OsTGAL1 suppresses the resistance of rice to bacterial blight disease by regulating the expression of salicylic acid glucosyltransferase OsSGT1.

Many TGA transcription factors participate in immune responses in the SA-mediated signaling pathway in Arabidopsis. This study identified a transcription factor OsTGAL1, which is induced upon infection by Xoo. Overexpression of OsTGAL1 increased the susceptibility of rice to Xoo. Plants overexpressing OsTGAL1 could affect the expression of many SA signaling-related genes. OsTGAL1 was able to interact with the promoter of OsSGT1, which encodes a key enzyme for SA metabolism. The transcript of OsSGT1 was induced by Xoo and this responsive expression was further increased in plants overexpressing OsTGAL1. OsSGT1 knockout lines had enhanced resistance to Xoo, and knocking out OsSGT1 in plants overexpressing OsTGAL1 blocked the susceptibility caused by OsTGAL1. Altered expression levels of several OsPRs in all the transgenic plants demonstrated that SA-mediated signaling had been affected. Furthermore, we identified an oxidoreductase of CC-type glutaredoxin, OsGRX17, which interacted with OsTGAL1. OsGRX17 reduced the regulation of OsTGAL1 on OsSGT1, and this may be due to its redox modulation. Thus, our results demonstrate that OsTGAL1 negatively regulates resistance to Xoo by its effects on SA metabolism via the activation of OsSGT1, which provides valuable targets for plant breeders in developing new cultivars that are resistant to Xoo.

Fecal microbiota transplantation improves intestinal inflammation in mice with ulcerative colitis by modulating intestinal flora composition and down-regulating NF-kB signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine. It is characterized with recurrent. The pathogenesis is mainly associated with environmental factors, genetic susceptibility, dysbiosis of the intestinal flora and autoimmunity. The role of intestinal flora disorders in the pathogenesis and progression of UC is becoming increasingly prominent. More and more studies have confirmed that fecal microbiota transplantation (FMT) could reshape the composition of UC intestinal flora and it is expected to be a new strategy for UC treatment. In this study, we used 2% Dextran sulfate sodium (DSS) for 7 days to induce acute colitis model in mice, and interfere with FMT and Enterotoxigenic Escherichia coli (ETEC). ELISA and immunohistochemistry were applied to detect the concentration and expression of NF-κB p65, STAT3 and IL-6. 16SrRNA high-throughput sequencing was performed to explore the composition of intestinal flora. The aim was to study the treatment effect of FMT on UC mice and explore its potential mechanism by observing the changes of intestinal flora composition and diversity, and its relationship with NF-κB p65, STAT3 and IL-6 expression. We conclude that FMT could improve intestinal flora disorder in mice with ulcerative colitis, regulate NF-κB signaling pathway, and significantly reduce intestinal inflammation in UC mice.

Enhanced aerobic granulation for treating low-strength wastewater in an anaerobic-aerobic-anoxic sequencing batch reactor by selecting slow-growing organisms and adding carriers.

The aerobic granular sludge (AGS) process is a promising technology for wastewater treatment. However, a long start-up period for granulation and instability during long-term operation still hinder the application of AGS technology, especially for low-strength wastewater. To solve these two problems, this study tested a novel strategy involving the selection of slow-growing organisms and the addition of carriers in an anaerobic-aerobic-anoxic sequencing batch reactor (AN/O/AX_SBR). Three identical AN/O/AX_SBRs (R_Ctrl, R_CCM, and R_GAC), fed with low-strength wastewater, were operated for 120 days. R_Ctrl had no carriers, R_CCM contained cell culture microcarriers (CCM), and R_GAC contained granular activated carbon (GAC). Mature AGS was achieved within 80 days in all reactors. The carriers could reduce the maturation period of AGS by approximately 10 days (76, 66, and 69 days in R_Ctrl, R_CCM, and R_GAC, respectively) and improve the physical strength of the AGS. AGS showed a strong structure without excessive proliferation of filamentous bacteria, full-grown size (900-1100 µm), and good settleability (SVI5 was 15.4-19.4 mL/g). Microbiological analysis showed that AN/O/AX_SBRs can provide a metabolic selective pressure to select slow-growing organisms such as nitrifying bacteria (norank_f__NS9_marine_group, Ellin6067, and Nitrospira), glycogen and phosphorus accumulating organisms (GAOs: Candidatus_Competibacter and Defluviicoccus; PAOs: Candidatus_Accumulibacter and Flavobacterium). All reactors showed good performance for simultaneous nitrification, endogenous denitrification, and phosphorus removal. The removal efficiencies of total nitrogen and total phosphorous were above 70% and 80%, respectively. The cycle test showed intermediate PAO-GAO metabolism prevailed in the system, and endogenous denitrification was primarily carried out by denitrifying GAOs.

