Reclassification of Variants Following Renal Genetics Testing: Uncommon Yet Impactful for Diagnosis and Management.

Introduction: Genetic testing is increasingly utilized in nephrology practice, but limited real-world data exist on variant reclassification following renal genetics testing. Methods: A cohort of patients at the Cleveland Clinic Renal Genetics Clinic who underwent genetic testing through clinical laboratories was assessed with their clinical and laboratory data analyzed. Results: Between January 2019 and June 2023, 425 new patients with variable kidney disorders from 413 pedigrees completed genetic testing through 10 clinical laboratories, including 255 (60%) females with median (25th, 75th percentiles) age of 36 (22-54) years. Multigene panel was the most frequently used modality followed by single-gene testing, exome sequencing (ES), chromosomal microarray (CMA), and genome sequencing (GS). At initial report, 52% of patients had ≥1 variants of uncertain significance (VUS) with or without concurrent pathogenic variant(s). Twenty amendments were issued across 19 pedigrees involving 19 variants in 17 genes. The overall variant reclassification rate was 5%, with 63% being upgrades and 32% downgrades. Of the reclassified variants, 79% were initially reported as VUS. The median time-to-amendments from initial reports was 8.4 (4-27) months. Following the variant reclassifications, 60% of the patients received a new diagnosis or a change in diagnosis. Among these, 67% of patients received significant changes in clinical management. Conclusion: Variant reclassification following genetic testing is infrequent but important for diagnosis and management of patients with suspected genetic kidney disease. The majority of variant reclassifications involve VUS and are upgrades in clinically issued amended reports. Further studies are needed to investigate the predictors of such events.

Glycyrrhiza polysaccharides may have an antitumor effect in γδT cells through gut microbiota and TLRs/NF-κB pathway in mice.

Tumor immunotherapy can be a suitable cancer treatment option in certain instances. Here we investigated the potential immunomodulatory effect of oral glycyrrhiza polysaccharides (GCP) on the antitumor function of γδT cells in intestinal epithelial cells in mice. We found that GCP can inhibit tumor growth and was involved in the regulation of systemic immunosuppression. GCP administration also promoted the differentiation of gut epithelia γδT cells into IFN-γ-producing subtype through regulation of local cytokines in gut mucosa. GCP administration increased local cytokine levels through gut microbiota and the gut mucosa Toll-like receptors / nuclear factor kappa-B pathway. Taken together, our results suggest that GCP might be a suitable candidate for tumor immunotherapy, although further clinical research, including clinical trials, are required to validate these results.

Mechanic evaluation of Wu-Mei-Pill on colitis-associated colorectal cancer: An integrated transcriptomics, metabolomics, and experimental validation study.

