Diisoprenyl-cyclohexene-type meroterpenoids from a mangrove endophytic fungus Aspergillus sp. GXNU-Y65 and their anti-nonalcoholic steatohepatitis activity in AML12 cells.

Nine previously undescribed diisoprenyl-cyclohexene-type meroterpenoids, aspergienynes A-I, together with five known analogues, were obtained from the mangrove endophytic fungal strain Aspergillus sp. GXNU-Y65. The diisoprenyl-cyclohexene-type meroterpenoids were elucidated based on multispectroscopic analysis, and the previously undescribed compounds' absolute configurations were established via electronic circular dichroism calculations. Biological activity results indicated that aspergienyne C (compound 3) had strong anti-nonalcoholic steatohepatitis activity against AML12 cells treated with PA (Palmitic acid) + OA (Oleic acid). At the same concentration of 20 µM, 3 significantly reduced triglyceride (TG) content compared with fenofibrate (positive control) in PA + OA treated AML12 cells, and obviously increased phosphorylation of acetyl-CoA carboxylase.

Photochemical reductive deamination of alpha-amino aryl alkyl ketones.

Photochemical reductive deamination of alpha-amino aryl alkyl ketones under photosensitizer-free conditions is presented. This protocol features high efficiency and selectivity. A plausible reaction pathway is proposed based on ultraviolet-visible absorption investigation, control experiments and deuterium-labelling studies. Mechanistic study reveals that the alpha-hydrogen atom of the ketone product originated from water.

The Role of Surveillance Inspections in Reducing False-Positives of SARS-CoV-2 Omicron Variants during the COVID-19 Epidemic.

Objective: This study aims to assess the effectiveness of surveillance inspections conducted by the provincial health committee in Quanzhou city during a COVID-19 outbreak in reducing false-positive results in SARS-CoV-2 RT-PCR assays. Method: The team conducted on-site inspections of laboratories that participated in mass screening, recording any violations of rules. Results: The positive cases in five rounds of mass screening were 23, 173, and 4 in Licheng District, Fengze District, and Luojang District, respectively. The false-positive rates in the five rounds of mass screening were 0.0099%, 0.0063%, 0.0018%, 0.0006%, and 0%, respectively. The study also recorded that the number of violations in the seven selected laboratories was 36, 68, 69, 42, 60, 54 and 47. The corresponding false-positive rates were 0.0012%, 0.0060%, 0.0082%, 0.0032%, 0.0060%, 0.0027%, and 0.0021%, respectively. The study found a positive correlation between false-positive rates and the number of violations (r = 0.905, P=0.005), and an inverse correlation between false-positive rates and the frequency of surveillance inspections (r = -0.950, P < 0.001). Conclusion: Daily surveillance inspection in laboratories can remind laboratories to strictly comply with standard procedures, focus on laboratory quality control, and reduce the occurrence of false-positive cases in SARS-CoV-2 nucleic acid tests to some extent. This study recommends that government decision-making departments establish policies and arrange experts to conduct daily surveillance inspections to improve laboratory quality control.

The fluorescence and colorimetric dual-readout probe for clinical rapid detection of mycophenolic acid by the poly(ethylenimine)/silica-coated CdTe quantum dots.