Rapid start-up and advanced nutrient removal of simultaneous nitrification, endogenous denitrification and phosphorus removal aerobic granular sequence batch reactor for treating low C/N domestic wastewater.

The rapid start-up and advanced nutrient removal of simultaneous nitrification, endogenous denitrification, and phosphorus (P) removal aerobic granular sequence batch reactor (SNEDPR-AGSBR) is a challenge in the treatment of low carbon/nitrogen (C/N) domestic sewage. In this study, the feasibility of the SNEDPR-AGSBR process was examined in an exceedingly single-stage anaerobic/aerobic/anoxic sequencing batch reactor for treating low C/N ratio (3.3-5.0) domestic sewage. The initial results showed that accompanied by the rapid formation of the mature aerobic granular sludge based on the selection for slow-growing organisms, the rapid start-up (38 d) of the SNEDPR-AGSBR process was successfully realized. The formed mature aerobic granules had a dense structure with an average diameter of 667.7 µm and SVI30 of 30.0 mL/g. Two conditions for achieving the competitive balance between phosphorus-accumulating organisms/denitrifying phosphorus-accumulating organisms (PAOs/DPAOs) and glycogen accumulating organisms/denitrifying glycogen accumulating organisms (GAOs/DGAOs) were revealed by the long-term operation results. First, the dissolved oxygen (DO) concentration needed to be decreased to 3.0 mg/L in the aerobic phase, and then, the aerobic and anoxic phase hydraulic retention time (HRT) should be increased to 3.0 h. Notably, high removal efficiencies for NH4+-N (100%), total nitrogen (84.3%), and P (91.8%) of the SNEDPR-AGSBR process were stably obtained with a low C/N ratio of 3.9 domestic sewage. Simultaneous nitrification and endogenous denitrification (SNED) efficiency of 61.6% was achieved during a long-term operation of 142 days. Finally, microbial community analysis confirmed that GAOs (Defluviicoccus)/DGAOs (Candidatus_Competibacter) were responsible for the removal N, and PAOs (Acinetobacter, Candidatus_Accumulibacter, Hypomicrobinm)/DPAOs (Pseudomonas and Dechloromonas) ensured P removal.

Pou3f1 mediates the effect of Nfatc3 on ulcerative colitis-associated colorectal cancer by regulating inflammation.

BACKGROUND: Ulcerative colitis-associated colorectal cancer (UC-CRC) is an important complication of ulcerative colitis. Pou3f1 (POU class 3 homeobox 1) is a critical regulator for developmental events and cellular biological processes. However, the role of Pou3f1 in the development of UC-CRC is unclear. METHODS: In vivo, a UC-CRC mouse model was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS). Body weight, colon length, mucosal damage, tumor formation, and survival rate were assessed to determine the progression of UC-CRC. Western blot, quantitative real-time PCR, ELISA, immunohistochemistry, immunofluorescence and TUNEL were performed to examine the severity of inflammation and tumorigenesis. In vitro, LPS-treated mouse bone marrow-derived macrophages (BMDMs) and RAW264.7 cells were used to study the role of Pou3f1 in inflammation. ChIP and luciferase reporter assays were used to confirm the interaction between Nfatc3 and Pou3f1. RESULTS: Pou3f1 expression was increased in the colons of UC-CRC mice, and its inhibition attenuated mucosal injury, reduced colon tumorigenesis and increased survival ratio. Knockdown of Pou3f1 suppressed cell proliferation and increased cell death in colon tumors. Both the in vivo and in vitro results showed that Pou3f1 depletion reduced the production of proinflammation mediators. In addition, ChIP and luciferase reporter assays demonstrated that Nfatc3 directly bound with the Pou3f1 promoter to induce its expression. The effect of Nfatc3 on the inflammatory response in macrophages was suppressed by Pou3f1 knockdown. CONCLUSION: Overall, it outlines that Pou3f1 mediates the role of Nfatc3 in regulating macrophage inflammation and carcinogenesis in UC-CRC development.

