8, Ca10V6O25, and Ca2V2O7), which is soluble in (NH4)2CO3 aqueous solution. However, a part of the vanadium-containing spinel phase is oxidized and decomposed to vanadium oxides (V2O5 and V6O13), which are insoluble in (NH4)2CO3 aqueous solution. This is not beneficial for vanadium extraction using (NH4)2CO3 aqueous solution. In addition, (NH4)2CO3 aqueous solution can restrain the leaching of C3P from the nC2S-C3P solid solution in the directly roasted vanadium slag with high CaO content.

Background: Renal tubulointerstitial fibrosis is the key pathological feature in chronic kidney diseases (CKDs) with no satisfactory therapies in clinic. Cilomilast is a second-generation, selective phosphodiesterase-4 inhibitor, but its role in renal tubulointerstitial fibrosis in CKD remains unclear.Material and Methods: Cilomilast was applied to the mice with unilateral ureteric obstruction (UUO) and renal fibroblast cells (NRK-49F) stimulated by TGF-β1. Renal tubulointerstitial fibrosis and inflammation after UUO or TGF-β1 stimulation were examined by histology, Western blotting, real-time PCR and immunohistochemistry. KIM-1 and NGAL were detected to evaluate tubular injury in UUO mice.Results:In vivo, immunohistochemistry and western blot data demonstrated that cilomilast treatment inhibited extracellular matrix deposition, profibrotic gene expression, and the inflammatory response. Furthermore, cilomilast prevented tubular injury in UUO mice, as manifested by reduced expression of KIM-1 and NGAL in the kidney. In vitro, cilomilast attenuated the activation of fibroblast cells stimulated by TGF-β1, as shown by the reduced expression of fibronectin, α-SMA, collagen I, and collagen III. Cilomilast also inhibited the activation of TGF-β1-Smad2/3 signaling in TGF-β1-treated fibroblast cells.Conclusion: The findings of this study suggest that cilomilast is protective against renal tubulointerstitial fibrosis in CKD, possibly through the inhibition of TGF-β1-Smad2/3 signaling, indicating the translational potential of this drug in treating CKD.

The coin-tap method performs nondestructive testing by measuring the width of the tapping response pulse on the surface of the material. Existing studies have shown that defects in the material will cause the width of the tapping response pulse to increase. However, experiments have confirmed that different detection positions in the defective area will show different values of the width of the tapping response pulse, and the physical laws behind it have not been studied yet. To discuss its physical meaning, a mathematical model of the defective area is established, a method for calculating the width of the tapping response pulse is proposed, and a composite honeycomb structure with preset defects is used for data testing. Both the test results and the calculation results show that the pulse width of the tapping response will decrease with the increase of the defect depth and the deviation of the tapping position from the defect center. The consistency between the calculated results and the experimental results shows that the established defect model and pulse width calculation method can better explain the distribution law of the pulse width of the tapping response in the defective area.

The littoral ecotone between land and lake makes an important part of the lake ecosystem which provide essential ecosystem services for human society. In this paper, the littoral wetland zone of Balagasi Lakeshore, Inner Mongolia, China and steppe being adjacent to was taken as the research object to discuss the characteristics of bacterial diversity and community structure in non-rhizosphere soils along zonal distribution of plants in the arid area. From the sediment of the exposed lakebed to the landward, according to the distribution of plant communities (Phragmites australis, Kalidium foliatum, Achnatherum splendens, Reaumuria songarica and Stipa klemenzii), the relationship between plant communities and soil physical and chemical factors were analysed. The Illumina HiSeq high-throughput sequencing method was used to measure bacterial community diversity and composition in their non-rhizosphere soils along the zonal distribution of plant. The results showed that the distribution of plant communities in the littoral zone of Balagasi Lake was mainly affected by soil bulk density, pH, TP, AP, TOC and TN. Meanwhile, the distribution of bacterial communities in non-rhizosphere soils was mainly affected by water content, salinity, AP, TOC, TP of soils. The communities of Achnatherum splendens, Reaumuria songarica, Stipa klemenzii were negatively correlated with pH, water content and nutrient content, while the Phragmites australis was opposite. There was a positive correlation between the Kalidium foliatum community and soil nutrient content. The species diversity of soil bacteria was the lowest in lakebed sediment. There was a significant negative correlation between Acidobacteria∖Verrucomicrobia∖Actinobacteria and soil salinity, so in the three sample groups near the lakebed area (lakebed sediment, Phragmites australis community, Kalidium foliatum community), the relative abundance of which was lower than slope and landward terrace. However, the relative abundance of Proteobacteria was opposite. Bacteroidetes was positively correlated with soil nutrients, and its relative abundance was the highest in the non-rhizosphere soil of Kalidium foliatum community with the highest soil nutrients.