It is particularly meaningful to therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) for transplant patients to maximize the drug efficacy and minimize the adverse effect. In this study, a novel fluorescence and colorimetric dual-readout probe was put forward to fast and reliable detect MPA. The blue fluorescence of MPA was largely enhanced in the presence of poly (ethylenimine) (PEI), while the red fluorescence of CdTe@SiO2 (silica-coated CdTe quantum dots) provided a reliable reference signal. Hence, combining PEI70,000 and CdTe@SiO2, a fluorescence and colorimetric dual-readout probe could be constructed. For fluorescence measurement of MPA, the linearity was obtained in the MPA concentration range of 0.5-50 µg/mL, with a limit of detection (LOD) of 33 ng/mL. For the visual detection, the fluorescent colorimetric card was established in the MPA concentration from 0.5 to 50 µg/mL corresponding to the fluorescence color from red to violet and then to blue, which could be used for semi-quantification. Furthermore, in the light of the ColorCollect APP by the smartphone, the ratio of blue and red brightness values was linear with the MPA concentration from 1 to 50 µg/mL; thus, quantification of MPA could be realized by APP with the LOD of 83 ng/mL. The developed method was successfully applied to the analysis of MPA in the plasma samples of three patients after oral administration of mycophenolate mofetil, which was the prodrug of MPA. The result was comparable to those obtained by the clinically widely-used enzyme multiplied immunoassay technique. The developed probe was fast, cost-effective and operational convenience, and possessed high potential for TDM of MPA.

Nonabelian Ginzburg-Landau theory for ferroelectrics.

The Ginzburg-Landau theory, which was introduced to phenomenologically describe the destruction of superconductivity by a magnetic field at the beginning, has brought up much more knowledge beyond the original one as a mean-field theory of thermodynamics states. There the complex order parameter plays an important role. Here we propose a macroscopic theory to describe the features of ferroelectrics by a two-component complex order parameter coupled to nonabelian gauge potentials that provide more freedom to reflect interplays between different measurables. Within this theoretical framework, some recently discovered empirical static and time-independent phenomena, such as vortex, anti-vortex, spiral orders can be obtained as solutions for different gauge potentials. It is expected to bring in a new angle of view with more elucidation than the traditional one that takes the polarization as order parameter.

Comparative analysis of the endophytic bacteria inhabiting the phyllosphere of aquatic fern Azolla species by high-throughput sequencing.

BACKGROUND: Azolla is a small floating fern living in symbiosis with nitrogen-fixing cyanobacteria and provides a variety of important ecosystem benefits. Previous studies have presented that Azolla harbors diverse bacteria that may play a key role in host fitness and productivity. However, the characteristics of endophytic bacteria inhabiting the phyllosphere of different species of Azolla have not yet been fully understood. RESULTS: In this study, the 16S ribosomal DNA (rDNA) V5-V7 region of bacteria was determined by Illumina high-throughput sequencing platform to study the diversity and richness of endophytic bacterial communities in the phyllosphere of five Azolla species collected from different countries. A total of 1150 operational taxonomic units (OTUs) were detected for the endophytic bacteria community. According to the α diversity indices, the diversity of bacteria was ordered as Azolla imbricata > A. pinnata > A. filiculoides > A. mexicana > A. caroliniana. The PCoA results displayed that the bacterial communities of A. mexicana and A. caroliniana shared the highest similarity, followed by the similarity between A. pinnata and A. imbricata, and they were significantly distinct from the community of A. filiculoides. The dominant bacteria of Azolla mainly belonged to the phylum of Proteobacteria, followed by Actinobacteria, Chlorobillobacteria, and Firmicutes. In detail, the relative abundance of Proteobacteria in A. imbricata was 52.23%, whereas it was more than 80.00% in the other four species of Azolla. Notably, Herbaspirillum (45.91%, 44.08%) and Methylophilus (29.97%, 37.96%) were the main genera inhabiting A. mexicana and A. caroliniana respectively. Ferrovibrio (18.54%) and Rhizobium (16.68%) were the dominant genera inhabiting A. filiculoides. The group of unidentified genera (41.63%, 44.92%) consisted most of the bacteria in A. imbricata and A. pinnata respectively. Further analysis suggested that the significant different bacteria identified in LDA Effect Size analysis existed Azolla species-specific patterns. CONCLUSIONS: In summary, all results suggested that the diversity and composition of the endophytic bacterial communities were different in Azolla species.

Pre-expanded muscle-sparing Latissimus Dorsi free flap: An ideal option for the reconstruction of extensive anterior knee contractures.

