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Influenza A virus (IAV) can infect respiratory epithelial cells where it replicates, triggers cellular innate immune responses, and even induces cell apoptosis. Ubiquitin-specific peptidase 18 (USP18) was reported to be associated with IAV replication and immune response homeostasis. Therefore, this study aimed to investigate the role of USP18 in IAV-infected lung epithelial cells. The cell viability was determined by the CCK-8 method. Viral titers were quantified by standard plaque assay. Innate immune response-associated cytokines were detected by RT-qPCR and ELISA and cell apoptosis was assessed by flow cytometry. The results showed that overexpression of USP18 promoted viral replication, innate immune factor secretion and apoptosis in IAV-infected A549 cells. Mechanistically, USP18 reduced cGAS degradation by decreasing its K48-linked ubiquitination to promote IAV-induced cGAS-STING pathway activation. In conclusion, USP18 is a pathological mediator of IAV in lung epithelial cells. [Display omitted] • IAV promote their own replication by increasing USP18 levels. • USP18 mediates innate immune responses in IAV-infected lung epithelial cells. • USP18 mediates apoptosis in IAV-infected lung epithelial cells. • USP18 reduces cGAS degradation by decreasing its ubiquitination to promote cGAS-STING pathway activation. [ABSTRACT FROM AUTHOR]

Nitrate pollution in surface water and ground water has drawn wide attention, which has brought challenges to human health and natural ecology. Electroreduction of nitrate to NH 3 in waste water was a way to turn waste into wealth, which has attracted interest of many researchers. Using Nickel foam as substrate, we prepared Pd/In bimetallic electrode (NF–Pd/In) according to a two-step electrodeposition method. There are many irregularly shaped particles in the size range of 10 nm–100 nm accumulated on the surface of prepared NF–Pd/In electrode, which could supply high specific area and more active sites for nitrate electroreduction. FESEM-EDS, XRD and XPS analysis confirmed the uniform distribution of Pd and In on the surface of prepared NF–Pd/In electrode, with a mass ratio of 4.5/1. Above 96% of 100 mg/L NO 3 −-N was removed and 95% of NH 3 selectivity was reached after 5 h of reaction under −1.6 V vs. Ag/AgCl sat. KCl when using 0.05 mol/L of Na 2 SO 4 as electrolyte. High concentration of NaCl (0.05 mol/L) in the test solution dramatically decreased the NH 3 selectivity because the produced NH 3 could be further oxidized to N 2 by the formed HClO from Cl−. EIS tests indicated that the prepared NF–Pd/In electrode showed much lower electrode resistance than NF due to the adsorptive property and electrocatalytic ability for nitrate removal. Density functional theory (DFT) calculations indicated that the presence of In could promote the conversion of NO 3 − to *NO 3 during the process of nitrate electroreduction to NH 3. Circulating tests demonstrated the stability of prepared NF–Pd/In electrode. Graphic abstract. [Display omitted] • Irregularly shaped particles of 10 nm–100 nm on NF–Pd/In surface. • High nitrate removal efficiency (96%) and high NH3 selectivity (95%). • In could promote the conversion of NO3- to *NO3. [ABSTRACT FROM AUTHOR]

A disintegrin and metalloproteinases 10 (ADAM10) and ADAM17 are transmembrane metalloproteinases that cleave the membrane-anchored proteins. They act as α-secretase that cleaves amyloid precursor protein (APP), precluding the production of amyloid-β, thus protecting against the onset of Alzheimer's disease (AD). However, the degradation pathway of ADAM10 and ADAM17 remains unknown. In this study, we show that ADAM10 and ADAM17 are degraded through the lysosomal pathway. The lysosomal cysteine protease, AEP, plays an important role in the degradation of ADAM10/17. AEP directly cleaves ADAM10/17. Knockout of AEP increases the content of ADAM10/17 in the brain. Given the protective role of ADAM10 and ADAM17 against AD, AEP-mediated degradation of ADAM10/17 may be involved in the pathogenesis of AD. • ADAM10 and ADAM17 were degraded by the lysosome pathway. • The lysosome enzyme, AEP, degraded ADAM10 and ADAM17 in vitro and in vivo. • Knockout of AEP elevated the content of ADAM10 and ADAM17. [ABSTRACT FROM AUTHOR]

Abstract Water purification provides a feasible way to relieve the pressure of water shortage and water pollution which we are facing and adsorption is one of the most effective ways to turn polluted water into clean water. Here, we prepared graphene-tannic acid hydrogel using graphene oxide and tannic acid, a natural green reducer and adsorbent, through one-step hydrothermal method. The composition, structure, and morphology of the compounds were systematically examined. The adsorption of dyes was mainly influenced by the morphology and chemical properties of gel. The addition of tannic acid, a molecule rich in oxygen containing functional groups, changed the surface chemistry of graphene sheets and microstructures of gels, which was beneficial for contaminate adsorption. Compared with reduced graphene oxide hydrogel, the graphene-tannic acid hydrogel showed an outstanding adsorption capacity for organic dye methylene blue, more than 500 mg/g at pH 10 and the maximum adsorption capacity was up to 714 mg/g. After adsorption, ethanol and inorganic acid solution can be used as desorption agent and there was no significant adsorption capacity loss after 5 cycles. Graphical abstract fx1 Highlights • Low-cost and environmental friendly tannic acid was used. • Tannic acid-graphene hydrogel was prepared by a facile one-step hydrothermal reaction. • Adsorption capacity of the composite gels increased significantly. [ABSTRACT FROM AUTHOR]

Abstract Long noncoding RNA (OGFRP1) has been reported to be involved in the progression of non-small cell lung cancer (NSCLC). However, the expression pattern, functions and molecular mechanisms of OGFRP1 in NSCLC remains unclear. In the present study, we found that OGFRP1 expression was significantly up-regulated in both NSCLC tissues and cell lines, and the upregulation of OGFRP1 expression is a powerful predictor of advanced clinical stage, lymph nodes metastasis and poor prognosis for NSCLC patients. Loss-of-function assay indicated that knockdown of OGFRP1 inhibited proliferation, migration and invasion, and induced apoptosis in vitro. Mechanistically, OGFRP1 could directly bind to miR-124-3p and effectively act as a competing endogenous RNA (ceRNA) for miR-124-3p to promote the expression of the target gene LYPD3. Taken together, OGFRP1 contributed to progression of NSCLC at least partly through upregulating LYPD3 expression by sponging miR-124-3p, indicating that OGFRP1 may be a novel prognostic biomarker and therapeutic target in NSCLC. Highlights • The expression levels of lncRNA OGFRP1 was up-regulated in NSCLC tissues and cell lines. • Overexpression of lncRNA OGFRP1 was associated with advanced clinical features and poor prognosis in NSCLC patients. • LncRNA OGFRP1 promoted NSCLC cells proliferation, migration and invasion by regulation of miR-124-3p-LYPD3 pathway. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer. Melanoma has an extremely poor prognosis because of its high potential for vascular invasion, metastasis and recurrence. The mechanism of melanoma metastasis is not well understood. ATP-binding cassette sub-family B member 5 (ABCB5) plays a key role in melanoma growth. However, it is uncertain what function ABCB5 may exert in melanoma metastasis. In this report, we for the first time demonstrate ABCB5 as a crucial factor that promotes melanoma metastasis. ABCB5 positive (ABCB5 + ) malignant melanoma initiating cells (MMICs) display a higher metastatic potential compared with ABCB5 negative (ABCB5 - ) melanoma subpopulation. Knockdown of ABCB5 expression reduces melanoma cell migration and invasion in vitro and melanoma pulmonary metastasis in tumor xenograft mice. ABCB5 and NF-κB p65 expression levels are positively correlated in both melanoma tissues and cell lines. Consequently, ABCB5 activates the NF-κB pathway by inhibiting p65 ubiquitination to enhance p65 protein stability. Our finding highlights ABCB5 as a novel pro -metastasis factor and provides a potential therapeutic target for melanoma. [ABSTRACT FROM AUTHOR]

Tributyltin chloride (TBTCL) is a widely used fungicide and heat stabilizer in compositions of PVC. TBTCL has been detected in human bodies and potentially causes harmful effects on humans' thyroid, cardiovascular and other organs. As one of the first examples of endocrine disruptors, the toxicity effects of TBTCL on the male reproduction system have aroused concerns. However, the potential cellular mechanisms are not fully explored. In the current study, by using Sertoli cells, a critical regulator of spermatogenesis as a cell model, we showed that with 200 nM exposure for 24 h, TBTCL causes apoptosis and cell cycle arrest. RNA sequencing analyses suggested that TBTCL probably activates endoplasmic reticulum (ER) stress, and disrupts autophagy. Biochemical analysis showed that TBTCL indeed induces ER stress and the dysregulation of autophagy. Interestingly, activation of ER stress and inhibition of autophagy is responsible for TBTCL-induced apoptosis and cell cycle arrest. Our results thus uncovered a novel insight into the cellular mechanisms for TBTCL-induced toxicology in Sertoli cells. [Display omitted] • Tributyltin chloride causes apoptosis and cell cycle arrest in mouse Sertoli cells. • Tributyltin chloride induces endoplasmic reticulum (ER) stress and autophagy flux blockade. • Tributyltin chloride induced apoptosis and cell cycle arrest via autophagy process. • Disordered autophagy process is responsible for tributyltin chloride-induced apoptosis and cell cycle arrest. • We provided a new understanding in the mechanisms of TBTCL-induced testis toxicity. [ABSTRACT FROM AUTHOR]

