Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing.

Diabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor (VEGF)-dependent angiogenesis remain uncertain and could reveal new therapeutic targets. In our study, the molecular underpinnings of endothelial dysfunction in diabetes were investigated, focusing on the roles of Disabled-2 (Dab2) and Forkhead Box M1 (FoxM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell (EC) function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high concentrations glucose treated primary mouse skin ECs, simulating hyperglycemic conditions in diabetes mellitus. In diabetic mice with a genetic EC deficiency of Dab2 angiogenesis was reduced in vivo and in vitro when compared with wild-type mice. Restoration of Dab2 expression by injected mRNA-containing lipid nanoparticles rescued impaired angiogenesis and wound healing in diabetic mice. At the same time, FoxM1 was downregulated in skin ECs subjected to high glucose conditions as determined by RNA-sequencing analysis. FoxM1 was found to bind to the Dab2 promoter, regulating its expression and influencing VEGFR2 signaling. The FoxM1 inhibitor FDI-6 reduced Dab2 expression and phosphorylation of VEGFR2. These findings indicate that restoring Dab2 expression through targeted therapies can enhance angiogenesis and wound repair in diabetes. To explore this therapeutic potential, we tested LyP-1-conjugated lipid nanoparticles (LNPs) containing Dab2 or control mRNAs to target ECs and found the former significantly improved wound healing and angiogenesis in diabetic mice. This study provides evidence of the crucial roles of Dab2 and FoxM1 in diabetic endothelial dysfunction and establishes targeted delivery as a promising treatment for diabetic vascular complications.

A Shape-Restorable hierarchical polymer membrane composite system for enhanced antibacterial and antiadhesive efficiency.

Intelligent shape memory polymer can be potentially used in manufacturing implantable devices that enables a benign variation of implant dimensions with the external stimuli, thus effectively lowering insertion forces and evading associated risks. However, in surgical implantation, biomaterials-associated infection has imposed a huge burden to healthcare system that urgently requires an efficacious replacement of antibiotic usages. Preventing the initial attachment and harvesting a biocidal function upon native surfaces may be deemed as a preferable strategy to tackle the issues of bacterial infection. Herein, a functionalized polylactic acid (PLA) composite membrane assembled with graphene (GE, a widely used photothermal agent) was fabricated through a blending process and then polydimethylsiloxane utilized as binders to pack hydrophobic SiO2 tightly onto polymer surface (denoted as PLA-GE/SiO2). Such an active platform exhibited a moderate shape-memory performance upon near-infrared (NIR) light stimulation, which was feasible for programmed deformation and shape recovery. Particularly stirring was that PLA-GE/SiO2 exerted a pronounced bacteria-killing effect under NIR illumination, 99.9 % of E. coli and 99.8 % of S. aureus were effectively eradicated in a lean period of 5 min. Furthermore, the obtained composite membrane manifested excellent antiadhesive properties, resulting in a bacteria-repelling efficacy of up to 99 % for both E. coli and S. aureus species. These findings demonstrated the potential value of PLA-GE/SiO2 as a shape-restorable platform in "kill&repel" integration strategy, further expanding its applications for clinical anti-infective treatment.

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo. ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2+ breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.

The response of nitrifying activated sludge to chlorophenols: Insights from metabolism and redox homeostasis.

The specialized wastewater treatment plants for the chemical industry are rapidly developed in China and many other countries. But there is a common bottleneck in that the toxic pollutants in chemical wastewater often cause shock impacts on biological nitrogen removal systems, which directly affects the stability and cost of operation. As the research on nitrification inhibition characteristics is not sufficient till now, there is a great lack of theoretical guidance on the control of the inhibition. This study investigated the response of nitrifying activated sludge to chlorophenols (CPs) inhibition in terms of metabolism disorder and oxidative stress. At the initial stage of reaction (i.e., 1 h), reactive oxygen species (ROS)-induced membrane damage which might account for declining nitrification performance. Simultaneously excessive extracellular polymeric substances (EPS) were secreted to alleviate oxidative stress injury and protected microorganisms to some extent. In particular tyrosine-like substances in LB-EPS with a Fmax increase of 242.30% were confirmed to efficiently resist phenols inhibition. Thus, as the inhibition proceeded, metabolism disorder replaced oxidative stress as the main cause of nitrification inhibition. The affected metabolic processes include weakened enzyme catalysis, restricted electron transport and lessened energy generation. At 4 h, nitrifying production of sludge amended with 5 mg/L chlorophenols was 89.27 ± 9.51%-98.15 ± 9.60% lower than blank, the inhibition could be attributed to comprehensively affected metabolism. The structural equation modeling indicated that phenols restricted nitrification enzymes and bacterial electron transport efficiency which was critical to nitrification performance. Moreover, the lessened energy generation weakens enzyme activity to further suppress nitrification. These findings enriched our knowledge of nitrifiers' responses to CPs inhibition and provided the basis for addressing nitrification inhibition.