Desertification is one of the most serious ecological environmental problems over the past several decades in the arid regions. The quantitative assessment of the desertification degree in sandy lands has also been an essential part of landscape ecology. Based on the character of relief, we proposed a new indicator system, i.e., Normalized Landscapes Index (NLI) to calculate the dynamic trend of the desertification process. The data from three periods of Mu Us sandy land and Kubuqi sandy land in Inner Mongolia were used to verify the accuracy of this method. The results show that, from 1990s to 2010s, the NLI change amount of fixed sandy land and semi-fixed sandy land all had positive values while bare sandy land and water had all negative values for both regions. Over the past 20 years, the desertification reversal phenomenon occurs in Mu Us with the desertification process (DP) of −0.36%, while a positive development of desertification in Kubuqi with the DP of 0.01%. The NLI dynamic degree of two sandy lands had the same trend as land use dynamic degree, while NLI was more accurate than the landscape dynamic degree. These findings can provide an important method for comparing the desertification process of the desert and also the meaningful information for prevention and control of desertification and sustainable development for the sandy lands in the arid regions.

Meiosis plays an essential role in the production of gametes and genetic diversity of posterities. The normal double-strand break (DSB) repair is vital to homologous recombination (HR) and occurrence of DNA fragment exchange, but the underlying molecular mechanism remain elusive. Here, we characterized a completely sterile Osmfs1 (male and female sterility 1) mutant which has its pollen and embryo sacs both aborted at the reproductive stage due to severe chromosome defection. Map-based cloning revealed that the OsMFS1 encodes a meiotic coiled-coil protein, and it is responsible for DSB repairing that acts as an important cofactor to stimulate the single strand invasion. Expression pattern analyses showed the OsMFS1 was preferentially expressed in meiosis stage. Subcellular localization analysis of OsMFS1 revealed its association with the nucleus exclusively. In addition, a yeast two-hybrid (Y2H) and pull-down assay showed that OsMFS1 could physically interact with OsHOP2 protein to form a stable complex to ensure faithful homologous recombination. Taken together, our results indicated that OsMFS1 is indispensable to the normal development of anther and embryo sacs in rice.

Background: Celastrol is an active ingredient of Chinese medicine Tripterygium wilfordii which is clinically used to treat the immune diseases. Currently, celastrol is documented as a potent agent for treating cancer and inflammatory disorders. This study was to investigate the effect of celastrol on cisplatin nephrotoxicity and the underlying mechanism. Methods: Male C57BL/6 mice were treated with cisplatin (20 mg/kg) with or without celastrol treatment (1 and 2 mg/kg/day). In vitro, human proximal tubule epithelial cell line (HK−2) and mouse renal tubule epithelial cells (RTECs) were treated with cisplatin (5 μg/mL) with or without celastrol administration. Then renal injury and cell damage were evaluated. Findings: In vivo, after celastrol treatment, cisplatin-induced kidney injury was significantly ameliorated as shown by the improvement of renal function (BUN, serum creatinine, and cystatin C), kidney morphology (PAS staining) and oxidative stress (MDA) and the suppression of renal tubular injury markers of KIM-1 and NGAL. Meanwhile, the renal apoptosis and inflammation induced by cisplatin were also strikingly attenuated in celastrol-treated mice. In vitro, celastrol treatment markedly inhibited cisplatin-induced renal tubular cell apoptosis, suppressed NF-κB activation, and improved mitochondrial function evidenced by the restored mtDNA copy number, mitochondrial membrane potential, and OXPHOS activity in cisplatin-treated renal tubular epithelial cells. Interpretation: This work suggested that celastrol could protect against cisplatin-induced acute kidney injury possibly through suppressing NF-κB and improving mitochondrial function. Fund: The National Natural Science Foundation of China, National Key Research and Development Program, and Natural Science Foundation of Jiangsu Province. Keywords: Celastrol, AKI, Cisplatin, NF-κB, Mitochondrial Dysfunction

