Inhibition of Drp1- Fis1 interaction alleviates aberrant mitochondrial fragmentation and acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common clinical disorder with complex etiology and poor prognosis, and currently lacks specific and effective treatment options. Mitochondrial dynamics dysfunction is a prominent feature in AKI, and modulation of mitochondrial morphology may serve as a potential therapeutic approach for AKI. METHODS: We induced ischemia-reperfusion injury (IRI) in mice (bilateral) and Bama pigs (unilateral) by occluding the renal arteries. ATP depletion and recovery (ATP-DR) was performed on proximal renal tubular cells to simulate in vitro IRI. Renal function was evaluated using creatinine and urea nitrogen levels, while renal structural damage was assessed through histopathological staining. The role of Drp1 was investigated using immunoblotting, immunohistochemistry, immunofluorescence, and immunoprecipitation techniques. Mitochondrial morphology was evaluated using confocal microscopy. RESULTS: Renal IRI induced significant mitochondrial fragmentation, accompanied by Dynamin-related protein 1 (Drp1) translocation to the mitochondria and Drp1 phosphorylation at Ser616 in the early stages (30 min after reperfusion), when there was no apparent structural damage to the kidney. The use of the Drp1 inhibitor P110 significantly improved kidney function and structural damage. P110 reduced Drp1 mitochondrial translocation, disrupted the interaction between Drp1 and Fis1, without affecting the binding of Drp1 to other mitochondrial receptors such as MFF and Mid51. High-dose administration had no apparent toxic side effects. Furthermore, ATP-DR induced mitochondrial fission in renal tubular cells, accompanied by a decrease in mitochondrial membrane potential and an increase in the translocation of the pro-apoptotic protein Bax. This process facilitated the release of dsDNA, triggering the activation of the cGAS-STING pathway and promoting inflammation. P110 attenuated mitochondrial fission, suppressed Bax mitochondrial translocation, prevented dsDNA release, and reduced the activation of the cGAS-STING pathway. Furthermore, these protective effects of P110 were also observed renal IRI model in the Bama pig and folic acid-induced nephropathy in mice. CONCLUSIONS: Dysfunction of mitochondrial dynamics mediated by Drp1 contributes to renal IRI. The specific inhibitor of Drp1, P110, demonstrated protective effects in both in vivo and in vitro models of AKI.

Innovative explorations: unveiling the potential of organoids for investigating environmental pollutant exposure.

As the economy rapidly develops, chemicals are widely produced and used. This has exacerbated the problems associated with environmental pollution, raising the need for efficient toxicological evaluation techniques to investigate the toxic effects and mechanisms of toxicity of environmental pollutants. The progress in the techniques of cell culture in three dimensions has resulted in the creation of models that are more relevant in terms of biology and physiology. This enables researchers to study organ development, toxicology, and drug screening. Adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs) can be obtained from various mammalian tissues, including cancerous and healthy tissues. Such stem cells exhibit a significant level of tissue memory and ability to self-assemble. When cultivated in 3D in vitro environments, the resulting organoids demonstrate a remarkable capacity to recapitulate the cellular composition and function of organs in vivo. Recently, many tumors' tissue-derived organoids have been widely used in research on tumor pathogenesis, drug development, precision medicine, and other fields, including those derived from colon cancer, cholangiocarcinoma, liver cancer, and gastric cancer. However, the application of organoid models for evaluating the toxicity of environmental pollutants is still in its infancy. This review introduces the characteristics of the toxicity responses of organoid models upon exposure to pollutants from the perspectives of organoid characteristics, tissue types, and their applications in toxicology; discusses the feasibility of using organoid models in evaluating the toxicity of pollutants; and provides a reference for future toxicological studies on environmental pollutants based on organoid models.

Effects of Cinnamomum camphora Leaves Extracts-Flocculants Composite Algaecide on Microcystis aeruginosa Growth and Microcystins Release.