Gradient Al-doped ZnO (AZO) thin films were deposited at 150 °C by atomic layer deposition (ALD) with different Al concentration gradient, and their photoelectric and passivation properties were investigated. With increasing Al concentration gradient from 0.09 to 1.21%/nm, Hall-effect showed that the resistivity of gradient AZO thin films deteriorates. The minimal resistivity (2.81 × 10 −3 Ω cm), the maximum mobility (9.03 cm 2 /Vs) and the maximum carrier concentration (2.46 × 10 20 cm −3 ) were obtained at 0.09%/nm Al concentration gradient. The average transmittance of all the gradient AZO films can be more than 85% in the visible region. In addition, gradient AZO thin films demonstrated excellent passivation properties. The maximum minority carrier lifetime (120.6 μs) and the minimal surface recombination velocity (≤208.3 cm/s) were obtained at 0.71%/nm Al concentration gradient. [ABSTRACT FROM AUTHOR]

With an increasing quantity of plastic waste being discharged into the oceans, marine microplastic (MP) pollution has received widespread attention. However, the global occurrence characteristics, environmental risks, driving factors, and source-sink relationships remain unclear. In this study, we conducted a meta-analysis based on 165 articles about marine MP pollution. It was found that the global marine MP abundance displayed a significant spatial heterogeneity, and the distribution pattern was influenced by offshore distance, population density, and economic development. The morphological characteristics of MPs showed a significant difference between seawater and marine sediment, and small-size MPs (<1 mm) accounted for the majority of all MPs in the marine environment. The environmental risk assessment revealed that most of the marine MP pollution still remains at low concentrations in the global context, with the Polyurethane (PU), Polyacrylonitrile (PAN), and Polyvinyl chloride (PVC) types of MPs showing high environmental-risk contributions. In addition, land-based waste and marine operations, which were considered to be the dominant sources of marine MPs, primarily aggregated at nearshore submarine areas, in the water column, and in the deep-sea bottom environment. This study suggested that the combination of a meta-analysis and Monte Carlo simulation can provide much valuable information regarding the global occurrence characteristics and environmental risks of marine MPs. [Display omitted] • There is a significant spatial heterogeneity for global distribution of marine MPs. • The majority of the oceans still at a low level of MPs pollution. • Small-size MPs (<1 mm) are mainly discovered in the marine environment. • MPs of PU, PAN, and PVC contribute highly to the risk assessment. • Source-sink of MPs in water column and sediment are analyzed. [ABSTRACT FROM AUTHOR]

Ferric citrate (FC) has been used as an iron fortifier and nutritional supplement, which is reported to induce colitis in rats, however the underlying mechanism remains to be elucidated. We performed a 16-week study of FC in male healthy C57BL/6 mice (nine-month-old) with oral administration of Ctr (0.9 % NaCl), 1.25 % FC (71 mg/kg/bw), 2.5 % FC (143 mg/kg/bw) and 5 % FC (286 mg/kg/bw). FC-exposure resulted in colon iron accumulation, histological alteration and reduce antioxidant enzyme activities, such as glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), together with enhanced lipid peroxidation level, including malondialdehyde (MDA) level and 4-Hydroxynonenal (4-HNE) protein expression. Exposure to FC was associated with upregulated levels of the interleukin (IL)− 6, IL-1β, IL-18, IL-8 and tumor necrosis factor α (TNF-α), while down-regulated levels of IL-4 and IL-10. Exposure to FC was positively associated with the mRNA and protein expressions of cysteine-aspartic proteases (Caspase)− 9, Caspase-3, Bcl-2-associated X protein (Bax), while negatively associated with B-cell lymphoma 2 (Bcl2) in mitochondrial apoptosis signaling pathway. FC-exposure changed the diversity and composition of gut microbes. Additionally, the serum lipopolysaccharide (LPS) contents increased in FC-exposed groups when compared with the control group, while the expression of colonic tight junction proteins (TJPs), such as Claudin-1 and Occludin were decreased. These findings indicate that the colonic mucosal injury induced by FC-exposure are associated with oxidative stress generation, inflammation response and cell apoptosis, as well as the changes in gut microbes diversity and composition. • FC-exposure induces iron accumulation in the colon and causes colon histopathological lesions. • FC-exposure induces oxidative stress in the colon by weakening the activities of antioxidant system and enhancing the lipid peroxidation levels. • FC-exposure induces inflammation activation by increasing the pro-inflammatory cytokines while decreasing the anti-inflammatory cytokines. • FC-exposure promotes the apoptosis via activating pro-apoptosis related gene, and inhibiting the anti-apoptosis related gene. • FC-exposure changes the diversity and composition of gut microbiome. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, and persistent inflammation in circulatory and renal tissues is an important pathophysiological basis for DN. The essence of the microinflammatory state is the innate immune response, which is central to the occurrence and development of DN. Members of the inflammasome family, including both “receptors” and “regulators”, are key to the inflammatory immune response. Nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) and other inflammasome components are able to detect endogenous danger signals, resulting in activation of caspase-1 as well as interleukin (IL)-1β, IL-18 and other cytokines; these events stimulate the inflammatory cascade reaction, which is crucial for DN. Hyperglycaemia, hyperlipidaemia and hyperuricaemia can activate the NLRP3 inflammasome, which then mediates the occurrence and development of DN through the K + channel model, the lysosomal damage model and the active oxygen cluster model. In this review, we survey the involvement of the NLRP3 inflammasome in various signalling pathways and highlight different aspects of their influence on DN. We also explore the important effects of the NLRP3 inflammasome on kidney function and structural changes that occur during DN development and progression. It is becoming more evident that NLRP3 inflammasome targeting has therapeutic potential for the treatment of DN. [ABSTRACT FROM AUTHOR]

Background Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage. Methods Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay. Results Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A. Conclusion Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage. [ABSTRACT FROM AUTHOR]

The antimicrobial and bacterial anti-adhesive properties of polysulfone (PSU) membranes modified with silver nanoparticles (AgNPs) and polyelectrolyte multilayers (PEMs) composed of poly(allylamine hydrochloride) and poly(acrylic acid) were investigated. The membranes’ antimicrobial properties were evaluated using a colony forming unit (CFU) enumeration method, while the anti-adhesive properties of the membranes were examined using a direct microscopy observation membrane filtration system. The AgNP mass loading required for the inhibition of bacterial growth on the AgNP/PEM-modified membranes was significantly lower than the AgNP loadings reported in other studies for membranes with the nanoparticles dispersed within the membrane matrix. The immobilization of AgNPs on the membrane surface maximized the opportunities for bacteria-nanoparticle contact, which allowed for effective bacteria inactivation. Furthermore, in comparison to unmodified PSU membranes, the bacterial deposition kinetics on all the modified membranes were reduced by ca. 50% and the bacterial removal efficiencies were significantly increased from close to 0% to as high as over 90%. Three-cycle filtration and rinsing experiments were also performed to evaluate the effectiveness of the surface modification over an extended time period of use. [ABSTRACT FROM AUTHOR]

Thioredoxins (Trx) can detoxify sulfide or act as electron donors in the reduction of disulfide and dithiol to protect yeast cells from ROS damage but remain poorly explored in filamentous fungi. Here we show more Trx homologs in Beauveria bassiana than in many other fungi and examine their functions. This filamentous entomopathogen has six Trx homologs, including four (Txr1–4) evidently localized in cytoplasm, one (Trx5) in nuclear membrane and another (Trx6) in mitochondria. Deletion of each trx had no effect on radial growth on rich or minimal medium but resulted in remarkable transcriptional up-regulation of other partners for compensation. Compared with wild-type, only Δ trx2 was significantly more sensitive to menadione whereas none of six Δ trx mutants was responsive to other oxidants including H 2 O 2 . Intriguingly, Δ trx2 showed uniquely a significant increase in total Trx activity in normal cultures but a remarkable decrease in total SOD activity in the cultures grown normally or co-cultivated with menadione. The ratio of reduced/oxidized glutathione accumulated in hyphal cells stressed with menadione decreased to only 0.4 in Δ trx2 from ∼1.0 observed in wild-type and other mutants. The six Δ trx mutants displayed one or more phenotypic changes associated with the fungal biocontrol potential, including conidiation, and germination, thermotolerance, UV-B resistance and virulence of their conidia. All the changes were restored by trx complementation. Taken together, the greater Trx diversity evolutionarily gained by B . bassiana could help it to maintain cellular redox homeostasis and infect insect hosts in diverse habitats. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate the association between fruit and vegetable consumption and the risk of epithelial ovarian cancer in southern Chinese women. Methods: A case–control study was undertaken in Guangzhou, Guangdong Province, between 2006 and 2008. Participants were 500 incident ovarian cancer patients and 500 hospital-based controls. Information on habitual fruit and vegetable consumption was obtained by face-to-face interview using a validated and reliable food frequency questionnaire. Unconditional logistic regression analyses were performed to assess the association between fruit and vegetable intakes and the ovarian cancer risk. Results: The mean fruit and vegetable daily intakes of ovarian cancer patients (324.2g (SD 161.9) and 582.7g (SD 250.2)) were significantly lower (p<0.001) than those of controls (477.3g (SD 362.1) and 983.3g (SD 739.9)). The adjusted odds ratios were 0.30 (95% confidence interval (CI) 0.21 to 0.44) and 0.07 (95% CI 0.04 to 0.12) for more than 490g of fruits and 970g of vegetables per day, relative to at most 320g and 690g per day, respectively. With the exception of lycopene, substantial risk reductions were evident for a variety of nutrients derived from fruits and vegetables. Conclusion: Consumption of fruits and vegetables was inversely associated with the incidence of epithelial ovarian cancer in southern Chinese women. [Copyright &y& Elsevier]

