The glycolytic enzyme PFKFB3 drives kidney fibrosis through promoting histone lactylation-mediated NF-κB family activation.

Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease (CKD). However, the underlying mechanism remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells (PTCs) following ischemia-reperfusion injury (IRI) in mice, as well as in multiple etiologies of patients with CKD. PFKFB3 expression was positively correlated with the severity of kidney fibrosis. Moreover, patients with CKD and mice exhibited increased urinary lactate/creatine levels and kidney lactate, respectively. PTC-specific deletion of PFKFB3 significantly reduced kidney lactate levels, mitigated inflammation and fibrosis, and preserved kidney function in the IRI mouse model. Similar protective effects were observed in mice with heterozygous deficiency of PFKFB3 or those treated with a PFKFB3 inhibitor. Mechanistically, lactate derived from PFKFB3-mediated tubular glycolytic reprogramming markedly enhanced histone lactylation, particularly H4K12la, which was enriched at the promoter of NF-κB signaling genes like Ikbkb, Rela, and Relb, activating their transcription and facilitating the inflammatory response. Further, PTC-specific deletion of PFKFB3 inhibited the activation of IKKß, I κ B α, and p65 in the IRI kidneys. Moreover, increased H4K12la levels were positively correlated with kidney inflammation and fibrosis in patients with CKD. These findings suggest that tubular PFKFB3 may play a dual role in enhancing NF-κB signaling by promoting both H4K12la-mediated gene transcription and its activation. Thus, targeting the PFKFB3-mediated NF-κB signaling pathway in kidney tubular cells could be a novel strategy for CKD therapy.

Smartphone-Based Fluorescent Profiling of Quaternary MicroRNAs in Urine for Rapid Diagnosis of Urological Cancers Using a Multiplexed Isothermal Exponential Amplification Reaction.

Urological cancers such as bladder or prostate cancer represent one of the most malignant tumors that accounts for an extremely high mortality. However, conventionally standard diagnostics for urological cancers are hardly available in low-resource settings. We developed herein a hand-held fluorescent imaging platform by integrating a multiplexed isothermal exponential amplification reaction (EXPAR) with a microgel-enriched methodology for sensitive profiling of quaternary microRNAs (miRNAs) in urine and quick diagnosis of urological cancers at the early stage. The target miRNA mixtures in the urine underwent four parallel EXPARs without cross-reactivity, followed by surface concentration and hybridization by the encoded polyacrylamide microgels. This mix-and-read strategy allowed for one-pot analysis of several key miRNAs simultaneously and provided 5-fold enhancement in fluorescent detection sensitivities compared to the individual EXPAR-based assays. Four urinary miRNAs (let-7a, miRNA-155, -223, and -143) could be quantitatively determined in a wide linear range from 50 fM to 30 nM, with the limits of detection at femtomolar levels. Using a smartphone-based imaging microreader, healthy and cancerous cohorts with prostate, bladder, and renal cell cancers could be discriminated in 30 min with the accuracy >83% using linear discriminant analysis. The developed detection platform has proven to be a portable, noninvasive, and useful complement to the toolbox for miRNA-based liquid biopsies, which holds immense potential and advantage for regular and large-scale applications in early cancer diagnosis.

Clinicopathological phenotype and outcomes of NCAM-1+ membranous lupus nephritis.

INTRODUCTION: No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. METHOD: We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. RESULTS: Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P = 0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = 0.007], serum creatinine [60 µmol/L (IQR 50-70) versus 70 (54-114); P = 0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P = 0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P = 0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P = 0.668 and P = 0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8% vs. 8.1%, P = 0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P = 0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. CONCLUSION: The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

A Perspective on the Controversy over Global Emission Fluxes of Microplastics from Ocean into the Atmosphere.