In this study, a composite algaecide containing flocculants and Cinnamomum. camphora leaves extracts (CCCLE) were synthesized. The inhibition and flocculation effects on Microcystis aeruginosa (M. aeruginosa) were investigated, and the release of microcystin-LR (MC-LR) was determined. Results showed that the CCLEC composite algaecide was effective for the inhibition and flocculation of M. aeruginosa, and the optimal dose of CCLEC composite algaecide was 1.8%, which resulted in an algae inhibition ratio of 98.00% and a flocculation efficiency of 99.44% within 5 days of M. aeruginosa culturing. Besides, the total amount of MC-LR decreased by 80.04% on day 20 compared with the control group, while the concentration of intracellular MC-LR on day 5 was 36.69 µg L-1, which was related to a portion of cells underwent apoptosis-like cell death under CCLEC composite algaecide stress. The results of this study may improve our understanding of the M. aeruginosa control by CCCLE composite algaecide.

Scientific Evidence of Xuebijing Injection in the Treatment of Sepsis.

OBJECTIVES: To systematically collate, appraise, and synthesize the current evidence on the Xuebijing injection (XBJI) for sepsis. METHODS: Eight databases were searched for systematic reviews (SRs) or meta-analyses (MAs) on XBJI for sepsis. Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2), Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA), and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methods were used to assess the methodological quality, reporting quality, and evidence quality of the enrolled studies, respectively. RESULTS: Out of the 13 studies that were included, all studies were rated critically low quality based on AMSTAR-2 results. Based on the results obtained from PRISMA, all studies were reported to be over 80%, while the GRADE system yielded three outcome measures rated high-quality, 16 were of moderate quality, and the rest were of low or critically low quality. CONCLUSIONS: The combination of XBJI and Western medicine (WM) showed significant synergy for the treatment of sepsis compared to WM alone. However, this conclusion should be treated with caution since the quality of the SRs/MAs providing the evidence was relatively low.

Rapid monitoring of heavy metal pollution in lake water using nitrogen and phosphorus nutrients and physicochemical indicators by support vector machine.

A novel method of predicting heavy metal concentration in lake water by support vector machine (SVM) model was developed, combined with low-cost, easy to obtain nutrients and physicochemical indicators as input variables. 115 surface water samples were collected from 23 sites in Chaohu Lake, China, during different hydrological periods. The particulate concentrations of heavy metals in water were much higher than the dissolved concentrations. According to Nemerow pollution index (Pi), pollution degrees by Fe, V, Mn and As ranged from heavy (2 ≤ Pi < 4) to serious (Pi ≥ 4). The concentrations of most heavy metals were the highest during the medium-water period and the lowest during the dry season. Non-metric Multidimensional Scaling Analysis confirmed heavy metal concentrations had slight spatial difference but relatively large seasonal variation. Redundancy Analysis indicated the close associations of heavy metals with nutrient and physicochemical indicators. When both nutrient and physicochemical indicators were used as input variables, the simulation effects for most elements in total and particulate were relatively better than those obtained using only nutrient or only physicochemical indicators. The simulation effects for As, Ba, Fe, Ti, V and Zn were generally good, based on their training R values of 0.847, 0.828, 0.856, 0.867, 0.817 and 0.893, respectively, as well as their test R values of 0.811, 0.836, 0.843, 0.873, 0.829 and 0.826, respectively; and meanwhile, in both the training and test stages, these metals also had relatively lower errors. The spatial distribution of heavy metals in Chaohu Lake was then predicted using the fully trained SVM models.

Pseudo-Bartter syndrome in Chinese children with cystic fibrosis: Clinical features and genotypic findings.