Abstract: As interactive multimedia communications are developing rapidly on the Internet, they present stringent challenges on end-to-end (E2E) performance. On the other hand, however, the Internet’s architecture (IPv4) remains almost the same as it was originally designed for only data transmission purpose, and has experienced big hurdle to actualize QoS universally. This paper designs a cooperatively overlay routing service (CORS) aiming to overcome the performance limit inherent in the Internet’s IP-layer routing service. The key idea of CORS is to efficiently compose a number of eligible application-layer paths with suitable relays in the overlay network. Besides the direct IP path, CORS can transfer data simultaneously through one or more application-layer paths to adaptively satisfy the data’s application-specific requirements on E2E performance. Simulation results indicate the proposed schemes are scalable and effective. Practical experiments based on a prototype implemented on PlanetLab show that CORS is feasible to enhance the transmission reliability and the quality of multimedia communications. [Copyright &y& Elsevier]

Abstract: A symbiotic bacterium of the entomopathogenic nematode, Steinernema abbasi, isolated from Taiwan, determined to be a species of Xenorhabdus based on its physiological and biochemical characteristics has been determined to be similar to Xenorhabdus indica of S. abbasi Oman isolate as based on sequence analyses of 16S rDNA. [Copyright &y& Elsevier]

The growth of cells and tissues is regulated by stress. When body is injured, it manifests a large spectrum of metabolic, endocrine, and immune alterations, which is named stress reaction. Among them, the production of growth factors may play a critical role. For osteoblasts and myoblasts, IGF-I has been shown to be involved in the process of cells in response to overloads. There are two splicing forms, one is IGF-Ea, the other is the IGF-IEb in the rodents and corresponds to IGF-IEc in humans. The latter is markedly up-regulated in response to overloads. Therefore, it has been named mechanogrowth factor. The link between the mechanical stimulus and the gene expression represents a new and important area in cell science. Understanding the process of splicing in IGF-I helps one to investigate the mechanotransduction of cells in response to mechanical stimulation at molecular level. [Copyright &y& Elsevier]

Citric acid (CA) can regulate the balance of anions and cations in plants, and improve their resistance to heavy metals. It is not clear if foliar application with CA has any effect on migration of Cd and Mn in rice plant. In this work, a low-Cd-accumulating indica rice line (P7) and a high-Cd-accumulating line (HZ) were used to investigate the influence of CA on the transport of Cd and Mn as well as amino acid metabolism in grains. Content of Cd in grains and other organs increased with the increase of Cd content (0.1–2.4 mg kg−1) in soil, while decreased with the foliar application with CA. With the increase of Cd content in rice grains, the content of most amino acids in HZ, P7, HZ + CA and P7 + CA showed an obvious decline trend. Foliar application with CA efficiently raised the Mn:Cd ratio in grains and nodes of both HZ and P7. Meanwhile, the expression levels of OsNramp2, 3 and 5 in panicles were efficiently enhanced by CA application when plants grew in soil with Cd content of 0.6–2.4 mg kg−1. The increasing effect of CA on the content of 4 amino acids (i.e., Glu, Phe, Thr and Ala) in grains was related to varieties and Cd pollution. These results indicate that foliar application with CA can regulate the transport of Cd and Mn in the opposite directions in tissues and inhibit Cd accumulation in grains by enhancing expression of OsNRAMP 2, 3 or 5 and triggering the defense response of some amino acids in Cd-contaminated environment. ga1 • Citric acid regulates migration of Cd and Mn in rice in the opposite directions and increase Mn:Cd ratio in grains and nodes. • The expression of Nramp family genes in panicles is inhibited by Cd stress and enhanced by exogenous citric acid. • Citric acid promotes the synthesis of Glu, Phe, His, Ser and Thr in rice for alleviating Cd toxicity. [ABSTRACT FROM AUTHOR]

• Bangga (1055-211BC) represents the first systemic archaeobotanical study in central Tibet. • This article dates the transition to a barley-dominant economy in high-elevation Tibet. • Research suggests that both ecological and social factors helped accelerate this crop transition. Historically, agricultural and culinary traditions on the Tibetan Plateau have centered on a specific variety of naked frost-tolerant barley. Single-crop-dominant cultivation systems were rare in the ancient world, and we know little about how, why, and exactly when and where this unique barley-dominant economy developed. Previous research has shown that early cultivation systems in Tibet relied on a mix of barley, wheat, and millets, and that a barley-dominant economy first formed around two millennia ago. However, systematically collected data from the transition period between a mixed-cropping and a barley-dominant system have been lacking. We present new archaeobotanical data from the Bangga site (ca. 1055-211BC) in central Tibet, and compare it with a growing corpus of data from other archaeological sites at high elevations across the plateau. We argue that a specialized barley-dominant farming system started to develop, due to a combination of ecological and social factors, at least a millennia earlier than previously recognized in central Tibet and this was eventually adopted across a large geographic area in high-altitude regions (3500 masl) of Tibet. [ABSTRACT FROM AUTHOR]

Acellular nerve allografts (ANAs) have been successfully applied to bridge facial nerve defects, and transplantation of stem cells may enhance the regenerative results. Up to now, application of hair follicle epidermal neural crest stem cell-derived Schwann cell-like cells (EPI–NCSC–SCLCs) combined with ANAs for bridging facial nerve defects has not been reported. The effect of ANAs laden with green fluorescent protein (GFP)-labeled EPI–NCSC–SCLCs (ANA + cells) on bridging rat facial nerve trunk defects (5-mm-long) was detected by functional and morphological examination, as compared with autografts and ANAs, respectively. (1) EPI–NCSC–SCLCs had good compatibility with ANAs in vitro. (2) In the ANA + cells group, the GFP signals were observed by in vivo imaging system for small animals within 8 weeks, and GFP-labeled EPI–NCSC–SCLCs were detected in the tissue slices at 16 weeks postoperatively. (3) The facial symmetry at rest after surgery in the ANA + cells group was better than that in the ANA group (p < 0.05), and similar to that in the autograft group (p > 0.05). The initial recovery time of vibrissal and eyelid movement in the ANA group was 2 weeks later than that in the other two groups. (4) The myelinated fibers, myelin sheath thickness and diameter of the axons of the buccal branches in the ANA group were significantly worse than those in the other two groups (P < 0.05), and the results in the ANA + cells group were similar to those in the autograft group (p > 0.05). EPI–NCSC–SCLCs could promote functional and morphological recovery of rat facial nerve defects, and GFP labeling could track the transplanted EPI–NCSC–SCLCs in vivo for a certain period of time. These may provide a novel choice for clinical treatment of peripheral nerve defects. [ABSTRACT FROM AUTHOR]

High nitrate concentration in water can lead to eutrophication and the disruption of healthy aquatic ecosystems. Additionally, in the human digestive system, it has the potential to be reduced to nitrite, which can be damaging to people's physical health. Catalytic hydrogenation of nitrate is one of the strategies for removing nitrate from water. Using A520E resin as support, we prepared Pd/Cu nano-catalyst (Pd/Cu@A520E) according to a liquid phase reduction method. A520E could improve the transfer process of nitrate in the solution to the activity sites of Pd/Cu nanoparticles, thus increase the reaction rate of nitrate reduction. Pd/Cu bimetallic nano-particles were evenly distributed on/in the resin with a size range from 2 nm to 10 nm. The External Circulating System equipped with Venturi tube (ECSV) was designed to improve the utilization efficiency of H 2 in both batch tests and long-term continuous-flow tests. Nearly 100% of nitrate removal efficiency and above 90% of N 2 selectivity were achieved in both batch tests and continuous-flow tests. Coexisting Cl− and SO 4 2− at 300 mg/L showed little impact on the property of Pd/Cu@A520E. Pd/Cu@A520E also showed high nitrate removal property and stability in continuous-flow tests of more than 800 h. NO 3 − was adsorbed onto the active sites (functional groups and Pd/Cu particle sites), meanwhile H 2 was adsorbed onto the active sites of Pd/Cu@A520E to form Pd [H]. Then the adsorbed NO 3 − was reduced into N 2 (main product) or NH 4 + by Pd [H]. In addition, Pd/Cu@A520E showed high nitrate removal property from municipal waste water. [Display omitted] • Pd/Cu bimetallic catalyst was prepared on anion exchange resin (A520E). • External Circulating System equipped with Venturi tube (ECSV) was designed. • High nitrate removal efficiency (100%) and High N 2 selectivity (90%). • Excellent stability in continuous flow tests of 823 h. [ABSTRACT FROM AUTHOR]