Since the transfer of microplastic across the sea-air interface was first reported in 2020, numerous studies have been conducted on its emission flux estimation. However, these studies have shown significant discrepancies in the estimated contribution of oceanic sources to global atmospheric microplastics, with evaluations ranging from predominant to negligible, varying by 4 orders of magnitude from 7.7 × 10-4 to 8.6 megatons per year, thereby creating considerable confusion in the research on the microplastic cycle. Here, we provide a perspective by applying the well-established theory of particulate transfer through the sea-air interface. The upper limit of global sea-air emission flux microplastics was calculated, aiming to constrain the controversy in the previously reported fluxes. Specifically, the flux of sub-100 µm microplastic cannot exceed 0.01 megatons per year, and for sub-0.1 µm nanoplastics, it would not exceed 3 × 10-7 megatons per year. Bridging this knowledge gap is crucial for a comprehensive understanding of the sea-air limb in the "plastic cycle", and facilitates the management of future microplastic pollution.

Exposure to microcystin-LR promotes the progression of colitis-associated colorectal cancer by inducing barrier disruption and gut microbiota dysbiosis.

Microcystins (MCs) are secondary metabolites generated by cyanobacterial blooms, among which microcystin-LR (MC-LR) stands out as the most widely distributed variant in aquatic environments. However, the effects of MC-LR on the colorectum and its role in promoting colorectal tumor progression remain unclear. Therefore, this study aims to scrutinize the impact of MC-LR on a mice model of colitis-associated colorectal cancer and elucidate the potential underlying molecular mechanisms. In this study, we used AOM/DSS mice and orally administered MC-LR at doses of 40 µg/kg or 200 µg/kg. Exposure to MC-LR increased tumor burden, promoted tumor growth, shortened colon size, and decreased goblet cell numbers and tight junction protein levels in intestinal tissues. Additionally, exposure to MC-LR induced alterations in the structure of gut microbiota in the mouse colon, characterized by an increase in the relative abundance of Escherichia_coli and Shigella_sonnei, and a decline in the relative abundance of Akkermansia_muciniphila. Transcriptomic analysis revealed that MC-LR exposure activated the IL-17 signaling pathway in mouse colorectal tissues and participated in inflammation regulation and immune response. Immunofluorescence results demonstrated an increase in T-helper 17 (Th17) cell levels in mouse colorectal tumors following MC-LR exposure. The results from RT-qPCR revealed that MC-LR induced the upregulation of IL-6, IL-1ß, IL-10, IL-17A, TNF-α, CXCL1, CXCL2, CXCL5 and CCL20. The novelty of this study lies in its comprehensive approach to understanding the mechanisms by which MC-LR may contribute to CRC progression, offering new perspectives and valuable reference points for establishing guidance standards regarding MC-LR in drinking water. Our findings suggest that even at guideline value, MC-LR can have profound effects on susceptible mice, emphasizing the need for a reevaluation of guideline value and a deeper understanding of the role of environmental toxins in cancer progression.

Aqueous-phase formation of N-containing secondary organic compounds affected by the ionic strength.

The reaction of carbonyl-to-imine/hemiaminal conversion in the atmospheric aqueous phase is a critical pathway to produce the light-absorbing N-containing secondary organic compounds (SOC). The formation mechanism of these compounds has been wildly investigated in bulk solutions with a low ionic strength. However, the ionic strength in the aqueous phase of the polluted atmosphere may be higher. It is still unclear whether and to what extent the inorganic ions can affect the SOC formation. Here we prepared the bulk solution with certain ionic strength, in which glyoxal and ammonium were mixed to mimic the aqueous-phase reaction. Molecular characterization by High-resolution Mass Spectrometry was performed to identify the N-containing products, and the light absorption of the mixtures was measured by ultraviolet-visible spectroscopy. Thirty-nine N-containing compounds were identified and divided into four categories (N-heterocyclic chromophores, high-molecular-weight compounds with N-heterocycle, aliphatic imines/hemiaminals, and the unclassified). It was observed that the longer reaction time and higher ionic strength led to the formation of more N-heterocyclic chromophores and the increasing of the light-absorbance of the mixture. The added inorganic ions were proposed to make the aqueous phase somewhat viscous so that the molecules were prone to undergo consecutive and intramolecular reactions to form the heterocycles. In general, this study revealed that the enhanced ionic strength and prolonged reaction time had the promotion effect on the light-absorbing SOC formation. It implies that the aldehyde-derived aqueous-phase SOC would contribute more light-absorbing particulate matter in the industrial or populated area where inorganic ions are abundant.

