Determinants and impact of calcium oxalate crystal deposition on renal outcomes in acute kidney injury patients.

OBJECTIVES: Calcium oxalate (CaOx) crystal deposition in acute kidney injury (AKI) patients is under recognized but impacts renal outcomes. This study investigates its determinants and effects. METHODS: We studied 814 AKI patients with native kidney biopsies from 2011 to 2020, identifying CaOx crystal deposition severity (mild: <5, moderate: 5-10, severe: >10 crystals per section). We assessed factors like urinary oxalate, citrate, urate, electrolytes, pH, tubular calcification index, and SLC26A6 expression, comparing them with creatinine-matched AKI controls without oxalosis. We analyzed how these factors relate to CaOx severity and their impact on renal recovery (eGFR < 15 mL/min/1.73 m2 at 3-month follow-up). RESULTS: CaOx crystal deposition was found in 3.9% of the AKI cohort (32 cases), with 72% due to nephrotoxic medication-induced tubulointerstitial nephritis. Diuretic use, higher urinary oxalate-to-citrate ratio induced by hypocitraturia, and tubular calcification index were significant contributors to moderate and/or severe CaOx deposition. Poor baseline renal function, low urinary chloride, high uric acid and urea nitrogen, tubular SLC26A6 overexpression, and glomerular sclerosis were also associated with moderate-to-severe CaOx deposition. Kidney recovery was delayed, with 43.8%, 31.2%, and 18.8% of patients having eGFR < 15 mL/min/1.73 m2 at 4, 12, and 24-week post-injury. Poor outcomes were linked to high urinary α1-microglobulin-to-creatinine (α1-MG/C) ratios and active tubular injury scores. Univariate analysis showed a strong link between this ratio and poor renal outcomes, independent of oxalosis severity. CONCLUSIONS: In AKI, CaOx deposition is common despite declining GFR. Factors worsening tubular injury, not just oxalate-to-citrate ratios, are key to understanding impaired renal recovery.

STUB1 exacerbates calcium oxalate-induced kidney injury by modulating reactive oxygen species-mediated cellular autophagy via regulating CFTR ubiquitination.

The formation of calcium oxalate (CaOx) crystals in the kidneys leads to renal epithelial damage and the progression of crystalline nephropathy. This study investigated the role of STIP1 homology and U-box protein 1 (STUB1), an E3 ubiquitin ligase, and cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel, in CaOx-related renal damage and autophagy regulation. HK-2 cells were treated with various doses of CaOx monohydrate (COM) to simulate kidney injury in vitro. Cell viability, reactive oxygen species (ROS) production, and apoptosis were assessed. The regulation of CFTR ubiquitination by STUB1 was confirmed by immunoprecipitation. An in vivo model was established by injecting mice with glyoxylate. COM treatment dose-dependently decreased cell viability, increased TNF-α and ROS production, and induced apoptotic cell death in HK-2 cells. COM-treated cells also showed decreased CFTR protein expression. CFTR overexpression improved cell viability and reduced ROS production in COM-stimulated HK-2 cells. Bioinformatics analysis predicted CFTR's ubiquitination binding site for STUB1. Further analysis confirmed the role of STUB1 as a ubiquitin ligase in CFTR degradation. Knockdown of STUB1 upregulated CFTR expression, while STUB1 overexpression had the opposite effect. Knockdown of CFTR reversed the impact of STUB1 deficiency on autophagy. The in vivo experiments showed that CFTR overexpression attenuated kidney tissue damage and CaOx deposition in mice. STUB1-mediated CFTR ubiquitination plays a crucial role in mitigating calcium oxalate-related renal damage by regulating autophagy. Targeting the STUB1/CFTR axis may hold therapeutic potential for treating kidney injury associated with calcium oxalate deposition.

Cymbopogon proximus and Petroselinum crispum seed ethanolic extract/Gum Arabic nanogel emulsion: Preventing ethylene glycol and ammonium chloride-induced urolithiasis in rats.

Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters' excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations.