• Caregiving for adults with epilepsy is strenuous due to the disease's complexity. • Coping strategies are related to the stress regulation of the caregivers. • The sense of obligation was rooted in love and devotion to their family. • Despite the Asian collectivist culture, caregivers were reluctant to seek help. Caregivers of adults with epilepsy (AWE) play an important role in the healthcare pathway of AWE and are described as the "co-client." Being caregivers can be stressful and the negative impacts might accumulate over time, affecting their quality of life and well-being. This qualitative study aimed to explore the lived experience of caregivers of AWE in Malaysian families and understand their caregiving challenges. Individual semi-structured interviews were held with 12 primary caregivers of AWE. Interpretative Phenomenological Approach (IPA) was used. The interview transcripts were analyzed using NVivo12 software. Primary caregivers of AWE were parents or siblings, with ages ranging from 56 to 80 years old and years of caregiving from 24 to 40 years. Most AWE (58%) were intellectually disabled and fully dependent on ADL needs. Two categories of themes emerged, including four themes on caregiver burden, i.e., physical, emotional, and social burdens, and challenges in future planning of care, and two themes on coping strategies (problem- or emotional-focused). In future planning of care, most caregivers especially parents carried a burden of responsibility and were reluctant to depend on others or institutional services. The caregiving burden among caregivers for adult AWE was not confined to current burdens only but also challenges in future planning. A better understanding of the caregiving burden for AWE and coping strategies is needed to provide tailored psychoeducation or psychosocial intervention to support this population. [ABSTRACT FROM AUTHOR]

Homeodomain (HD)-containing proteins are typically recognized as transcription factors. Engrailed 2 (EN2) is an HD-containing protein that is highly expressed in various types of cancers, however, the mechanism underlying the biological function of EN2 is not fully understood. Here, we report a transcription-independent function of EN2 in addition to its role as a transcription factor. EN2 expression leads to the activation of multiple signaling pathways mediated by phosphorylation cascades. A phosphoproteomic analysis revealed that the phosphorylation status of numerous protein sites was altered after EN2 is expressed. Notably, EN2 was shown to interact with a myriad of proteins implicated in phosphorylation signaling cascades, as determined by immunoprecipitation–mass spectrometry (IP–MS). We validated the interaction between EN2 and B55α, the regulatory subunit of the PP2A-B55α complex, and confirmed that the phosphatase activity of the complex was suppressed by EN2 binding. To target EN2-induced malignancy, two kinds of small molecules were utilized to inhibit the EN2-activated NF-κB and AKT signaling pathways. A clear synergistic effect was observed when the activation of the two pathways was simultaneously blocked. Collectively, the data show that EN2 functions in a transcription-independent manner in addition to its role as a transcription factor. This finding may have therapeutic implications in treating esophageal squamous cell carcinoma (ESCC). • EN2 activates multiple oncogenic signaling pathways. • EN2 alters the expression of numerous genes related to the signaling pathways, indicating a transcription-dependent manner. • EN2 interacts with the proteins involved in the signaling pathways, suggesting a transcription-independent mechanism. • EN2 interacts with B55α and consequently inhibits its phosphatase activity. • The perturbation of the EN2-induced signaling pathways inhibits the malignant phenotype in ESCC. [ABSTRACT FROM AUTHOR]

Background Oxidative injury, inflammation, and apoptosis are involved in the progression of abdominal aortic aneurysm (AAA). Melatonin (MLT) has been reported with an effective antioxidant activity. The objective of the present study was to investigate whether MLT could suppress the development of AAA. Methods The AAA model was introduced by intraluminal perfusion of elastase in rats. All rats were divided into three groups as follows: (1) sham; (2) AAA + vehicle; and (3) AAA + MLT. Daily administration of MLT (10 mg/kg/d) or vehicle started 3 d before the perfusion and continued for 28 d after perfusion. An ultrasound system was applied to measure the dilation of the aorta. Histologic assays were performed to evaluate the structure, morphology, and apoptotic cells of the aortas; biochemical assays to determine the levels of proteins and lipid peroxide, activities of superoxide dismutase and NADPH oxidases, and cell viability; dihydroethidium fluorescence staining and flow cytometry to detect the presence of reactive oxygen species, and/or cell apoptosis; and electron microscopy to observe the ultrastructure of mitochondria. Cell lines A7R5 and RAW 264.7 were used for in vitro experiments. Results MLT treatment inhibited dilation of the aorta very likely through its antioxidant property; significantly reduced the levels of lipid peroxide, activities of NADPH oxidases, and content of reactive oxygen species; remarkably inhibited NF-κB signaling pathway and activities of matrix metalloproteinases triggered by elastase perfusion. As a result, the mitochondrion-dependent apoptosis was suppressed, cellular energy (ATP) supply was recovered, and mitochondrial morphology remained intact. Conclusions Our results demonstrate the beneficial effects of MLT on inhibition of AAA formation, suggesting that MLT could be a potential agent for prevention of the development of human AAA. [ABSTRACT FROM AUTHOR]

• The intermodal interference of microfiber was enhanced by forming the micro-arched transition region. • The RI sensitivity of the sensor was up to 12,620.0 nm/RIU in the RI range of 1.3940–1.3980, respectively. • The sensor showed a sensitivity of 0.3 nm/(mg/ml) to the concentration of bovine serum albumin solution. A novel refractive index (RI) sensor based on micro-fiber with micro-arched transition (MMAT) was proposed. The power extinction ratio of interference spectra was enhanced by the micro-arched transition. Although the waist diameter of micro-fiber was less than 6 μm, the power extinction ratio was larger than 10 dB, which was critical to the spectral dip measurement. The relationship between waist diameter of micro-fiber and RI sensitivity was systematically investigated. It turned out that higher RI sensitivity of MMAT could be obtained by decreasing the waist diameter of micro-fiber. While the waist diameter was 5.6 μm, the RI sensitivities of MMATs were up to 2739.8 nm/RIU, 4515.7 nm/RIU and 12,620.0 nm/RIU in the RI range of 1.333–1.3580, 1.3705–1.3905 and 1.3940–1.3980 respectively. The sensor was applied to detecting the concentrations of bovine serum albumin (BSA) solutions and showed the sensitivity of 0.3 nm/(mg/ml). Owing to its small volume and high sensitivity, this kind of senor can be expected to widely apply in fields of biology, chemistry and physics. [ABSTRACT FROM AUTHOR]

KDM2A is a histone demethylase, which primarily catalyzes the demethylation of H3K36me2. Abnormal expression of KDM2A is observed in many types of cancers; however, the molecular events connected to KDM2A expression remain unclear. We report that KDM2A performs an oncogenic function in esophageal squamous cell carcinoma (ESCC) and is robustly expressed in ESCC cells. ShRNA-mediated knockdown of KDM2A resulted in a significant inhibition of the malignant phenotype of ESCC cell lines, whereas ectopic expression of KDM2A showed the opposite effect. We also analyzed the function of KDM2A using a CRISPR-CAS9 depletion system and subsequent rescue experiment, which also indicated a cancerous role of KDM2A. Interestingly, analysis of the gene expression network controlled by KDM2A using RNA-seq revealed an unexpected feature: KDM2A could induce expression of a set of well-documented oncogenic genes, including IL6 and LAT2, while simultaneously suppressing another set of oncogenes, including MAT2A and HMGCS1. Targeted inhibition of the upregulated oncogene in the KDM2A-depleted cells led to a synergistic suppressive effect on the malignant phenotype of ESCC cells. Our results revealed the dual role of KDM2A in ESCC cells, which may have therapeutic implications. • Ablation of KDM2A attenuates the malignant phenotype of ESCC cell lines. • Augmented expression of KDM2A promotes the malignant phenotype of ESCC cells. • KDM2A activates one set of oncogenic genes and represses another set of cancerous genes simultaneously. • Inhibition of activated oncogenes generates a synergistic antitumor effect in KDM2A-deficient ESCC cells. • The dual role of KDM2A may be used to develop a combination treatment for ESCC. [ABSTRACT FROM AUTHOR]