BACKGROUND: Extensive and complex contractures in the anterior knee area can pose a significant challenge for reconstruction due to insufficient skin and soft tissue coverage and poor cosmetic and functional outcomes using traditional methods. We presented our experience with pre-expanded muscle-sparing latissimus dorsi (LD) free flap as an alternative option for large-scale anterior knee reconstruction. METHODS: From January 2016 to December 2020, we applied this surgical technique in six patients with large postburn or post-traumatic contractures of the anterior knee. After tissue expansion of several months, the expanded muscle-sparing LD free flap was harvested and transferred to resurface the lesions. Operative procedures, postoperative complications, and long-term outcomes were evaluated. RESULTS: A total of six patients aged 7 to 32 years (mean: 20 years) were reconstructed successfully without any major complication. The flap ranged from 20 × 8 cm to 40 × 16 cm. All donor sites were primarily closed. Follow-up (range: 12 to 24 months) evaluation showed satisfactory results in both cosmetic and functional aspects. CONCLUSIONS: Pre-expanded muscle-sparing LD free flap is a reliable and effective choice for extensive anterior knee contracture reconstruction with satisfactory esthetic and functional outcome. It can provide substantial amount of soft tissue coverage with minimal complications and donor-site morbidity. Furthermore, it offers a good basis for next-step orthopedic surgery, such as total knee arthroplasty (TKA).

Comparisons between short-peptide formula and intact-protein formula for early enteral nutrition initiation in patients with acute gastrointestinal injury: a single-center retrospective cohort study.

Background: Early enteral nutrition (EN) in critically ill patients is important and most of them have suffered acute gastrointestinal injury (AGI). In this study, we investigated the influence of short-peptide EN formula and intact-protein EN formula on the prognosis of patients with AGI grades I-II to provide some guidance. Methods: A retrospective cohort study was performed. The primary outcomes were the percentage of EN calories (25 kcal/kg/d) and protein (1.2 g/kg/d) on the 3rd and 7th days of intensive care unit (ICU) admission, EN percent elevation in calories and protein on days 3-7, and the incidence of gastric retention and diarrhea after EN administration. Secondary outcomes included ICU and 28-day mortality, length of ICU stay, total hospitalization cost, and ventilator-free days. Univariate and multivariate Cox regression analysis was used to identify factors associated with gastric retention and diarrhea. And we used Kaplan-Meier survival curves to compare 28-day mortality rates between the two groups. Results: There were no statistically significant differences in ICU and 28-day mortality, ICU length of stay, total hospitalization cost, or ventilator-free days in the short-peptide formula group compared with the intact-protein formula group. Kaplan-Meier survival curves of 28-day mortality also showed no statistically significant difference. The EN percent elevation in calories and protein on days 3-7 in the short-peptide formula group was significantly higher than the intact-protein formula group (48% vs. 38%, P=0.03 and 37% vs. 38%, P=0.04, respectively). For gastrointestinal (GI) adverse events, the incidence of gastric retention (15.5% vs. 29.8%, P=0.03) and diarrhea (8.5% vs. 19.8%, P=0.04) were lower in the short-peptide group. In the multivariate-adjusted model, the use of short-peptide formula was the only independent variable of reduction in gastric retention and diarrhea [HR =0.469 (95% CI: 0.239-0.922), P=0.028; and HR =0.394 (95% CI: 0.161-0.965), P=0.041, respectively]. Conclusions: Short-peptide formula is more easily tolerated by patients in the acute phase of AGI and can quickly achieve nutritional goals by EN provision, making it the preferred formula for the initiation of EN in the acute phase of AGI.

1-Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway.

