Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Boosting Glioblastoma Therapy with Targeted Pyroptosis Induction.

Glioblastoma (GBM) is a highly aggressive cancer that currently lacks effective treatments. Pyroptosis has emerged as a promising therapeutic approach for cancer, but there is still a need for new pyroptosis boosters to target cancer cells. In this study, it is reported that Aloe-emodin (AE), a natural compound derived from plants, can inhibit GBM cells by inducing pyroptosis, making it a potential booster for pyroptosis-mediated GBM therapy. However, administering AE is challenging due to the blood-brain barrier (BBB) and its non-selectivity. To overcome this obstacle, AE@ZIF-8 NPs are developed, a biomineralized nanocarrier that releases AE in response to the tumor's acidic microenvironment (TAM). Further modification of the nanocarrier with transferrin (Tf) and polyethylene glycol-poly (lactic-co-glycolic acid) (PEG-PLGA) improves its penetration through the BBB and tumor targeting, respectively. The results show that AE-NPs (Tf-PEG-PLGA modified AE@ZIF-8 NPs) significantly increase the intracranial distribution and tumor tissue accumulation, enhancing GBM pyroptosis. Additionally, AE-NPs activate antitumor immunity and reduce AE-related toxicity. Overall, this study provides a new approach for GBM therapy and offers a nanocarrier that is capable of penetrating the BBB, targeting tumors, and attenuating toxicity.

Pharmacokinetic and tissue distribution study of eight volatile constituents in rats orally administrated with the essential oil of Artemisiae argyi Folium by GC-MS/MS.

Artemisia argyi is commonly used as a remedy for gynecological and respiratory disease in traditional Chinese medicine. The essential oil is considered as the major active ingredients of A. argyi, mainly composed of eucalyptol, α-thujone, camphor, borneol, bornyl acetate, eugenol, ß-caryophyllene, and caryophyllene oxide, while limited study addresses the in vivo disposition of these volatile ingredients. In present study, a rapid, sensitive and selective GC-MS/MS method has been developed and validated for the quantification of the eight volatile constituents in rat plasma and tissues after orally dosing with the essential oil of Artemisiae Argyi Folium (AAEO) using naphthalene as an internal standard (IS). The analytes were extracted from biosamples by liquid-liquid extraction with hexane/ethyl acetate. The GC separation was achieved on a TG-5SILMS column (30 m × 0.25 mm, 0.25 µm film thickness) and MS detection was performed on selective reaction monitoring (SRM) mode. The assay had a lower limit of quantification (LLOQ) less than 2 ng/ml for the analytes with good linearity (r ≥ 0.9907). Their disposition profile in rat plasma and tissues was characterized after orally giving AAEO, and the data revealed the analytes underwent rapid absorption from GI tract and were mainly transferred to the liver, heart, kidney, lung, and spleen with prompt elimination. The results provided a meaningful basis for guiding the pharmacodynamic study and clinical applications of this herbal medicine.

The Mediating Role of Perceived Stress in Associations Between Self-Compassion and Anxiety and Depression: Further Evidence from Chinese Medical Workers.

OBJECTIVE: Medical workers report high rates of stress, anxiety and depression, which need urgent attention. Providing evidence for intervention measures in the face of a mental health crisis, the present study validates the relation between self-compassion and anxiety and depression mediated by perceived stress amongst medical workers. The goal is also to replicate a similar mediation model though multigroup analysis. METHODS: Medical workers were randomly selected to investigate by paper-and-pencil survey among 1,223 medical workers from three hospitals in Shiyan, China. The measures were comprised of four parts: the Chinese version of the Goldberg Anxiety and Depression Scale (GADS), the Self-Compassion Scale-Short Form (SCS-SF), the Perceived Stress Questionnaire (PSQ) and a socio-demographic questionnaire. Applying structural equation modeling (SEM, single-group analysis), we estimated the effects of self-compassion on anxiety/depression through perceived stress. Furthermore, based on multigroup analysis, we used two sets of internal samples (gender groups, medical groups) and an external sample (nursing students) for testing multigroup invariance. RESULTS: The average scores of anxiety, depression, self-compassion and perceived stress in medical workers were 5.93 ± 2.46, 4.91 ± 2.62, 38.87 ± 4.66 and 71.96 ± 15.14, respectively. In some departments engaged in the research, the medical workers showed higher levels of anxiety and depression. The SEM results indicated that the original relationship between self-compassion and anxiety and depression was beta = -0.42 (P < 0.001) and reduced to beta = -0.17 (P < 0.001) while introducing perceived stress as a mediating variable. Perceived stress was positively associated with anxiety and depression (beta = 0.60, P < 0.001), and self-compassion was negatively associated with perceived stress (beta = -0.56, P < 0.001). Multigroup analysis showed acceptable changes in fit indices across gender (male and female), medical (clinician and non-clinician), and population (medical workers and nursing students) groups. CONCLUSION: Medical workers were experiencing high levels of anxiety and depression and perceived stress. Perceived stress might have a partial mediating effect on self-compassion and anxiety and depression amongst medical workers, which was similar to a previous study in nursing students. The findings supported multigroup invariance across gender, medical and population groups. The study concluded that the mediation model may be generalized across these multiple samples. Psychological intervention could be used to improve levels of self-compassion of medical workers.