Sustaining the development of rural and pastoral communities' hinges on livelihood resilience. Pastoralist household resilience relies on resource availability and decision-making abilities. Despite extensive studies on pastoralist livelihoods, a significant knowledge gap remains in understanding the nuanced adaptive capacities of diverse households, particularly amid grassland degradation. Thus, this study investigates the household-based livelihood resilience of pastoralists in China's Three-River Headwater Region, offering policy recommendations for resilient livelihoods. Using stratified random sampling, 758 pastoralist household heads underwent semi-structured interviews to collect data. Five household characteristics, encompassing age, gender, energy use, well-being perception, and multi-household grazing participation, were evaluated. Looking ot the nature of data, descriptive statistics and non-parametric tests were performed in this study to draw the valid inferences. The results revealed a positive correlation (p < 0.05) between household head age and livelihood resilience, with divergent resilience across age groups. Varied energy usage yielded distinct impacts; households employing solar or mixed energy sources exhibited heightened resilience (p < 0.05). Household well-being emerged as an invariant variable concerning resilience. Furthermore, engagement in multi-household grazing (an informal institution) significantly (p < 0.05) influenced pastoralist livelihood resilience. These insights advocate targeted support for young household heads and the adoption of clean energy. Exploring the deeper strategies and mechanisms of multi-household grazing can enhance understanding and policy integration, guiding eco-friendly progress within rustic landscapes for pastoral communities. [Display omitted] • Socio-personal practices shape pastoralists' livelihood resilience. • Solar-yak dung integration boosts pastoral community resilience. • Multi-household grazing enhances interconnectivity, cooperation, risk mitigation. [ABSTRACT FROM AUTHOR]

Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic. [Display omitted] • Gut microbiota is involved in TP-induced liver injury. • LGG supplementation could ameliorates TP hepatotoxicity. • LGG-mediated BA metabolism plays a vital role in TP hepatotoxicity. • The protective role of LGG in TP hepatotoxicity by regulating the BA-FXR Axis. [ABSTRACT FROM AUTHOR]

Patulin (PAT) in food is a menace to human health. Hence, a sensitive and precise approach to PAT detection is significant. In this research, an innovative electrochemical assay was developed for sensitively determining PAT by assembling aptamers on a carboxylation hierarchically porous carbon (HPC-COOH) modified glassy carbon electrode. Diverse analytical methods were used to describe electrode morphology, structure, chemical composition, and electrochemistry properties. The HPC-COOH, with a large surface area, played a crucial role as a unique substrate to effectively immobilize aptamers and enhance target PATs' recognition and capture ability. Simultaneously, the excellent electrical conductivity of HPC-COOH was significant for the signal amplification of sensors. Under optimized conditions, the aptasensor enabled efficient PAT detection in a broad concentration range (0.5–5.0×106 ng/L) with a low detection limit (0.25 ng/L). The designed aptasensor showed high sensitivity, selectivity, reproducibility, and stability under optimized conditions. The sensors' feasibility for practical applications was further demonstrated by analyzing apple juice and haw juice samples. • A novel patulin electrochemical aptasensor was developed using carboxylation hierarchically porous carbon. • The performance of designed sensor was significantly improved due to the unique properties of porous carbon. • The test results were agreed with standard method suggesting the practicability of sensor. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP) overdose induces acute liver injury (ALI), even acute liver failure (ALF). There is a significant unmet need to furtherly elucidate the mechanisms and find new therapeutic target. Recently, emerging evidence indicates that nicotinamide adenine dinucleotide (NAD+) plays a crucial role in APAP-induced ALI. Herein, we firstly investigated the protein expression of NAD kinase (NADK), as the rate-limiting enzyme converting NAD+ to nicotinamide adenine dinucleotide phosphate (NADP+), and found it was positively correlated with APAP-induced ALI in a dose- and time-dependent manner. Additionally, supplementation of N-acetylcysteine (NAC), known as an antidote of APAP, mitigated the ALI and downregulated the expression of NADK which was also in a dose-dependent manner. Moreover, pretreatment with methotrexate (MTX), the inhibitor of NADK, attenuated the levels of transaminases, alleviated morphological abnormalities, and improved oxidative stress triggered by APAP overdose, which was attributed to elevated hepatic NAD+ pool. Subsequently, the increased NAD+ upregulated the expression of Sirt1, SOD2 and attenuated DNA damage. Collectively, elevated expression of NADK is related to APAP-induced ALI, and inhibition of NADK alleviates the ALI through elevating liver NAD+ level and improving antioxidant capacity. • The expression of NADK was positively correlated with APAP-induced ALI. • Inhibition of NADK alleviated APAP-induced ALI. • Inhibition of NADK increased the level of NAD+ and activated Sirt1/SOD2. [ABSTRACT FROM AUTHOR]

Functionalization of mesoporous silica foam (MSF) is a feasible strategy to enhance the electrocatalytic performance of designed sensors. Herein, an organic ligand, pyrene-1-carboxaldehyde hydrazone (PCH), is used to functionalize MSF and as a modifier for carbon paste electrodes to construct a Cu2+ detection sensor. The experimental results demonstrate that the PCH functionalization can significantly enhance the sensor's sensitivity and selectivity. Under optimized conditions, the linear range of the prepared electrochemical sensor are 0.0050–1.0 μM and 1.0–10 μM, and the Cu2+ detection limit is 0.0020 μM. The developed sensor is applied to detect Cu2+ content in standard rice control samples, and the obtained results fall well within the range of marked values. Moreover, the recoveries of the standard addition method are 98.4–102.6 %, suggesting the developed sensor's good accuracy and practicability. • An organic ligand functionalized mesoporous silica foam material was prepared and used to construct Cu2+ sensor. • The highly sensitive and selective of sensor were derived from a novel organic ligand pyrene-1-carboxaldehyde hydrazone. • The accurate results were obtained in the real samples analysis demonstrated the practicability of the prepared sensor. [ABSTRACT FROM AUTHOR]

Copper (II) (Cu2+) and 3-nitropropionic acid (3-NPA) are harmful substances usually found in foods. Therefore, establishing rapid, sensitive, and accurate detection method for both of these substances is significant research work. A pyrene-based fluorescent sensor (PP) was synthesized to enable highly selective and sensitive simultaneous detection of Cu2+ and 3-NPA in food samples. Initially, PP showed weak fluorescence because of the photo–induced electron transfer process (PET). Upon the presence of Cu2+, the emission of PP at 454 nm enhanced owing to the coordination between PP and Cu2+ which hindered the PET. Additionally, under 365 nm UV irradiation, the color of the PP solution transitions from orange to bright blue, allowing for naked-eye detection. The sensor PP demonstrated high selectivity and sensitivity toward Cu2+ compared to other competitive metal ions, with the detection limit was 0.036 μM, within a linear range of 0–20 μM. The binding stoichiometry between PP and Cu2+ is determined to be 2:1 using the Job's plot method, with a binding constant (K a) of 7.2 ×103 M−1/2. Furthermore, at lower pH (in the range 2.55–5.98), the emission of PP was also enhanced due to the protonation of PP which suppresses the PET process. Given its sensitive and linear response to acidic pH, PP exhibits excellent sensing performance for detecting 3-NPA, with a low detection limit of 0.32 μM, surpassing previously reported methods in terms of detection sensitivity. • A novel signal turn-on fluorescent sensor was constructed for detecting Cu2+ and 3-NPA. • The constructed method has the characteristics of convenience, good selectivity, and high sensitivity. • The developed method was successfully used to analysis of real food samples. [ABSTRACT FROM AUTHOR]

Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO 2 -based ICPB system has been widely studied. There are many ways to improve the degradation efficiency of the ICPB process, but no crystal facet engineering method has been reported yet. In this work, a new ICPB system coated with NaF–TiO 2 exposing high energy facets was designed to degrade biorecalcitrant psychotropic drug - venlafaxine (VNF). Initially, the TiO 2 crystal surface was modified with NaF, resulting in the formation of NaF–TiO 2 with a 14.4% increase in the exposure ratio of (001). The contribution rate of ·OH was increased by 9.5%, and the contribution rate of h+ was increased by 33.2%. Next, NaF–TiO 2 was loaded onto the surface of the sponge carrier, and then the ICPB system was constructed after about 15 days of biofilm formation. After the ICPB system was acclimated with VNF, the removal rate of COD decreased significantly (the lowest was 62.7%), but that of ammonia nitrogen remained at 50.5 ± 6.0% and the extracellular polymeric substance (EPS) secretion increased by 84.1 mg/g VSS. According to the high throughput results, at the phylum level, Proteobacteria and Chloroflexi together maintain the nitrogen removal capability and structural stability of the ICPB system. The relative abundance of Bacteroidota was significantly increased by 14.2%, suggesting that there may be some correlation between Bacteroidota and certain metabolites of the anti-depressant active ingredients. At the genus level, the Thauera (3.1%∼11.5%) is the major bacterial group that secretes EPS, protecting biofilm against external influences. Most of the changes in microorganisms are consistent with the decontamination properties and macroscopic appearance of EPS in the ICPB system. Finally, the degradation efficiency of ICPB system for VNF was investigated (92.7 ± 3.8%) and it was mostly through hydroxylation and demethylation pathways, with more small molecular products detected, providing the basis for biological assimilation of VNF. Collectively, the NaF–TiO 2 based ICPB system would be lucrative for the future degradation of venlafaxine. [Display omitted] • NaF–TiO 2 was integrated with biofilm for bio-recalcitrant VNF removal in ICPB. • NaF can increase the proportion of (001) facets in TiO 2 by 14.4%. • Acclimation of VNF makes COD removal ratio decrease and EPS secretion increase. • ICPB system has better operational stability of degradation efficiency. • The degradation of VNF are hydroxylation, demethylation and cyclohexane cleavage. [ABSTRACT FROM AUTHOR]

