Proteomic analysis of aqueous humor reveals novel regulators of diabetic macular edema.

Diabetic macular edema (DME) is the most common cause of blindness in patients with diabetic retinopathy. To investigate the proteomic profiles of the aqueous humor (AH) of individuals with diabetic macular edema (DME), AH samples were collected from patients with non-diabetes mellitus (NDM), DM, nonproliferative diabetic retinopathy (NPDR), and DME. We performed comparative proteomic analyses using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses. We identified 425 proteins in these AH samples, of which 113 showed changes in expression in DME compared with NDM, 95 showed changes in expression in DME vs. DM, and 84 showed changes in expression in DME compared with NPDR. The bioinformatics analysis suggested that DME is closely associated with platelet degranulation, oxidative stress-related pathway, and vascular-related pathways. Upregulation of haptoglobin (HP) and downregulation of fibrillin 1 (FBN1) were validated by ELISA. Receiver operating characteristic (ROC) analysis showed that HP and FBN1 could distinguish DME from NPDR with areas under the curve of 0.987 (p = 0.00608) and 0.791 (p = 0.00629), respectively. The findings provide potential clues for further analysis of the molecular mechanisms and the development of new treatments for DME. HP and FBN1 may be potential key proteins and therapeutic targets in human DME. The proteomics dataset generated has been deposited to the ProteomeXchange/iProX Consortium with Identifier: PXD033404/IPX0004353001.

Electroactive Ultrafiltration Membrane for Simultaneous Removal of Antibiotic, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes from Wastewater Effluent.

To combat the spread of antibiotic resistance into the environment, we should adequately manage wastewater effluent treatment to achieve simultaneous removal of antibiotics, antibiotic resistant bacteria (ARB), and antibiotic resistance genes (ARGs). Herein, we fabricate a multifunctional electroactive poly(vinylidene fluoride) ultrafiltration membrane (C/PVDF) by phase inversion on conductive carbon cloth. The membrane possesses not only excellent retention toward ARB and ARGs but also exhibits high oxidation capacity as an electrode. Notably, sulfamethoxazole degradation involving hydroxylation and hydrolysis by the anode membrane is predominant, and the degradation efficiency is up to 81.5% at +4 V. Both electro-filtration processes exhibit significant ARB inactivation, anode filtration is superior to cathode filtration. Moreover, the degradation of intracellular ARGs (iARGs) located in the genome is more efficient than those located in the plasmid, and these degradation efficiencies at -2 V are higher than +2 V. The degradation efficiencies of extracellular ARGs (eARGs) are opposite and are lower than iARGs. Compared with regular filtration, the normalized flux of electroactive ultrafiltration membrane is improved by 18.0% at -2 V, 15.9% at +2 V, and 30.4% at +4 V during treating wastewater effluent, confirming its antifouling properties and feasibility for practical application.

Photocatalytic Reactive Ultrafiltration Membrane for Removal of Antibiotic Resistant Bacteria and Antibiotic Resistance Genes from Wastewater Effluent.

Biological wastewater treatment is not effective in removal of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). In this study, we fabricated a photocatalytic reactive membrane by functionalizing polyvinylidene fluoride (PVDF) ultrafiltration (UF) membrane with titanium oxide (TiO2) nanoparticles for the removal of ARB and ARGs from a secondary wastewater effluent. The TiO2-modified PVDF membrane provided complete retention of ARB and effective photocatalytic degradation of ARGs and integrons. Specifically, the total removal efficiency of ARGs (i.e., plasmid-mediated floR, sul1, and sul2) with TiO2-modified PVDF membrane reached ∼98% after exposure to UV irradiation. Photocatalytic degradation of ARGs located in the genome was found to be more efficient than those located in plasmid. Excellent removal of integrons (i.e., intI1, intI2, and intI3) after UV treatment indicated that the horizontal transfer potential of ARGs was effectively controlled by the TiO2 photocatalytic reaction. We also evaluated the antifouling properties of the TiO2-UF membrane to demonstrate its potential application in wastewater treatment.

Regulation of quorum sensing for the manipulation of conjugative transfer of antibiotic resistance genes in wastewater treatment system.