BACKGROUND AND PURPOSE: In chronic kidney disease (CKD), patients inevitably reach end-stage renal disease and require renal transplant. Evidence suggests that CKD is associated with metabolite disorders. However, the molecular pathways targeted by metabolites remain enigmatic. Here, we describe roles of 1-hydroxypyrene in mediating renal fibrosis. EXPERIMENTAL APPROACH: We analysed 5406 urine and serum samples from patients with Stage 1-5 CKD using metabolomics, and 1-hydroxypyrene was identified and validated using longitudinal and drug intervention cohorts as well as 5/6 nephrectomised and adenine-induced rats. KEY RESULTS: We identified correlations between the urine and serum levels of 1-hydroxypyrene and the estimated GFR in patients with CKD onset and progression. Moreover, increased 1-hydroxypyrene levels in serum and kidney tissues correlated with decreased renal function in two rat models. Up-regulated mRNA expression of aryl hydrocarbon receptor and its target genes, including CYP1A1, CYP1A2 and CYP1B1, were observed in patients and rats with progressive CKD. Further we showed up-regulated mRNA expression of aryl hydrocarbon receptor and its three target genes, plus up-regulated nuclear aryl hydrocarbon receptor protein levels in mice and HK-2 cells treated with 1-hydroxypyrene, which caused accumulation of extracellular matrix components. Treatment with aryl hydrocarbon receptor short hairpin RNA or flavonoids inhibited mRNA expression of aryl hydrocarbon receptor and its target genes in 1-hydroxypyrene-induced HK-2 cells and mice. CONCLUSION AND IMPLICATIONS: Metabolite 1-hydroxypyrene was demonstrated to mediate renal fibrosis through activation of the aryl hydrocarbon receptor signalling pathway. Targeting aryl hydrocarbon receptor may be an alternative therapeutic strategy for CKD progression.

Sensory root demyelination: Transforming touch into pain.

The normal feeling of touch is vital for nearly every aspect of our daily life. However, touching is not always felt as touch, but also abnormally as pain under numerous diseased conditions. For either mechanistic understanding of the faithful feeling of touch or clinical management of chronic pain, there is an essential need to thoroughly dissect the neuropathological changes that lead to painful touch or tactile allodynia and their corresponding cellular and molecular underpinnings. In recent years, we have seen remarkable progress in our understanding of the neural circuits for painful touch, with an increasing emphasis on the upstream roles of non-neuronal cells. As a highly specialized form of axon ensheathment by glial cells in jawed vertebrates, myelin sheaths not only mediate their outstanding neural functions via saltatory impulse propagation of temporal and spatial precision, but also support long-term neuronal/axonal integrity via metabolic and neurotrophic coupling. Therefore, myelinopathies have been implicated in diverse neuropsychiatric diseases, which are traditionally recognized as a result of the dysfunctions of neural circuits. However, whether myelinopathies can transform touch into pain remains a long-standing question. By summarizing and reframing the fragmentary but accumulating evidence so far, the present review indicates that sensory root demyelination represents a hitherto underappreciated neuropathological change for most neuropathic conditions of painful touch and offers an insightful window into faithful tactile sensation as well as a potential therapeutic target for intractable painful touch.

Efficacy, toxicity, and quality-of-life outcomes of ultrahypofractionated radiotherapy in patients with localized prostate cancer: A single-arm phase 2 trial from Asia.

AIMS: Ultra-hypofractionated radiotherapy (UHF-RT) is widely utilized in men with localized prostate cancer (PCa). There are limited data in Asian cohorts. We report the outcomes of a single-arm, phase II trial of UHF-RT from an Asian center. METHODS: We recruited men with histologically confirmed, nonmetastatic localized PCa. UHF-RT regimens were 36.25 Gy (Cohort A) and 37.5 Gy (Cohort B) delivered in five fractions every other day over 1.5-2.5 weeks. Primary endpoint was physician-scored late genitourinary (GU) and gastrointestinal (GI) adverse events (AEs). Quality-of-life (QoL) was assessed by Expanded Prostate Cancer Index Composite (EPIC) at baseline, 1- and 2-year post-UHF-RT. RESULTS: Between March 2014 and August 2019, 105 men were recruited; four were subsequently excluded from analysis. Median age was 68.0 (Interquartile range (IQR): 63.8-73.0) years. 26 (24.8%) and 68 (64.8%) men had NCCN-defined low-and intermediate-risk PCa, respectively. No late ≥G3 GU or GI toxicities were reported in both cohorts. Peak incidence of acute ≥G2 GU AEs at 14 days post-UHF-RT was 23.6% (17/72) and 24.0% (6/25) in Cohorts A and B, respectively; ≥G2 GI AEs were observed in 9.7% (7/72) and 36.0% (9/25), respectively. Late ≥G2 GU and GI AEs occurred in 4.7% and 3.1% of Cohort A patients, and 5.0% in Cohort B at 12 months, with no AEs at 24 months. EPIC scores changed minimally across all domains. At a median follow-up of 44.9 months, we recorded one (1.3%) biochemical relapse by the Phoenix criteria (Cohort A). CONCLUSION: UHF-RT is well tolerated in Asian men and can be a recommended fractionation schema for localized PCa.