[Spatial Differentiation Characteristics and Influencing Factors of Surface Soil Cd in Karst Plateau Area of Guiyang City].

In order to explore the spatial differentiation characteristics and variation law of soil Cd content in a high geological background area, 14 421 topsoil samples were collected from topsoil in the karst area of Guiyang City. Global Moran's I index, cold hot spot analysis, semi-variance function, and Kriging interpolation were used to reveal the spatial structure and distribution law of soil Cd content. The influence of environmental factors on soil Cd content and its main controlling factors were analyzed through analysis of variance and geographic detector. The results showed that： ① The Cd content of karst surface soil in Guiyang varied from 0.03 to 1.36 mg·kg-1, with an average of 0.440 mg·kg-1, which was 1.77 times and 5.95 times the Guizhou soil Cd background value and Chinese soil Cd background value, respectively. The over-standard rate of soil Cd was 30%, which was 4.29 times that of 7% of soil Cd in China. ② There was a significant spatial positive correlation of soil Cd content, showing an aggregation trend in the global space, whereas in the local region, the northeast and southwest were hot spots, and the north was a cold spot. The nugget coefficient of soil Cd content was 10.37%, indicating that soil Cd was mainly affected by structural factors. ③ In terms of spatial distribution, soil Cd showed different accumulation trends. In some massive soils, such as Xifeng County, Xiuwen County, Qingzhen City, Huaxi District, and Nanming District, the soil ω（Cd）was less than 0.3 mg·kg-1. The soil ω（Cd）was between 0.3 and 0.6 mg·kg-1,and soil Cd in Baiyun District, Wudang District, Guanshan Lake area, and Yunyan area as a whole lied within this range. The soil ω（Cd）between 0.6 and 0.9 mg·kg-1 was concentrated in the southwest of Qingzhen City, the south of Huaxi District, and the north of Kaiyang County, whereas soil ω（Cd） between 0.9 and 1.2 mg·kg-1 was mainly concentrated in the southwest of Qingzhen City. The extreme value of soil Cd content （ > 1.2 mg·kg-1） was mostly distributed in Kaiyang County, Xiuwen County, Qingzhen City, and Huaxi District. ④ The results of analysis of variance and geo-detector showed that different environmental factors had significant effects on the spatial differentiation of soil Cd, but their explanatory power on soil Cd content varied： stratum （0.176 5） > soil type （0.026 0） > organic matter （0.025 1） > altitude （0.010 5） > parent rock （0.007 3） > land use （0.006 4） > pH （0.001 3）, and the interaction between stratum and arbitrary environmental factors was the greatest. Therefore, stratum was the main factor affecting the spatial differentiation of soil Cd content.

Exposure to Microcystin-LR Promotes Colorectal Cancer Progression by Altering Gut Microbiota and Associated Metabolites in APCmin/+ Mice.

Microcystins (MCs), toxins generated by cyanobacteria, feature microcystin-LR (MC-LR) as one of the most prevalent and toxic variants in aquatic environments. MC-LR not only causes environmental problems but also presents a substantial risk to human health. This study aimed to investigate the impact of MC-LR on APCmin/+ mice, considered as an ideal animal model for intestinal tumors. We administered 40 µg/kg MC-LR to mice by gavage for 8 weeks, followed by histopathological examination, microbial diversity and metabolomics analysis. The mice exposed to MC-LR exhibited a significant promotion in colorectal cancer progression and impaired intestinal barrier function in the APCmin/+ mice compared with the control. Gut microbial dysbiosis was observed in the MC-LR-exposed mice, manifesting a notable alteration in the structure of the gut microbiota. This included the enrichment of Marvinbryantia, Gordonibacter and Family_XIII_AD3011_group and reductions in Faecalibaculum and Lachnoclostridium. Metabolomics analysis revealed increased bile acid (BA) metabolites in the intestinal contents of the mice exposed to MC-LR, particularly taurocholic acid (TCA), alpha-muricholic acid (α-MCA), 3-dehydrocholic acid (3-DHCA), 7-ketodeoxycholic acid (7-KDCA) and 12-ketodeoxycholic acid (12-KDCA). Moreover, we found that Marvinbryantia and Family_XIII_AD3011_group showed the strongest positive correlation with taurocholic acid (TCA) in the mice exposed to MC-LR. These findings provide new insights into the roles and mechanisms of MC-LR in susceptible populations, providing a basis for guiding values of MC-LR in drinking water.