BACKGROUND: Chronic intestinal inflammatory diseases play a crucial role in the onset of colorectal cancer (CRC). Effectively impeding the progression of colitis-associated colorectal cancer (CAC) can be instrumental in hindering CRC development. Wu-Mei-Pill (WMP), a formulation comprising various herbal extracts, is clinically employed for CAC treatment, yet the underlying mechanism of WMP's efficacy in CAC remains unclear. Our study firstly demonstrated the effects and mechanisms of WMP on transcriptional and metabolic levels based on integrated transcriptomics and untargeted metabolomics and relative experimental validations. MATERIALS AND METHODS: A CAC mouse model was established through a single injection of azoxymethane (AOM) followed by intermittent dextran sodium sulfate (DSS) intervention, with subsequent WMP administration. Initially, the therapeutic impact of WMP on the CAC model was assessed by observing survival rate, body weight change, colon length, tumor number, tumor load, and pathological changes in the colon tissue of CAC mice post-WMP intervention. Subsequently, differential genes and metabolites in the colorectal tissue of CAC mice following WMP intervention were identified through transcriptomics and non-targeted metabolomics. Finally, the influence of WMP on the peroxisome proliferator activated receptor (PPAR) pathway, Wnt pathway, and CC motif chemokine ligand 3 (CCL3)/ CC motif chemokine receptor 1 (CCR1) axis in CAC mice was verified through western blot, immunofluorescence, and ELISA based on the results of transcriptomics and non-targeted metabolomics. RESULTS: WMP intervention enhanced survival, alleviated body weight loss, shortened colon length, tumor occurrence, and pathological changes in the colorectal tissue of CAC mice, such as glandular damage, tumourigenesis, and inflammatory cell infiltration. Transcriptomic and non-targeted metabolomic results revealed that WMP intervention up-regulated the expression of key regulatory mechanisms of fatty acid oxidation PPAR pathway-related genes (Pparg, Ppara, Cpt1a, and Acadm) and metabolites (L-carnitine and L-palmitoylcarnitine). Additionally, it down-regulated Wnt pathway-related genes (Wnt3, Axin2, Tcf7, Mmp7, Lgr5, Wnt5a, Fzd6, Wnt7b, Lef1, and Fzd10 etc.) and pro-inflammatory related genes (Il1b, Il6, Il17a, Ccl3, and Ccr1 etc.). Experimental validation demonstrated that WMP up-regulated PPAR pathway-related proteins [PPARγ, PPARα, carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA dehydrogenase medium chain (ACADM)] in the colorectal tissue of CAC mice. It also down-regulated Wnt pathway-related proteins [ß-catenin, T-cell factor (TCF), lymphoid enhancer-binding factor (LEF), and matrix metallopeptidase 7 (MMP7)], inhibited the nuclear translocation of the key transcription factor ß-catenin in the Wnt pathway, and suppressed epithelial-to-mesenchymal transition (EMT) activation induced by the Wnt pathway (up-regulated E-cadherin and down-regulated Vimentin). Furthermore, WMP intervention reduced pro-inflammatory factors [interleukin (IL)-6, IL-1ß, and IL-17A] and decreased CCL3/CCR1 axis factors, including CCL3 protein levels and diminished F4/80+CCR1+ positive expressed cells. CONCLUSION: WMP significantly inhibits CAC tumorigenesis by up-regulating PPARα-mediated fatty acid oxidation, inhibiting the Wnt signaling pathway-mediated EMT, and suppressing CCL3/CCR1-mediated inflammatory responses.

Alleviation of cotton growth suppression caused by salinity through biochar is strongly linked to the microbial metabolic potential in saline-alkali soil.

Biochar is a typical soil organic amendment; however, there is limited understanding of its impact on the metabolic characteristics of microorganisms in saline-alkaline soil microenvironment, as well as the advantages and disadvantages of plant-microorganism interactions. To elucidate the mechanisms underlying the impact of saline-alkali stress on cotton, a 6-month pot experiment was conducted, involving the sowing of cotton seedlings in saline-alkali soil. Three different biochar application levels were established: 0 % (C0), 1 % (C1), and 2 % (C2). Results indicated that biochar addition improved the biomass of cotton plants, especially under C2 treatment; the dry weight of cotton bolls were 8.15 times that of C0. Biochar application led to a rise in the accumulation of photosynthetic pigments by 8.30-51.89 % and carbohydrates by 7.4-10.7 times, respectively. Moreover, peroxidase (POD) activity, the content of glutathione (GSH), and ascorbic acid (ASA) were elevated by 23.97 %, 118.39 %, and 48.30 % under C2 treatment, respectively. Biochar caused a reduction in Na+ uptake by 8.21-39.47 %, relative electrical conductivity (REC) of plants, and improved K+/Na+ and Ca2+/Na+ ratio indicating that biochar alleviated salinity-caused growth reduction. Additionally, the application of biochar enhanced the absorption intensity of polysaccharide fingerprints in cotton leaves and roots. Two-factor co-occurrence analysis indicated that the key differential metabolites connected to several metabolic pathways were L-phenylalanine, piperidine, L-tryptophan, and allysine. Interestingly, biochar altered the metabolic characteristics of saline-alkali soil, especially related to the biosynthesis and metabolism of amino acids and purine metabolism. In conclusion, this study demonstrates that biochar may be advantageous in saline soil microenvironment; it has a favorable impact on how plants and soil microbial metabolism interact.

