Effects of Toxin-Antitoxin System HicAB on Biofilm Formation by Extraintestinal Pathogenic E. coli.

The type II toxin-antitoxin (T-A) HicAB system is abundant in several bacteria and archaea, such as Escherichia coli, Burkholderia Pseudomallei, Yersinia pestis, Pseudomonas aeruginosa, and Streptococcus pneumoniae. This system engages in stress response, virulence, and bacterial persistence. This study showed that the biofilm-forming ability of the hicAB deletion mutant was significantly decreased to moderate ability compared to the extra-intestinal pathogenic Escherichia coli (ExPEC) parent strain and the complemented strain, which are strong biofilm producers. Congo red assay showed that the hicAB mutant maintained the ability to form curli fimbriae. Using RNA-seq and comparative real-time quantitative RT-PCR, we observed the difference in gene expression between the hicAB mutant and the parent strain, which was associated with biofilm formation. Our data indicate that the HicAB type II T-A system has a key role in biofilm formation by ExPEC, which may be associated with outer membrane protein (OMP) gene expression. Collectively, our results indicate that the hicAB type II T-A system is involved in ExPEC biofilm formation.

Gata4 regulates hedgehog signaling and Gata6 expression for outflow tract development.

Dominant mutations of Gata4, an essential cardiogenic transcription factor (TF), were known to cause outflow tract (OFT) defects in both human and mouse, but the underlying molecular mechanism was not clear. In this study, Gata4 haploinsufficiency in mice was found to result in OFT defects including double outlet right ventricle (DORV) and ventricular septum defects (VSDs). Gata4 was shown to be required for Hedgehog (Hh)-receiving progenitors within the second heart field (SHF) for normal OFT alignment. Restored cell proliferation in the SHF by knocking-down Pten failed to rescue OFT defects, suggesting that additional cell events under Gata4 regulation is important. SHF Hh-receiving cells failed to migrate properly into the proximal OFT cushion, which is associated with abnormal EMT and cell proliferation in Gata4 haploinsufficiency. The genetic interaction of Hh signaling and Gata4 is further demonstrated to be important for OFT development. Gata4 and Smo double heterozygotes displayed more severe OFT abnormalities including persistent truncus arteriosus (PTA). Restoration of Hedgehog signaling renormalized SHF cell proliferation and migration, and rescued OFT defects in Gata4 haploinsufficiency. In addition, there was enhanced Gata6 expression in the SHF of the Gata4 heterozygotes. The Gata4-responsive repressive sites were identified within 1kbp upstream of the transcription start site of Gata6 by both ChIP-qPCR and luciferase reporter assay. These results suggested a SHF regulatory network comprising of Gata4, Gata6 and Hh-signaling for OFT development.

IPD-Net: Infrared Pedestrian Detection Network via Adaptive Feature Extraction and Coordinate Information Fusion.

Infrared pedestrian detection has important theoretical research value and a wide range of application scenarios. Because of its special imaging method, infrared images can be used for pedestrian detection at night and in severe weather conditions. However, the lack of pedestrian feature information in infrared images and the small scale of pedestrian objects makes it difficult for detection networks to extract feature information and accurately detect small-scale pedestrians. To address these issues, this paper proposes an infrared pedestrian detection network based on YOLOv5, named IPD-Net. Firstly, an adaptive feature extraction module (AFEM) is designed in the backbone network section, in which a residual structure with stepwise selective kernel was included to enable the model to better extract feature information under different sizes of the receptive field. Secondly, a coordinate attention feature pyramid network (CA-FPN) is designed to enhance the deep feature map with location information through the coordinate attention module, so that the network gains better capability of object localization. Finally, shallow information is introduced into the feature fusion network to improve the detection accuracy of weak and small objects. Experimental results on the large infrared image dataset ZUT show that the mean Average Precision (mAP50) of our model is improved by 3.6% compared to that of YOLOv5s. In addition, IPD-Net shows various degrees of accuracy improvement compared to other excellent methods.

Gata4 potentiates second heart field proliferation and Hedgehog signaling for cardiac septation.