Performance and microbial structure of partial denitrification in response to salt stress: Achieving stable nitrite accumulation with municipal wastewater.

The effects of inorganic salts on partial denitrification (PD) was investigated in a sequencing batch reactor for simultaneously treating saline nitrate sewage and municipal wastewater. After 230-day operation, a high nitrate-to-nitrite transformation ratio (NTR) of ~ 80% was achieved with the salinity of 1.25 wt% and the initial chemical oxygen demand to nitrate ratio of 3.7. Microbial community analysis revealed that, Thauera was remained predominant in PD system but with a relative abundance decreasing from 53.02% (0.0 wt%) to 42.36% (1.25 wt%). Moreover, as a suitable ratio of nitrite to ammonia (~1.6) in effluent was obtained, it would be a promising method to treat saline nitrate sewage by combing PD with anammox.

Metabolic profiles of Xiao Chai Hu Tang in mouse plasma, bile and urine by the UHPLC-ESI-Q-TOF/MS technique.

Xiao Chai Hu Tang (XCHT) is sold as traditional medicine or dietary supplement in worldwide. To understand metabolism profile of traditional medicine is key point in their logical pharmacological research and clinical application. Based on our previous research of the chemical and absorption signature of XCHT in vitro, we proposed a novel strategy to identify the bioactive components of XCHT in vivo. This strategy have two steps: firstly, based on the parents' database in vitro, built-in and editable biotransformations for phase I and phase II metabolism reactions with MassHunter Metabolite ID software (building metabolites database). Secondly, mouse plasma, bile and urine samples were analyzed by UHPLC-ESI-Q-TOF/MS technique, and the absorbed parents and metabolites were compared and identified with the XCHT's digital library using MassHunter Metabolite ID software. In total, 27 parent compounds and 26 metabolites of XCHT were identified in vivo, 2'-O-xylosyl saikosaponin b2 or b1 was reported for the first time. Saponins and their related metabolites were predominantly excreted into the bile, but flavonoids were excreted by both hepatic as well as renal excretion. Flavonoids, saponins, gingerol and their related metabolites were the absorbed components in cardiovascular system and bioactive components of XCHT. Phase I reactions (hydrolysis, hydroxylation and oxidation) and phase II reactions (glucuronidation) were identified and involved in the mouse metabolism of XCHT.

Achieving deep-level nutrient removal via combined denitrifying phosphorus removal and simultaneous partial nitrification-endogenous denitrification process in a single-sludge sequencing batch reactor.

The feasibility of coupling denitrifying phosphorus removal (DPR) with simultaneous partial nitrification-endogenous denitrification (SPNED) was investigated in a single-sludge sequencing batch reactor for deep-level nutrient removal from municipal and nitrate wastewaters. After 160-day operation, the DPR process simultaneously reduced most PO43--P and NO3--N anoxically, and the SPNED process achieved further total nitrogen (TN) removal at low dissolved oxygen condition with TN removal efficiency of 90.8%. The effluent NH4+-N, PO43--P and TN concentrations were 1.0, 0.1 and 7.2 mg/L, respectively. Microbial analysis revealed that Dechloromonas (6.7%) dominated DPR process, whereas the gradually enriched Nitrosomonas (4.5%) and Candidatus Competibacter (6.8%) conducted SPNED process accompanied with sharply eliminated Nitrospirae (1.4%). Based on these findings, a novel strategy was proposed to achieve further nutrient removal in conventional treatment through integrating the DPR-SPNED process. As a result, ∼100% of extra carbon and ∼10% of oxygen consumptions would be reduced with satisfactory effluent quality.