Correlation research demonstrates that an inflammatory diet is a risk factor for calcium oxalate renal stone formation.

BACKGROUND AND AIMS: Previous studies have demonstrated associations between the Dietary Inflammatory Index (DII®), an analytical tool which evaluates the inflammatory potential of the diet according to the pro- and anti-inflammatory properties of its components, and renal stone formation. However, these have not comprehensively addressed important parameters such as stone type, gender, DII scores in stone formers (SFs) and healthy controls (Cs) and associations of DII with urine and blood chemistries. These were adopted as the survey parameters for the present study, the purpose of which was to test whether the contributory role of an inflammatory diet on stone formation could be further confirmed. METHODS: 97 calcium oxalate (CaOx) SFs and 63 Cs, matched for age and gender each completed a semi-quantitative food frequency questionnaire from which nutrient composition was computed. These data were used to calculate the DII® score. To control the effect of energy intake, energy-adjusted DII scores were calculated per 1000 kcal consumed (E-DII™). A single blood sample and two consecutive overnight (8h) urine samples were collected from a subset (n = 59 SFs and n = 54 Cs) of the overall number of particpants (n = 160). These were analysed for renal stone risk factors. Data were analysed using regression models fit in R software. RESULTS: E-DII scores were found to fit the data better than DII, so they were used throughout. E-DII scores were significantly more positive (more pro-inflammatory) in SFs than in controls in the combined gender group (-0.34 vs. -1.73, p < 0.0001) and separately in males (-0.43 vs. -1.78, p = 0.01) and females (-0.26 vs. - 1.61, p = 0.05). In blood, a significant negative correlation was seen between E-DII and HDL cholesterol. In urine significant positive correlations were seen between E-DII and each of calcium (ρ = 0.25, p = 0.02), phosphate (ρ = 0.48, p < 0.001), magnesium (ρ = 0.33, p < 0.0001) and uric acid (ρ = 0.27, p = 0.004) concentrations. A significant negative correlation was seen between E-DII and urinary volume ρ = -0.27, p = 0.003). There was no correlation between E-DII scores and the relative supersaturations of urinary CaOx, calcium phosphate (brushite) and uric acid. CONCLUSIONS: Our findings provide hitherto unreported quantitative evidence in support of the notion that the diet of calcium oxalate renal stone patients is significantly more pro-inflammatory than that of healthy controls.

N-acetylcysteine regulates oxalate induced injury of renal tubular epithelial cells through CDKN2B/TGF-ß/SMAD axis.

This study was aimed to investigate the preventive effects of N-acetyl-L-cysteine (NAC) against renal tubular cell injury induced by oxalate and stone formation and further explore the related mechanism. Transcriptome sequencing combined with bioinformatics analysis were performed to identify differentially expressed gene (DEG) and related pathways. HK-2 cells were pretreated with or without antioxidant NAC/with or silencing DEG before exposed to sodium oxalate. Then, the cell viability, oxidative biomarkers of superoxidase dismutase (SOD) and malondialdehyde (MDA), apoptosis and cell cycle were measured through CCK8, ELISA and flow cytometry assay, respectively. Male SD rats were separated into control group, hyperoxaluria (HOx) group, NAC intervention group, and TGF-ß/SMAD pathway inhibitor group. After treatment, the structure changes and oxidative stress and CaOx crystals deposition were evaluated in renal tissues by H&E staining, immunohistochemical and Pizzolato method. The expression of TGF-ß/SMAD pathway related proteins (TGF-ß1, SMAD3 and SMAD7) were determined by Western blot in vivo and in vitro. CDKN2B is a DEG screened by transcriptome sequencing combined with bioinformatics analysis, and verified by qRT-PCR. Sodium oxalate induced declined HK-2 cell viability, in parallel with inhibited cellular oxidative stress and apoptosis. The changes induced by oxalate in HK-2 cells were significantly reversed by NAC treatment or the silencing of CDKN2B. The cell structure damage and CaOx crystals deposition were observed in kidney tissues of HOx group. Meanwhile, the expression levels of SOD and 8-OHdG were detected in kidney tissues of HOx group. The changes induced by oxalate in kidney tissues were significantly reversed by NAC treatment. Besides, expression of SMAD7 was significantly down-regulated, while TGF-ß1 and SMAD3 were accumulated induced by oxalate in vitro and in vivo. The expression levels of TGF-ß/SMAD pathway related proteins induced by oxalate were reversed by NAC. In conclusion, we found that NAC could play an anti-calculus role by mediating CDKN2B/TGF-ß/SMAD axis.