GATA4, an essential cardiogenic transcription factor, provides a model for dominant transcription factor mutations in human disease. Dominant GATA4 mutations cause congenital heart disease (CHD), specifically atrial and atrioventricular septal defects (ASDs and AVSDs). We found that second heart field (SHF)-specific Gata4 heterozygote embryos recapitulated the AVSDs observed in germline Gata4 heterozygote embryos. A proliferation defect of SHF atrial septum progenitors and hypoplasia of the dorsal mesenchymal protrusion, rather than anlage of the atrioventricular septum, were observed in this model. Knockdown of the cell-cycle repressor phosphatase and tensin homolog (Pten) restored cell-cycle progression and rescued the AVSDs. Gata4 mutants also demonstrated Hedgehog (Hh) signaling defects. Gata4 acts directly upstream of Hh components: Gata4 activated a cis-regulatory element at Gli1 in vitro and occupied the element in vivo. Remarkably, SHF-specific constitutive Hh signaling activation rescued AVSDs in Gata4 SHF-specific heterozygous knockout embryos. Pten expression was unchanged in Smoothened mutants, and Hh pathway genes were unchanged in Pten mutants, suggesting pathway independence. Thus, both the cell-cycle and Hh-signaling defects caused by dominant Gata4 mutations were required for CHD pathogenesis, suggesting a combinatorial model of disease causation by transcription factor haploinsufficiency.

Gene network and familial analyses uncover a gene network involving Tbx5/Osr1/Pcsk6 interaction in the second heart field for atrial septation.

Atrial septal defects (ASDs) are a common human congenital heart disease (CHD) that can be induced by genetic abnormalities. Our previous studies have demonstrated a genetic interaction between Tbx5 and Osr1 in the second heart field (SHF) for atrial septation. We hypothesized that Osr1 and Tbx5 share a common signaling networking and downstream targets for atrial septation. To identify this molecular networks, we acquired the RNA-Seq transcriptome data from the posterior SHF of wild-type, Tbx5(+/) (-), Osr1(+/-), Osr1(-/-) and Tbx5(+/-)/Osr1(+/-) mutant embryos. Gene set analysis was used to identify the Kyoto Encyclopedia of Genes and Genomes pathways that were affected by the doses of Tbx5 and Osr1. A gene network module involving Tbx5 and Osr1 was identified using a non-parametric distance metric, distance correlation. A subset of 10 core genes and gene-gene interactions in the network module were validated by gene expression alterations in posterior second heart field (pSHF) of Tbx5 and Osr1 transgenic mouse embryos, a time-course gene expression change during P19CL6 cell differentiation. Pcsk6 was one of the network module genes that were linked to Tbx5. We validated the direct regulation of Tbx5 on Pcsk6 using immunohistochemical staining of pSHF, ChIP-quantitative polymerase chain reaction and luciferase reporter assay. Importantly, we identified Pcsk6 as a novel gene associated with ASD via a human genotyping study of an ASD family. In summary, our study implicated a gene network involving Tbx5, Osr1 and Pcsk6 interaction in SHF for atrial septation, providing a molecular framework for understanding the role of Tbx5 in CHD ontogeny.

Pathogenicity and Whole Genome Sequence Analysis of a Pseudorabies Virus Strain FJ-2012 Isolated from Fujian, Southern China.

The outbreaks of pseudorabies have been frequently reported in Bartha-K61-vaccinated farms in China since 2011. To study the pathogenicity and evolution of the circulating pseudorabies viruses in Fujian Province, mainland China, we isolated and sequenced the whole genome of a wild-type pseudorabies virus strain named "FJ-2012." We then conducted a few downstream bioinformatics analyses including phylogenetic analysis and pathogenic analysis and used the virus to infect 6 pseudorabies virus-free piglets. FJ-2012-infected piglets developed symptoms like high body temperature and central nervous system disorders and had high mortality rate. In addition, we identified typical micropathological changes such as multiple gross lesions in infected piglets through pathological analysis and conclude that the FJ-2012 genome is significantly different from known pseudorabies viruses, in which insertions, deletions, and substitutions are observed in multiple immune and virulence genes. In summary, this study shed lights on the molecular basis of the prevalence and pathology of the pseudorabies virus strain FJ-2012. The genome of FJ-2012 could be used as a reference to study the evolution of pseudorabies viruses, which is critical to the vaccine development of new emerging pseudorabies viruses.