Toxicity studies of condensed fuzheng extract in mice and rats.

Nutritional supplements have been used to improve immune function. Condensed fuzheng extract (CFE) is a well-known traditional Chinese medicine (TCM) formula that is predominantly made from sheep placenta, Astragalus mongholicus Bunge, and Polygonatum kingianum Collett & Hemsl. However, the toxicological profile of CFE has not been determined. In this study, we investigated the acute (14 days) and sub-chronic (90 days) oral toxicities of CFE in mice and rats and the phytochemical composition of CFE. Materials and methods: For the assessment of acute toxicity, 80 ICR mice of both sexes were randomly divided into four groups. Three groups were treated with 4500, 2250 and 1125 mg/kg/d bw CFE daily (n = 10/group per sex) for 14 days; a separate group was used as control. To test the sub-chronic toxicity, male and female Sprague Dawley rats were orally administered 8150, 4075 or 2037 mg/kg bw of CFE for 90 days; a control group was included. Hematological, biochemical, and histopathological markers were tested at the end of the experiment. The chemical composition of CFE was determined by UPLC-HRMS method. Results: In both acute and sub-chronic toxicity studies, no mortalities, indications of abnormality, or treatment-related adverse effects were observed. The LD50 of CFE was higher than 4500 mg/kg. There were no significant changes in the hematological and biochemical data in the treatment group compared with the control group (p > 0.05). Histopathological analyses of the heart, liver, spleen, lungs, kidneys, thymus, testes (male rats) and ovaries (female rats) revealed no anatomical changes of each organ. Phytochemical analysis of CFE revealed the presence of flavonoids (highest abundance), phenols and alkaloids. In conclusion, our results showed that CFE is a safe and non-toxic formula. We also reported phytochemicals in CFE that may possess important pharmacological effects.

Alterations in the composition and metabolite profiles of the saline-alkali soil microbial community through biochar application.

Saline-alkali soil poses significant chanllenges to sustainable development of agriculture. Although biochar is commonly used as a soil organic amendment, its microbial remediation mechanism on saline-alkali soil requires further confirmation. To address this, we conducted a pot experiment using cotton seedlings to explore the potential remediation mechanism of rice straw biochar (BC) at three different levels on saline-alkaline soil. The results showed that adding of 2% biochar greatly improved the quality of saline-alkaline soil by reducing pH levels, electrical conductivity (EC), and water-soluble ions. Moreover, biochar increased the soil organic matter (SOM), nutrient availability and extracellular enzyme activity. Interestingly, it also reduced soil salinity and salt content in various cotton plant tissues. Additionally, biochar had a notable impact on the composition of the microbial community, causing changes in soil metabolic pathways. Notably, the addition of biochar promoted the growth and metabolism of dominant salt-tolerant bacteria, such as Proteobacteria, Bacteroidota, Acidobacteriota, and Actinobacteriota. By enhancing the positive correlation between microorganisms and metabolites, biochar alleviated the inhibitory effect of salt ions on microorganisms. In conclusion, the incorporation of biochar significantly improves the soil microenvironment, reduces soil salinity, and shows promise in ameliorating saline-alkaline soil conditions.

Efficacy and safety of a pyrotinib-based regimen in non-small cell lung cancer patients harboring HER2 alterations: A real-world retrospective study.