Effectiveness and safety of different catechol-o-methyl transferase inhibitors for patients with parkinson's disease: Systematic review and network meta-analysis.

BACKGROUND: Levodopa treatment requires the addition of other drugs, such as catechol-O-methyl transferase (COMT) inhibitors, to alleviate motor fluctuations in advanced parkinson's disease (PD). However, the optimal strategy, including the type and dose of COMT inhibitors remains unknown. This systematic review and network meta-analysis aimed to assess the efficacy and safety of different COMT inhibitors and for treating PD patients. METHODS: PubMed, Embase, Cochrane Library and Web of Science were screened up to November 20, 2022. Randomized controlled trials (RCTs) of COMT inhibitors (entacapone, opicapone, tolcapone) for PD patients were included. Eligible outcomes were total ON-time, rate of ON-time >1 h, total daily dose of levodopa therapy, mean change from baseline to final follow up in Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, adverse events and dyskinesia. Network meta-analyses integrated direct and indirect evidence with placebo as a common comparator. RESULTS: We identified 18 studies with 7564 patients. Opicapone, entacapone, and tolcapone could increase total ON-time when compared with placebo. However, opicapone (25 mg, MD 4.0, 95%CrI: 1.1-7.5) and opicapone (50 mg, MD 5.1, 95%CrI: 2.2-8.7) statistically significant increase the total ON-time. opicapone and entacapone could increase the rate of ON-time >1 h when compared with placebo. Only opicapone (5 mg) showed no statistically significant with placebo (OR 1.4, 95%CrI: 0.74-2.4). We found that opicapone (50 mg, SURCA, 0.796) is the best option compared with other treatments. TOL (200 mg) was ranked highest in the rank probability test for total daily dose of levodopa therapy, followed by OPI (50 mg), TOL (400 mg) and TOL (100 mg) in order. SUCRA rankings identified TOL (200 mg) as the most likely therapy for increasing adverse events (SUCRA 27.19%), followed by TOL (400 mg, SUCRA 27.20%) and OPI (5 mg, SUCRA 30.81%). The SUCRA probabilities were 91.6%, 75.2%, 67.9%, 59.3%, 45.6%, 41.1%, 35.1%, 24.6% and 9.4% for PLA, TOL (400 mg), ENT (100 mg), ENT (200 mg), OPI (5 mg), TOL (100 mg), OPI (25 mg), OPI (50 mg), and TOL (200 mg) respectively. CONCLUSION: In conclusion, opicapone (50 mg) may be a better choice for treatment PD when compared with other COMT inhibitors.

Impact of microplastics on nicosulfuron accumulation and bacteria community in soil-earthworms system.

Microplastics (MPs) widely co-occur with various pollutants in soils. However, the data related to the impacts of MPs on terrestrial animal and microbial properties in pesticide-contaminated soils are few. In this study, the influence of MPs (0.01%, 0.1%, and 1%) on nicosulfuron concentrations in soil (10 µg/g) and earthworms were investigated, moreover, microbial community structure and diversity in soil and earthworm gut were also measured. After 30 days, the concentration of nicosulfuron in soil decreased to 1.27 µg/g, moreover, the residual concentration of nicosulfuron in soil (1%MPs and nicosulfuron) was only 44.8% of that in the single nicosulfuron treatment group. The accumulation of nicosulfuron in earthworms (1%MPs and nicosulfuron) was 7.37 µg/g, which was 1.82 times of that in the single nicosulfuron treatment group. In addition, 1% MPs decreased the richness and diversity of the soil and gut bacterial community in earthworms as well as altered microbial community composition, leading to the enrichment of specific microbial community. Our findings imply that MPs may change the migration of pesticides to terrestrial animal and as well as microbial diversity in earthworms and soil.