Piezoelectric tuning of narrowband perfect plasmonic absorbers via an optomechanic cavity.

Optical antennas enable the control of light-matter interaction on the nanometer scale. Efficient on-chip electrical switching of plasmonic resonances is a crucial step toward the integration of optical antennas into practical optoelectronic circuits. We propose and numerically investigate the on-chip low-voltage linear electrical tuning of a narrowband optical antenna perfect absorber via a piezoelectric optomechanic cavity. Near unity absorption is realized by an array of gold nanostrip antennas separated from a membrane-based deformable backreflector by a small gap. A narrow linewidth of 33 nm at 2.58 µm is realized through the coupling between the plasmonic mode and photonic mode in the cavity-enhanced antenna structure. An aluminum nitride piezoelectric layer enabled efficient actuation of the backreflector and therefore changed the gap size, allowing for the tuning of the spectral absorption. The peak wavelength can be shifted linearly by 250 nm with 10 V of tuning voltage, and the tuning range is not limited by the pull-in effect. The polarization dependence of the nanostrip antenna coupled with the optomechanic cavity allows the use of our device as a voltage tunable polarization control device.

Application of liquid chromatographic/tandem mass spectrometric method to a urinary excretion study of subutinib and active metabolite in human urine.

A novel and selective liquid chromatographic-mass spectrometric method (LC-MS/MS) has been established and validated for simultaneous determination of subutinib and active metabolite in human urine. Urine samples were extracted by liquid-liquid extraction with ethyl acetate and separated on a Wondasil C18 (150 × 2.1 mm, 3.5 µm), with methanol-0.2% formic acid solution (73:27, v/v) as mobile phase at flow rate of 0.2 mL/min. The linear range was 0.5000-200.0 ng/mL for subutinib and active metabolite, with a lower limit of quantitation of 0.5000 ng/mL. Intra- and inter-run precisions were all <11.8 and 14.3%, and the accuracies were all <4.5 and 5.4%, with the extraction recoveries 88.8-97.5 and 93.8-99.4% for the two analytes, respectively. The carryover values were all <15% for the two anayltes. The method was successfully applied to study urinary excretion of subutinib and active metabolite in human after oral administration of subutinib maleate capsules in fed and fasting states.

Tbx5 and Osr1 interact to regulate posterior second heart field cell cycle progression for cardiac septation.

RATIONALE: Mutations of TBX5 cause Holt-Oram syndrome (HOS) in humans, a disease characterized by atrial or occasionally ventricular septal defects in the heart and skeletal abnormalities of the upper extremity. Previous studies have demonstrated that Tbx5 regulates Osr1 expression in the second heart field (SHF) of E9.5 mouse embryos. However, it is unknown whether and how Tbx5 and Osr1 interact in atrial septation. OBJECTIVE: To determine if and how Tbx5 and Osr1 interact in the posterior SHF for cardiac septation. METHODS AND RESULTS: In the present study, genetic inducible fate mapping showed that Osr1-expressing cells contribute to atrial septum progenitors between E8.0 and E11.0. Osr1 expression in the pSHF was dependent on the level of Tbx5 at E8.5 and E9.5 but not E10.5, suggesting that the embryo stage before E10.5 is critical for Tbx5 interacting with Osr1 in atrial septation. Significantly more atrioventricular septal defects (AVSDs) were observed in embryos with compound haploinsufficiency for Tbx5 and Osr1. Conditional compound haploinsufficiency for Tbx5 and Osr1 resulted in a significant cell proliferation defect in the SHF, which was associated with fewer cells in the G2 and M phases and a decreased level of Cdk6 expression. Remarkably, genetically targeted disruption of Pten expression in atrial septum progenitors rescued AVSDs caused by Tbx5 and Osr1 compound haploinsufficiency. There was a significant decrease in Smo expression, which is a Hedgehog (Hh) signaling pathway modulator, in the pSHF of Osr1 knockout embryos at E9.5, implying a role for Osr1 in regulating Hh signaling. CONCLUSIONS: Tbx5 and Osr1 interact to regulate posterior SHF cell cycle progression for cardiac septation.

Simultaneous natural attenuation of Cr(VI) and nitrate in the hyporheic zone sediments from an upstream tributary of the Jinsha River in the Sichuan Basin.