Abstract Background/aims ErbB3 is an oncogene which has proliferation and metastasis promotion effects by several signaling pathways. However, the individual expression difference regulated by miRNA was almost still unknown. We focused on the miRNAs associated SNPs in the 3′-UTR of ErbB3 to investigate the further relationship of the SNPs with miRNAs among Chinese gastric cancer (GC) patients. Methods We performed case–control study including 851 GC patients and 799 cancer-free controls. Genotyping, real-time PCR assay, cell transfection, the dual luciferase reporter assay, western-blot, cell proliferation and trans-well based cell invasion assay were used to investigate the effects of the SNP on ErbB3 expression. Moreover, a 5-years-overall survival and relapse free survival were investigated between different genotypes. Results We found that patients suffering from Helicobacter pylori (Hp.) infection indicated to be the susceptible population by comparing with controls. Besides, SNP rs3202538 (G/T) in ErbB3 3′-UTR was involved in the occurrence of GC by acting as tumor risk factors. SNP rs3202538 (G/T) could be regulated by both miR-204 and miR-211 which caused an upregulation of ErbB3 in patients. Furthermore, the carriers of T genotype was related to the significantly high expression of ErbB3, and to big tumor size, poor differentiation as well as the high probability of metastasis. Both miR-211 and miR-204 can significantly decrease cell proliferation, metastasis as well as downstream AKT activation through G but not T allele of ErbB3 3′UTR. Moreover, the SNP of G/T was associated with shorter survival of post-surgery GC patients with 5 years of follow up study. Conclusion In conclusion, our findings have shown that the SNP rs3202538 (G/T) in ErbB3 3′-UTR acted as promotion factors in the GC development through disrupting the regulatory role of miR-204 and miR-211 in ErbB3 expression.

Abstract The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively. Patients with elevated ANLN expression level was correlated with poorer cancer-specific (median, 22.4 vs. 37.3 months, p = 0.001), progression-free (median, 19.7 vs. 27.9 months, p = 0.001) and recurrence-free survival (median, 17.1 vs. 25.2 months, p = 0.011) compared with low ANLN expression. Public datasets TCGA and NCBI-GEO were analyzed for external validation. Knockdown of ANLN in J82 and 5637 cells using small interfering RNA significantly inhibited cell proliferation, migration, and invasion ability. Moreover, knockdown of ANLN resulted in G2/M phase arrest and decreased expression of cyclin B1 and D1. Microarray analysis suggested that ANLN played a major role in cell migration and was closely associated with several cancer-related signaling pathways. In conclusion, ANLN was identified as a promising prognostic biomarker which could be used to stratify different risks of BLCA.

Acetaminophen (APAP) overdose causes acute liver injury and leads to fatal liver damage. However, the therapies are quite limited. Shikonin is a natural product with antioxidant and anti-inflammatory activities. In the present study, the hepatoprotective effects and the underlying mechanisms of shikonin in APAP-induced hepatotoxicity in vivo and in vitro were investigated. APAP-induced acute liver injury and shikonin pretreatment models were established in vivo and in vitro, as evidenced by serum hepatic enzymes, histological changes, oxidative stress indicators and proinflammatory cytokines. The results revealed that shikonin pretreatment prevented the elevation of serum alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) levels and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, shikonin restored superoxide dismutase (SOD) expression and glutathione (GSH) content in line with the blockade of oxidative stress. The changes in gene expression involved in oxidative stress including methionine sulfoxide reductase (such as MsrA and MsrB1), heme oxygenase-1 (HO-1), SOD2 and cytochrome P450 2E1 (CYP2E1), were markedly reversed after shikonin therapy. Furthermore, shikonin markedly attenuated the APAP-induced production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) and suppressed the expression of genes related to inflammation. In AML-12 cells, shikonin pretreatment decreased APAP-induced cytotoxicity as measured by CCK-8 assay and LDH release. The changes in gene expression involved in oxidative stress and the inflammatory response were consistent with those in mouse livers. This study indicated that shikonin attenuated APAP-induced acute liver injury via inhibiting oxidative stress and inflammatory responses in vivo and in vitro. These findings offer new insights into the potential therapy for APAP hepatotoxicity.