Mass-Manufactured Beam-Steering Metasurfaces for High-Speed Full-Duplex Optical Wireless-Broadcasting Communications.

Beam-steering devices, which are at the heart of optical wireless-broadcasting communication links, play an important role in data allocation and exchange. An ideal beam-steering device features large steering angles, arbitrary channel numbers, reconfigurability, and ultracompactness. However, these criteria have been achieved only partially with conventional beam-steering devices based on waveguides, micro-electricalmechanical systems, spatial light modulators, and gratings, which will substantially limit the application of optical wireless-broadcasting communication techniques. In this study, an ultracompact full-duplex metabroadcasting communication system is designed and experimentally demonstrated, which exhibits beam steering angles up to ±40°, 14 broadcasting channels with capacity for downstream and upstream links up to 100 and 10 Gbps for each user channel, three operating modes for flexible signal switching, and metadevice dimensions as small as 2 mm × 2 mm. In particular, the beam-steering metadevices are mass-manufactured by a complementary metal-oxide-semiconductor (CMOS) processing platform, which shows their potential for large-scale commercial applications. The demonstrated metabroadcasting communication system merges optical wireless-broadcasting communications and metasurfaces, which reduces the complexity of beam-steering devices while significantly increasing their performance, opening up a new avenue for high-quality optical wireless-broadcasting communications.

Artificial Chiral Interfaces against Amyloid-ß Peptide Aggregation: Research Progress and Challenges.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an imbalance between the production and clearance of amyloid-ß (Aß) species. AD not only influences the life quality of the patients but also heavily burdens the families and society. Therefore, it is an urgent mission to research and develop some new anti-amyloid aggregation drugs. In recent years, there were research and development of engineered nanostructures as Aß amyloid inhibitors have attracted extensive attention and become a new frontier in nanomedicine. The effects of nanostructural surface properties (e.g., morphology, charge, hydrophobicity) on inhibition of Aß aggregation are modulated by adsorbed Aß peptides. Nevertheless, chirality has been seldom considered in recognition of Aß species and modulation of Aß aggregations. Moreover, a more relevant question for chiral inhibitors is little known about the molecular mechanism of how to interface chiral effects Aß targeting recognition and effective mitigation of amyloidosis at the molecular level. Herein, we review recent experimental and theoretical results acquired in the specific areas of artificial chiral nanostructure inhibitors. This article will be essential to provide a microlevel insight into the effects of chiral nanointerfaces on amyloidosis processes as well as the development of chiral inhibitor drugs against Aß fibrillation.

Assessment of probiotic adhesion and inhibitory effect on Escherichia coli and Salmonella adhesion.