BACKGROUND: Pyrotinib, a novel irreversible pan-HER tyrosine kinase inhibitor, has been approved for the treatment of HER2-positive metastatic breast cancer in China. The aim of this study was to evaluate the efficacy and safety of pyrotinib in advanced nonsmall cell lung cancer (NSCLC) patients with HER2 alterations in real-world practice. MATERIALS AND METHODS: A retrospective analysis of advanced NSCLC with HER2 mutations or amplifications who received pyrotinib-based treatment at the Qilu Hospital in Shandong University was performed. The primary end points were objective response rate and safety. The secondary end points were progression-free survival, disease control rate, and overall survival. RESULTS: Twenty three eligible patients from a single center were enrolled between June 2019 and March 2023; among them, 21 had HER2 mutation and two harbored HER2 amplification. Evaluation of the efficacy in 21 patients revealed an objective response rate of 28.6% (6/21; 95% confidence interval [CI]: 7.5%-49.6%) and disease control rate of 85.7% (18/21). The median progression-free survival and overall survival were 7.7 months (95% CI: 6.07-9.33) and 20.8 months (95% CI: 8.42-33.18), respectively. The most common adverse events (AEs) included diarrhea (n = 14, 60.9%), nausea (n = 5, 21.7%), and liver dysfunction (n = 5, 21.7%). Seven patients (7/23, 30.4%) had grade 3-4 AE; no grade 5 AE was observed. Furthermore, one patient (1/23, 4.3%) experienced dose withdrawal and two (2/23, 8.7%) presented with dose reduction symptoms. CONCLUSION: Pyrotinib-based therapy showed promising antitumor activity and acceptable safety in advanced NSCLC patients with HER2 alterations.

Black Patients Equally Benefit From Renal Genetics Evaluation but Substantial Barriers in Access Exist.

Introduction: Genetic testing is increasingly accessible to patients with kidney diseases. Racial disparities in renal genetics evaluations have not been investigated. Methods: A cohort of patients evaluated by the Cleveland Clinic Renal Genetics Clinic (RGC) from January 2019 to March 2022 was analyzed. Results: Forty-eight Black patients, including 27 (56.3%) males, median age 34 (22-49) years and 232 White patients, including 76 (32.8%) males, median age 35 (21-53) years, were evaluated. Black patients were more likely to have end-stage kidney disease (ESKD) at the time of referral compared with White patients (23% vs. 7.3%, P = 0.004), more likely to be covered by Medicaid (46% vs. 15%, P < 0.001), and less likely to be covered by private insurance (35% vs. 66%, P < 0.001). Black patients were more likely to "no show" to scheduled appointment(s) or not submit specimens for genetic testing compared with White patients (24.1% vs. 6.7%, P = 0.0005). Genetic testing was completed in 35 Black patients. Of these, 37% had a positive result with 9 unique monogenic disorders and 1 chromosomal disorder diagnosed. Sixty-nine percent of Black patients with positive results received a new diagnosis or a change in diagnosis. Of these, 44% received a significant change in disease management. No differences in diagnostic yield and implications of management were noted between Black and White patients. Conclusion: Black patients equally benefit from renal genetics evaluation, but barriers to access exist. Steps must be taken to ensure equitable and early access for all patients. Further studies investigating specific interventions to improve access are needed.

Effect of co-application of straw and various nitrogen fertilizers on N2O emission in acid soil.

In order to explore the alteration of N transformation and N2O emissions in acid soil with the co-application of straw and different types of nitrogen (N) fertilizers, an incubation experiment was carried out for 40 days. There are totally five treatments in the study: (a) without straw and N fertilizer (N0), (b) straw alone application (SN0), (c) straw with NH4Cl (SN1), (d) straw with NaNO3 (SN2), and (e) straw with NH4NO3 (SN3). N2O emissions, soil physicochemical properties, and abundance/activity of ammonia-oxidizing archaea (AOA) were measured. The results showed that the combined application of straw and N enhanced N2O emissions, particularly, SN2 and SN3 treatments. Moreover, the soil pH was lower in co-application treatments and the average decreasing rate was 9.69%. Specially, the pH was lowest in the SN1 treatment. The results of correlation analysis indicated a markedly negative relationship between pH and N2O, as well as a negative relationship between pH and net mineralization rate. These findings suggest that pH alteration can affect the N transformation process in soil and thus influence N2O emissions. In addition, the dominant AOA at the genus level in the SN2 treatment was Nitrosopumilus, and Candidatus nitrosocosmicus in the SN3 treatment. The reshaped AOA structure can serve as additional evidence of the changes in the N transformation process. In conclusion, as the return of straw, the cumulation of N2O from arable acid soil depends on the form of N fertilizer. It is also important to consider how N fertilizer is applied to reduce the possibility of N being lost in the soil as gas.

" Assessing the impact of biochar on microbes in acidic soils: Alleviating the toxicity of aluminum and acidity".