[Nitrogen and Phosphorus Removal from Low C/N Municipal Wastewater Treated by a SPNDPR System with Different Aeration and Aerobic Times].

An anaerobic (180 min)/aerobic operated sequencing batch reactor (SBR) fed with urban sewage was optimized by regulating the aeration quantity to investigate the deep-level nitrogen (N) and phosphorus (P) removal. The amount of aeration was regulated by adjusting the volume of gas per unit volume of reactor passed in unit time, when the unit is L·(min·L)-1, from 0.125 L·(min·L)-1 gradually to 0.025 L·(min·L)-1, and aerobic times from 3 h to 6 h. The experimental results show that the effluent NH4+-N, NO2--N, NO3--N, and PO43--P concentrations of the optimized SPNDPR system were 0, 8.62, 0.06, and 0.03 mg·L-1. The effluent TN concentration was about 9.22 mg·L-1, and the TN removal efficiency was up to 87.08%. When the aeration quantity was decreased from 0.125 L·(min·L)-1 to 0.100 L·(min·L)-1; then decreased to 0.075 L·(min·L)-1, the nitrification rate of the system recovered and stabilized at 0.16 mg·(L·min)-1. However, when the aeration quantity continuously decreased to 0.050 L·(min·L)-1 and then to 0.025 L·(min·L)-1, the nitrification rate decreased to 0.09 mg·(L·min)-1 and 0.06 mg·(L·min)-1. With reduction of the aeration quantity[from 0.125 L·(min·L)-1 to 0.100, 0.075, 0.050 and 0.025 L·(min·L)-1] and extension of aerobic time (from 3 h to 6 h), the TN removal efficiency increased gradually from 62.82% to 87.08%, and the SND efficiency increased from 19.57% to 72.11%. It was proven that reducing the aeration quantity can enhance the SPND function and deep denitrification by the system was realized. By enhancing the anaerobic intracellular carbon storage and aerobic phosphorus uptake, denitrifying phosphorus removal, partial nitrification, and endogenous nitrification were achieved. The SPNDPR system, after reducing aeration and prolonging aerobic time, was able to realize deep-level denitrification and dephosphorization using low C/N urban sewage.

Evaluating the potential for sustaining mainstream anammox by endogenous partial denitrification and phosphorus removal for energy-efficient wastewater treatment.

This study demonstrated a novel process configuration for sustaining mainstream anammox by integrating the anammox and endogenous partial denitrification-and-phosphorus removal (EPDPR) in two-stage sequencing batch reactors (SBRs). In the EPDPR-SBR, high nitrate-to-nitrite transformation (68.2%) and P removal (99.3%) were achieved by adjusting the anaerobic/anoxic/aerobic durations and influent nitrate concentration, providing a suitable NO2--N/NH4+-N (∼1.37) for subsequent anammox reaction. In the Anammox-SBR, ∼95% of TN was removed without external carbon and oxygen demands. Satisfactory effluent quality (∼6 mgTN/L and 0.2 mgP/L) achieved in the integrated EPDPR/anammox opens a new window towards the energy-efficient wastewater treatment. Microbial analysis further revealed that Dechloromonas (1.6-9.6%) and Candidatus Competibacter (6.4-5.8%) respectively conducted P removal and NO2--N production (79.2%) from NO3--N denitrification in the EPDPR-SBR, whereas Candidatus Kuenenia (7.0-29.7%) dominated NO2--N and NH4+-N removal (91.3% and 99.5%) in the Anammox-SBR, with 10 genera identified as denitrifying bacteria (0.6-8.1%) further reduced 18.9% of the produced NO3--N.

Gut microbiome interventions in human health and diseases.

Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome-based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.

[Effect of the Influent C/P Ratio on the Nutrient Removal Characteristics of the SNEDPR System].