A novel anthocyanin electrospun film by caffeic acid co-pigmentation for real-time fish freshness monitoring.

In recent years, the use of intelligent and efficient food freshness indicators (FFIs) for monitoring food freshness has been studied widely. In this work, we employed polyacrylonitrile as polymer, blueberry anthocyanins as an indicator, and caffeic acid as a co-pigment and fabricated a novel colorimetric sensing film for real-time monitoring the freshness of fish. The total volatile basic nitrogen (TVB-N) level is one of the potential indicators to evaluate meat freshness. Visual observation confirmed that the polyacrylonitrile-anthocyanin-caffeic acid film changed from pink to light purple, and then to dark purple providing a good indication of spoilage, which correlated well with the TVB-N content and pH values in fish. It is because the volatile ammonia combined with water to form NH3·H2O, and then NH3·H2O is hydrolyzed to form OH- and NH4+. The change of the polyacrylonitrile-anthocyanin film was caused by OH-. Compared with the polyacrylonitrile-anthocyanin film without caffeic acid, the addition of the caffeic acid film had enhanced significantly ammonia responsiveness with a total color difference value of 29.897. And it was also observed that caffeic acid obviously improved the storage stability of the film. This study provided a reference for detecting food freshness using co-pigmentation and electrospinning encapsulation technology in combination.

Factors Associated with School Sports Injury among Elementary and Middle School Students in Shanghai, China.

School sports activity (SSA) is beneficial to gaining and maintaining optimal health among elementary and middle school students but might increase risks for school sports injury (SSI). This cross-sectional study aimed to investigate the incidence and identify risk factors of SSI among Chinese elementary and middle school students in Shanghai. Students in grades 4-5 (elementary) and 7-9 (middle) from three k-12 schools (aged from 9 to 16 years old) in Shanghai selected via the method of cluster random sampling were invited to participate in the study. Information on socio-demography, sleep duration, individual internal and external risk factors, and SSI experiences in the past 12 months was collected. A multivariate logistic regression model was performed to estimate the risk factors of SSI. A total of 1303 participants completed the questionnaires, with an overall SSI incidence rate of 29.5%. Along with boys, elementary school students, and sports team members, students scoring high on internal and external risk factors were at higher risk for SSA. In summary, SSI was prevalent among elementary and middle school students in Shanghai, China, and was associated with several modifiable risk factors. The findings provide insights regarding actions that could be taken to reduce the occurrence of SSI and maximize the benefits of SSA, including improvements in safety education, maintenance of facilities and equipment, and completion of warm-up exercises.

Albumin nanoparticle containing a PI3Kγ inhibitor and paclitaxel in combination with α-PD1 induces tumor remission of breast cancer in mice.

Immunomodulators that remodel the tumor immunosuppressive microenvironment have been combined with anti-programmed death 1 (α-PD1) or anti-programmed death ligand 1 (α-PDL1) immunotherapy but have shown limited success in clinical trials. However, therapeutic strategies to modulate the immunosuppressive microenvironment of lymph nodes have been largely overlooked. Here, we designed an albumin nanoparticle, Nano-PI, containing the immunomodulators PI3Kγ inhibitor (IPI-549) and paclitaxel (PTX). We treated two breast cancer mouse models with Nano-PI in combination with α-PD1, which remodeled the tumor microenvironment in both lymph nodes and tumors. This combination achieved long-term tumor remission in mouse models and eliminated lung metastases. PTX combined with IPI-549 enabled the formation of a stable nanoparticle and enhanced the repolarization of M2 to M1 macrophages. Nano-PI not only enhanced the delivery of both immunomodulators to lymph nodes and tumors but also improved the drug accumulation in the macrophages of these two tissues. Immune cell profiling revealed that the combination of Nano-PI with α-PD1 remodeled the immune microenvironment by polarizing M2 to M1 macrophages, increasing CD4+ and CD8+ T cells, B cells, and dendritic cells, decreasing regulatory T cells, and preventing T cell exhaustion. Our data suggest that Nano-PI in combination with α-PD1 modulates the immune microenvironment in both lymph nodes and tumors to achieve long-term remission in mice with metastatic breast cancer, and represents a promising candidate for future clinical trials.