The coexistence of hexavalent chromium (Cr(VI)) and nitrate (NO3-) in groundwater and surface water presents a considerable challenge for the natural attenuation of these two contaminants because their interactions in nature remain contentious. This study investigated the interplay between Cr(VI) and NO3- in hyporheic zone (HZ) sediments by integrating Cr(VI) reduction kinetics, NO3- transformation, microbial community structure, and a three-rate model. The concurrent natural attenuation of Cr(VI) and NO3- in the sediments was significantly influenced by their initial concentrations and redox conditions. The reduction of low concentrations of Cr(VI) (37.1 and 96.2 µM) was slightly enhanced by NO3-, while inhibitory effects were observed at high concentrations of Cr(VI) (200.0 µM). However, except for an initial low concentration of Cr(VI) (37.1 µM) and NO3- (450 µM), the reduction of NO3- was adversely affected by Cr(VI). The reduction rates and efficiencies of Cr(VI) and NO3- were noticeably lower under aerobic conditions than under anaerobic conditions. This phenomenon can be attributed to the presence of O2, which decreased the selectivity of sediments-associated Fe(II) towards Cr(VI) and NO3- and induced alterations in the microbial community structure, leading to subsequent changes in NO3- transformation. Furthermore, the three-rate model represents a robust approach for elucidating the reduction of Cr(VI) in the presence of co-contaminants, such as NO3- contamination under diverse redox conditions. This study provides further insights into the interaction mechanism between Cr(VI) and NO3- within the HZ, necessitating the consideration of the microbial toxicity of Cr(VI) and electron competition among Cr(VI), NO3-, and O2.

Ribonucleotide reductase small subunit M2 serves as a prognostic biomarker and predicts poor survival of colorectal cancers.

The overexpression of RRM2 [RR (ribonucleotide reductase) small subunit M2] dramatically enhances the ability of the cancer cell to proliferate and to invade. To investigate further the relevance of RRM2 and CRCs (colorectal cancers), we correlated the expression of RRM2 with the clinical outcome of CRCs. A retrospective outcome study was conducted on CRCs collected from the COH [(City of Hope) National Medical Center, 217 cases] and ZJU (Zhejiang University, 220 cases). IHC (immunohistochemistry) was employed to determine the protein expression level of RRM2, and quantitative real-time PCR was employed to validate. Multivariate logistic analysis indicated that the adjusted ORs (odds ratios) of RRM2-high for distant metastases were 2.06 [95% CI (confidence interval), 1.01-4.30] and 5.89 (95% CI, 1.51-39.13) in the COH and ZJU sets respectively. The Kaplan-Meier analysis displayed that high expression of RRM2 had a negative impact on the OS (overall survival) and PFS (progress-free survival) of CRC in both sets significantly. The multivariate Cox analysis further demonstrated that HRs (hazard ratios) of RRM2-high for OS were 1.88 (95% CI, 1.03-3.36) and 2.06 (95% CI, 1.10-4.00) in the COH and ZJU sets respectively. Stratification analysis demonstrated that the HR of RRM2 dramatically increased to 12.22 (95% CI, 1.62-258.31) in the MMR (mismatch repair) gene-deficient subgroup in the COH set. Meanwhile, a real-time study demonstrated that down-regulation of RRM2 by siRNA (small interfering RNA) could significantly and specifically reduce the cell growth and adhesion ability in HT-29 and HCT-8 cells. Therefore RRM2 is an independent prognostic factor and predicts poor survival of CRCs. It is also a potential predictor for identifying good responders to chemotherapy for CRCs.

High Prevalence, Genetic Diversity, and Recombination of Porcine Sapelovirus in Pig Farms in Fujian, Southern China.

