Enhanced aerobic granular sludge by thermally-treated dredged sediment in wastewater treatment under low superficial gas velocity.

The positive contributions of carriers to aerobic granulation have been wildly appreciated. In this study, as a way resource utilization, the dredged sediment was thermally-treated to prepared as carriers to promote aerobic granular sludge (AGS) formation and stability. The system was started under low superficial gas velocity (SGV, 0.6 cm/s)for a lower energy consumption. Two sequencing batch reactors (SBR) labeled R1 (no added carriers) and R2 (carriers added), were used in the experiment. R2 had excellent performance of granulation time (shortened nearly 43%). The maximum mean particle size at the maturity stage of AGS in R2 (0.545 mm) was larger compared to R1 (0.296 mm). The sludge settling performance in R2 was better. The reactors exhibited high chemical oxygen demand (COD) and ammonia nitrogen (NH3-N) removal rates. The total phosphorus (TP) removal rate in R2 was higher than R1 (almost 15% higher) on stage II (93-175d). R2 had a higher microbial abundance and dominant bacteria content. The relative abundance of dominant species was mainly affected by the carrier. However, the enrichment of dominant microorganisms and the evolution of subdominant species were more influenced by the increase of SGV. The results indicated that the addition of carriers induced the secretion of extracellular polymeric substances (EPS) by microorganisms and accelerated the rapid formation of initial microbial aggregates. This work provided a low-cost method and condition to enhance aerobic granulation, which may be helpful in optimizing wastewater treatment processes.

Symmetry in thermal cycles and processes.

Symmetry analysis is a cutting-edge research approach in physics, yet its application in macroscopic energy systems remains limited. This study demonstrates its potential to provide valuable insights for a deeper understanding and development of thermodynamic cycles. This article first studies the symmetry of the proposed C-P diagrams and finds rich symmetries including reflection symmetry, translation symmetry, and rotational symmetry within Carnot cycles. Then, it emphasizes that one can use symmetry alone to prove that the highest efficiency for any cycle operating in a certain temperature range is the Carnot efficiency, without relying on the entropy concept in the second law of thermodynamics. Lastly, it is found that this symmetry analysis framework can also be used for thermal cycles with phase transitions, as exemplified by applying in Rankine cycles. This research not only contributes groundbreaking insights into unraveling the symmetry inherent in thermodynamic cycles, but also promotes symmetry analysis to be an alternative analysis mean.

Translating in-person care to telehealth: analysis of GP consultations on musculoskeletal conditions.

BACKGROUND: The COVID-19 pandemic led to a rapid transition to telehealth particularly in general practice (GP) where continuous care for chronic conditions such as musculoskeletal (MSK) is provided. AIM: To determine the appropriateness of telehealth for MSK by identifying whether in-person tasks can be supported remotely via telehealth. DESIGN & SETTING: This study is a secondary analysis of the HaRI dataset. This dataset comprises of 281 videos of recorded GP consultations. The data set includes 10 general practitioners, across 8 separate clinics and was collected during 2017 in the United Kingdom. METHOD: Content analysis was conducted to identify the clinical tasks, physical examinations and physical artefacts used during the consultations. A scoring method applying two key metrics was developed to assess the translatability of clinical tasks to telehealth. RESULTS: Across the 31 MSK consultations analysed, 12 clinical tasks, five physical examinations and 12 physical artefacts were observed. Of clinical tasks, 17% (2/12) were deemed to be 'easily translatable over telehealth' and 50% (5/12) were deemed 'relatively easy to be translated over telehealth'. Only 17% (2/12) of tasks were rated 'moderately translatable over telehealth', and 17% (2/12) were deemed 'potentially translatable over telehealth'. No clinical tasks in this study were categorised as untranslatable to telehealth. The average telehealth translatability score was 7.1/10. CONCLUSION: Most clinical tasks observed during in-person GP consultations with MSK patients are translatable to telehealth. Further research is necessary to investigate the long-term efficacy and safety of telehealth utilisation for MSK in primary care.

The efficacy of adjuvant chemotherapy in patients with different midpoint-radiotherapy Epstein-Barr virus DNA plasma loads.