This study focuses on the nitrogen (N) and phosphorus (P) removal characteristics in a simultaneous nitrification-endogenous denitrification and phosphorus removal (SNEDPR) system at different influent C/P ratios. An extended anaerobic/low aerobic (dissolved oxygen:0.5-1.0 mg·L-1) sequencing batch reactor (SBR) fed with municipal sewage was studied by adjusting different C/P ratios (10, 15, 20, 30, and 60). The experimental results show that the proper reduction of the influent C/P ratio (C/P ratio reduced from 60 to 30) enhances the competitive advantages of phosphorus-accumulating organisms (PAOs) in the SNEDPR system. The highest phosphorus removal efficiency was achieved at a C/P ratio of 30, with the anaerobic phosphorus release rate (PRR) and aerobic phosphorus uptake rate (PUR, used as P/MLSS) reaching 3.5 mg·(g·h)-1 and 4.2 mg·(g·h)-1 respectively, and an average effluent PO43--P concentration below 0.3 mg·L-1. The percentage of PAOs contributing to the storage of endogenesis carbon (PPAO, An) reached 88.1%. However, a poor phosphorus removal performance was observed with further reduction of the influent C/P ratios to 10; both the PO43--P removal efficiency and PPAO, An decreased from 38.1% and 82.4% to 3.1% and 5.3%, respectively. The PRR and PUR were 0.2 mg·(g·h)-1 and 0.24 mg·(g·h)-1, respectively. The COD removal performance was not affected by the decreasing influent C/P ratios; the average COD removal efficiency stabilized at 85%. In addition, the nitrification performance became worse with decreasing C/P ratios (from 60 to 20) because the effluent NH4+-N and NO2--N concentrations increased from 0 and 6.9 mg·L-1 to 5.1 mg·L-1 and 16.2 mg·L-1, respectively. The nitrificaton performance recovered when the C/P ratios further decreased to 10, but the nitrite accumulation was disturbed as both the effluent NH4+-N and NO2--N concentrations reduced to 0. The effluent NO3--N concentration increased from 0.08 mg·L-1 to 14.1 mg·L-1. The SNED efficiency first decreased from 62.1% to 36.4% and then increased to 56.4%. The advantageous competition of glycogen accumulating organisms (GAOs) improved when the influent C/P ratio was lower than 15. The enhancement of the endogenous denitrification ability of GAOs might explain the recovery denitrification performance of the system when the influent C/P ratios decreased from 20 to 10.

[Effect of Different Sludge Retention Time (SRT) Operations on the Nutrient Removal Characteristics of a SNEDPR System].

This study focuses on the nitrogen (N) and phosphorus (P) removal characteristics in a simultaneous nitrification endogenous denitrification and phosphorus removal (SNEDPR) system operating at different sludge retention time (SRT). Four extended anaerobic/low aerobic (dissolved oxygen:0.5-1.0 mg·L-1)-operated sequencing batch reactors (SBRs) fed with municipal sewage were studied at different SRT of 5, 10, 15, and 25 d. The experimental results show that a shorter SRT at an SRT ≥ 10 d enhances the competitive advantage of PAOs in the system and an efficient phosphorus removal performance of the SNEDPR system was achieved at a SRT of 10 d and 15 d. Especially at an SRT of 10 d; the average PPAOs, An was 68.4%, the PRA and PUA reached 31.9 and 34.3 mg·L-1, respectively. The nitrification performance of the system was not affected by SRT changes. The most efficient nitrogen removal performance was achieved at a SRT of 15 d, with a high average TN removal and SNED efficiencies reaching 89.6% and 71.8%, respectively. At a SRT ≥ 10 d, the COD removal performance of the SNEDPR system was also not affected by SRT changes. The COD removal efficiencies were higher than 78%. However, when the SRT was shortened to 5 d, the C, N, and P performances of the system worsened due to the loss of biomass; the SNED and PO43--P removal efficiencies were as low as 5.7% and 0.5%, respectively. In addition, at an SRT=15 d, the sludge-settling performance of the system was the best. The SV and SVI were 20% and 64 mL·g-1, respectively, and the sludge concentration increased with the extension of the SRT. Under long SRT (25 d) operation, the system showed a good resistance to shock loads, but the sedimentation performance of the sludge deteriorated.

[Characteristics of Ammonia Adsorption and Kinetics by Nitrifying Sludge Immobilized Pellets].