In this study, we screened bacterial strains to identify specific probiotics to treat pig diarrhea caused by Escherichia coli or Salmonella. The potential probiotics were assayed for their survival in gastrointestinal solution, their antimicrobial activity, cell-surface properties, adhesion to Caco-2 cells, and inhibition of pathogen adhesion. Nine out of the 20 strains tested showed high tolerance of a simulated gastrointestinal environment and six strains exerted antagonistic effects against enterohemorrhagic E. coli (EHEC) O157:H7 and Salmonella Typhimurium MQ. Lactobacillus johnsonii pDX1e exhibited a higher potent antibacterial activity. Four strains (pDX1a, pDX1e, pDX3a, and pDX5a) displayed auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells similar to those of the reference strain Lacticaseibacillus rhamnosus GG (LGG). Enterococcus durans pDX5a showed the highest adhesion capacity (13.86%), followed by the reference strain LGG (11.20%). All the tested strains competitively suppressed the attachment of pathogens to Caco-2 cells (by 30.73-55.18%); L. johnsonii pDX1e and Ent. durans pDX5a significantly inhibited the adhesion of pathogens by substitution and exclusion, respectively. Therefore, pDX1e and pDX5a were selected as probiotic strains for further investigation and application.

Manganese-Pincer-Catalyzed Nitrile Hydration, α-Deuteration, and α-Deuterated Amide Formation via Metal Ligand Cooperation.

A simple and efficient system for the hydration and α-deuteration of nitriles to form amides, α-deuterated nitriles, and α-deuterated amides catalyzed by a single pincer complex of the earth-abundant manganese capable of metal-ligand cooperation is reported. The reaction is selective and tolerates a wide range of functional groups, giving the corresponding amides in moderate to good yields. Changing the solvent from tert-butanol to toluene and using D2O results in formation of α-deuterated nitriles in high selectivity. Moreover, α-deuterated amides can be obtained in one step directly from nitriles and D2O in THF. Preliminary mechanistic studies suggest the transformations contributing toward activation of the nitriles via a metal-ligand cooperative pathway, generating the manganese ketimido and enamido pincer complexes as the key intermediates for further transformations.

Programmable 1.47 Tb/s (92 Gb/s x 16) optical wireless broadcasting system empowered by a single spatial light modulator and a modified RSS algorithm.

We have proposed and experimentally demonstrated a programmable multi-access-point optical wireless broadcasting system with ±15° field-of-view by employing a single spatial light modulator (SLM) and a modified rotated-splitting-SLM algorithm. The 16 access points are generated and arbitrarily distributed by the proposed continuous tunable broadcasting algorithm. The optical beams for each point carry 92-Gb/s PAM-4 optical signal and transmitted over 1 km standard single mode fiber and 1.2 m indoor free space distance, offering a total wireless capacity beyond 1.47 Tb/s. The measured results show that the proposed multi-access-points transmission system with ultra-high transmission capacity and reconfigurability can be used for future indoor wireless mobile networks.

Sterics and Hydrogen Bonding Control Stereochemistry and Self-Sorting in BINOL-Based Assemblies.

Here we demonstrate how the hydrogen-bonding ability of a BINOL-based dialdehyde subcomponent dictated the stereochemical outcome of its subsequent self-assembly into one diastereomeric helicate form when bearing free hydroxy groups, and another in the case of its methylated congener. The presence of methyl groups also altered the self-sorting behavior when mixed with another, short linear dialdehyde subcomponent, switching the outcome of the system from narcissistic to integrative self-sorting. In all cases, the axial chirality of the BINOL building block also dictated helicate metal center handedness during stereospecific self-assembly. A new family of stereochemically pure heteroleptic helicates were thus prepared using the new knowledge gained. We also found that switching from FeII to ZnII, or the incorporation of a longer linear ligand, favored heteroleptic structure formation.

Optimized strategy of rotational atherectomy of underexpanded coronary stents in patients with acute coronary syndrome.