OBJECTIVES: This study aimed to evaluate the efficacy of adjuvant chemotherapy (AC) in patients with different midpoint-radiotherapy (mid-RT) Epstein-Barr virus (EBV) DNA plasma loads for locoregionally advanced nasopharyngeal carcinoma (NPC), and to provide decision-making regarding the use of AC. MATERIALS AND METHODS: A total of 675 consecutive patients diagnosed with stage III-IVa NPC were enrolled in this study. All patients underwent concurrent chemoradiotherapy (CCRT), either with or without induction chemotherapy or AC, or a combination of both. The primary endpoint of this study was progression-free survival (PFS). RESULTS: Among the 675 enrolled patients, 248 (36.7 %) received AC and 427 (63.3 %) were only observed after CCRT. In total, 149 (22.1 %) patients had detectable mid-RT EBV DNA levels, whereas 526 (77.9 %) had undetectable mid-RT EBV DNA levels. Patients with detectable mid-RT EBV DNA had worse 5-year PFS than those with undetectable mid-RT EBV DNA (74.8 % vs. 81.9 %, P = 0.045). AC group showed significantly better 5-year PFS than observation in patients with detectable mid-RT EBV DNA (82.8 % vs. 66.8 %; HR, 0.480; 95 % CI 0.250-0.919, P = 0.027). Multivariate analyses demonstrated that the treatment methods (AC vs. observation) were independent prognostic factors for PFS (HR, 0.37; 95 % CI 0.19-0.74, P = 0.005). However, in patients with undetectable mid-RT EBV DNA (5-year PFS: HR 0.873, 95 % CI 0.565-1.349, P = 0.52), AC group showed no survival benefit for observation. CONCLUSION: AC could reduce the risk of disease progression compared to observation in patients with detectable mid-RT EBV DNA. Our findings suggest that AC is effective in patients at a high risk of treatment failure.

Improvement of a Model of Brain Death for Transplant-Associated Studies in Rats.

BACKGROUND: The most common method of inducing brain death in rats is inflating an intracranially placed balloon of a Fogarty catheter inserted through a burr hole. However, because of the poor controllability of balloon position, the standardization and stability of the model are compromised. This study examined an improved technique in which the balloon is placed and fixed through double holes. METHODS: Forty adult male Sprague-Dawley (SD) rats were randomly and equally assigned into the single-hole (SH) group and the double-hole (DH) group. In each rat in the DH group, 2 holes were made, at the left frontal bone and parietal bone. A Fogarty catheter was inserted outside of the dura mater through the frontal hole, and its tip was guided out through the parietal hole using an arc-shaped needle. The SH group served as a control. In both groups, normal saline was injected into the balloon at 40 µL/minute until breathing stopped. Mechanical ventilation was instituted immediately and provided for another 6 hours after the determination of brain death. RESULTS: Typical blood pressure patterns were observed in both groups during the brain death induction period, whereas the fluctuation seemed relatively mild in the DH group. Stable brain death with normotension for 6 hours was induced successfully in 18 rats (90%) in the DH group and in 9 rats (45%) in the SH group (P = .002). The mean arterial pressure at 3 hours and thereafter was significantly higher in the DH group compared to the SH group (P < .05). CONCLUSIONS: Our results demonstrate that the DH method is a simple and effective technique to make the brain death model more stable and standardized, possibly due to precise control of the direction of the cannulation and the position of the balloon.