Cortical screw placement with a spinous process clamp guide: a cadaver study accessing accuracy.

BACKGROUND AND OBJECTIVE: The Cortical Bone Trajectory (CBT) technique provides an alternative method for fixation in the lumbar spine in patients with osteoporosis. An accuracy CBT screw placement could improve mechanical stability and reduce complication rates. PURPOSE: The purpose of this study is to explore the accuracy of cortical screw placement with the application of implanted spinous process clip (SPC) guide. METHODS AND MATERIALS: Four lumbar specimens with T12-S1 were used to access the accuracy of the cortical screw. The SPC-guided planning screws were compared to the actual inserted screws by superimposing the vertebrae and screws preoperative and postoperative CT scans. According to preoperative planning, the SPC guide was adjusted to the appropriate posture to allow the K-wire drilling along the planned trajectory. Pre and postoperative 3D-CT reconstructions was used to evaluate the screw accuracy according to Gertzbein and Robbins classification. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to examine SPC-guided agreements for CBT screw placement. RESULTS: A total of 48 screws were documented in the study. Clinically acceptable trajectory (grades A and B) was accessed in 100% of 48 screws in the planning screws group, and 93.8% of 48 screws in the inserted screws group (p = 0.242). The incidence of proximal facet joint violation (FJV) in the planning screws group (2.1%) was comparable to the inserted screws group (6.3%) (p = 0.617). The lateral angle and cranial angle of the planned screws (9.2 ± 1.8° and 22.8 ± 5.6°) were similar to inserted screws (9.1 ± 1.7° and 23.0 ± 5.1°, p = 0.662 and p = 0.760). Reliability evaluated by intraclass correlation coefficients and Bland-Altman showed good consistency in cranial angle and excellent results in lateral angle and distance of screw tip. CONCLUSIONS: Compared with preoperative planning screws and the actually inserted screws, the SPC guide could achieve reliable execution for cortical screw placement.

SmKFB5 protein regulates phenolic acid biosynthesis by controlling the degradation of phenylalanine ammonia-lyase in Salvia miltiorrhiza.

Phenolic acids are the major secondary metabolites and significant bioactive constituents of the medicinal plant Salvia miltiorrhiza. Many enzyme-encoding genes and transcription factors involved in the biosynthesis of phenolic acids have been identified, but the underlying post-translational regulatory mechanisms are poorly understood. Here, we demonstrate that the S. miltiorrhiza Kelch repeat F-box protein SmKFB5 physically interacts with three phenylalanine ammonia-lyase (PAL) isozymes and mediates their proteolytic turnover via the ubiquitin-26S proteasome pathway. Disturbing the expression of SmKFB5 reciprocally affected the abundance of SmPAL protein and the accumulation of phenolic acids, suggesting that SmKFB5 is a post-translational regulator responsible for the turnover of PAL and negatively controlling phenolic acids. Furthermore, we discovered that treatment of the hairy root of S. miltiorrhiza with methyl jasmonate suppressed the expression of SmKFB5 while inducing the transcription of SmPAL1 and SmPAL3. These data suggested that methyl jasmonate consolidated both transcriptional and post-translational regulation mechanisms to enhance phenolic acid biosynthesis. Taken together, our results provide insights into the molecular mechanisms by which SmKFB5 mediates the regulation of phenolic acid biosynthesis by jasmonic acid, and suggest valuable targets for plant breeders in tailoring new cultivars.

Investigation of control region sequences of mtDNA in Naqu Tibetan population from Northwestern China.