Electrospun Nanofibers: Current Progress and Applications in Food Systems.

Electrospinning has the advantages of simple manufacturing equipment, a low spinning cost, wide range of spinnable materials, and a controllable mild process, which can continuously fabricate submicron or nanoscale ultrafine polymer fibers without high temperature or high pressure. The obtained nanofibrous films may have a large specific surface area, unique pore structure, and easy-to-modify surface characteristics. This review briefly introduces the types and fiber structures of electrospinning and summarizes the applications of electrospinning for food production (e.g., delivery systems for functional food, filtration of beverages), food packaging (e.g., intelligent packaging, antibacterial packaging, antioxidant packaging), and food analysis (e.g., pathogen detection, antibiotic detection, pesticide residue detection, food compositions analysis), focusing on the advantages of electrospinning applications in food systems. Furthermore, the limitations and future research directions of the technique are discussed.

CD36 and DGAT2 facilitate the lipid-lowering effect of chitooligosaccharides via fatty acid intake and triglyceride synthesis signaling.

This study examined the impact of chitobiose (GlcN)2 and chitotriose (GlcN)3 on lipid accumulation modification and their inhibitory functionalities. (GlcN)2 and (GlcN)3 significantly inhibited the total cholesterol (TC), triglyceride (TG), and low-density lipid cholesterol (LDL-c) levels in the liver of the ob/ob-/- mice fed a non-high-fat diet. This phenomenon was associated with a reduction in the mRNA and protein expression of TG synthesis and fatty acid uptake-related signaling, significantly affecting the cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2). Furthermore, the CD36 and DGAT2 genes were overexpressed by constructing a plasmid and transfecting it into HepG2 cells, after which the phenotypic traits of lipid accumulation were assessed in vitro. Consequently, it was evident that (GlcN)2 and (GlcN)3 reduced the overexpression of these proteins and relieved cellular lipid accumulation. In conclusion, these results indicated that (GlcN)2 and (GlcN)3 acted positively against NAFLD while regulating steatosis in the non-high-fat diet NAFLD model. The potential NAFLD treatment strategies, such as targeting CD36 and DGAT2 signaling, could provide scientific insight into further applying food-derived ingredients to reduce the risk of high-fat metabolism.

Reappraisal of anticancer nanomedicine design criteria in three types of preclinical cancer models for better clinical translation.

Anticancer nanomedicines are designed to improve anticancer efficacy by increasing drug accumulation in tumors through enhanced permeability retention (EPR) effect, and to reduce toxicity by decreasing drug accumulation in normal organs through long systemic circulation. However, the inconsistent efficacy/safety of nanomedicines in cancer patients versus preclinical cancer models have provoked debate for nanomedicine design criteria. In this study, we investigate nanomedicine design criteria in three types of preclinical cancer models using five clinically used nanomedicines, which identifies the factors for better clinical translations of their observed clinical efficacy/safety compared to free drug or clinical micelle formulation. When those nanomedicines were compared with drug solution or clinical micelle formulation in breast tumors, long and short-circulating nanomedicines did not enhance tumor accumulation by EPR effect in transgenic spontaneous breast cancer model regardless of their size or composition, although they improved tumor accumulations in subcutaneous and orthotopic breast cancer models. However, when tumors were compared to normal breast tissue, nanomedicines, drug solution and clinical micelle formulation showed enhanced tumor accumulation regardless of the breast cancer models. In addition, long-circulating nanomedicines did not further increase tumor accumulation in transgenic mouse spontaneous breast cancer nor universally decrease drug accumulations in normal organs; they decreased or increased accumulation in different organs, potentially changing the clinical efficacy/safety. In contrast, short-circulating nanomedicines decreased blood concentration and altered drug distribution in normal organs, which are correlated with their clinical efficacy/safety. A reappraisal of current nanomedicine design criteria is needed to ensure consistent clinical translation for improvement of their clinical efficacy/safety in cancer patients.

Caveolae-Mediated Endocytosis Drives Robust siRNA Delivery of Polymeric Nanoparticles to Macrophages.