In arable soils, anthropogenic activities such as fertilizer applications have intensified soil acidification in recent years. This has resulted in frequent environmental problems such as aluminum (Al) and H+ stress, which negatively impact crop yields and quality in acidic soils. Biochar, as a promising soil conditioner, has attracted much attention globally. The present study was conducted in a greenhouse by setting up 2% biochar rate to investigate how biochar relieves Al3+ hazards in acidic soil by affecting soil quality, soil environment, and soil microbiomes. The addition of biochar significantly improved soil fertility and enzyme activities, which were attributed to its ability to enhance the utilization of soil carbon sources by influencing the activity of soil microorganisms. Moreover, the Al3+ contents were significantly decreased by 66.61-88.83% compared to the C0 level (without biochar treatment). In particular, the results of the 27Al NMR suggested that forms of AlVI (Al(OH)2+, Al(OH)+ 2, and Al3+) were increased by 88.69-100.44% on the surface of biochar, reducing the Al3+ stress on soil health. The combination of biochar and nitrogen (N) fertilizer contributed to the augmentation of bacterial diversity. The application of biochar and N fertilizer increased the relative abundance of the majority of bacterial species. Additionally, the application of biochar and N fertilizer had a significant impact on soil microbial metabolism, specifically in the biosynthesis of secondary metabolites (lipids and organic acids) and carbon metabolic ability. In conclusion, biochar can enhance soil microbial activity and improve the overall health of acidic soil by driving microbial metabolism. This study offers both theoretical and technical guidance for enhancing biochar in acidified soil and promoting sustainable development in farmland production.

Can the co-application of biochar and different inorganic nitrogen fertilizers repress N2O emissions in acidic soil?

The sole application of nitrogen (N) fertilizer with lower N2O emission potential or combined with biochar may help for mitigating N2O production. However, how biochar applied with various inorganic N fertilizers affected N2O emission in acidic soil remains unclear. Thus, we examined N2O emission, soil N dynamics and relating nitrifiers (i.e., ammonia-oxidizing archaea, AOA) in acidic soil. The study contained three N fertilizers (including NH4Cl, NaNO3, NH4NO3) and two biochar application rates (i.e., 0% and 0.5%). The results indicated that the alone application of NH4Cl produced more N2O. Meanwhile, the co-application of biochar and N fertilizers enhanced N2O emission as well, especially in the combined treatment of biochar and NH4NO3. Soil pH was decreased with the application of various N fertilizers, especially with NH4Cl, and the average decrease rate was 9.6%. Meanwhile, correlation analysis showed a negative relationship between N2O and pH, dramatically, which might indicate that the alteration of pH was one factor relating to N2O emission. However, there was no difference between the same N addition treatments with or without biochar on pH. Interestingly, in the combined treatment of biochar and NH4NO3, the lowest net nitrification rate and net mineralization rate appeared during days 16-23. Meanwhile, the highest emission rate of N2O in the same treatment also appeared during days 16-23. The accordance might indicate that N transformation alteration was another factor relating to N2O emissions. In addition, compared to NH4NO3 alone application, co-applied with biochar had a lower content of Nitrososphaera-AOA, which was a main contributor to nitrification. The study emphasizes the importance of using a suitable form of N fertilizers and further indicates that two factors, namely alteration of pH and N transformation rate, are related to N2O emission. Moreover, in future studies, it is necessary to explore the soil N dynamics controlled by microorganisms.

Could S-1-based non-platinum doublet chemotherapy be a new option as a second-line treatment for advanced non-small cell lung cancer patients? A multicenter retrospective study.