BACKGROUND: The sequence polymorphisms of mitochondrial DNA (mtDNA) are valuable in forensic medicine and anthropological genetics. AIM: We analysed the sequences of the mtDNA control region in 207 unrelated Tibetan individuals from the Naqu region, Tibet Autonomous Region in the People's Republic of China, and investigated the population structure of the region by population comparison with other groups. SUBJECTS AND METHODS: Genomic DNA was extracted and hypervariable regions (HVS-I and HVS-II) were amplified and sequenced. Subsequently, sequences were aligned and compared with the revised Cambridge sequence. Moreover, population comparison was performed between the Naqu Tibetan group and the other groups. CONCLUSION: Our study provided available data for exploring the mtDNA haplotype of the Tibetan population in the Naqu region, and population comparisons found that the Naqu Tibetan population has its own unique structure.

Pollution zone identification research during ozone pollution processes.

Identifying an ozone pollution zone during the pollution processes is significant for ozone pollution management and environmental health risk assessment. However, few studies have focused on ozone pollution zone identification during pollution processes. A spatial-temporal clustering framework for identifying pollution zones during ozone pollution processes was initially proposed in this study, and an ozone pollution process in China in May 2017 was selected as a case. The results showed that the framework can help selecting one more accurate method to identify the pollution zone according to the pollution characteristics of air pollution process. In addition, different ozone pollution zone identification methods work well in different scenarios: The self-organizing map (SOM) method was suitable for identifying the zone with the duration of pollution between 24 and 48 h, the image fusion based on wavelet transform (IFbWT) method for the zone with the duration of pollution over 48 h and the Apriori method for the zone with obvious boundaries between high-value and low-value ozone concentrations. The proposed procedure can also be applied to identify the pollution zone of the pollution process of other pollutants.

Improvement of butanol production by the development and co-culture of C. acetobutylicum TSH1 and B. cereus TSH2.

Butanol fermentation comprises two successive and distinct stages, namely acidogenesis and solventogenesis. The current lack of clarity regarding the underlying metabolic regulation of fermentation impedes improvements in biobutanol production. Here, a proteomics study was performed in the acidogenesis phase, the lowest pH point (transition point), and the solventogenesis phase in the butanol-producing symbiotic system TSH06. Forty-two Clostridium acetobutylicum proteins demonstrated differential expression levels at different stages. The protein level of butanol dehydrogenase increased in the solventogenesis phase, which was in accordance with the trend of butanol concentration. Stress proteins were upregulated either at the transition point or in the solventogenesis phase. The cell division-related protein Maf was upregulated at the transition point. We disrupted the maf gene in C. acetobutylicum TSH1, and Bacillus cereus TSH2 was added to form a new symbiotic system. TSH06△maf produced 13.9 ± 1.0 g/L butanol, which was higher than that of TSH06 (12.3 ± 0.9 g/L). Butanol was furtherly improved in fermentation at variable temperature with neutral red addition for both TSH06 and TSH06△maf. The butanol titer of the maf deletion strain was higher than that of the wild type, although the exact mechanism remains to be determined.

Visualization of microvasculature and thrombi by X-ray phase-contrast computed tomography in hepatocellular carcinoma.

Visualization of the microvascular network and thrombi in the microvasculature is a key step to evaluating the development of tumor growth and metastasis, and influences treatment selection. X-ray phase-contrast computed tomography (PCCT) is a new imaging technique that can detect minute changes of density and reveal soft tissues discrimination at micrometer-scale resolution. In this study, six human resected hepatocellular carcinoma (HCC) tissues were investigated with PCCT. A histological stain was added to estimate the accuracy of PCCT. The results showed that the fine structures of the microvasculature (measuring 30-100 µm) and thrombi in tiny blood vessels were displayed clearly on imaging the HCC tissues by PCCT. Moreover, density distributions of the thrombi were obtained, which could be reliably used to distinguish malignant from benign thrombi in HCC. In conclusion, PCCT can clearly show the three-dimensional subtle structures of HCC that cannot be detected by conventional absorption-based computed tomography and provides a new method for the imageology of HCC.

[Pharmacological activity of Terminalia chebula].