OBJECTIVES: To characterize the clinical and genotypic features of cystic fibrosis-associated pseudo-Bartter syndrome (CF-PBS) in Chinese children. METHODS: We recruited and characterized the clinical manifestations of 12 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, and abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and Sanger sequencing validation were performed to define the genotypes. RESULTS: CF-PBS was accompanied by recurrent and/or persistent pneumonia (91.7%), pancreatitis (83.3%), vomiting and/or diarrhea (66.7%), failure to thrive and liver disease (58.3% respectively), among our patients. The predominant organisms found in the airways were Pseudomonas aeruginosa (83.3%) and Staphylococcus aureus (75.0%). The mean concentrations of blood gas and electrolytes were pH 7.58, bicarbonate 40.8 mmol/L, sodium 125.9 mmol/L, chloride 77.5 mmol/L, and potassium 2.6 mmol/L. A high recurrence rate (50.0%) of CF-PBS was observed despite continued electrolyte supplementation during follow-up. In all, 19 different variants of CFTR gene were identified, and 10 of these were found to be novel observations (c.262_266delTTATA[p.L88FfsX21], c.579+2insACAT, c.1210-3C>G, c.1733T>C[p.L578P], c.2236_2246delGAGGCGATACTinsAAAAATC[p.E746KfsX8], c.3068T>G [p.I1023R], c.3635delT[p.V1212AfsX16], c.3859delG[p.G1287EfsX2], c.3964-7A>G and ΔE23 [c.3718-?_3873+?del]). The c.2909G>A[p.G970D] was the most common variant, with an allele frequency of 16.6%. A homozygous genotype of c.1521_1523delCTT[p.F508del] was discovered for the first time in patients of Chinese origin. CONCLUSIONS: In China, CF-PBS usually presents early and recurs frequently in infancy, accompanied by multiple comorbidities. Recurrence of CF-PBS in school-going patients does occur but is rare. The p.G970D is the most frequent variant, with a significant ethnic tendency of Chinese origin.

Application of the QUAL2K model to design an ecological purification scheme for treated effluent of a wastewater treatment plant.

Treated effluent from wastewater treatment plants has become an important source of excess nutrients causing eutrophication in water. In this study, an ecological purification method was used to further treat eutrophic water. A three-season ecological purification scheme which comprised an emergent plant (Eme.), a submerged plant (Sub.) and a novel biological rope (Bio.), was designed for the treated effluent canal of a wastewater treatment plant. The removal parameters determined from the experiment were input into a QUAL2K model to simulate downstream water quality of the treated effluent canal. Respective removal rates of total nitrogen and total phosphorus of the Eme., Sub. and Bio. were 32.48-37.33% and 31.63-39.86% in summer, 14.12-33.61% and 17.74-23.80% in autumn, and 14.13-18.03% and 10.05-12.75% in winter, with 1-day reaction time. Optimal combinations for summer, autumn/spring, and winter are Eme. + Bio., Eme. + Bio. + Sub., and Sub. + Bio., respectively. Simulated load reduction rates of total nitrogen and total phosphorus for the treated effluent canal were 42.64-78.40% and 30.98-78.29%, respectively, year round with 2.5-day reaction time. This study provides an efficient evaluation and design method for ecological purification engineering.

Selection of optimal river water quality improvement programs using QUAL2K: a case study of Taihu Lake Basin, China.

In recent years, water quality degradation associated with rapid socio-economic development in the Taihu Lake Basin, China, has attracted increasing attention from both the public and the Chinese government. The primary sources of pollution in Taihu Lake are its inflow rivers and their tributaries. Effective water quality improvement programs need to be implemented in these rivers to improve the water quality of Taihu Lake, and to ensure sustainable development in the region. To ensure effectiveness and efficiency, it is important that the optimal water quality improvement program for a specific situation be selected. The aim of this study was to facilitate the selection of this optimal program. The QUAL2K model for river and stream water quality was used to simulate the effects of a range of water quality improvement scenarios in the Hongqi River, which is a polluted tributary in the Taihu Lake Basin. These scenarios consisted of a series of three water treatment technologies in different configurations, from upstream to downstream. The results showed that the optimal scenario comprised a bio-contact oxidation system upstream, followed by an ecological floating bed, and a vertical moveable eco-bed downstream. The reduction rates achieved by this scenario for biochemical oxygen demand (BOD), ammonia nitrogen (NH(3)-N), total nitrogen (TN), and total phosphorus (TP) were 49.50%, 32.81%, 35.94%, and 45.27%, respectively. The QUAL2K model proved to be an effective tool in the comparative evaluation of potential water quality improvement programs. The method applied in this study can prevent the implementation of water quality improvement programs that would not achieve the desired goals.