Porcine sapelovirus (PSV) is a ubiquitous virus in farmed pigs that is associated with SMEDI syndrome, polioencephalomyelitis, and diarrhea. However, there are few reports on the prevalence and molecular characterization of PSV in Fujian Province, Southern China. In this study, the prevalence of PSV and a poetical combinative strain PSV2020 were characterized using real-time PCR, sequencing, and bioinformatics analysis. As a result, an overall sample prevalence of 30.8% was detected in 260 fecal samples, and a farm prevalence of 76.7% was observed in 30 Fujian pig farms, from 2020 to 2022. Noteably, a high rate of PSV was found in sucking pigs. Bioinformatics analysis showed that the full-length genome of PSV2020 was 7550 bp, and the genetic evolution of its ORF region was closest to the G1 subgroup, which was isolated from Asia and America; the similarity of nucleotides and amino acids to other PSVs was 59.5~88.7% and 51.7~97.0%, respectively. However, VP1 genetic evolution analysis showed a distinct phylogenetic topology from the ORF region; PSV2020 VP1 was closer to the DIAPD5469-10 strain isolated from Italy than strains isolated from Asia and America, which comprise the G1 subgroup based on the ORF region. Amino acid discrepancy analysis illustrated that the PSV2020 VP1 gene inserted twelve additional nucleotides, corresponding to four additional amino acids (STAE) at positions 898-902 AAs. Moreover, a potential recombination signal was observed in the 2A coding region, near the 3' end of VP1, owing to recombination analysis. Additionally, 3D genetic evolutionary analysis showed that all reference strains demonstrated, to some degree, regional conservation. These results suggested that PSV was highly prevalent in Fujian pig farms, and PSV2020, a PSV-1 genotype strain, showed gene diversity and recombination in evolutionary progress. This study also laid a scientific foundation for the investigation of PSV epidemiology, molecular genetic characteristics, and vaccine development.

Guggulsterone from Commiphora mukul potentiates anti-glioblastoma efficacy of temozolomide in vitro and in vivo via down-regulating EGFR/PI3K/Akt signaling and NF-κB activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Myrrh is an aromatic oleo-gum resin extracted from the stem of Commiphora myrrha (Nees) Engl., and has the efficacies to promote blood circulation and remove blood stasis. Myrrh is mainly used for the treatment of chronic diseases including cancer. Guggulsterone, a major active steroid extracted from myrrh, has been found to inhibit cancer cell growth. Glioblastoma is the most common malignancy of central nervous system, and its prognosis remains very poor mainly due to chemotherapeutic resistance. The active status of EGFR/PI3K/Akt and NF-κB signaling in glioblastoma contributed to poor response for chemotherapy, and blocking this signaling with antagonists sensitized glioblastoma cells to chemotherapy. AIM OF THE STUDY: The present study will investigate whether guggulsterone potentiates the anti-glioblastoma efficacy of temozolomide by down-regulating EGFR/PI3K/Akt signaling and NF-κB activation. MATERIALS AND METHODS: Cell viability and proliferation was determined by cell counting Kit-8 and colony formation assays. Cell apoptosis was evaluated by Annexin V/PI and hoechst 33342 staining assays. Molecular techniques such as western blotting and real-time quantitative PCR were used to demonstrate guggulsterone in vitro effect on EGFR/PI3K/Akt signaling and NF-κB activation. Finally, in vivo studies were performed in orthotopic mouse models of glioblastoma. RESULTS: The results demonstrated that guggulsterone enhanced temozolomide-induced growth inhibition and apoptosis in human glioblastoma U251 and U87 cells. Furthermore, the synergistic anti-glioblastoma efficacy between guggulsterone and temozolomide was intimately associated with the inhibition of EGFR/PI3K/Akt signaling and NF-κB activation in U251 and U87 cells. Our in vivo results on orthotopic xenograft models similarly indicated that guggulsterone potentiated temozolomide-induced tumor growth inhibition through suppressing EGFR/PI3K/Akt signaling pathway and NF-кB activity. CONCLUSIONS: The present study suggested that guggulsterone potentiated anti-glioblastoma efficacy of temozolomide through down-regulating EGFR/PI3K/Akt signaling pathway and NF-кB activation.

MTNet: A combined diagnosis algorithm of vessel segmentation and diabetic retinopathy for retinal images.