Background: For patients who have contraindications to or have failed checkpoint inhibitors, chemotherapy remains the standard second-line option to treat non-oncogene-addicted advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of S-1-based non-platinum combination in advanced NSCLC patients who had failed platinum doublet chemotherapy. Methods: During January 2015 and May 2020, advanced NSCLC patients who received S-1 plus docetaxel or gemcitabine after the failure of platinum-based chemotherapy were consecutively retrieved from eight cancer centers. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. By using the method of matching-adjusted indirect comparison, the individual PFS and OS of included patients were adjusted by weight matching and then compared with those of the docetaxel arm in a balanced trial population (East Asia S-1 Trial in Lung Cancer). Results: A total of 87 patients met the inclusion criteria. The ORR was 22.89% (vs. 10% of historical control, p < 0.001) and the DCR was 80.72%. The median PFS and OS were 5.23 months (95% CI: 3.91-6.55 months) and 14.40 months (95% CI: 13.21-15.59 months), respectively. After matching with a balanced population in the docetaxel arm from the East Asia S-1 Trial in Lung Cancer, the weighted median PFS and OS were 7.90 months (vs. 2.89 months) and 19.37 months (vs. 12.52 months), respectively. Time to start of first subsequent therapy (TSFT) from first-line chemotherapy (TSFT > 9 months vs. TSFT ≤ 9 months) was an independent predictive factor of second-line PFS (8.7 months vs. 5.0 months, HR = 0.461, p = 0.049). The median OS in patients who achieved response was 23.5 months (95% CI: 11.8-31.6 months), which was significantly longer than those with stable disease (14.9 months, 95% CI: 12.9-19.4 months, p < 0.001) or progression (4.9 months, 95% CI: 3.2-9.5 months, p < 0.001). The most common adverse events were anemia (60.92%), nausea (55.17%), and leukocytopenia (33.33%). Conclusions: S-1-based non-platinum combination had promising efficacy and safety in advanced NSCLC patients who had failed platinum doublet chemotherapy, suggesting that it could be a favorable second-line treatment option.

Iron-modified biochar reduces nitrogen loss and improves nitrogen retention in Luvisols by adsorption and microbial regulation.

Nitrogen (N) loss poses a great threat to global environmental sustainability. The application of modified biochar is a novel strategy to improve soil nitrogen retention and alleviate the negative effects caused by N fertilizers. Therefore, in this study iron modified biochar was used as a soil amendment to investigate the potential mechanisms of N retention in Luvisols. The experiment comprised five treatments i.e., CK (control), 0.5 % BC, 1 % BC, 0.5 % FBC and 1 % FBC. Our results showed that the intensity of functional groups and surface structure of FBC was improved. The 1 % FBC treatment showed a significant increment in soil NO3--N, dissolved organic nitrogen (DON), and total nitrogen (TN) content by 374.7 %, 51.9 %, and 14.4 %, respectively, compared with CK. The accumulation of N in cotton shoots and roots was increased by 28.6 % and 6.6 % with 1 % FBC addition. The application of FBC also stimulated the activities of soil enzymes related to C and N cycling i.e., ß-glucosidase (ßG), ß-Cellobiohydrolase (CBH), and Leucine aminopeptidase (LAP). In the soil treated with FBC, a significant improvement in the structure and functions of the soil bacterial community was found. FBC addition altered the taxa involved in the N cycle by affecting soil chemical properties, especially for Achromobacte, Gemmatimonas, and Cyanobacteriales. In addition to direct adsorption, the regulation of FBC on organisms related to N-cycling also played an important role in soil nitrogen retention.

Pathogenic BCS1L Mutation Resulting in Hypertrophic Cardiomyopathy: A Unique Presentation of Nuclear Mitochondrial Disease.

A 21-year-old man with sensorineural hearing loss and glaucoma presented with severely limited exercise capacity since childhood. He was found to have biventricular concentric hypertrophy with greatest wall thickening at the posterior and lateral walls of the left ventricle apex (1.7 cm) and the free wall of the right ventricle (1.1 cm). There was no inducible left ventricular outflow tract obstruction. Metabolic testing revealed marked lactic aciduria (1,650.1 µmol/mmol creatinine) and plasma lactate (3.9 mmol/L). A sarcomeric hypertrophic cardiomyopathy gene panel was unremarkable, but mitochondrial gene analysis revealed a homozygous c.385G>A (p.Gly129Arg) pathogenic mutation in the BCS1L gene. This gene is responsible for an assembly subunit of cytochrome complex III in the respiratory transport chain and is the rarest respiratory chain defect. This gene has not frequently been implicated in cardiomyopathy. Mitochondrial hypertrophic cardiomyopathy is more rare than hypertrophic cardiomyopathy resulting from sarcomeric mutations and is more likely to be symmetric, less frequently results in left ventricular outflow tract obstruction, and is more likely to progress to dilated cardiomyopathy. Evidence-based screening protocols have not been established; treatment follows guideline-directed medical therapy for congestive heart failure, including evaluation for heart transplantation. This report expands the phenotype of the BCS1L mutation and suggests that affected patients may need screening for underlying cardiomyopathy.