Oxalate nephropathy after pancreaticoduodenectomy: a case report.

A 75-year-old male developed acute kidney injury KDIGO stage 3 a few weeks after Whipple surgery was performed for a distal cholangiocarcinoma. Kidney biopsy revealed oxalate nephropathy. This was attributed to post-Whipple malabsorption, poor compliance with pancreatic enzyme replacement therapy, and daily intake of vitamin C supplements. Pancreatic enzyme replacement therapy was resumed and calcium carbonate initiated, with an improvement in glomerular filtration rate. Unfortunately, due to oncological progression, best supportive care was initiated.We review the pathophysiology and conditions predisposing to secondary hyperoxaluria and oxalate nephropathy. This diagnosis should be considered among the main causes of acute kidney injury following pancreatectomy, with important therapeutic implications.

[Determination of dimethyl oxalate and diethyl oxalate in workplace air by high performance liquid chromatography].

Objective: To establish a high performance liquid chromatography method for the simultaneous determination of dimethyl oxalate (DMO) and diethyl oxalate (DEO) in workplace air. Methods: From January 2022 to January 2023, air samples were collected by silica gel tubes, desorbed by acetonitrile, separated by C18 chromatographic column, detected by photo-array detector, and retention time was used to characterize and peak area was used to quantify at 210 nm wavelength. Results: The linear relationships of DMO and DEO were good, r>0.999. The detection limits of DMO and DEO were 0.39 and 0.52 µg/ml, respectively. The quantitative limit was 1.28 µg/ml for DMO and 1.72 µg/ml for DEO. Average desorption efficiency for DMO was 82.40%-92.72%, and DEO was 94.13%-97.69%. The intra-assay precision of DMO was 1.87%-6.18%, and DEO was 2.25%-3.31%. Inter-assay precision of DMO was 3.29%-5.73%, and DEO was 1.38%-2.94%. Average sampling efficiencies were 100% for both DMO and DEO. Breakthrough capacity of DMO was 37.61 mg (200 mg solid adsorbent), DEO was >28.11 mg (200 mg solid adsorbent). Samples should be stored at 4 ℃ for at least 7 days. Conclusion: This method is easy to operate and has strong practicability. All indicators meet the requirements of the specification, and it is suitable for the simultaneous determination of DMO and DEO in the workplace air.

Mechanism of Porphyra Yezoensis Polysaccharides in Inhibiting Hyperoxalate-Induced Renal Injury and Crystal Deposition.

Oxidative damage to the kidneys is a primary factor in the occurrence of kidney stones. This study explores the inhibitory effect of Porphyra yezoensis polysaccharides (PYP) on oxalate-induced renal injury by detecting levels of oxidative damage, expression of adhesion molecules, and damage to intracellular organelles and revealed the molecular mechanism by molecular biology methods. Additionally, we validated the role of PYP in vivo using a crystallization model of hyperoxalate-induced rats. PYP effectively scavenged the overproduction of reactive oxygen species (ROS) in HK-2 cells, inhibited the adhesion of calcium oxalate (CaOx) crystals on the cell surface, unblocked the cell cycle, restored the depolarization of the mitochondrial membrane potential, and inhibited cell death. PYP upregulated the expression of antioxidant proteins, including Nrf2, HO-1, SOD, and CAT, while decreasing the expression of Keap-1, thereby activating the Keap1/Nrf2 signaling pathway. PYP inhibited CaOx deposition in renal tubules in the rat crystallization model, significantly reduced high oxalate-induced renal injury, decreased the levels of the cell surface adhesion proteins, improved renal function in rats, and ultimately inhibited the formation of kidney stones. Therefore, PYP, which has crystallization inhibition and antioxidant properties, may be a therapeutic option for the treatment of kidney stones.