Cytosolic delivery of small interfering RNA (siRNA) remains challenging, and a profound understanding of the cellular uptake and intracellular processing of siRNA delivery systems could greatly improve the development of siRNA-based therapeutics. Here, we show that caveolae-mediated endocytosis (CvME) accounts for the robust siRNA delivery of mannose-modified trimethyl chitosan-cysteine/tripolyphosphate nanoparticles (MTC/TPP NPs) to macrophages by circumventing lysosomes. We show that the Golgi complex and ER are key organelles required for the efficient delivery of siRNA to macrophages in which the siRNA accumulation positively correlates with its silencing efficiency (r = 0.94). We also identify syntaxin6 and Niemann-Pick type C1 (NPC1) as indispensable regulators for MTC/TPP NPs-delivered siRNA into macrophages both in vitro and in vivo. Syntaxin6 and NPC1 knockout substantially decrease the cellular uptake and gene silencing of the siRNA delivered in MTC/TPP NPs in macrophages, which result in poor therapeutic outcomes for mice bearing acute hepatic injury. Our results suggest that highly efficient siRNA delivery can be achieved via CvME, which would give ideas for designing optimal delivery vectors to facilitate the clinical translation of siRNA drugs.

Inhibition and removal of trichloroacetaldehyde by biological acidification with glucose co-metabolism.

Biological acidification plays a crucial role in biological removal of organic compounds during petrochemical wastewater treatment. Trichloroacetaldehyde is a typical organic pollutant in petrochemical wastewater, however, no studies have been conducted on its effect on biological acidification. In this study, batch bioassays of volatile fatty acids were conducted to explore the inhibitory effect of trichloroacetaldehyde on biological acidification, the variations of key enzymes and extracellular polymeric substances under trichloroacetaldehyde shock, and the mechanism of trichloroacetaldehyde removal. The results of these bioassays indicated that trichloroacetaldehyde inhibited the acid yield at higher concentrations (EC50 112.20 mg/L), and butyric fermentation was predominant. Moreover, the contents of extracellular polymeric substances and several key acidifying enzymes greatly decreased when the trichloroacetaldehyde concentration exceeded 100 mg/L, which was due to the toxicity that trichloroacetaldehyde poses to the microbes involved in biological acidification. The trichloroacetaldehyde mechanism was as follows: first, trichloroacetaldehyde was adsorbed by extracellular polymeric substances and anaerobic granular sludge, and then transformed into trichloroethanol, trichloroethane, dichloroacetaldehyde, and dichloroethanol under the combined action of the aldehyde reductase and reductive dehalogenases secreted from the microbial consortium. The ability of biological acidification to remove trichloroacetaldehyde was limited; therefore, trichloroacetaldehyde should be pretreated before it enters biological treatment systems.

siRNA release kinetics from polymeric nanoparticles correlate with RNAi efficiency and inflammation therapy via oral delivery.

Despite many efforts in the rational design of nanoparticles (NPs) to overcome the biological barriers to small interfering RNA (siRNA) delivery for improving gene silencing efficiency, little is known about the correlations between siRNA release kinetics and RNA interference (RNAi) efficiency and inflammation therapy via oral delivery. On the basis of mannose-modified trimethyl chitosan-cysteine (MTC) polymers, seven types of MTC NPs containing tumor necrosis factor (TNF)-α siRNA were prepared through ionic gelation. The siRNA release kinetics from MTC NPs were finely tuned by adjusting the kinds and amounts of the crosslinkers involved. These MTC NPs exhibited no disparities in siRNA protection against enzymatic degradation in physiological fluids and cellular uptake in macrophages; however, they showed distinct in vitro siRNA release profiles and intracellular unpacking kinetics. MTC NPs with relatively rapid and sustained siRNA release were responsible for efficient, prompt, and prolonged RNAi, contributing to desired therapeutic efficacy in acute and chronic inflammatory murine models following oral delivery. However, MTC NPs insufficiently releasing siRNA could not elicit effective RNAi. Collectively, the present investigation might provide broad insights into the optimization of siRNA nanocarriers with respect to their release kinetics for improving RNAi efficacies aiming at different types of inflammatory diseases. STATEMENT OF SIGNIFICANCE: siRNA release kinetics in the cytoplasm and pathological characteristics of diseases themselves determine the therapeutic efficacy of siRNA delivery. Herein, by adjusting the kinds and amounts of the crosslinkers involved, we developed seven types of MTC NPs containing TNF-α siRNA with distinct siRNA release kinetics. MTC NPs with relatively rapid and sustained siRNA release were responsible for prompt and prolonged RNAi, respectively, contributing to desired therapeutic efficacy in acute and chronic inflammation following oral delivery. These results might provide broad insights into the optimization of siRNA nanocarriers in respect to their release kinetics for improving therapeutic outcomes toward different clinical requirements.