In order to explore the characteristics and mechanisms of ammonia adsorption by both nitrifying sludge waterborne polyurethane (WPU)-immobilized pellets and nitrifying sludge polyvinyl alcohol-sodium alginate (PVA-SA)-immobilized pellets, the ammonia adsorption characteristics of immobilized pellets under different initial ammonia concentrations, and the influences of temperature, pH, and salinity on ammonia adsorption were studied respectively. Moreover, the adsorption isotherms, thermodynamics, and kinetics model analysis were employed to investigate the adsorption process. The adsorption capacity increased as the initial ammonia concentration increased. The optimal pH was 7.0, and salinity and temperature exhibited an inhibitory effect on adsorption. The adsorption capacity for nitrifying sludge-immobilized pellets was higher than the pellets with no sludge; the adsorption capacity of WPU pellets was higher than that of PVA-SA pellets. The thermodynamics demonstrated that the adsorption process was a spontaneous exothermic process and that low temperature favored ammonia adsorption. The process was fitted to the Langmuir and Freundlich isotherm. It exhibited multilevel adsorption at higher energy (Freundlich isotherm) and single adsorption at lower energy by electrostatic force (Langmuir isotherm). Additionally, the process was consistent with the pseudo-second-order kinetic model, as it explained that chemical adsorption was the primary mechanism of ammonia adsorption by immobilized pellets.

[Nitrite Accumulation Characteristics of Partial Denitrification in Different Sludge Sources Using Sodium Acetate as Carbon Source].

In order to explore the characteristics of nitrite accumulation during the operational period of partial denitrification in different sludge sources using sodium acetate as a carbon source, No.1 SBR and No.2 SBR were used to inoculate with surplus sludge taken separately from a secondary sedimentation tank of a sewage treatment plant and simultaneous nitrification and denitrifying phosphorus removal system. By reasonably controlling the initial nitrate concentration and anoxic time, partial denitrification was realized. The carbon and nitrogen removal characteristics under different initial COD and NO3--N concentrations were investigated. The results showed that, using sodium acetate as the carbon source, the partial denitrification process in No.1 SBR and No.2 SBR sludge successfully began in 21 d and 20 d, respectively. The accumulation of NO2--N and nitrite accumulation rate (NAR) in reactors were maintained at high levels (12.61 mg·L-1, 79.76% and 13.85 mg·L-1, 87.60%, respectively). When the initial NO3--N concentration of No.2 SBR was 20 mg·L-1 and the initial COD concentration increased from 60 mg·L-1 to 140 mg·L-1, the operation time for achieving the highest NO2--N accumulation in the system was shortened from 160 min to 6 min. The NO3--N ratio of the denitrification rate (in VSS) increased from 3.84 mg·(g·h)-1 to 7.35 mg·(g·h)-1. Increased initial COD concentration was beneficial to the accumulation of NO2--N during partial denitrification. When the initial COD concentration of No.2 SBR was 100 mg·L-1 and the initial NO3--N concentration increased from 20 mg·L-1 to 30 mg·L-1, NAR was maintained above 90% and up to 100% (the initial NO3--N concentration was 25 mg·L-1). When the initial NO3--N concentration was ≥ 35 mg·L-1, insufficient COD caused NO3--N to be completely reduced to NO2--N. Under different initial COD concentrations (80, 100, or 120 mg·L-1) and different initial NO3--N concentrations (20, 25, 30, or 40 mg·L-1), the nitrogen and carbon removal and partial denitrification performance of the No.2 SBR was better than that of No.1 SBR.

[Operating Characteristics of a DPR-SNED System Treating Low C/N Municipal Wastewater and Nitrate-containing Sewage].