Insights into metal tolerance and resistance mechanisms in Trichoderma asperellum unveiled by de novo transcriptome analysis during bioleaching.

This study investigates the genetic responses of the fungus Trichoderma asperellum (T. asperellum) during bioleaching of ore and tailing samples, comparing one-step, two-step, and spent media bioleaching processes. HPLC analysis quantified oxalic acid, citric acid, and propionic acids, with oxalic acid identified as the primary organic acid involved in metal bioleaching. Metal analysis revealed differences in recovery between ore and tailing samples and among bioleaching processes. The two-step bioleaching process yielded the highest zinc (>54%) and nickel (>60%) recovery in tailings and ore, respectively. Nickel's efficient recovery in ore bioleaching was attributed to the presence of manganese, while its precipitation as nickel oxalate in tailings hindered recovery. Additional metals such as Co, Mn, Mg, Cu, and As were also successfully recovered. Transcriptomic analyses showed significant upregulation of genes associated with biological processes and cellular components, particularly those related to cell membrane structure and function, indicating T. asperellum's adaptation to environmental stresses during metal bioleaching. These findings enhance our understanding of the diverse mechanisms influencing metal recovery rates in bioleaching processes.

Oxalic acid secretion alleviates saline-alkali stress in alfalfa by improving photosynthetic characteristics and antioxidant activity.

Saline-alkali stress significantly affects the growth and yield of alfalfa (Medicago sativa L.). Organic acid secretion is crucial in alleviating abiotic stress-induced damage in plants. In this study, we evaluated the contents of the major organic acids secreted by the roots of tolerant (ZD) and sensitive (LYL) varieties of alfalfa under saline-alkali stress and investigated the effects of these organic acids on the growth, and physiological functions of alfalfa. Our results indicated that the oxalic acid (OA) content was the highest among the organic acids secreted from alfalfa roots under saline-alkali stress, and oxalic acid content was the most significantly different between the two varieties, ZD and LYL, compared to the contents of the other organic acids. Oxalic acid alleviated the inhibition of alfalfa growth caused by saline-alkali stress, improved photosynthetic characteristics, reduced the accumulation of reactive oxygen species, and increased the activity of antioxidant enzymes and content of osmoregulatory substances. Furthermore, oxalic acid resulted in significantly increased expression of genes involved in photosynthesis and antioxidant system in alfalfa under saline-alkali stress. This study revealed the effects of oxalic acid secreted by the root system on stress-related physiological processes, providing valuable insights into the functions of root secretions in plant saline-alkali resistance.

Oxalate nephropathy and chronic turmeric supplementation: a case report.

We present a case of a 69-year-old man who presented for routine check-up and was incidentally found to have kidney failure with an initially unrevealing history and bland urinary sediment. He was diagnosed with oxalate nephropathy in the setting of chronic turmeric supplementation and chronic antibiotic therapy with associated diarrhea. Our case provides several key insights into oxalate nephropathy. First, the diagnosis requires a high index of clinical suspicion. It is uncommonly suspected clinically unless there is an obvious clue in the history such as Roux-en-Y gastric bypass or ethylene glycol poisoning. Diagnosis can be confirmed by histopathologic findings and corroborated by serum levels of oxalate and 24-hour urinary excretion. Second, the diagnosis can often be missed by the pathologist because of the characteristics of the crystals unless the renal pathologist has made it a rule to examine routinely all H&E sections under polarized light. This must be done on H&E, as the other stains dissolve the crystals. Third, one oxalate crystal in a routine needle biopsy is considered pathologic and potentially contributing to the AKI or to the CKD in an important way. Fourth, secondary oxalosis can be largely mitigated or prevented in many cases, especially iatrogenic cases. This can come through the surgeon or the gastroenterologist providing proper instructions to patients on an oxalate-restricted diet or other specific dietary measures. Lastly, this case highlights the success that results from cooperation and communication between the pathologist and the treating physician.