Learning and depicting lobe-based radiomics feature for COPD Severity staging in low-dose CT images.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition that imposes a significant healthcare burden worldwide. Accurate staging of COPD severity is crucial for patient management and treatment planning. METHODS: The retrospective study included 530 hospital patients. A lobe-based radiomics method was proposed to classify COPD severity using computed tomography (CT) images. First, we segmented the lung lobes with a convolutional neural network model. Secondly, the radiomic features of each lung lobe are extracted from CT images, the features of the five lung lobes are merged, and the selection of features is accomplished through the utilization of a variance threshold, t-Test, least absolute shrinkage and selection operator (LASSO). Finally, the COPD severity was classified by a support vector machine (SVM) classifier. RESULTS: 104 features were selected for staging COPD according to the Global initiative for chronic Obstructive Lung Disease (GOLD). The SVM classifier showed remarkable performance with an accuracy of 0.63. Moreover, an additional set of 132 features were selected to distinguish between milder (GOLD I + GOLD II) and more severe instances (GOLD III + GOLD IV) of COPD. The accuracy for SVM stood at 0.87. CONCLUSIONS: The proposed method proved that the novel lobe-based radiomics method can significantly contribute to the refinement of COPD severity staging. By combining radiomic features from each lung lobe, it can obtain a more comprehensive and rich set of features and better capture the CT radiomic features of the lung than simply observing the lung as a whole.

Novel method for recovering valuable metals from Sn ash: Vacuum carbothermal reduction-directional condensation.

Sn ash recycling is an industry with positive development prospects, as it provides better-protected resources, promotes sustainable development, and lays a solid foundation for future development. In this study, an innovative vacuum carbothermal reduction-directional condensation process was developed. The thermodynamic analysis results indicated that the initial reaction pressure and temperature for the carbothermal reduction of the system was 1-10 Pa and 998-1063 K, respectively. The saturation vapor pressure, separation coefficient, and condensation temperature of Sn, Pb, and Zn in the reduced products differed significantly, and their separation could be achieved by controlling the volatilization and condensation temperatures. A single-factor experiment investigated the effects of carbon ratio, temperature, and time on the reduction efficiency, direct yield, and recovery rate. The optimal experimental conditions were the ratio of MeO to C of 4:1, temperature of 1373 K, and time of 120 min. Sn, Pb, and Zn products were obtained at different positions. This process shortens the traditional process, reduces the reduction cost of Sn, and enables the implementation of the process, making it environmentally friendly.

NEMF-mediated Listerin-independent mitochondrial translational surveillance by E3 ligase Pirh2 and mitochondrial protease ClpXP.

The ribosome-associated protein quality control (RQC) pathway acts as a translational surveillance mechanism to maintain proteostasis. In mammalian cells, the cytoplasmic RQC pathway involves nuclear export mediator factor (NEMF)-dependent recruitment of the E3 ligase Listerin to ubiquitinate ribosome-stalled nascent polypeptides on the lysine residue for degradation. However, the quality control of ribosome-stalled nuclear-encoded mitochondrial nascent polypeptides remains elusive, as these peptides can be partially imported into mitochondria through translocons, restricting accessibility to the lysine by Listerin. Here, we identify a Listerin-independent organelle-specific mitochondrial RQC pathway that acts on NEMF-mediated carboxy-terminal poly-alanine modification. In the pathway, mitochondrial proteins carrying C-end poly-Ala tails are recognized by the cytosolic E3 ligase Pirh2 and the ClpXP protease in the mitochondria, which coordinately clear ribosome-stalled mitochondrial nascent polypeptides. Defects in this elimination pathway result in NEMF-mediated aggregates and mitochondrial integrity failure, thus providing a potential molecular mechanism of the RQC pathway in mitochondrial-associated human diseases.

Combating land degradation through human efforts: Ongoing challenges for sustainable development of global drylands.

Drylands, as highly vulnerable ecosystems, support environmental functions and human well-being. Nevertheless, widespread land degradation and desertification present significant global and regional environmental challenges, with limited consensus on their area and degree. This study used time-series vegetation productivity and meteorological data from 2000 to 2020 to quantify global land degradation trends and driving factors in drylands. The results show a notable restoration of land degradation in drylands worldwide, with the area of improved land exceeding the degraded area by 1.4 times, although the threat of degradation persists. India and China emerge as pioneers in effective land improvement strategies, offering valuable experiences for other regions. Combined effects, as quantitatively distinguished by our established model, dominate the degradation and improvement processes. Notably, human activities play a decisive role in influencing land degradation trends, with the potential for either exacerbation or reversal. This study provides new perspectives on environmental health and human activities from global and regional observations. Finally, our research provides scientific support for desertification control and contributes to the overall advancement of the SDGs globally.