Medical studies have shown that the condition of human retinal vessels may reveal the physiological structure of the relationship between age-related macular degeneration, glaucoma, atherosclerosis, cataracts, diabetic retinopathy, and other ophthalmic diseases and systemic diseases, and their abnormal changes often serve as a diagnostic basis for the severity of the condition. In this paper, we design and implement a deep learning-based algorithm for automatic segmentation of retinal vessel (CSP_UNet). It mainly adopts a U-shaped structure composed of an encoder and a decoder and utilizes a cross-stage local connectivity mechanism, attention mechanism, and multi-scale fusion, which can obtain better segmentation results with limited data set capacity. The experimental results show that compared with several existing classical algorithms, the proposed algorithm has the highest blood vessel intersection ratio on the dataset composed of four retinal fundus images, reaching 0.6674. Then, based on the CSP_UNet and introducing hard parameter sharing in multi-task learning, we innovatively propose a combined diagnosis algorithm vessel segmentation and diabetic retinopathy for retinal images (MTNet). The experiments show that the diagnostic accuracy of the MTNet algorithm is higher than that of the single task, with 0.4% higher vessel segmentation IoU and 5.2% higher diagnostic accuracy of diabetic retinopathy classification.

Research on Filling Strategy of Pipeline Multi-Layer Welding for Compound Narrow Gap Groove.

With the increase in transmission pressure and pipe diameter of long-distance oil and gas pipelines, automatic welding of the pipeline has become the mainstream welding method. The multi-layer and multi-pass welding path planning of large-diameter pipelines with typical narrow gap grooves are studied, and a welding strategy for pipeline external welding robot is proposed. By analyzing the shape of the weld bead section of the narrow gap groove and comparing the advantages and disadvantages of the equal-height method and the equal-area method, the mathematical model of the filling layer is established. Through the test and analysis in the workshop, the predicted lifting value meets the actual welding requirements. The microstructure of the weld was analyzed by SEM. The main structure of the weld was fine acicular ferrite, which could improve the mechanical properties of the welded joint. After multi-layer filling, the filling layer is flush with the edge of the groove. The establishment of this model lays a foundation for the formulation of welding process parameters for large-diameter pipes and the off-line programming of welding procedures.

Study on the Pyrolysis and Adsorption Behavior of Activated Carbon Derived from Waste Polyester Textiles with Different Metal Salts.

In this study, the effects of the catalysis of heavy metals on the pyrolysis of waste polyester textiles (WPTs) and the adsorption behaviors of the pyrolysis products of WPTs for Cr(VI) were explored. TG-DTG analysis indicated that the metal ions catalyzed the pyrolysis process by reducing the temperature of the decomposition of WPTs. The surface morphology and pore structure of the carbons were analyzed using SEM and BET. The results demonstrated that Zn-AC possessed the largest specific surface area of 847.87 m2/g. The abundant acidic functional groups on the surface of the activated carbons were proved to be involved in the Cr(VI) adsorption process via FTIR analysis. Cr(VI) adsorption experiments indicated that the adsorption process was more favorable at low pH conditions, and the maximum adsorption capacities of Zn-AC, Fe-AC, and Cu-AC for Cr(VI) were 199.07, 136.25, and 84.47 mg/g, respectively. The FTIR and XPS analyses of the carbons after Cr(VI) adsorption, combined with the adsorption kinetics and isotherm simulations, demonstrated that the adsorption mechanism includes pore filling, an electrostatic effect, a reduction reaction, and complexation. This study showed that metal salts catalyze the pyrolysis processes of WPTs, and the activated carbons derived from waste polyester textiles are promising adsorbents for Cr(VI) removal.

The Immune Efficacy of Inactivated Pseudorabies Vaccine Prepared from FJ-2012ΔgE/gI Strain.

An emerging pseudorabies virus (PRV) variant has been reported on Bartha-K61-vaccinated farms since 2011, causing great economic losses to China's swine-feeding industry. In this study, two vaccines, FJ-2012ΔgE/gI-GEL02 and FJ-2012ΔgE/gI-206VG, were administered to piglets for immune efficacy investigation. Humoral immunity response, clinical signs, survival rate, tissue viral load, and pathology were assessed in piglets. The results showed that both vaccines were effective against the PRV FJ-2012 challenge, the piglets all survived while developing a high level of gB-specific antibody and neutralizing antibody, the virus load in tissue was alleviated, and no clinical PR signs or pathological lesions were displayed. In the unimmunized challenged group, typical clinical signs of pseudorabies were observed, and the piglets all died at 7 days post-challenge. Compared with commercial vaccines, the Bartha-K61 vaccine group could not provide full protection, which might be due to a lower vaccine dose; the inactivated vaccine vPRV* group piglets survived, displaying mild clinical signs. The asterisk denotes inactivation. These results indicate that FJ-2012ΔgE/gI-GEL02 and FJ-2012ΔgE/gI-206VG were effective and could be promising vaccines to control or eradicate the new PRV epidemic in China.