Insights into physiological and molecular mechanisms underlying efficient utilization of boron in different boron efficient Beta vulgaris L. varieties.

Boron (B) deficiency and consequent limitation of plant yield and quality, particularly of sugar beet (Beta vulgaris L.) has emerged as a maior problem,which is exacerbating due to cultivar dependent variability in B deficiency tolerance. Pertinently, the current study was designed to elucidate the physiological and molecular mechanisms of B deficiency tolerance of sugar beet varieties KWS1197 (B-efficient variety) and KWS0143 (B-inefficient variety). A hydroponic experiment was conducted employing two B levels B0.1 (0.1 µM L-1 H3BO3, deficiency) and B50 (50 µM L-1 H3BO3, adequacy). Boron deficiency greatly inhibited root elongation and dry matter accumulation; however, formation of lateral roots stimulated and average root diameter was increased. Results exhibited that by up-regulating the expression of NIP5-1, NIP6-1, and BOR2, and suppressing the expression of BOR4, cultivar KWS1197, in contrast to KWS0143, managed to transfer sufficient amount of B to the aboveground plant parts, facilitating its effective absorption and utilization. Accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS) was also mellowed in KWS1197, as well as the oxidative damage to root cells via preservation of the antioxidant enzyme system. Additionally, the expression of essential enzymes for biosynthesis of phytohormone (PYR/PYL) and lignin (COMT, POX, and CCoAOMT) were found to be highly up-regulated in KWS1197. Deductively, through effective B absorption and transportation, balanced nutrient accumulation, and an activated antioxidant enzyme system, B-efficient cultivars may cope with B deficiency while retaining a superior cellular structure to enable root development.

Insight into mechanisms of biochar-fertilizer induced of microbial community and microbiology of nitrogen cycle in acidic soil.

Biochar has been shown to affect the nitrogen (N) cycle in soil, however, it is unknown how this occurs. Therefore, we used metabolomics, high-throughput sequencing, and quantitative PCR to explore biochar and nitrogen fertilizer effects on the mitigation mechanisms of adverse environments in acidic soil. In the current research, we used acidic soil and maize straw biochar (pyrolyzed at 400 °C with limited oxygen). Three maize straw biochar levels (B1; 0t ha-1, B2; 45 t ha-1, and B3; 90 t ha-1) along with three N fertilizer (urea) levels (N1; 0 kg ha-1, N2; 225 kg ha-1 mg kg-1, and N3; 450 kg ha-1 mg kg-1) were employed in a sixty-day pot experiment. We found that the formation of NH+ 4-N was faster at 0-10 days, while the formation of NO- 3-N occurred at 20-35 days. Furthermore, the combined application of biochar and N fertilizer most effectively boosted soil inorganic N contents compared to biochar and N fertilizer treatments alone. The B3 treatment increased the total N and total inorganic N by 0.2-24.2% and 55.2-91.7%, respectively. Soil microorganism, N fixation, and nitrification capabilities increased with biochar and N fertilizer addition in terms of N-cycling-functional genes. Biochar-N fertilizer had a greater impact on the soil bacterial community and their diversity and richness. Metabolomics revealed 756 distinct metabolites, including 8 substantially upregulated metabolites and 21 significantly downregulated metabolites. A significant amount of lipids and organic acids were formed by biochar-N fertilizer treatments. Thus, biochar and N fertilizer triggered soil metabolism by affecting bacterial community structure, and N-cycling of the soil micro-ecological environment.