The emergence and transmission of antibiotic resistance genes (ARGs) through plasmid-mediated conjugation has become a significant worldwide public health threat. Biofilms are widely recognized as the primary reservoirs for ARGs, providing favorable conditions for horizontal gene transfer. Quorum sensing (QS) plays a critical role in bacterial biofilm formation, which further influences the spread of bacterial resistance. In this study, we examined the effects of vanillin, a QS inhibitor (QSI), at subinhibitory concentrations (sub-MICs) ranging from 0 - 0.1 g/L, on the transfer of ARGs between Escherichia coli and Pseudomonas aeruginosa. Our findings indicated that vanillin at sub-MICs inhibited the conjugative transfer frequency of the RP4 plasmid. This inhibition was supported by the downregulation of plasmid transfer genes. The suppression of conjugation can mainly be attributed to the inhibition of biofilm formation, the synthesis of extracellular polymeric substances (EPS), and the secretion of virulence factors, all of which are regulated by the bacterial QS system. On the other hand, the levels of ROS and cell membrane permeability were not primary explanations for this phenomenon. Furthermore, vanillin also reduced the conjugative transfer frequency of ARGs in wastewater effluent, providing a potential approach to alleviate bacterial resistance in water environments. These findings underscore the regulatory role of QSI in controlling ARGs transfer and have significant implications for manipulating the dissemination of bacterial resistance in the environment.

Mendelian Randomization Analysis Reveals Causal Effects of Polyunsaturated Fatty Acids on Subtypes of Diabetic Retinopathy Risk.

Polyunsaturated fatty acids (PUFAs) affect several physiological processes, including visual acuity, but their relationship with diabetic retinopathy (DR) remains elusive. The aim of this study was to determine whether PUFAs have a causal effect on DR. PUFAs- (total and omega-3 [FAw3] and omega-6 [FAw6] fatty acids and their ratio) and DR-associated single nucleotide polymorphisms derived from genome-wide association studies; sample sizes were 114,999 for fatty acids and 216,666 for any DR (ADR), background DR (BDR), severe non-proliferative DR (SNPDR), and proliferative DR (PDR). We hypothesized that the intra-body levels of PUFAs have an impact on DR and conducted a two-sample Mendelian randomization (MR) study to assess the causality. Pleiotropy, heterogeneity, and sensitivity analyses were performed to verify result reliability. High levels of PUFAs were found to be associated with reduced risk of both ADR and PDR. Moreover, FAw3 was associated with a decreased risk of PDR, whereas FAw6 demonstrated an association with lowered risks of both BDR and PDR. Our findings provide genetic evidence, for the first time, for a causal relationship between PUFAs and reduced DR risk. Consequently, our comprehensive MR analysis strongly urges further investigation into the precise functions and long-term effects of PUFAs, FAw3, and FAw6 on DR.

Removal of pharmaceutical and personal care products (PPCPs) by MOF-derived carbons: A review.

Nowadays, the increasing demand for pharmaceuticals and personal care products (PPCPs) has resulted in the uncontrolled release of large amounts of PPCPs into the environment, which poses a great challenge to the existing wastewater treatment technologies. Therefore, novel materials for efficient treatment of PPCPs need to be developed urgently. MOF-derived carbons (MDCs), have many advantages such as high mechanical strength, excellent water stability, large specific surface area, excellent electron transfer capability, and environmental friendliness. These advantages give MDCs an excellent ability to remove PPCPs. In this review, the effects of different substances on the properties and functions of MDCs are discussed. In addition, representative applications of MDCs and composites for the removal of PPCPs in the field of adsorption and catalysis are summarized. Finally, the future challenges of MDCs and composites are foreseen.

Treatment of decentralized low-strength livestock wastewater using microcurrent-assisted multi-soil-layering systems: performance assessment and microbial analysis.