Modification of MgH2 hydrogen storage performance by nickel-based composite catalyst Ni/NiO.

In this study, the Ni/NiO catalyst was demonstrated to enhance the hydrogen storage performance of MgH2. The dehydrogenation of MgH2+10 wt% Ni/NiO started at approximately 180 °C, achieving 5.83 wt% of dehydrogenation within 10 min at 300 °C. Completely dehydrogenated, MgH2 began to rehydrogenate at about 50 °C, absorbing about 4.56 wt% of hydrogen in 10 min at 150 °C. In addition, the activation energies of dehydrogenation and rehydrogenation of MgH2+10 wt% Ni/NiO were 87.21 and 34.84 kJ/mol. During the dehydrogenation/rehydrogenation cycle, Mg2Ni/Mg2NiH4 could promote hydrogen diffusion, thus enhancing the hydrogen storage performance of Mg/MgH2.

A case report of integrating Chinese and Western medicine: A new era in the treatment of stiff person syndrome.

RATIONALE: At present, there are limitations to the treatment of stiff person syndrome (SPS). Current treatments are still ineffective or financially burdensome for some patients, so it is imperative to explore more appropriate treatments for patients. This is a case report of a SPS with a more significant effect of combined Chinese and Western medicine, which may provide new treatment ideas for other patients. PATIENT CONCERNS: This patient presented with episodes of stiffness and pain in the lower back and lower extremities. His electromyography shows continued activation of normal motor units in the paraspinal and abdominal muscles. However, relevant laboratory tests including glutamic acid decarboxylase antibody and Amphiphysin antibody were negative. After a period of treatment including clonazepam, baclofen, prednisone and intravenous immunoglobulin, this patient experiences a shortened maintenance period of medication, accompanied by symptoms such as emotional anxiety and cognitive decline, which severely affects his life. DIAGNOSES: This patient was diagnosed with SPS. INTERVENTIONS: In May 2022 the patient decided to combine Chinese medicine for simultaneous treatment. OUTCOMES: During the period of simultaneous treatment with Chinese and Western medicine, the patient experienced remission of clinical symptoms, reduction of concomitant symptoms and improved quality of life. CONCLUSION: A combination of Western and Chinese medicine was effective in relieving this patient pain and stiffness and reducing the patient anxiety. Combined Chinese and Western medicine treatment may be able to bring better results to more patients with stiff person syndrome.

RBF neural network dynamic sliding mode control based on lambert W function for piezoelectric stick-slip actuator.

This paper presents a novel approach for increasing the precision of high-precision positioning control experiments for a piezoelectric stick-slip actuator system. This is achieved through dynamic sliding mode control with a radial basis function neural network (RBFNN) based on the Lambert W function. The proposed control strategy is divided into two parts: scanning mode control and stepping mode control. For scanning control, a dynamic sliding mode controller was designed to solve the jitter problem in traditional sliding mode control. The introduction of the RBFNN avoids the effects of uncertainty terms and unknown disturbances in the model; reduces the controller gain, which must be adjusted; and improves the robustness of the system to disturbances. The stability of the dynamic sliding mode controller based on the RBFNN was verified through a Lyapunov analysis, and the Lambert W function was introduced to optimize the controller parameters responsible for the time lag in the closed-loop control system. This optimization improved the system's robustness against time delays, which can adversely affect its performance. Simulation and experimental results indicated that the proposed control strategy achieved a positioning control accuracy of <40 nm during the scanning phase and was robust in the presence of a load. In long-distance positioning control experiments, the control strategy achieved a control target of 40 µm while maintaining the positioning control accuracy and reducing the impact of time lag on the system.

Hydroxylamine-induced activation of permanganate for enhanced oxidation of sulfamethoxazole: Mechanism and products.