Genetic Susceptibility to Chronic Kidney Disease: Links, Risks and Management.

Chronic kidney disease (CKD) is associated with significant morbidity and mortality worldwide. In recent years, our understanding of genetic causes of CKD has expanded significantly with several renal conditions having been identified. This review discusses the current landscape of genetic kidney disease and their potential treatment options. This review will focus on cystic kidney disease, glomerular disease with genetic associations, congenital anomalies of kidneys and urinary tract (CAKUT), autosomal dominant-tubulointerstitial kidney disease (ADTKD), inherited nephrolithiasis and nephrocalcinosis.

Renal Genetics Clinic: 3-Year Experience in the Cleveland Clinic.

Rationale & Objective: There has been an increasing demand for the expertise provided by a renal genetics clinic. Such programs are limited in the United States and typically operate in a genomics research setting. Here we report a 3-year, real-world, single-center renal genetics clinic experience. Study Design: Retrospective cohort. Setting & Participants: Outpatient cases referred to the renal genetics clinic of the Cleveland Clinic between January 2019 and March 2022 were reviewed. Analytical Approach: Clinical and laboratory characteristics were analyzed. All genetic testing was performed in clinical labs. Results: 309 new patients referred from 15 specialties were evaluated, including 118 males and 191 females aged 35.1 ± 20.3 years. Glomerular diseases were the leading presentation followed by cystic kidney diseases, electrolyte disorders, congenital anomalies of kidneys and urinary tract, nephrolithiasis, and tubulointerstitial kidney diseases. Dysmorphic features were noted in 27 (8.7%) patients. Genetic testing was recommended in 292 (94.5%) patients including chromosomal microarray (8.9%), single-gene tests (19.5%), multigene panels (77.3%), and exome sequencing (17.5%). 80.5% of patients received insurance coverage for genetic testing. 45% (115/256) of patients had positive results, 25% (64/256) had variants of unknown significance, and 22.3% (57/256) had negative results. 43 distinct monogenic disorders were diagnosed. Family history of kidney disease was present in 52.8% of patients and associated with positive genetic findings (OR, 2.28; 95% CI, 1.40-3.74). 69% of patients with positive results received a new diagnosis and/or a change in the diagnosis. Among these, 39.7% (31/78) of patients received a significant change in disease management. Limitations: Retrospective and single-center study. Conclusions: The renal genetics clinic plays important roles in the diagnosis and management of patients with genetic kidney diseases. Multigene panels are the most frequently used testing modality with a high diagnostic yield. Family history of kidney disease is a strong indication for renal genetics clinic referral.

30-Month Pot Experiment: Biochar Alters Soil Potassium Forms, Soil Properties and Soil Fungal Diversity and Composition in Acidic Soil of Southern China.

Biochar has a significant impact on improving soil, nutrient supply, and soil microbial amounts. However, the impacts of biochar on soil fungi and the soil environment after 30 months of cultivation experiments are rarely reported. We studied the potential role of peanut shell biochar (0% and 2%) in the soil properties and the soil fungal communities after 30 months of biochar application under different soil potassium (K) levels (100%, 80%, 60%, 0% K fertilizer). We found that biochar had a promoting effect on soil K after 30 months of its application, such as the available K, water-soluble K, exchangeable K, and non-exchangeable K; and increments were 125.78%, 124.39%, 126.01%, and 26.63% under biochar and K fertilizer treatment, respectively, compared to control treatment. Our data revealed that p_Ascomycota and p_Basidiomycota were the dominant populations in the soil, and their sub-levels showed different relationships with the soil properties. The relationships between c_sordariomycetes and its sub-level taxa with soil properties showed a significant positive correlation. However, c_Dothideomycetes and its sub-group demonstrated a negative correlation with soil properties. Moreover, soil enzyme activity, especially related to the soil C cycle, was the most significant indicator that affected the community and structure of fungi through structural equation modeling (SEM) and redundancy analysis (RDA). This work emphasized that biochar plays an important role in improving soil quality, controlling soil nutrients, and regulating fungal diversity and community composition after 30 months of biochar application.