The biotic nitrate reduction rate in freshwater ecosystems is typically constrained by the scarcity of carbon sources. In this study, 'two-chambers' - 'two-electrodes' photoautotrophic biofilm-soil microbial fuel cells (P-SMFC) was developed to accelerate nitrate reduction by activating in situ electron donors that originated from the soil organic carbon (SOC). The nitrate reduction rate of P-SMFC (0.1341 d−1) improved by ∼ 1.6 times on the 28th day compared to the control photoautotrophic biofilm. The relative abundance of electroactive bacterium increased in the P-SMFC and this bacterium contributed to obtain electrons from SOC. Biochar amendment decreased the resistivity of P-SMFC, increased the electron transferring efficiency, and mitigated anodic acidification, which continuously facilitated the thriving of putative electroactive bacterium and promoted current generation. The results from physiological and ecological tests revealed that the cathodic photoautotrophic biofilm produced more extracellular protein, increased the relative abundance of Lachnospiraceae , Magnetospirillaceae , Pseudomonadaceae , and Sphingomonadaceae , and improved the activity of nitrate reductase and ATPase. Correspondingly, P-SMFC in the presence of biochar achieved the highest reaction rate constant for nitrate reduction (k obs) (0.2092 d−1) which was 2.4 times higher than the control photoautotrophic biofilm. This study provided a new strategy to vitalize in situ carbon sources in paddy soil for nitrate reduction by the construction of P-SMFC. [Display omitted] • Photic biofilm-soil microbial fuel cells (PSMFC) were tested for nitrate removal. • Electroactive bacteria activated the in situ electron donor pools in soil. • Denitrifiers of the photic biofilm thrived in PSMFC, in the presence of biochar. • The denitrifiers made the main contribution to nitrate reduction among all the species. [ABSTRACT FROM AUTHOR]

High-altitude de-acclimatization (HADA) significantly impacts physiological functions when individuals acclimatize to high altitudes return to lower altitudes. This study investigates HADA's effects on renal function and structure in rats, focusing on oxidative and endoplasmic reticulum stress as potential mechanisms of renal injury. To elucidate the pathophysiological mechanisms of renal damage in HADA and evaluate the efficacy of antioxidants Vitamin C (Vit C) and tauroursodeoxycholic acid (TUDCA) in mitigating these effects. 88 male Sprague-Dawley rats were randomly divided into a control group, a high-altitude (HA) group, a high-altitude de-acclimatization (HADA) group, and a treatment group. The control group was housed in a sea level environment (500 m), while the HA, HADA, and treatment groups were placed in a simulated high-altitude chamber (5000 m) for 90 days. After this period, the HA group completed the modeling phase; the HADA group was further subdivided into four subgroups, each continuing to be housed in a sea level environment for 3, 7, 14, and 30 days, respectively. The treatment group was split into the Vit C group, the TUDCA group, and two placebo groups, receiving medication for 3 consecutive days, once daily upon return to the sea level. The Vit C group received 100 mg/kg Vit C solution via intravenous injection, the TUDCA group received 250 mg/kg TUDCA solution via intraperitoneal injection, and the placebo groups received an equivalent volume of saline similarly. Serum, urine, and kidney tissues were collected immediately after the modeling phase. Renal function and oxidative stress levels were assessed using biochemical and ELISA methods. Renal histopathology was observed with H&E, Masson's trichrome, PAS, and PASM staining. Transmission electron microscopy was used to examine the ultrastructure of glomeruli and filtration barrier. TUNEL staining assessed cortical apoptosis in the kidneys. Metabolomics was employed for differential metabolite screening and pathway enrichment analysis. Compared to the control and HA groups, the HADA 3-day group (HADA-3D) exhibited elevated renal function indicators, significant pathological damage, observable ultrastructural alterations including endoplasmic reticulum expansion and apoptosis. TUNEL-positive cells significantly increased, indicating heightened oxidative stress levels. Various differential metabolites were enriched in pathways related to oxidative and endoplasmic reticulum stress. Early intervention with Vit C and TUDCA markedly alleviated renal injury in HADA rats, significantly reducing the number of apoptotic cells, mitigating endoplasmic reticulum stress, and substantially lowering oxidative stress levels. This study elucidates the pivotal roles of oxidative and endoplasmic reticulum stress in the early-stage renal injury in rats undergoing HADA. Early intervention with the Vit C and TUDCA significantly mitigates renal damage caused by HADA. These findings provide insights into the pathophysiological mechanisms of HADA and suggest potential therapeutic strategies for its future management. • Study on renal effects of high-altitude de-acclimatization (HADA) in rats. • Vitamin C and TUDCA reduce oxidative stress and kidney damage from HADA. • Identifies key metabolites and pathways in HADA-related kidney damage. • Advances understanding of physiological impacts in high-altitude medicine. [ABSTRACT FROM AUTHOR]

Abstract: Liver transplantation (LT) in patients with hepatitis B virus (HBV) infection is associated with a high rate of graft loss and poor survival, unless re-infection can be prevented. Human hepatitis B immune globulin (HBIG) and nucleoside analogues (NA) have long been utilized to prevent re-infection. Previously, we generated a human monoclonal antibody (mAb), HB that recognizes the surface antigen of hepatitis B virus (HBV). We have constructed a secreted version of HB and cloned its genes into recombinant adeno-associated virus (AAV). We compared the efficiency of AAV vector after a single injection via intramuscular or intravenous routes without additional intervention. Then, we evaluated the activity of antibody HB in tree shrews treated with rAAV-HB and in vitro experiments. So, intramuscular injection of rAAV-HB was a suitable method for the immunoprophylaxis of HBV infection. This human antibody will be useful for the immunoprophylaxis of HBV infection. [Copyright &y& Elsevier]

Abstract: Human astrovirus is one of the important causes for viral gastroenteritis in young children. In previous study where we examined the molecular epidemiology of human astrovirus (HAstV) infection in infants in Wuhan City, we isolated and identified a new subtype (WH1859) of HAstV genotype 3 from an infant with diarrhea. The sequence analysis of this strain showed that the complete region of ORF2 of WH1859 contains 2385-bp of nucleotides that encode 795 amino acids. Because WH1859 strain has the identity of less than 95% with the distance of more than 0.05 to the reference strains of HAstV-3, WH1859 represents a distinct subtype within HAstV-3 strains. Further studies are needed to determine the role of this new subtype strain of HAstV in viral gastroenteritis among young children. [Copyright &y& Elsevier]

Antiproliferative therapies are crucially important for improving the success rate of the glaucoma filtration surgeries. In this study, we investigated the potential efficacy of Forkhead Domain Inhibitory-6 (FDI-6) in inhibiting post-trabeculectomy subconjunctival fibrosis. In vitro, the effect of FDI-6 (10 μM) on fibrotic response and its underlying mechanism were investigated in rabbit tenon's fibroblasts (RTFs) treated with or without transforming growth factor-β1 (TGF-β1, 20 ng/mL). In vivo, FDI-6 (40 μM) was injected subconjunctivally to a rabbit trabeculectomy model. Intraocular pressure (IOP) changes were monitored within the 14-day period post-surgery. Bleb morphology and subepithelial fibrosis at the operating area were evaluated with slit lamp and confocal microscopic examinations and with histologic examinations. The results showed that, in cell culture studies, FDI-6 suppressed the proliferation, migration, collagen gel contraction and the expression levels of fibronectin (FN) and α-smooth muscle actin (α-SMA) in RTFs with TGF-β treatment by down-regulating the TGF-β1/Smad2/3 signaling pathway. In animal studies, the IOPs of the FDI-6-treated group were significantly lower than those of the saline-treated group after trabeculectomy. The FDI-6-treated eyes showed a better bleb appearance with fewer blood vessels compared to the saline-treated eyes. The analysis of confocal microscopy in vivo and histopathology revealed that subconjunctival fibrosis after trabeculectomy was significantly attenuated in the FDI-6-treated group compared to the controls. In conclusion, our studies indicate that FDI-6 exerts an inhibitory effect on subconjunctival fibrosis caused by trabeculectomy, holding potentials as a new antiproliferative agent used in anti-glaucoma filtration surgeries in the future. [Display omitted] • Forkhead Domain Inhibitory-6 was firstly reported as used in resistance to scarring in animal model with trabeculectomy. • Forkhead Domain Inhibitory-6 prevented postoperative scarring and further maintained the decreased IOP. • The application of Forkhead Domain Inhibitory-6 in rabbit eyes with trabeculectomy displayed efficacy and acceptable safety profiles. [ABSTRACT FROM AUTHOR]