Effect of influent pH on hydrolytic acidification performance and bacterial community structure in EGSB for pretreating crotonaldehyde manufacture wastewater after ozonation.

The objective of this work was to evaluate the effect of influent pH on the hydrolytic acidification (HA) performance and microbial community structure in an expanded granular sludge bed (EGSB) pretreating crotonaldehyde manufacture wastewater (CMW) after ozonation. The results showed that higher chemical oxygen demand (COD) removal rate (40.1%) and acidification degree (27.6%) were obtained at pH 8.0 than those at pH 6.0 and pH 4.0. The concentration of extractable extracellular polymeric substance (EPS) in the sludge gradually decreased with the pH decreasing from 8.0 to 4.0. A similar change was also observed for the concentration of total volatile fatty acids (TVFA) in the effluent. The optimal detoxification efficiency by the HA process was obtained at pH 8.0, with higher removal efficiency (all higher than 90%) of the main toxic pollutants (crotonaldehyde, 5-formyl-6-methyl-4,5-dihydropyran, etc.) and higher anaerobic biodegradation rate (44.5%) in biochemical methane potential (BMP) assay. Among the predominant genera, the Acinetobacter and Pseudomonas were possibly related to biodegradation of pollutants, since their higher relative abundance also coincided with the better performance of the HA process at pH 8.0.

Combination antitumor immunotherapy with VEGF and PIGF siRNA via systemic delivery of multi-functionalized nanoparticles to tumor-associated macrophages and breast cancer cells.

Given that vascular endothelial growth factor (VEGF) and placental growth factor (PIGF), over-expressed in breast cancer cells and M2-like tumor-associated macrophages (M2-TAMs) within tumor microenvironment (TME), work synergistically and independently in mediating tumor progression and immunosuppression, combinatorial immune-based approaches targeting them are expected to be a potent therapeutic modality for patients. Here, polyethylene glycol (PEG) and mannose doubly modified trimethyl chitosan (PEG = MT) along with citraconic anhydride grafted poly (allylamine hydrochloride) (PC)-based nanoparticles (NPs) (PEG = MT/PC NPs) with dual pH-responsiveness were developed to deliver VEGF siRNA (siVEGF)/PIGF siRNA (siPIGF) to both M2-TAMs and breast cancer cells for antitumor immunotherapy. With prolonged blood circulation and intelligent pH-sensitivity, PEG = MT/PC NPs were highly accumulated in tumor tissues and then internalized in M2-TAMs and breast cancer cells via mannose-mediated active targeting and passive targeting, respectively. With the charge-reversal of PC, PEG = MT/PC NPs presented effective endosomal/lysosomal escape and intracellular siRNA release, resulting in efficient gene silencing. Due to the synergism between siVEGF and siPIGF in anti-proliferation of tumor cells and reversal of the TME from pro-oncogenic to anti-tumoral, PEG = MT/PC/siVEGF/siPIGF NPs (PEG = MT/PC/siV-P NPs) exerted robust suppression of breast tumor growth and lung metastasis. This combination strategy may provide a promising alternative for breast cancer therapy.

Identification of toxic substances in phenol-acetone wastewater on activated sludge and selective toxicity removal performance with ferrous pretreatment.

We investigated the effects of toxic wastewater generated during the production of phenol-acetone on activated sludge and tested pretreatment methods to selectively remove the toxicity. We found that the microbial activity in the activated sludge was inhibited by the wastewater, in which cumene hydroperoxide (CHP) with a medium effective concentration (EC50) of 225 mg L-1 was the main toxic substance. We tested one pretreatment method with ferrous iron to selectively remove the CHP. The CHP decomposition process, which mainly produced acetophenone, was very quick. The CHP was selectively transformed into low-toxicity organics, and a maximum of 92% was removed when 1.08 mmol L-1 of ferrous iron was added, for a reaction time of 10 min, a pH of 5, and a temperature of 25 °C, and the resulting wastewater only slightly inhibited the oxygen uptake rate of activated sludge. The acclimation of activated sludge was accelerated, and a COD removal rate of more than 85% was achieved within a week. Our results confirm that ferrous iron provides a cost-effective method to selectively remove toxins from wastewater.

Enhanced antitumor efficacy of arginine modified amphiphilic nanoparticles co-delivering doxorubicin and iSur-pDNA via the multiple synergistic effect.