Process optimization and character evaluation of Bletilla striata polysaccharide (BSP) and chitosan (CS) composite hemostatic sponge (BSP-CS).

Bletilla striata polysaccharide (BSP) and chitosan (CS) were chemically cross-linked using oxalyl chloride to prepare a composite hemostatic sponge (BSP-CS), and the process parameters were optimized using the Box-Behnken design (BBD) with response surface methodology. To optimize the performance of the hemostatic sponge, we adjusted the ratio of independent variables, the amount of oxalyl chloride added, and the freeze-dried volume. A series of evaluations were conducted on the hemostatic applicability of BSP-CS. The characterization results revealed that BSP-CS had a stable bacteriostatic effect on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa within 72 h, and the bacteriostatic rate was above 30%. The CCK-8 cytotoxicity test demonstrated that BSP-CS had a certain effect on promoting cell proliferation of L929 cells. In the mouse tail-cutting experiment, the hemostasis time of BSP-CS was 463.0±38.16 s, shortened by 91.3 s on average compared with 554.3±34.67 s of the gauze group. The blood loss of the BSP-CS group was 28.47±3.74 mg, which was 34.7% lower than that of the control gauze group (43.6±3.83 mg). In the in vitro coagulation experiment, the in vitro coagulation index of the BSP-CS group was 97.29%±1.8%, which was reduced to 8.6% of the control group. The CT value of the BSP-CS group was 240±15 s, which was 155 s lower than that of the gauze group (355±31.22 s). All characterization results indicate that BSP-CS is an excellent hemostatic material.

Confining calcium oxalate crystal growth in a carbonated apatite-coated microfluidic channel to better understand the role of Randall's plaque in kidney stone formation.

Effective prevention of recurrent kidney stone disease requires the understanding of the mechanisms of its formation. Numerous in vivo observations have demonstrated that a large number of pathological calcium oxalate kidney stones develop on an apatitic calcium phosphate deposit, known as Randall's plaque. In an attempt to understand the role of the inorganic hydroxyapatite phase in the formation and habits of calcium oxalates, we confined their growth under dynamic physicochemical and flow conditions in a reversible microfluidic channel coated with hydroxyapatite. Using multi-scale characterization techniques including scanning electron and Raman microscopy, we showed the successful formation of carbonated hydroxyapatite as found in Randall's plaque. This was possible due to a new two-step flow seed-mediated growth strategy which allowed us to coat the channel with carbonated hydroxyapatite. Precipitation of calcium oxalates under laminar flow from supersaturated solutions of oxalate and calcium ions showed that the formation of crystals is a substrate and time dependent complex process where diffusion of oxalate ions to the surface of carbonated hydroxyapatite and the solubility of the latter are among the most important steps for the formation of calcium oxalate crystals. Indeed when an oxalate solution was flushed for 24 h, dissolution of the apatite layer and formation of calcium carbonate calcite crystals occurred which seems to promote calcium oxalate crystal formation. Such a growth route has never been observed in vivo in the context of kidney stones. Under our experimental conditions, our results do not show any direct promoting role of carbonated hydroxyapatite in the formation of calcium oxalate crystals, consolidating therefore the important role that macromolecules can play in the process of nucleation and growth of calcium oxalate crystals on Randall's plaque.

Deficient butyrate metabolism in the intestinal microbiome is a potential risk factor for recurrent kidney stone disease.