Angiogenesis plays a vital role in tumor progression and metastasis. To better understand the role of anesthesia in tumor biology, we previously reported that bupivacaine displayed the inhibitory effects in endothelial cells. In this work, we demonstrated that fentanyl, an opioid medication commonly used in cancer patients, stimulated tumor angiogenesis. We found that fentanyl at nanomolar concentrations significantly stimulated capillary network formation of human lung tumor-associated endothelial cell (HLT-EC) in a similar manner as vascular endothelial growth factor (VEGF), and furthermore that the stimulatory effect of fentanyl was mainly involved in early stage of HLT-EC vascular structure assembly. Particularly, fentanyl significantly increased HLT-EC growth and migration. Fentanyl also protected HLT-EC from apoptosis induced by growth factor withdrawal. In contrast, the same concentrations of fentanyl did not affect human lung cancer cell growth and survival. Fentanyl stimulated migration of some but not all tested human lung cancer cells. Mechanism analysis suggested that fentanyl activates multiple pro-angiogenic signaling pathways, including VEGFR2/FAK/PI3K/Akt and small GTPases. Our work systematically demonstrates that fentanyl stimulates tumor angiogenesis via activating multiple pro-angiogenic signaling pathways. Our findings highlight the potential adverse effect of fentanyl in cancer patients. • Fentanyl stimulates early stage of lung tumor angiogenesis. • Fentanyl increases HLT-EC migration, growth and survival. • Fentanyl activates VEGFR2/FAK, small GTPases and PI3K/Akt in HLT-EC. • Fentanyl increases lung cancer cell migration but not proliferation. [ABSTRACT FROM AUTHOR]

The roles of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in embryonic development remain unclear. We performed a comprehensive analysis of lncRNA and circRNA profiles in rabbit embryos at different stages by whole transcriptome sequencing. We identified 719 lncRNAs and 744 circRNAs that were differentially expressed between stages S1, S2 and S3. A total of 241 differentially expressed lncRNAs and 166 differentially expressed circRNAs were significantly involved in embryonic morphogenesis and development. An RNA network was established and of the embryonic development-associated RNAs, the lncRNAs TCONS_00009253 and TCONS_00010436 were persistently downregulated, while circRNA_07129, circRNA_15209, and circRNA_12526 were persistently upregulated, and their co-expressed mRNAs TBX1, WNT3 and FGFR2 were persistently downregulated during embryonic development. These candidate RNAs were mainly involved in the Wnt, PI3K-Akt, and calcium signaling pathways. This study reports candidate lncRNAs and circRNAs that may be indispensable for the morphogenesis and development of rabbit embryos. • RNA-seq reveals the lncRNAs and circRNAs involved in rabbit embryonic development. • A lncRNA/circRNA-mRNA network involved in embryonic development was established. • TCONS_00009253 and TCONS_00010436 may be vital for embryonic development. • circRNA_07129, circRNA_15209 and circRNA_12526 may be vital for embryonic development. [ABSTRACT FROM AUTHOR]

Vibrio mimicus (V. mimicus) is a significant pathogen in freshwater catfish, though knowledge of virulence determinants and effective vaccine is lacking. Multiplex genome editing by natural transformation (MuGENT) is an easy knockout method, which has successfully used in various bacteria except for V. mimicus. Here, we found V. mimicus strain SCCF01 can uptake exogenous DNA and insert it into genome by natural transformation assay. Subsequently, we exploited this property to make five mutants (△Hem, △TS1, △TS2, △TS1△TS2, and △II), and removed the antibiotic resistance marker by Flp-recombination. Finally, all of the mutants were identified by PCR and RT-PCR. The results showed that combination of natural transformation and FLP-recombination can be applied successfully to generate targeted gene disruptions without the antibiotic resistance marker in V. mimicus. In addition, the five mutants showed mutant could be inherited after several subcultures and a 668-fold decrease in the virulence to yellow catfish (Pelteobagrus fulvidraco). This study provides a convenient method for the genetic manipulation of V. mimicus. It will facilitate the identification and characterization of V. mimicus virulence factors and eventually contribute to a better understanding of V. mimicus pathogenicity and development of attenuated vaccine. • Natural transformation occurred in Vibrio mimicus. • Natural transformation is a rapid method to create genetic deletions in V. mimicus. • Natural transformation holds potential in the development of attenuated vaccine. [ABSTRACT FROM AUTHOR]

Cyprinid herpesvirus 3 (CyHV-3), a virus that encodes an interleukin10 (IL-10) homologue, causes severe economic losses to the common carp and koi culture industry. The present study was devoted to this IL-10 homologue. Recombinant viral IL-10 (vIL-10) protein encoded by CyHV-3 ORF134 gene using prokaryotic expression system was obtained successfully. Bioinformatics analysis revealed that the amino acid sequence of CyHV-3 vIL-10 has low homology with other host IL-10 or viruses encoded IL-10s. However, their tertiary structure is quite similar, suggesting conservative biological functions between IL-10s and vIL-10s. The biological activity of CyHV-3 vIL-10 was detected by using CCK-8 kit and real time quantitative PCR. The results showed that CyHV-3 vIL-10 down regulate epithelioma papulosum cyprini (EPC) cellular activity at 72 h. Moreover, CyHV-3 vIL-10 inhibits the LPS-induced expression of proinflammatory genes, similar to common carp IL-10. Altogether, the results of this study demonstrate that a clear biological activity of CyHV-3 vIL-10 on its host cells and indicates CyHV-3 vIL-10 may play an important role in viral immune evasion. • Bioinformatics analysis demonstrated that CyHV-3 vIL-10 function is conserved compared to IL-10s or other vIL-10s. • CyHV-3 vIL-10 down regulates EPC cells cellular activity at 72 h. • CyHV-3 vIL-10 inhibits the LPS-induced expression of proinflammatory genes, similar to common carp IL-10. • CyHV-3 vIL-10 may play a role in viral immune evasion. [ABSTRACT FROM AUTHOR]

The growing increasing occurrence of perfluorooctanoic acid (PFOA) in wastewater has raised concerns about its potential impact on the environment. Nevertheless, the impact of PFOA at environmentally relevant level on the formation of aerobic granular sludge (AGS) is still a 'black box'. This study thus aims to fill this gap by comprehensive investigation of sludge properties, reactor performance and microbial community during the formation of AGS. It was found that 0.1 mg/L PFOA delayed the formation of AGS, causing relatively lower proportion of large size AGS at the end of operation process. Interestingly, the microorganisms contribute to the reactor's tolerance to PFOA by secreting more extracellular polymeric substances (EPS) to slow or block the entry of toxic substances into the cells. During the granule maturation period, the reactor nutrient removal especially chemical oxygen demand (COD) and total nitrogen (TN) were affected by PFOA, decreasing the corresponding removal efficiencies to ∼81.2% and ∼69.8%, respectively. Microbial analysis further revealed that PFOA decreased the abundances of Plasticicumulans , Thauera , Flavobacterium and Cytophagaceae_uncultured , but it has promoted Zoogloea and Betaproteobacteria_unclassified growth, which maintained the structures and functions of AGS. The above results revealed that the intrinsic mechanism of PFOA on the macroscopic representation of sludge granulation process was revealed, and it is expected to provide theoretical insights and practical support for direct adoption of municipal or industrial wastewater containing perfluorinated compounds to cultivate AGS. [Display omitted] • PFOA at environmentally relevant level delayed the formation of AGS. • PFOA exposure significantly increased polysaccharide and protein content in the EPS. • PFOA led to a decrease of reactor nutrient removal. • Microbial community of AGS changed after long-term PFOA exposure. [ABSTRACT FROM AUTHOR]

Receptor-like cytoplasmic kinases (RLCKs) play important roles in various developmental processes and stress responses in plants. Whereas, the detailed information of this family in cassava has not clear yet. In this study, A total of 322 MeRLCK genes were identified in the cassava genome, and they could be divided into twelve clades (Clades I-XII) according to their phylogenetic relationships. Most RLCK members in the same clade have similar characteristics and motif compositions. Over half of the RLCK s possess cis-elements in their promoters that respond to ABA, MeJA, defense reactions, and stress. Under Xpm 11 infection, the expression levels of four genes show significant changes, suggesting their involvement in Xpm 11 resistance. Two RLCK (MeRLCK 11 and MeRLCK 84) genes potentially involved in resistance to cassava bacterial blight were identified through VIGS experiments. This work laid the foundation for studying the function of the cassava RLCK genes, especially the genes related to pathogen resistance. • We have identified a total of 322 MeRLCK genes in the cassava genome, then we performed bioinformatics analysis and expression pattern analysis on these genes. • We have found Two RLCK (MeRLCK 11 and MeRLCK 84) genes potentially involved in resistance to cassava bacterial blight were identified through VIGS experiments. • This work laid the foundation for studying the function of the cassava RLCK gene, especially the genes related to pathogen resistance. [ABSTRACT FROM AUTHOR]