PURPOSE: To explore the morbidity, mortality and oncological results of laparoscopic radical cystectomy (LRC) in the elderly patients over 75-year-old in contrast with open radical cystectomy (ORC). MATERIALS AND METHODS: We analyzed 46 radical cystectomies from January 2009 to December 2013 in patients over 75-year-old in our institute, 21 patients in the LRC group and 25 in the ORC group. Demographic parameters, operative variables and perioperative outcome were retrospectively collected and analyzed between the two groups. Perioperative morbidity and mortality were categorized as early (within 90 days after surgery) or late (more than 90 days) according to the time of occurrence. RESULTS: Patients in both groups had comparable preoperative characteristics. A significant longer operative time (418 vs. 337 min, p = 0.018) and less estimated blood loss (400 vs. 500 ml p = 0.038) were observed in LRC group compared with ORC group. Infection and ileus were the most common early complications after surgery. Patients underwent ORC suffered from significantly more postoperative ileus (28.0% vs. 4.8%, P = 0.038) and infection (40% vs. 9.5%, P = 0.019) than LRC group within 90 days after surgery. The mortality rate was 4.7% (1/21) and 4% (1/25) for LRC group and ORC group respectively. At a median follow-up of 21 months (range 2-61 months), the Kaplan-Meier survival curves and log-rank analysis demonstrate that there were no significant differences between the LRC and ORC groups in the 3-year overall, cancer-specific, or recurrence-free survival rates. CONCLUSIONS: It is suggested that LRC should be recommended as the primary intervention to treat muscle invasive or high risk non-muscle invasive bladder cancer in elderly patients with a relative long life expectancy.

Patterns of biomass and carbon (C) storage distribution across Chinese pine (Pinus tabulaeformis) natural secondary forests are poorly documented. The objectives of this study were to examine the biomass and C pools of the major ecosystem components in a replicated age sequence of P. tabulaeformis secondary forest stands in Northern China. Within each stand, biomass of above- and belowground tree, understory (shrub and herb), and forest floor were determined from plot-level investigation and destructive sampling. Allometric equations using the diameter at breast height (DBH) were developed to quantify plant biomass. C stocks in the tree and understory biomass, forest floor, and mineral soil (0-100 cm) were estimated by analyzing the C concentration of each component. The results showed that the tree biomass of P. tabulaeformis stands was ranged from 123.8 Mg·ha-1 for the young stand to 344.8 Mg·ha-1 for the mature stand. The understory biomass ranged from 1.8 Mg·ha-1 in the middle-aged stand to 3.5 Mg·ha-1 in the young stand. Forest floor biomass increased steady with stand age, ranging from 14.9 to 23.0 Mg·ha-1. The highest mean C concentration across the chronosequence was found in tree branch while the lowest mean C concentration was found in forest floor. The observed C stock of the aboveground tree, shrub, forest floor, and mineral soil increased with increasing stand age, whereas the herb C stock showed a decreasing trend with a sigmoid pattern. The C stock of forest ecosystem in young, middle-aged, immature, and mature stands were 178.1, 236.3, 297.7, and 359.8 Mg C ha-1, respectively, greater than those under similar aged P. tabulaeformis forests in China. These results are likely to be integrated into further forest management plans and generalized in other contexts to evaluate C stocks at the regional scale.

The HIV-1 envelope glycoprotein (Env) gp41 plays a crucial role in the viral fusion process. The peptides derived from the C-terminal heptad repeat (CHR) of gp41 are potent HIV fusion inhibitors. However, the activity of these anti-HIV-1 peptides in vivo may be attenuated by their induction of anti-gp41 antibodies. Thus, it is essential to identify antiviral peptides or proteins with low, or no, immunogenicity to humans. Here, we found that the C-terminal fragment (aa 462-521) of the human POB1 (the partner of RalBP1), designated C60, is an HIV-1 fusion inhibitor. It bound to N36, the peptide derived from the N-terminal heptad repeat (NHR) of gp41, and to the six-helix bundle (6-HB) formed by N36 and C34, a CHR-peptide, but it did not bind to C34. Unlike the CHR-peptides, C60 did not block gp41 6-HB formation. Rather, results suggest that C60 inhibits HIV-1 fusion by binding to the 6-HB, in particular, the residues in the gp41 NHR domain that are exposed on the surface of 6-HB. Since 6-HB plays a crucial role in the late stage of fusion between the viral envelope and endosomal membrane during the endocytic process of HIV-1, C60 may serve as a host restriction factor to suppress HIV-1 entry into CD4+ T lymphocytes. Taken together, it can be concluded from these results that C60 can be used as a lead for the development of anti-HIV-1 therapeutics or microbicides for the treatment and prevention of HIV-1 infection, as well as a molecular probe to study the fusogenic mechanism of HIV-1.