BACKGROUND: Stent under-expansion is a main cause of acute coronary syndrome (ACS), which can lead to serious clinical outcomes. The rotational atherectomy of underexpanded coronary stents (academically called stent ablation, SA) by intravascular ultrasound (IVUS) may provide more visual reference in the intervention. We aim to analyze the procedural and long-term outcomes of the optimized strategy of SA in patients with ACS and to provide real-world data on this technique. METHODS: A total of 11 patients with ACS who underwent SA between April 2017 and January 2019 were analyzed. Clinical follow-ups were obtained either by telephone call or by scheduled visit. Clinical end-points included periprocedural and postprocedural myocardial infarction, stent thrombosis, target lesion revascularization, and major adverse cardiac events. RESULTS: The mean age of patients was 69.6±6.5 years, and five (45.5%) patients were males. All cases presented with unstable angina and were admitted with ACS. All patients required at least two burrs during the intervention and the size of the burr was selected based on the data of minimum lumen diameter (MLD), and the first and the second burr/stent MLD ratios were 0.93 (0.88-0.99) and 1.09 (1.02-1.14), respectively. Nine patients were treated with drug-eluting stents and two were treated with drug-coated balloons. There were no complications including no flow, perforation, or burr entrapment during the intervention. No in-hospital deaths or major adverse cardiac events were documented during the follow-up period. In our study, less contrast agent and a lower dose of radiation were used during the intervention. CONCLUSIONS: SA guided by IVUS can reduce the risk of complications, assess the results of surgery, inform the selection of stent size, and decrease the required dose of radiation and contrast.

Reciprocal Regulation between Fur and Two RyhB Homologs in Yersinia pestis, and Roles of RyhBs in Biofilm Formation.

OBJECTIVE: To investigate reciprocal regulation between Fur and two RyhB homologs in Yersinia pestis( Y. pestis), as well as the roles of RyhBs in biofilm formation. METHODS: Regulatory relationships were assessed by a combination of colony morphology assay, primer extension, electrophoretic mobility shift assay and DNase I footprinting. RESULTS: Fur bound to the promoter-proximal DNA regions of ryhB1 and ryhB2 to repress their transcription, while both RyhB1 and RyhB2 repressed the expression of Fur at the post-transcriptional level. In addition, both RyhB1 and RyhB2 positively regulated Y. pestis biofilm exopolysaccharide (EPS) production and the expression of hmsHFRS and hmsT. CONCLUSION: Fur and the two RyhB homologs exert negative reciprocal regulation, and RyhB homologs have a positive regulatory effect on biofilm formation in Y. pestis.

ROS-Triggered Autophagy Is Involved in PFOS-Induced Apoptosis of Human Embryo Liver L-02 Cells.

The liver is the primary target organ for perfluorooctane sulphonate (PFOS), a recently discovered persistent organic pollutant. However, the mechanisms mediating hepatotoxicity remain unclear. Herein, we explored the relationship between reactive oxygen species (ROS) and autophagy and apoptosis induced by PFOS in L-02 cells, which are incubated with different concentrations of PFOS (0, 50, 100, 150, 200, or 250 µmol/L) for 24 or 48 hrs at 37°C. The results indicated that PFOS exposure decreased cell activities, enhanced ROS levels in a concentration-dependent manner, decreased mitochondrial membrane potential (MMP), and induced autophagy and apoptosis. Compared with the control, 200 µmol/L PFOS increased ROS levels; enhanced the expression of Bax, cleaved-caspase-3, and LC3-II; induced autophagy; decreased MMP; and lowered Bcl-2, p62, and Bcl-2/Bax ratio. The antioxidant N-acetyl cysteine (NAC) protected MMP against PFOS-induced changes and diminished apoptosis and autophagy. Compared with 200 µmol/L PFOS treatment, NAC pretreatment reversed the increase in ROS, Bax, and cleaved-caspase-3 protein caused by PFOS, lowered the apoptosis rate increased by PFOS, and increased the levels of MMP and Bcl-2/Bax ratio decreased by PFOS. The autophagy inhibitor 3-methyladenine and chloroquine decreased apoptosis and cleaved-caspase-3 protein level and increased the Bcl-2/Bax ratio. In summary, our results suggest that ROS-triggered autophagy is involved in PFOS-induced apoptosis in L-02 cells.