Exogenous hydrogen sulfide prevents SOD2 degradation to safeguard renal function in diabetic kidney disease.

Diabetic kidney disease (DKD) is a major contributor to chronic kidney disease. Hydrogen sulfide (H2S) serves as an endogenous gaseous signaling molecule capable of safeguarding renal function within the context of DKD. However, the underlying mechanisms need to be elucidated. This study was undertaken to unveil the mechanisms by which H2S counteracts against DKD. Utilizing mice and human renal tubular epithelial (HK-2) cells, we demonstrated a reduction in cystathionine-γ-lyase/H2S levels within renal tissues of db/db mice and in HK-2 cells subjected to hyperglycemic and hyperlipidemic environments. Notably, we observed that sodium hydrosulfide (NaHS) supplementation could serve as an exogenous source of H2S. Exogenous H2S exhibited the capacity to mitigate the accumulation of reactive oxygen species and attenuate the degradation of superoxide dismutase 2 (SOD2) by Lon protease homolog 1 induced by hyperglycemia and hyperlipidemia, thus affording cellular protection against mitochondrial apoptosis. Consequently, NaHS treatment led to decreased serum levels of blood urea nitrogen and serum creatinine, reflecting alleviated renal damage and thereby preserving renal function in db/db mice. Based on these findings, we propose that exogenous H2S exerts a protective role against DKD by inhibiting SOD2 degradation.

Efficient removal of tetracycline hydrochloride through novel Fe/BiOBr/Bi2WO6 photocatalyst prepared by dual-strategy under visible-light irradiation.

It is important to investigate whether combining two modification strategies has a synergistic effect on the activity of photocatalysts. In this manuscript, Fe-doped BiOBr/Bi2WO6 heterojunctions were synthesized by a one-pot solvothermal method, and excellent photocatalytic performance was obtained for the degradation of tetracycline hydrochloride (TCH) in water without the addition of surfactant. Combining experiments and characterization, the synergistic effect between Fe ion doping and the BiOBr/Bi2WO6 heterojunction was elucidated. The Fe/BiOBr/Bi2WO6 composite photocatalyst had a beneficial void structure, enhanced visible light response, and could inhibit the recombination of photogenerated support well, which improved the photocatalytic activity. The presented experiments demonstrate that Fe/BiOBr/Bi2WO6 removes 97% of TCH from aqueous solution, while pure BiOBr and Bi2WO6 only remove 56% and 65% of TCH, respectively. Finally, the separation and transfer mechanisms of photoexcited carriers were determined in conjunction with the experimental results. This study provides a new direction for the design of efficient photocatalysts through the use of a dual co-modification strategy.

Development of Adjustable High- to Low-Adhesive Superhydrophobicity Using Aligned Electrospun Fibers.

Superhydrophobic surfaces based on electrospun fibrous structures exhibit advantages of additive manufacturing and enable the passage of gases. Compared to randomly deposited fibers, directionally aligned fibers improve the control of surface wetting by a specified fiber orientation and predictable liquid-fiber contact interface. In this article, we create superhydrophobicity with adjustable adhesion based on the understanding of droplet wetting behavior on directionally aligned fibers. Directionally aligned polystyrene fibers with different diameters and interfiber distances (l) are produced using electrospinning with a rotating fin collector. The wetting behavior of droplets on the surfaces dressed by aligned fibers is characterized, and a thermodynamic model of wetting behavior is established to guide the experimental studies. As a result, high-adhesive superhydrophobicity is achieved on weak hydrophobic substrate surfaces dressed by aligned polystyrene fibers with a diameter of 1.8 µm and l between 5 and 130 µm. Water droplets (2 µL) exhibit a maximum contact angle of 156° and adhere to the fiber-dressed surfaces by tilting upside down. Low-adhesive superhydrophobicity is achieved by introducing an additional layer of aligned fibers to increase the transition energy barrier. On the dual-layer structure with an upper-layer l of 9 µm, droplets show a contact angle of 155° and can readily roll off the surface. Moreover, increasing the upper-layer l to 15 µm reserves the surface to high-adhesive superhydrophobicity.