Formononetin Inhibits Hepatic I/R-Induced Injury through Regulating PHB2/PINK1/Parkin Pathway.

Formononetin (FN), an isoflavone compound mainly isolated from soy and red clover, had showed its anti-inflammation, antioxidative effects in some degenerative diseases and cholestasis. However, the role of FN in protecting ischemia/reperfusion- (I/R-) induced liver injury and the possible mechanism were unclear. In this study, effects of FN on liver injury were investigated in a rat hepatic I/R model; further, mitophagy-related proteins were measured by immunoblotting or immunofluorescence. The possible roles of PHB2 and PINK1 in regulating mitophagy by FN were verified using adeno-associated virus knockdown. The results showed that FN had protective effects against hepatic I/R injury through regulating PINK1/Parkin-regulated mitophagy. Further, we found that FN inhibited PARL expression and prevented PGAM5 cropped by increasing the expression of PHB2. The knockdown of PINK1 or PHB2 both abolished the protective effects of FN. Taken together, our findings indicated that the isoflavone compound FN promoted PHB2/PINK1/Parkin-mediated mitophagy pathway to protect liver from I/R-induced injury. These results provided novel insights into the potential prevention strategies of FN and its underlying mechanisms.

Effect of the rapid increase of salinity on anoxic-oxic biofilm reactor for treatment of high-salt and high-ammonia-nitrogen wastewater.

The washing wastewater from the desulfuration and denitration of power plants has high salt (chloride and sulfate) and ammonia-nitrogen concentrations and is difficult to treat using microbiological methods. A novel anoxic/oxic biofilm process was developed to remove ammonia from wastewater. Three rapid strategies (sulfate concentration was increased from 0 to 60 g/L in 6, 13, and 22 days (R1, R2, and R3, respectively)) were applied and produced biofilm with the same nitrification capacity as slow strategies (100-203 days). Excessive organics inhibited the nitrification capacity of the biofilm. R1 excelled at ammonia removal (from 30% to 95%, 70 mg/(L·d), with an effluent ammonia concentration of 4 mg/L) at 60 g/L salinity after the organic load was reduced. The content of extracellular polymeric substances in biofilm depended on its capacity to remove organics. Pseudomonas and Thauera were enriched in the three reactors. Controlling the organic load might prevent the sulfur cycle.

Acute Kidney Injury Is Associated With In-hospital Mortality in Older Patients With COVID-19.

BACKGROUND: The epidemic of COVID-19 presents a special threat to older adults. However, information on kidney damage in older patients with COVID-19 is limited. Acute kidney injury (AKI) is common in hospitalized adults and associated with poor prognosis. We sought to explore the association between AKI and mortality in older patients with COVID-19. METHODS: We conducted a retrospective, observational cohort study in a large tertiary care university hospital in Wuhan, China. All consecutive inpatients older than 65 years with COVID-19 were enrolled in this cohort. Demographic data, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between patients with AKI and without AKI. The association between AKI and mortality was analyzed. RESULTS: Of 1764 in-hospital patients, 882 older adult cases were included in this cohort. The median age was 71 years (interquartile range: 68-77), 440 (49.9%) were men. The most presented comorbidity was cardiovascular diseases (58.2%), followed by diabetes (31.4%). Of 882 older patients, 115 (13%) developed AKI and 128 (14.5%) died. Patients with AKI had higher mortality than those without AKI (68 [59.1%] vs 60 [7.8%]; p < .001). Multivariable Cox regression analysis showed that increasing odds of in-hospital mortality are associated with higher interleukin-6 on admission, myocardial injury, and AKI. CONCLUSIONS: Acute kidney injury is not an uncommon complication in older patients with COVID-19 but is associated with a high risk of death. Physicians should be aware of the risk of AKI in older patients with COVID-19.