Recently, many reagents have been introduced to accelerate the formation of highly reactive intermediate Mn species from permanganate (KMnO4), thereby improving the oxidation activity of KMnO4 towards pollutants. However, most studies have mainly focused on sulfur-containing reducing agents (e.g., bisulfite and sodium sulfite), with little attention paid to nitrogen-containing reducing agents. This study found that hydroxylamine (HA) and hydroxylamine derivatives (HAs) can facilitate KMnO4 in pollutant removal. Taking sulfamethoxazole (SMX) as a target contaminant, the effect of pH, SMX concentration, KMnO4 and HA dosages, and the molar ratio of HA and KMnO4 on the degradation of SMX in the KMnO4/HA process was systematically investigated. Quenching experiments and probe analysis revealed MnO2-catalyzed KMnO4 oxidation, Mn(III) and reactive nitrogen species as the primary active species responsible for SMX oxidation in the KMnO4/HA system. Proposed transformation pathways of SMX in the KMnO4/HA system mainly involve hydroxylation and cleavage reactions. The KMnO4/HA system was more conducive to selective oxidation of SMX, 2,4-dichlorophenol, and several other pollutants, but reluctant to bisphenol S (BPS). Overall, this study proposed an effective system for eliminating pollutants, while providing mechanistic insight into HA-driven KMnO4 activation for environmental remediation.

Effect of ozone treatment on phenylpropanoid metabolism in harvested cantaloupes.

Phenylpropanoid metabolism plays an important role in cantaloupe ripening and senescence, but the mechanism of ozone regulation on phenylpropanoid metabolism remains unclear. This study investigated how ozone treatment modulates the levels of secondary metabolites associated with phenylpropanoid metabolism, the related enzyme activities, and gene expression in cantaloupe. Treating cantaloupes with 15 mg/m3 of ozone after precooling can help maintain postharvest hardness. This treatment also enhances the production and accumulation of secondary metabolites, such as total phenols, flavonoids, and lignin. These metabolites are essential components of the phenylpropanoid metabolic pathway, activating enzymes like phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, 4CL, chalcone synthase, and chalcone isomerase. The results of the transcriptional expression patterns showed that differential gene expression related to phenylpropanoid metabolism in the peel of ozone-treated cantaloupes was primarily observed during the middle and late storage stages. In contrast, the pulp exhibited significant differential gene expression mainly during the early storage stage. Furthermore, it was observed that the level of gene expression in the peel was generally higher than that in the pulp. The correlation between the relative amount of gene changes in cantaloupe, activity of selected enzymes, and concentration of secondary metabolites could be accompanied by positive regulation of the phenylpropanoid metabolic pathway. Therefore, ozone stress induction positively enhances the biosynthesis of flavonoids in cantaloupes, leading to an increased accumulation of secondary metabolites. Additionally, it also improves the postharvest storage quality of cantaloupes.

A global transcriptional activator involved in the iron homeostasis in cyanobacteria.

Cyanobacteria use a series of adaptation strategies and a complicated regulatory network to maintain intracellular iron (Fe) homeostasis. Here, a global activator named IutR has been identified through three-dimensional chromosome organization and transcriptome analysis in a model cyanobacterium Synechocystis sp. PCC 6803. Inactivation of all three homologous IutR-encoding genes resulted in an impaired tolerance of Synechocystis to Fe deficiency and loss of the responses of Fe uptake-related genes to Fe-deplete conditions. Protein-promoter interaction assays confirmed the direct binding of IutR with the promoters of genes related to Fe uptake, and chromatin immunoprecipitation sequencing analysis further revealed that in addition to Fe uptake, IutR could regulate many other physiological processes involved in intracellular Fe homeostasis. These results proved that IutR is an important transcriptional activator, which is essential for cyanobacteria to induce Fe-deficiency response genes. This study provides in-depth insights into the complicated Fe-deficient signaling network and the molecular mechanism of cyanobacteria adaptation to Fe-deficient environments.