Growth Axis Somatostatin, Growth Hormone Receptor, and Insulin-like Growth Factor-1 Genes Express and Are Affected by the Injection of Exogenous Growth Hormone in Chinemys reevesii.

In this study, to explore the effect of growth hormone changes on the related genes and regulatory roles of the turtle, PCR amplification, real-time fluorescence quantitative analysis, and enzyme cutting technology were used to clone and sequence the somatostatin (SS) gene, growth hormone receptor (GHR), and insulin-like growth factor-1 (IGF-I) sequence of Chinemys reevesii. The effects of human growth hormone on the mRNA expression of growth-axis-related genes SS, GHR, and IGF-1 in different sexes were observed. The study of the SS gene in turtles using real-time fluorescence quantitative PCR showed that the SS gene was mainly expressed in the nervous system and the digestive system, with the highest expression found in the brain, while the GHR gene and the IGF-I gene were expressed in all tissues of Chinemys reevesii. The SS gene was expressed in the brain, pituitary, liver, stomach, and intestine, with the highest expression in the brain and the lowest expression in the liver. Within 4 weeks of the injection of exogenous growth hormone, the expression level of the SS gene in the brain of both sexes first increased and then decreased, showing a parabolic trend, and the expression level of the experimental group was lower than that of the control group. After the injection of growth hormone (GH), the expression of the GHR gene in the liver of both sexes showed a significant increase in the first week, decreasing to the control group level in the second week, and then gradually increasing. Finally, a significant level of difference in the expression of the GHR gene was reached at 3 and 4 weeks. In terms of the IGF-I gene, the changing trend of the expression level in the liver was the same as that of the GHR gene. After the injection of exogenous growth hormone, although the expression of the SS gene increased the inhibition of the secretion of the GHR gene by the Reeves' turtle, exogenous growth hormone could replace the synthesis of GH and GHR, accelerating the growth of the turtle. The experiments showed that the injection of recombinant human growth hormone affects the expression of SS, GHR, and IGF-1 genes, and promotes the growth of the Reeves' turtle.

Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial.

Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0-51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.

Integrated Network Pharmacology and Experimental Validation Approach to Investigate the Mechanisms of Stigmasterol in the Treatment of Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints associated with systemic comorbidities. Sinomenium acutum is regarded as an effective traditional Chinese medicine (TCM) for the treatment of RA. Materials and Methods: Based on network pharmacology and Gene Expression Omnibus (GEO) database, 33 RA-related differentially-expressed genes (DEGs) targeting active compounds of Sinomenium acutum were initially screened in our investigation. Results: Gene Ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) analyses found the important involvement of these DEGs in osteoclast differentiation, and finally 5 core DEGs, including NCF4, NFKB1, CYBA, IL-1ß and NCF1 were determined through protein-protein interaction (PPI) network. We also identified the related active component of Sinomenium acutum include Stigmasterol. Finally, in order to experimentally verify these results, a rat model of collagen-induced arthritis (CIA) was established, and subsequently treated with Stigmasterol solution. Conclusion: Similar to the healing effect of Indomethacin, Stigmasterol was observed to reduce the levels of inflammatory factors (IL-6 and IL-1ß) and osteoclast differentiation-related factors (RANKL, ACP5 and Cathepsin K), which can also reduce the arthritis index score and alleviate the degree of pathological injury of rat ankle joints. The predictions and experimental data uncover the involvement of Stigmasterol, an active component of Sinomenium acutum, in regulation of osteoclast differentiation, exerting great medicinal potential in the treatment of RA.

Bayesian inference for survival prediction of childhood Leukemia.