Discharge of decentralized livestock wastewater without effective treatment has become a common problem in rural areas, threatening the regional water environment. A new microcurrent-assisted multi-soil-layering (MSL) system was developed for treating rural decentralized livestock wastewater. The results showed the highest removal rates of chemical oxygen demand (COD) and total phosphorus (TP) in MSL systems reached 95.45% and 92.0%, respectively. The removal rate of total nitrogen (TN) in MSL systems ranged from 60 to 75%. The bacterial diversity changes among MSL systems showed that high-level height of bottom submergence had a positive effect on the abundance of denitrifying bacteria, while low-level height of bottom submergence had a positive impact on the abundance of nitrifying bacteria. The effect of low-level external voltage on bacterial abundance was better than that of high-level external voltage. Both high- and low-level influent C/N ratios had no significant effect on bacterial abundance. The metabolism and activity of microorganisms were promoted with microcurrent stimulation from the perspective of increased bacterial abundance in MSL systems with improved treatment performance.

Mechanisms of metabolic performance enhancement during electrically assisted anaerobic treatment of chloramphenicol wastewater.

The anaerobic process is a favorable alternative for the treatment of antibiotic pharmaceutical wastewater. The electrically assisted anaerobic process can be used to accelerate contaminant removal, especially for persistent organic pollutants such as antibiotics. In this study, an electrically assisted anaerobic system for chloramphenicol (CAP) wastewater treatment was developed. The system performance and the underlying metabolic mechanisms were evaluated under different applied voltages. With the increase of applied voltage from 0 to 2 V, the CAP removal efficiencies increased from 53.3% to 89.7%, while the methane production increased more than three times. The microbial community structure and correlation analysis showed that electrical stimulation selected the dominant functional bacteria and increased antibiotic resistance in dominant functional bacteria, both of which enhanced CAP removal and methane production. The improved CAP removal was a result of the presence of dechlorination-related bacteria (Acidovorax, Sedimentibacter, Thauera, and Flavobacterium) and potential electroactive bacteria (Shewanella and Comamonas), both of which carried ARGs and therefore could survive the biotoxicity of CAP. The enhanced methane production could be partly attributed to the surviving fermentative-related bacteria (Paludibacter, Proteiniclasticum, and Macellibacteroides) in the anaerobic bioreactor. The increased abundances of methanogenic genes (mcrA and ACAS genes) under high voltage further confirmed the enhanced methane production of this electrically assisted anaerobic system. The fundamental understanding of the mechanisms underlying metabolic performance enhancement is critical for the further development of anaerobic wastewater treatment.

Response of antibiotic resistance to the co-existence of chloramphenicol and copper during bio-electrochemical treatment of antibiotic-containing wastewater.

Concerns have been raised regarding co-selection for antibiotic resistance among microorganisms exposed to antibiotics and metals. As a promising approach for treating antibiotics and heavy metal-containing wastewater, a bio-electrochemical system (BES) can be used for antibiotic and heavy metal removal. This study determined the fate of antibiotic resistance genes (ARGs) in a BES when exposed to chloramphenicol (CAP) and Cu2+. The ARGs encoding the efflux pump (cmlA, floR, and tetC), the class 1 integron integrase-encoding gene, and the sul1 gene were analyzed. The results indicated that the co-existence of CAP and different concentrations of Cu2+ had significant influence on the relative abundances of the ARGs. The changes in the bacterial community structure and the results of a quantitative correlation analysis between the bacterial community and the ARGs confirmed that the shift in the potential hosts was the key reason for the changes of the ARGs. This study sheds new light on the mechanisms of ARGs variations in BES under the co-selection pressure of antibiotics and heavy metals.

OH-initiated transformation and hydrolysis of aspirin in AOPs system: DFT and experimental studies.

Advanced oxidation processes (AOPs) are widely used in wastewater treatment of pharmaceutical and personal care products (PPCPs). In this work, the OH-initiated transformation as well as the hydrolysis of a typical PPCPs, aspirin, was investigated using density functional theory (DFT) calculations and laboratory experiments. For DFT calculations, the frontier electron densities and bond dissociation energies were analyzed. Profiles of the potential energy surface were constructed, and all the possible pathways were discussed. Additionally, rate constants for each pathway were calculated with transition state theory (TST) method. UV/H2O2 experiments of aspirin were performed and degradation intermediates were identified by UPLC-MS-MS analysis. Different findings from previous experimental works were reported that the H-abstraction pathways at methyl position were dominated and OH-addition pathways on benzene ring were also favored. Meantime, hydroxyl ASA was confirmed as the main stable intermediate. Moreover, it was the first time to use DFT method to investigate the hydrolysis mechanisms of organic ester compound.