High-valent metal-oxo species transformation and regulation by co-existing chloride: Reaction pathways and impacts on the generation of chlorinated by-products.

High-valent metal-oxo species (HMOS) have been extensively recognized in advanced oxidation processes (AOPs) owing to their high selectivity and high chemical utilization efficiency. However, the interactions between HMOS and halide ions in sewage wastewater are complicated, leading to ongoing debates on the intrinsic reactive species and impacts on remediation. Herein, we prepared three typical HMOS, including Fe(IV), Mn(V)-nitrilotriacetic acid complex (Mn(V)NTA) and Co(IV) through peroxymonosulfate (PMS) activation and comparatively studied their interactions with Cl- to reveal different reactive chlorine species (RCS) and the effects of HMOS types on RCS generation pathways. Our results show that the presence of Cl- alters the cleavage behavior of the peroxide OO bond in PMS and prohibits the generation of Fe(IV), spontaneously promoting SO4•- production and its subsequent transformation to secondary radicals like Cl• and Cl2•-. The generation and oxidation capacity of Mn(V)NTA was scarcely influenced by Cl-, while Cl- would substantially consume Co(IV) and promote HOCl generation through an oxygen-transfer reaction, evidenced by density functional theory (DFT) and deuterium oxide solvent exchange experiment. The two-electron-transfer standard redox potentials of Fe(IV), Mn(V)NTA and Co(IV) were calculated as 2.43, 2.55 and 2.85 V, respectively. Due to the different reactive species and pathways in the presence of Cl-, the amounts of chlorinated by-products followed the order of Co(II)/PMS > Fe(II)/PMS > Mn(II)NTA/PMS. Thus, this work renovates the knowledge of halide chemistry in HMOS-based systems and sheds light on the impact on the treatment of salinity-containing wastewater.

The Spermine Oxidase/Spermine Axis Coordinates ATG5-Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis.

Decreased plasma spermine levels are associated with kidney dysfunction. However, the role of spermine in kidney disease remains largely unknown. Herein, it is demonstrated that spermine oxidase (SMOX), a key enzyme governing polyamine metabolism, is predominantly induced in tubular epithelium of human and mouse fibrotic kidneys, alongside a reduction in renal spermine content in mice. Moreover, renal SMOX expression is positively correlated with kidney fibrosis and function decline in patients with chronic kidney disease. Importantly, supplementation with exogenous spermine or genetically deficient SMOX markedly improves autophagy, reduces senescence, and attenuates fibrosis in mouse kidneys. Further, downregulation of ATG5, a critical component of autophagy, in tubular epithelial cells enhances SMOX expression and reduces spermine in TGF-ß1-induced fibrogenesis in vitro and kidney fibrosis in vivo. Mechanically, ATG5 readily interacts with SMOX under physiological conditions and in TGF-ß1-induced fibrogenic responses to preserve cellular spermine levels. Collectively, the findings suggest SMOX/spermine axis is a potential novel therapy to antagonize renal fibrosis, possibly by coordinating autophagy and suppressing senescence.

Ultrasonic humidifier aerosols: Observed high heavy metal enrichment and a new emission control method.

Ultrasonic humidifiers are commonly used in households to maintain indoor humidity and generate a large number of droplets or spray aerosols. However, there have been various health concerns associated with humidifier use, largely due to aerosols generated during operation. Here, we investigated the size distribution, chemical composition, and charged fraction of aerosol particles emitted from commercial ultrasonic humidifiers. Heavy metals in water used for humidifiers were found to be highly enriched in the ultrasonic humidifier aerosols (UHA), with the enrichment factors ranging from 102 to 107. This enrichment may pose health concerns for the building occupants, as UHA concentrations of up to 106 particles/cm3 or 3 mg/m3 were observed. Furthermore, approximately 90% of UHA were observed to be electrically charged, for the first time according to our knowledge. Based on this discovery, we proposed and tested a new method to remove UHA by using a simple electrical field. The designed electrical field in this work can efficiently remove 81.4% of UHA. Therefore, applying this electrical field could be an effective method to significantly reduce the health risks by UHA.