Terminalia chebula Retz, known as the "king" of Mongolian and Tibetan medicines, is a drug for a wide range of diseases. The main chemical components of myrobalan include triterpene acid, galloyl glucose, anthraquinonoid. The modern pharmacological studies show that myrobalan has multiple biological activities, including antimicrobial, anti-inflammatory, antioxidation as well as anti-tumor. Based on domestic and foreign literatures in recent years, this paper gave a review on the advance of studies for pharmacological activity of T. chebula. and its active components, so as to provide a reference for the in-depth studies on the pharmacological action of myrobalan, and the further development and utilization of myrobalan.

Full-featured electrochemiluminescence sensing platform based on the multichannel closed bipolar system.

In this work, we have developed a full-featured electrochemiluminescence (ECL) sensing platform based on a multichannel closed bipolar system. Owing to the three-channel and double-bipolar electrode (BPE) configuration, all the oxidants, reductants, or chemicals that are directly related to the ECL process can be detected in a single device, which greatly expanded the application range of the Ru(bpy)3(2+)-TPA (tripropylamine) anodic ECL reaction. First of all, a more universal and accurate mechanism for all the bipolar systems was proposed by observing the reactions that occurred in the device with universal pH indicator and ITO BPEs. On the basis of that, Pt was electrodeposited onto all the ITO cathodes to improve the signal stability and construct the multifunctional ECL sensor. With this design, the determination of H2O2, ascorbic acid (AA), TPA, glucose, and blood sugar were achieved in a single device. More importantly, we have demonstrated that the constructed sensor array can be used as a high-throughput molecular keypad lock in the visual ECL experiment. This design therefore shows great promise in various fields.

CylinderTag: An Accurate and Flexible Marker for Cylinder-Shape Objects Pose Estimation Based on Projective Invariants.

High-precision pose estimation based on visual markers has been a thriving research topic in the field of computer vision. However, the suitability of traditional flat markers on curved objects is limited due to the diverse shapes of curved surfaces, which hinders the development of high-precision pose estimation for curved objects. Therefore, this paper proposes a novel visual marker called CylinderTag, which is designed for developable curved surfaces such as cylindrical surfaces. CylinderTag is a cyclic marker that can be firmly attached to objects with a cylindrical shape. Leveraging the manifold assumption, the cross-ratio in projective invariance is utilized for encoding in the direction of zero curvature on the surface. Additionally, to facilitate the usage of CylinderTag, we propose a heuristic search-based marker generator and a high-performance recognizer as well. Moreover, an all-encompassing evaluation of CylinderTag properties is conducted by means of extensive experimentation, covering detection rate, detection speed, dictionary size, localization jitter, and pose estimation accuracy. CylinderTag showcases superior detection performance from varying view angles in comparison to traditional visual markers, accompanied by higher localization accuracy. Furthermore, CylinderTag boasts real-time detection capability and an extensive marker dictionary, offering enhanced versatility and practicality in a wide range of applications. Experimental results demonstrate that the CylinderTag is a highly promising visual marker for use on cylindrical-like surfaces, thus offering important guidance for future research on high-precision visual localization of cylinder-shaped objects. The code is available at: https://github.com/wsakobe/CylinderTag.

Carbon metabolism characteristics of quorum quenching bacteria Rhodococcus sp. BH4 determine the bioaugmentation efficiency under different carbon source conditions.