Intestinal microbiome dysbiosis is a known risk factor for recurrent kidney stone disease (KSD) with prior data suggesting a role for dysfunctional metabolic pathways other than those directly utilizing oxalate. To identify alternative mechanisms, the current study analyzed differences in the metabolic potential of intestinal microbiomes of patients (n = 17) and live-in controls (n = 17) and determined their relevance to increased risk for KSD using shotgun metagenomic sequencing. We found no differences in the abundance of genes associated with known oxalate degradation pathways, supporting the notion that dysfunction in other metabolic pathways plays a role in KSD. Further analysis showed decreased abundance of key enzymes involved in butyrate biosynthesis in patient intestinal microbiomes. Furthermore, de novo construction of microbial genomes showed that the majority of genes significantly enriched in non-stone formers are affiliated with Faecalibacterium prausnitzii, a major butyrate producer. Specifically pertaining to butyrate metabolism, the majority of abundant genes mapped back to F. prausnitzii, Alistipes spp., and Akkermansia muciniphila. No differences were observed in ascorbate or glyoxylate metabolic pathways. Collectively, these data suggest that impaired bacterial-associated butyrate metabolism may be an oxalate-independent mechanism that contributes to an increased risk for recurrent KSD. This indicates that the role of the intestinal microbiome in recurrent KSD is multi-factorial, which is representative of the highly intertwined metabolic nature of this complex environment. Future bacteria-based treatments must not be restricted to targeting only oxalate metabolism.

A Genome-Wide Association Study Reveals the Genetic Mechanisms of Nutrient Accumulation in Spinach.

Spinach is a significant source of vitamins, minerals, and antioxidants. These nutrients make it delicious and beneficial for human health. However, the genetic mechanism underlying the accumulation of nutrients in spinach remains unclear. In this study, we analyzed the content of chlorophyll a, chlorophyll b, oxalate, nitrate, crude fiber, soluble sugars, manganese, copper, and iron in 62 different spinach accessions. Additionally, 3,356,182 high-quality, single-nucleotide polymorphisms were found using resequencing and used in a genome-wide association study. A total of 2077 loci were discovered that significantly correlated with the concentrations of the nutritional elements. Data mining identified key genes in these intervals for four traits: chlorophyll, oxalate, soluble sugar, and Fe. Our study provides insights into the genetic architecture of nutrient variation and facilitates spinach breeding for good nutrition.

The catalytic action of human d-lactate dehydrogenase is severely inhibited by oxalate and is impaired by mutations triggering d-lactate acidosis.

d-lactate dehydrogenases are known to be expressed by prokaryotes and by eukaryotic invertebrates, and over the years the functional and structural features of some bacterial representatives of this enzyme ensemble have been investigated quite in detail. Remarkably, a human gene coding for a putative d-lactate dehydrogenase (DLDH) was identified and characterized, disclosing the occurrence of alternative splicing of its primary transcript. This translates into the expression of two human DLDH (hDLDH) isoforms, the molecular mass of which is expected to differ by 2.7 kDa. However, no information on these two hDLDH isoforms is available at the protein level. Here we report on the catalytic action of these enzymes, along with a first analysis of their structural features. In particular, we show that hDLDH is strictly stereospecific, with the larger isoform (hDLDH-1) featuring higher activity at the expense of d-lactate when compared to its smaller counterpart (hDLDH-2). Furthermore, we found that hDLDH is strongly inhibited by oxalate, as indicated by a Ki equal to 1.2 µM for this dicarboxylic acid. Structurally speaking, hDLDH-1 and hDLDH-2 were determined, by means of gel filtration and dynamic light scattering experiments, to be a hexamer and a tetramer, respectively. Moreover, in agreement with previous studies performed with human mitochondria, we identified FAD as the cofactor of hDLDH, and we report here a model of FAD binding by the human d-lactate dehydrogenase. Interestingly, the mutations W323C and T412 M negatively affect the activity of hDLDH, most likely by impairing the enzyme electron-acceptor site.

StoneMod 2.0: Database and prediction of kidney stone modulatory proteins.