In order to realize the simultaneous treatment of low C/N municipal wastewater and high nitrate wastewater, a sequencing batch reactor (SBR), inoculated with activated sludge, was used to initiate the denitrifying phosphorus removal coupled with simultaneous nitrification and endogenous denitrification (DPR-SNED). The anaerobic/anoxic/hypoxic durations and dissolved oxygen (DO) concentration were appropriately controlled, and the nitrogen and phosphorus removal characteristics were examined. The experimental results demonstrated that, in the anaerobic/hypoxia operation mode, with an anaerobic duration of 3 h and DO concentration of 0.5-1.0 mg·L-1, the simultaneous nitrification of phosphorus removal (SNEDPR) system successfully began in 60 d. The effluent PO43--P concentration was below 0.5 mg·L-1, the nutrient and COD removal efficiencies were stably maintained above 90% and 80%, respectively, and the SNED efficiency and CODins efficiency reached 70% and 95%, respectively. When the operation mode was anaerobic/anoxic/hypoxic and nitrate-containing sewage was added at the beginning of the anoxic stage, DPR-SNED was achieved with the effluent PO43--P concentration<0.5 mg·L-1, nutrient and COD removal efficiencies above 88% and 90%, respectively, and SNED efficiency and CODins efficiency maintained at 62% and 90%, respectively. After the successful initiation of DPR-SNED, enhanced intracellular carbons storage was achieved by phosphorus-and glycogen-accumulating organisms using the limited carbons in raw municipal wastewater to provide sufficient carbon sources for subsequent nutrient removal. In addition, the endogenous partial denitrification ensured the efficient nitrogen removal performance of the DPR-SNED system at low C/N conditions (average 4).

Recent Advances in the Genomic Profiling of Bacterial Epigenetic Modifications.

Bacterial epigenetic modifications play key roles in cellular processes such as stress responses, DNA replication, segregation, antimicrobial resistance, etc. In recent years, emerging new sequencing technologies, including single-molecule real-time (SMRT) sequencing, and nanopore sequencing, have enabled the directed reading of epigenetic modifications without pre-treatment of DNA or DNA amplification. The applications of SMRT and nanopore sequencing open the door for the identification of more diverse epigenetic modifications of DNA bases and backbones and potentially facilitate the understanding of the novel functions of these epigenetic markers in cell physiology. With ongoing improvements in throughput and accuracy, new-generation sequencing has become a contender as an alternative to second-generation sequencing technologies. Here, the authors review recent advances in bacterial epigenetic analysis using SMRT sequencing and nanopore sequencing to provide insights regarding the detection and analysis of DNA epigenetic modifications in bacterial genomes.

Genetic mechanisms of arsenic detoxification and metabolism in bacteria.

Arsenic, distributed pervasively in the natural environment, is an extremely toxic substance which can severely impair the normal functions of living cells. Research on the genetic mechanisms of arsenic metabolism is of great importance for remediating arsenic-contaminated environments. Many organisms, including bacteria, have developed various strategies to tolerate arsenic, by either detoxifying this harmful element or utilizing it for energy generation. This review summarizes arsenic detoxification as well as arsenic respiratory metabolic pathways in bacteria and discusses novel arsenic resistance pathways in various bacterial strains. This knowledge provides insights into the mechanisms of arsenic biotransformation in bacteria. Multiple detoxification strategies among bacteria imply possible functional relationships among different arsenic detoxification/metabolism pathways. In addition, this review sheds light on the bioremediation of arsenic-contaminated environments and prevention of antibiotic resistance.

Pharmacokinetics, Bioavailability, and Tissue Distribution Study of Angoroside C and Its Metabolite Ferulic Acid in Rat Using UPLC-MS/MS.

Angoroside C is a phenylpropanoid glycoside compound isolated from the dried root of Scrophularia ningpoensis Hemsl., which possesses the effects of preventing ventricular remodeling, reducing pulmonary oedema, and reducing blood pressure, as well as having the properties of anti-platelet aggregation, hepatoprotection and anti-nephritis, etc. However, few investigations have been conducted on the absorption, distribution, metabolism, and excretion (ADME) study of angoroside C. Thus, a fast ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) method was established for the determination of angoroside C and its metabolite ferulic acid in rat plasma and tissue homogenate. The two analytes were extracted from the biosamples using a simple protein precipitation with acetonitrile. The developed method was validated and successfully applied to the pharmacokinetics, bioavailability and tissue distribution study after the intragastric administration of angoroside C (100 mg/kg) or the intravenous administration of angoroside C (5 mg/kg), respectively. The results showed that angoroside C can be absorbed extremely quickly (T max = 15 min), can be eliminated very rapidly (t 1/2 = 1.26 h), and its oral bioavailability is only about 2.1%. Furthermore, angoroside C was extensively distributed in all main organs (liver, heart, spleen, lung, kidney, and brain), and the highest concentration was detected in the lung 15 min after oral administration. This paper also indicated that angoroside C could be converted to the active metabolite ferulic acid in vivo. The maximum concentrations of ferulic acid in the kidney occurred at 6 h after oral administration. In summary, this study explored some of the pharmacokinetic characteristics of angoroside C in vivo, and the data produced could provide a basis for the further investigation of angoroside C.