Carbon sources are critical factors influencing bacterial bioaugmentation, however, the underlying mechanisms, particularly the metabolic characteristics of bioaugmented bacteria remain poorly understood. The bioaugmented bacterium Rhodococcus sp. BH4 secretes the quorum quenching (QQ) enzyme QsdA to disrupt the quorum sensing (QS) in the activated sludge (AS) process, reducing AS yield in-situ. This study investigated the carbon metabolic characteristics of BH4 and explored the effects on bioaugmentation with different influent carbon sources. Because of the absence of glucose-specific phosphoenol phosphotransferase system (PTS), BH4 prefers sodium acetate to glucose. However, the lactones produced during extracellular glucose metabolism enhance BH4 qsdA expression. Moreover, BH4 possess carbon catabolite repression (CCR), acetate inhibits glucose utilization. BH4 microbeads were added to reactors with different carbon sources (R1: sodium acetate; R2: glucose; R3: a mixture of sodium acetate and glucose) for in-situ AS yield reduction. During operation, AS reduction efficiency decreased in the following order: R1 > R3 > R2. R2 and R3 microbeads exhibited similar QQ activity to R1, with less BH4 biomass at 5 d. 13C labeling and Michaelis-Menten equation showed that, due to differences in the competitiveness of carbon sources, R1 BH4 obtained the most carbon, whereas R2 BH4 obtained the least carbon. Moreover, acetate inhibited glucose utilization of R3 BH4. Transcriptome analysis showed that R1 BH4 qsdA expression was the lowest, R2 BH4 was the most serious form of programmed cell death, and the R3 BH4 PTS pathway was inhibited. At 10 d, R1 BH4 biomass and microbead QQ activity were higher than that in R3, and the R2 BH4 lost viability and QQ activity. This study provides new insights into bioaugmentation from the perspectives of carbon source competitiveness, carbon metabolism pathways, and CCR.

Is there a risk of further displacement of the fractured fragment into the spinal canal in osteoporotic vertebral burst fractures after unilateral PKP? A prospective study.

BACKGROUND CONTEXT: The optimal treatment for osteoporotic vertebral burst fracture (OVBF) without neurological symptoms is still a matter of debate. PURPOSE: To evaluate the safety and efficacy of percutaneous kyphoplasty (PKP) for OVBF. STUDY DESIGN: The study is a prospective study and is registered in the China Clinical Trials Registry with the registration number ChiCTR-OOC-17013227. PATIENT SAMPLE: The study involved 119 patients with 137 fractured vertebrae who underwent unilateral PKP for OVBF. OUTCOME MEASURES: The measurements were carried out independently by two physicians and measured with picture archiving and communication system (PACS) and ImageJ software (National Institutes of Health, Bethesda, MD, USA). METHODS: The change in the spinal canal area and posterior wall protrusions (PWP) were measured before and after surgery via three-dimensional computed tomographic imaging (CT). Preoperative, postoperative, and final follow-up standing X-rays were used to measure the height of the anterior wall (HAW), height of the posterior wall (HPW), and local kyphotic angle (LKA). Additionally, visual analogue scale (VAS) and the Oswestry Disability Index (ODI) were also determined. RESULTS: Among the 137 vertebrae assessed, 79 exhibited an increased postoperative canal area, while 57 showed a decrease, with mean values of 8.28±6.871 mm² and -9.04±5.991 mm², respectively. Notably, no significant change in postoperative canal area was identified on the entire dataset (p>.01). There was a significant decrease between median preoperative (3.9 [IQ1-IQ3=3.3-4.8] mm) and postoperative (3.7 [IQ1-IQ3=3.0-4.4] mm) PWP (p<.01). Preoperative and postoperative HAW measurements were 19.4±6.1 mm and 23.2±5.2 mm, respectively (p<.01). However, at the final follow-up, the HAW was lower than the postoperative value. The HPW was also significantly improved after surgery (p<.01), but at the final follow-up, it was significantly decreased compared with the postoperative measurement. Following surgery, KA was significantly corrected (p<.01); however, at the final follow-up, relapse was detected (average KA: 18.4±10.3°). At the final follow-up, both VAS and ODI were significantly improved compared with the preoperative period (p<.01). As for complications, 50 patients experienced cement leakage, and 16 patients experienced vertebral refracture. All patients did not develop neurological symptoms during the follow-up. CONCLUSIONS: OVBF without neurological deficits showed significant improvement in symptoms during the postoperative period after PKP. There was no notable alteration in the spinal canal area, but a significant decrease in PWP was observed. Consequently, we posit that PKP stands as a secure and efficacious surgical intervention for treating OVBF cases devoid of neurological symptoms.

Responses of the intestinal microbiota to exposure of okadaic acid in marine medaka Oryzias melastigma.