Stone modulators are various kinds of molecules that play crucial roles in promoting/inhibiting kidney stone formation. Several recent studies have extensively characterized the stone modulatory proteins with the ultimate goal of preventing kidney stone formation. Herein, we introduce the StoneMod 2.0 database (https://www.stonemod.org), which has been dramatically improved from the previous version by expanding the number of the modulatory proteins in the list (from 32 in the initial version to 17,130 in this updated version). The stone modulatory proteins were recruited from solid experimental evidence (via PubMed) and/or predicted evidence (via UniProtKB, QuickGO, ProRule, STITCH and OxaBIND to retrieve calcium-binding and oxalate-binding proteins). Additionally, StoneMod 2.0 has implemented a scoring system that can be used to determine the likelihood and to classify the potential stone modulatory proteins as either "solid" (modulator score ≥ 50) or "weak" (modulator score < 50) modulators. Furthermore, the updated version has been designed with more user-friendly interfaces and advanced visualization tools. In addition to the monthly scheduled update, the users can directly submit their experimental evidence online anytime. Therefore, StoneMod 2.0 is a powerful database with prediction scores that will be very useful for many future studies on the stone modulatory proteins.

Analytical methods for selectively determining hydrogen peroxide, peroxymonosulfate and peroxydisulfate in their binary mixtures.

Hydrogen peroxide (H2O2), peroxymonosulfate (PMS), and peroxydisulfate (PDS) are key bulk oxidants in many advanced oxidation processes (AOPs) for treating chemically contaminated water. In some systems these peroxides may coexist in solution either through intentional co-addition or their inadvertent formation (especially H2O2) due to reaction chemistry. While many analytical methods to determine these peroxides individually have been established, mutual interference among the peroxides in such methods has seldom been evaluated, and new methods or variants of established methods to selectively determine peroxides in binary mixtures are lacking. We re-examined five established colorimetric methods-the Permanganate, Titanium Oxalate (Ti-oxalate), Iodide, N.N­diethyl-p-phenylenediamine (DPD), and 2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonate (ABTS) methods-for mutual interference among peroxides and devised variants of these methods for selectively quantifying one peroxide in the presence of another. Hydrogen peroxide can be selectively determined by the Permanganate method at short reaction time; by the Ti-oxalate method; by the DPD method with added peroxidase (POD); or by the ABTS method with added POD. PMS can be selectively determined by the Iodide method; by the DPD or ABTS methods with added iodide ion as catalyst; or by the DPD method with added catalase (CAT) (with co-existing H2O2 but not PDS). The DPD method can be used to determine PDS without interference by H2O2 and-provided the sample is pretreated with l-histidine-without interference by PMS. The recommended methods were successfully applied to binary peroxide mixtures in complex waters, including a tap water and a synthetic water. Overall, the new selective methods will assist mechanistic investigation of AOPs based on these peroxides and support efforts to apply them commercially.

Beneficial roles of gastrointestinal and urinary microbiomes in kidney stone prevention via their oxalate-degrading ability and beyond.

Formation of calcium oxalate (CaOx) crystal, the most common composition in kidney stones, occurs following supersaturation of calcium and oxalate ions in the urine. In addition to endogenous source, another main source of calcium and oxalate ions is dietary intake. In the intestinal lumen, calcium can bind with oxalate to form precipitates to be eliminated with feces. High intake of oxalate-rich foods, inappropriate amount of daily calcium intake, defective intestinal transporters for oxalate secretion and absorption, and gastrointestinal (GI) malabsorption (i.e., from gastric bypass surgery) can enhance intestinal oxalate absorption, thereby increasing urinary oxalate level and risk of kidney stone disease (KSD). The GI microbiome rich with oxalate-degrading bacteria can reduce intestinal oxalate absorption and urinary oxalate level. In addition to the oxalate-degrading ability, the GI microbiome also affects expression of oxalate transporters and net intestinal oxalate transport, cholesterol level, and short-chain fatty acids (SCFAs) production, leading to lower KSD risk. Recent evidence also shows beneficial effects of urinary microbiome in KSD prevention. This review summarizes the current knowledge on the aforementioned aspects. Potential benefits of the GI and urinary microbiomes as probiotics for KSD prevention are emphasized. Finally, challenges and future perspectives of probiotic treatment in KSD are discussed.