Signature Arsenic Detoxification Pathways in Halomonas sp. Strain GFAJ-1.

Since the original report that Halomonas sp. strain GFAJ-1 was capable of using arsenic instead of phosphorus to sustain growth, additional studies have been conducted, and GFAJ-1 is now considered a highly arsenic-resistant but phosphorus-dependent bacterium. However, the mechanisms supporting the extreme arsenic resistance of the GFAJ-1 strain remain unknown. In this study, we show that GFAJ-1 has multiple distinct arsenic resistance mechanisms. It lacks the genes to reduce arsenate, which is the essential step in the well-characterized resistance mechanism of arsenate reduction coupled to arsenite extrusion. Instead, GFAJ-1 has two arsenic resistance operons, arsH1-acr3-2-arsH2 and mfs1-mfs2-gapdh, enabling tolerance to high levels of arsenate. mfs2 and gapdh encode proteins homologous to Pseudomonas aeruginosa ArsJ and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), respectively, which constitute the equivalent of an As(V) efflux system to catalyze the transformation of inorganic arsenate to pentavalent organoarsenical 1-arseno-3-phosphoglycerate and its subsequent extrusion. Surprisingly, the arsH1-acr3-2-arsH2 operon seems to consist of typical arsenite resistance genes, but this operon is sufficient to confer both arsenite and arsenate resistance on Escherichia coli AW3110 even in the absence of arsenate reductase, suggesting a novel pathway of arsenic detoxification. The simultaneous occurrence of these two unusual detoxification mechanisms enables the adaptation of strain GFAJ-1 to the particularly arsenic-rich environment of Mono Lake.IMPORTANCEHalomonas sp. strain GFAJ-1 was previously reported to use arsenic as a substitute for phosphorus to sustain life under phosphate-limited conditions. Although this claim was later undermined by several groups, how GFAJ-1 can thrive in environments with high arsenic concentrations remains unclear. Here, we determined that this ability can be attributed to the possession of two arsenic detoxification operons, arsH1-acr3-2-arsH2 and mfs1-mfs2-gapdhmfs2 and gapdh encode proteins homologous to ArsJ and GAPDH in Pseudomonas aeruginosa; these proteins create an arsenate efflux pathway to reduce cellular arsenate accumulation. Interestingly, the combination of acr3-2 with either arsH gene was sufficient to confer resistance to both arsenite and arsenate in E. coli AW3110, even in the absence of arsenate reductase, suggesting a new strategy for bacterial arsenic detoxification. This study concludes that the survival of GFAJ-1 in high arsenic concentrations is attributable to the cooccurrence of these two unusual arsenic detoxification mechanisms.

Nanotechnology-Based Strategies for Early Cancer Diagnosis Using Circulating Tumor Cells as a Liquid Biopsy.

Circulating tumor cells (CTCs) are cancer cells that shed from a primary tumor and circulate in the bloodstream. As a form of "tumor liquid biopsy", CTCs provide important information for the mechanistic investigation of cancer metastasis and the measurement of tumor genotype evolution during treatment and disease progression. However, the extremely low abundance of CTCs in the peripheral blood and the heterogeneity of CTCs make their isolation and characterization major technological challenges. Recently, nanotechnologies have been developed for sensitive CTC detection; such technologies will enable better cell and molecular characterization and open up a wide range of clinical applications, including early disease detection and evaluation of treatment response and disease progression. In this review, we summarize the nanotechnology-based strategies for CTC isolation, including representative nanomaterials (such as magnetic nanoparticles, gold nanoparticles, silicon nanopillars, nanowires, nanopillars, carbon nanotubes, dendrimers, quantum dots, and graphene oxide) and microfluidic chip technologies that incorporate nanoroughened surfaces and discuss their key challenges and perspectives in CTC downstream analyses, such as protein expression and genetic mutations that may reflect tumor aggressiveness and patient outcome.