It is still limited that how the microalgal toxin okadaic acid (OA) affects the intestinal microbiota in marine fishes. In the present study, adult marine medaka Oryzias melastigma was exposed to the environmentally relevant concentration of OA (5 µg/L) for 10 days, and then recovered in fresh seawater for 10-days depuration. Analysis of taxonomic composition and diversity of the intestinal microbiota, as well as function prediction analysis and histology observation were carried out in this study. Functional prediction analysis indicated that OA potentially affected the development of colorectal cancer, protein and carbohydrate digestion and absorption functions, and development of neurodegenerative diseases like Parkinson's disease, which may be associated with changes in Proteobacteria and Firmicutes in marine medaka. Significant increases of C-reactive protein (CRP) and inducible nitric oxide synthase (iNOS) levels, as well as the changes of histology of intestinal tissue demonstrated that an intestinal inflammation was induced by OA exposure in marine medaka. This study showed that the environmental concentrations of OA could harm to the intestinal microbiota thus threatening the health of marine medaka, which hints that the chemical ecology of microalgal toxins should be paid attention to in future studies.

Non-filamentous bulking of activated sludge induced by graphene oxide: Insights from extracellular polymeric substances.

Widespread use of nanomaterials raises concerns. The underlying mechanism by which graphene oxide (GO) nanoparticles causes poor settleability of activated sludge remains unclear. To explore this mechanism, three reactors with different GO concentrations were established. Extended Derjaguin-Landau-Verwey-Overbeek theory indicated that GO destroyed the property of extracellular polymeric substances (EPS), increasing the energy barrier between bacteria. Low levels of uronic acid and hydrogen bonding in exopolysaccharide weakened the EPS gelation increasing aggregation repulsion. Lager amounts of hydrophilic amino acid and looser structure of extracellular proteins for exposing inner hydrophilic groups significantly contributed to the hydrophilicity of EPS. Both changes implied deterioration in EPS structure under GO stress. Metagenome demonstrated a decrease in genes responsible for capsular polysaccharide colonization and genes regulated the translocation of loose proteins were increased, which increased repulsion between bacteria. This study elucidated that changes in EPS secretion under GO exposure are the underlying causes of poor settleability.

HIV-1 NNRTIs: structural diversity, pharmacophore similarity, and implications for drug design.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) nowadays represent very potent and most promising anti-AIDS agents that specifically target the HIV-1 reverse transcriptase (RT). However, the effectiveness of NNRTI drugs can be hampered by rapid emergence of drug-resistant viruses and severe side effects upon long-term use. Therefore, there is an urgent need to develop novel, highly potent NNRTIs with broad spectrum antiviral activity and improved pharmacokinetic properties, and more efficient strategies that facilitate and shorten the drug discovery process would be extremely beneficial. Fortunately, the structural diversity of NNRTIs provided a wide space for novel lead discovery, and the pharmacophore similarity of NNRTIs gave valuable hints for lead discovery and optimization. More importantly, with the continued efforts in the development of computational tools and increased crystallographic information on RT/NNRTI complexes, structure-based approaches using a combination of traditional medicinal chemistry, structural biology, and computational chemistry are being used increasingly in the design of NNRTIs. First, this review covers two decades of research and development for various NNRTI families based on their chemical scaffolds, and then describes the structural similarity of NNRTIs. We have attempted to assemble a comprehensive overview of the general approaches in NNRTI lead discovery and optimization reported in the literature during the last decade. The successful applications of medicinal chemistry strategies, crystallography, and computational tools for designing novel NNRTIs are highlighted. Future directions for research are also outlined.

Synthesis and biological evaluation of pyridazine derivatives as novel HIV-1 NNRTIs.

In continuation of our efforts toward identification and optimization of novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), we have employed a structure-based bioisosterism strategy, with which a new series of diarylpyridazine (DAPD) derivatives were synthesized and evaluated for their anti-HIV-1 (human immunodeficiency virus type 1) activity. Most of the title compounds displayed excellent anti-HIV-1 activity at submicromolar concentrations ranging from 34 nM to 5.08 µM. The most promising compound 8g inhibited HIV-1 IIIB in MT-4 cells at a low EC50 value (0.034 µM), which was lower than the reference drug nevirapine and delavirdine. The structure activity relationships (SARs) were discussed and rationalized by docking simulations.