Three kinds of bioretention were designed to explore the effects of zero-valent iron (ZVI) and biochar on the nitrogen removal performance and to seek a more reasonable packing method in this study. The results showed that the effluent removal rates of nitrate, ammonium and total nitrogen were 53.30 ± 12.68%, 98.41 ± 0.38% and 64.03 ± 8.72% respectively in Bioretention-3 during the rainfall events, while the nitrate concentration decreased gradually with the increase of drying time. According to the batch experiment, it was found that zero-valent iron could release continuously and stably in Bioretention-3 and Bioretention-1 due to the interception effect of biochar on dissolved oxygen. In addition, biochar in soil layer could protect zero-valent iron from excessive oxidation while biochar in the substrate layer could release organic matter to promote heterotrophic denitrification. Microbial community analysis showed that the dominant phyla were Proteobacteria (20.92–40.81%) and Actinobacteriota (9.89–24.54%). The dominant nitrifying genera was Nitrospira while there were also aerobic denitrifying bacteria (Sphingomonas , Bradyrhizobium and Chryseolinea , etc.) in soil layer. In the substrate layer, there was more ferrous iron-mediated autotrophic denitrification process (Thiobacillus, Geobacter and Denitratisoma , etc.) in Bioretention-1 and Bioretention-3 while a larger proportion of Dissimilatory Nitrate Reduction to Ammonium process (DNRA) (Bacillus , Desulfovibrio and Pseudomonas , etc.) in Bioretention-2. In general, this study showed that biochar addition in soil coupled with mixing zero-valent iron and biochar as substrate layer was a more stable and efficient design through various aspects of evidence. It provides a new way for how to use zero-valent iron and biochar to improve nitrogen removal capacity in stormwater management. [Display omitted] • The nitrogen removal of bioretention was studied from spatial-temporal dimensions. • The average total nitrogen removal could reach approximately 80% in Bioretention-3. • Mixed biochar and ZVI as substrate layer increased denitrification capacity. • Biochar protects ZVI from excessive oxidation and enriches Fe-mediated denitrifiers. • Nitrification, denitrification, DNRA and Fe-cycling microbes functioned in the cell. [ABSTRACT FROM AUTHOR]

PITX2 and FOXC1 are the most common pathogenic genes associated with Axenfeld-Rieger syndrome (ARS). In this study, we aimed to explore the variation spectrum of PITX2 and FOXC1 and their associated phenotype based on data from our study and previously reported literatures. Whole exome sequencing was performed on eight probands in our study. Multistep bioinformatic and co-segregation analyses were performed to detect pathogenic variants. Genotype-phenotype correlations of PITX2 and FOXC1 and the differences between them were determined. We detected three variants of FOXC1 and two variants of PITX2 in five unrelated families with ARS. Macular retinoschisis had been observed in AR1 with variant in PITX2 and it is not reported before. Additionally, a review of published literature and our study led to the identification of 593 families with variants of PITX2 or FOXC1 , including 316 families with heterozygous variants in FOXC1 , 251 families with heterozygous variants in PITX2 , 13 families with variants in double genes, seven families with homozygous or compound heterozygous variants in FOXC1 , and six families with variants in ADAMTS17, PRDM5, COL4A1 or CYP1B1. Significant differences were observed between the prevalence of missense and in-frame, truncation, and large deletion variants in PITX2 (32.00%, 42.67%, and 25.33%, respectively) and FOXC1 (34.49%, 35.13%, 30.38%, respectively) (p = 1.16E-43). Enrichment and frequency analyses revealed that missense variants were concentrated in the forkhead domain of FOXC1 (76.14%) and homeodomain of PITX2 (87.50%). The percentage of Caucasians with variants in FOXC1 was significantly higher than that of PITX2 (p = 2.00E-2). Significant differences between PITX2 and FOXC1 were observed in glaucoma (p = 3.00E-2), corectopia (p = 3.050E-6), and polycoria (p = 5.21E-08). Additionally, we observed a significant difference in best-corrected visual acuity (BCVA) between FOXC1 and PITX2 (p = 3.80E-2). Among all the family members with PITX2 or FOXC1 variants, the prevalence of systemic abnormalities was significantly higher in PITX2 than in FOXC1 (89.16% vs. 58.77%, p = 5.44E-17). In conclusion, macular retinoschisis as a novel phenotype had been observed in patient with variant in PITX2. Significant differences were detected in phenotypes and genotypes between PITX2 and FOXC1. • Macular retinoschisis are detected in PITX2. • PITX2 and FOXC1 are the most common genes for ARS. • Missense concentrated on the forkhead domain of FOXC1 and homeodomain of PITX2. • The phenotypes and genotypes significantly differ between PITX2 and FOXC1. [ABSTRACT FROM AUTHOR]

Iron-based ecological floating beds (EFBs) are often used to treat the secondary effluent from wastewater treatment plant to enhance the denitrification process. However, the impact and necessity of plants on iron-based EFBs have not been systematically studied. In this research, two iron-based EFBs with and without plants (EFB-P and EFB) were performed to investigate the response of plants on nutrient removal, GHG emissions, microbial communities and functional genes. Results showed the total nitrogen and total phosphorus removal in EFB-P was 45–79% and 48–72%, respectively, while that in EFB was 31–67% and 44–57%. Meanwhile, plants could decrease CH 4 emission flux (0–3.89 mg m−2 d−1) and improve CO 2 absorption (4704–22321 mg m−2 d−1). Plants could increase the abundance of Nitrosospira to 1.6% which was a kind of nitrifying bacteria dominant in plant rhizosphere. Among all denitrification related genera, Simplicispira (13.08%) and Novosphingobium (6.25%) accounted for the highest proportion of plant rhizosphere and iron scrap, respectively. Anammox bacteria such as Candidatus_Brocadia was more enriched on iron scraps with the highest proportion was 1.21% in EFB-P, and 2.20% in EFB. Principal co-ordinates analysis showed that plants were the critical factor determining microbial community composition. TN removal pathways were mixotrophic denitrification and anammox in EFB-P while TP removal pathways were plant uptake and phosphorus-iron coprecipitation. In general, plants play an important directly or indirectly role in iron-based EFBs systems, which could not only improve nutrients removal, but also minimize the global warming potential and alleviate the greenhouse effect to a certain extent. • Plants and ZVI simultaneously enhanced nitrogen and phosphorus removal in EFBs. • Plants enhanced TN and TP removal of iron-based EFB by 11–15% and 4–16%, respectively. • Less methane emissions and more carbon dioxide absorption occurred in EFB-P. • TN removal pathways were mixotrophic denitrification and anammox in EFB-P. • TP removal pathways were plant uptake and P–Fe coprecipitation in EFB-P. [ABSTRACT FROM AUTHOR]

The regulatory mechanism of tautomycetin (TMC) biosynthesis remains largely unknown, although it has been of great interest to the pharmaceutical industry. Our previous study showed that intracellular adenosine triphosphate (inATP) level is negatively correlated with secondary metabolite biosynthesis in various Streptomyces spp. In this study, by exogenous treatment of ATP, we also found a negative correlation between TMC biosynthesis and inATP level in Streptomyces griseochromogenes ( S. griseochromogenes ). However, the underlying mechanism remains unclear. TmcN, a pathway-specific transcriptional regulator of TMC biosynthetic genes, was previously revealed as a large ATP-binding LuxR (LAL) family protein. The predicted amino acid sequence of TmcN shows highly conserved Walker A and B binding motifs, which suggest an ATPase function of TmcN. We therefore hypothesized that the ATPase domain of TmcN may play a role in sensing endogenous pool of ATP, and is thus involved in the ATP regulation of TMC biosynthesis. To test the hypothesis, we first explored the key residue that affects the ATPase activity of TmcN by amino acid sequence alignment and structural simulation. After that, we disrupted tmcN gene in S. griseochromogenes , and the tmcN or site-direct-mutated tmcN were re-introduced to get the complementary and ATPase domain disrupted strains. The transcription level of tmcN , TMC yield, and inATP, as well as the effect of ATP on TMC production of different mutants were evaluated. Deletion of tmcN or site-direct mutation of ATPase domain of TmcN in S. griseochromogenes significantly reduced the TMC production, and it was not affected by exogenous ATP treatment. In addition, a relatively high level of inATP was detected in tmcN deletion and site-direct mutation strains. Our results here suggested that TmcN, especially its ATPase domain, is involved in consuming of endogenous ATP pool and thus plays pivotal role in connecting the primary and secondary metabolite in S. griseochromogenes . [ABSTRACT FROM AUTHOR]