Arginine and α-tocopherol succinate (α-TOS) double grafted N-trimethyl chitosan chloride (TMC) nanoparticles (TAS NPs) were designed and developed for effective co-delivery of doxorubicin (DOX) and Survivin shRNA-expressing pDNA (iSur-pDNA). With DOX loading into the hydrophobic core and iSur-pDNA combining to the hydrophilic shell, TAS/DOX/pDNA NPs demonstrated favorable structural stability and sustained release properties in vitro. With the special non-clathrin-dependent endocytosis, TAS/DOX/pDNA NPs presented higher cellular uptake and mainly distributed in ER and Golgi rather than lysosomes following internalization. The in vitro nuclear localization, gene silencing efficiency, cell apoptosis, and growth inhibition of tumor cells were significantly promoted by arginine modification. In the tumor-bearing mice model, TAS/DOX/pDNA NPs possessed the maximum antitumor efficiency as compared with single delivery of DOX or iSur-pDNA. Particularly, blank TAS NPs were selectively be toxic to tumor cells as evidenced by their capabilities to inhibit proliferation and induce apoptosis of tumor cells. The promising tumor treatment of TAS/DOX/pDNA NPs via a multiple synergistic manner arising from DOX and pDNA as well as the vectors would provide a potential strategy for a dual-delivery system to improve their therapeutic efficacies.

Effects of rapid temperature rising on nitrogen removal and microbial community variation of anoxic/aerobic process for ABS resin wastewater treatment.

ABS resin wastewater is a high-temperature nitrogenous organic wastewater. It can be successfully treated with anoxic/aerobic (A/O) process. In this study, the effect of temperature on nitrogen removal and microbial community after quick temperature rise (QTR) was investigated. It was indicated that QTR from 25 to 30 °C facilitated the microbial growth and achieved a similar effluent quality as that at 25 °C. QTR from 25 to 35 °C or 40 °C resulted in higher effluent concentration of chemical oxygen demand (COD), biochemical oxygen demand (BOD5), total nitrogen (TN), and total phosphorus (TP). Illumina MiSeq pyrosequencing analysis illustrated that the richness and diversity of the bacterial community was decreased as the temperature was increased. The percentage of many functional groups was changed significantly. QTR from 25 to 40 °C also resulted in the inhibition of ammonia oxidation rate and high concentration of free ammonia, which then inhibited the growth of NOB (Nitrospira), and thus resulted in nitrite accumulation. The high temperature above 35 °C promoted the growth of a denitrifying bacterial genus, Denitratisoma, which might increase N2O production during the denitrification process.

Human infection with a novel tick-borne Anaplasma species in China: a surveillance study.

BACKGROUND: Anaplasma phagocytophilum and Anaplasma ovis cause human infections. We investigated the potential for human pathogenicity of a newly discovered Anaplasma species infecting goats in China. METHODS: We collected blood samples from patients with a history of tick bite in the preceding 2 months at Mudanjiang Forestry Central Hospital of Heilongjiang Province from May 1, to June 10, 2014, to detect the novel Anaplasma species by PCR. We inoculated positive samples into cell cultures. We characterised the isolated pathogen by morphological and phylogenetic analyses. We tested serum antibodies by indirect immunofluorescence assay. FINDINGS: 28 (6%) of 477 patients assessed were infected with the novel Anaplasma species according to PCR and sequencing. We isolated the pathogen in vitro from three patients. Phylogenetic analyses of rrs, gltA, groEL, msp2, and msp4 showed that the pathogen was distinct from all known Anaplasma species. We provisionally nominate it "Anaplasma capra". 22 (92%) of 24 patients with data available had seroconversion or a four-fold increase in antibody titres. All 28 patients developed non-specific febrile manifestations, including fever in 23 (82%), headache in 14 (50%), malaise in 13 (46%), dizziness in nine (32%), myalgia in four (14%), and chills in four (14%). Additionally, ten (36%) of 28 patients had rash or eschar, eight (29%) had lymphadenopathy, eight (29%) had gastrointestinal symptoms, and three (11%) had stiff neck. Five patients were admitted to hospital because of severe disease. Six (35%) of 17 patients with data available had high hepatic aminotransferase concentrations. INTERPRETATION: The emergence of "A capra" as a cause of human disease suggests that individuals living in or travelling to endemic regions in northern China should take precautions to reduce their risk of exposure to this novel tick-borne pathogen. FUNDING: Natural Science Foundation of China and the US National Institutes of Health.