BACKGROUND: Childhood Leukemia is the most common type of cancer among children. Nearly 39% of cancer-induced childhood deaths are attributable to Leukemia. Nevertheless, early intervention has long been underdeveloped. Moreover, there are still a group of children succumbing to their cancer due to the cancer care resource disparity. Therefore, it calls for an accurate predictive approach to improve childhood Leukemia survival and mitigate these disparities. Existing survival predictions rely on a single best model, which fails to consider model uncertainties in predictions. Prediction from a single model is brittle, with model uncertainty neglected, and inaccurate prediction could lead to serious ethical and economic consequences. METHODS: To address these challenges, we develop a Bayesian survival model to predict patient-specific survivals by taking model uncertainty into account. Specifically, we first develop a survival model predict time-varying survival probabilities. Second, we place different prior distributions over various model parameters and estimate their posterior distribution with full Bayesian inference. Third, we predict the patient-specific survival probabilities changing with respect to time by considering model uncertainty induced by posterior distribution. RESULTS: Concordance index of the proposed model is 0.93. Moreover, the standardized survival probability of the censored group is higher than that of the deceased group. CONCLUSIONS: Experimental results indicate that the proposed model is robust and accurate in predicting patient-specific survivals. It can also help clinicians track the contribution of multiple clinical attributes, thereby enabling well-informed intervention and timely medical care for childhood Leukemia.

Methane emission reduction oriented extracellular electron transfer and bioremediation of sediment microbial fuel cell: A review.

Sediment is the internal and external source of water environment pollution, so sediment remediation is the premise of water body purification. Sediment microbial fuel cell (SMFC) can remove the organic pollutants in sediment by electroactive microorganisms, compete with methanogens for electrons, and realize resource recycling, methane emission inhibiting and energy recovering. Due to these characteristics, SMFC have attracted wide attention for sediment remediation. In this paper, we comprehensively summarized the recent advances of SMFC in the following areas: (1) The advantages and disadvantages of current applied sediment remediation technologies; (2) The basic principles and influencing factors of SMFC; (3) The application of SMFC for pollutant removal, phosphorus transformation and remote monitoring and power supply; (4) Enhancement strategies for SMFC in sediments remediation such as SMFC coupled with constructed wetland, aquatic plant and iron-based reaction. Finally, we have summarized the drawback of SMFC and discuss the future development directions of applying SMFC for sediment bioremediation.

Recent advances in constructed wetlands methane reduction: Mechanisms and methods.

Constructed wetlands (CWs) are artificial systems that use natural processes to treat wastewater containing organic pollutants. This approach has been widely applied in both developing and developed countries worldwide, providing a cost-effective method for industrial wastewater treatment and the improvement of environmental water quality. However, due to the large organic carbon inputs, CWs is produced in varying amounts of CH4 and have the potential to become an important contributor to global climate change. Subsequently, research on the mitigation of CH4 emissions by CWs is key to achieving sustainable, low-carbon dependency wastewater treatment systems. This review evaluates the current research on CH4 emissions from CWs through bibliometric analysis, summarizing the reported mechanisms of CH4 generation, transfer and oxidation in CWs. Furthermore, the important environmental factors driving CH4 generation in CW systems are summarized, including: temperature, water table position, oxidation reduction potential, and the effects of CW characteristics such as wetland type, plant species composition, substrate type, CW-coupled microbial fuel cell, oxygen supply, available carbon source, and salinity. This review provides guidance and novel perspectives for sustainable and effective CW management, as well as for future studies on CH4 reduction in CWs.

Alpha-kinase1 promotes tubular injury and interstitial inflammation in diabetic nephropathy by canonical pyroptosis pathway.

BACKGROUND: Alpha-kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1ß in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1ß and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. METHODS: Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1ß, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1ß and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. RESULTS: The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1ß in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1ß, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. CONCLUSIONS: Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.

mRNA Turnover Protein 4 Is Vital for Fungal Pathogenicity and Response to Oxidative Stress in Sclerotinia sclerotiorum.

Ribosome assembly factors have been extensively studied in yeast, and their abnormalities may affect the assembly process of ribosomes and cause severe damage to cells. However, it is not clear whether mRNA turnover protein 4 (MRT4) functions in the fungal growth and pathogenicity in Sclerotinia sclerotiorum. Here, we identified the nucleus-located gene SsMRT4 using reverse genetics, and found that knockdown of SsMRT4 resulted in retard mycelia growth and complete loss of pathogenicity. Furthermore, mrt4 knockdown mutants showed almost no appressorium formation and oxalic acid production comparing to the wild-type and complementary strains. In addition, the abilities to ROS elimination and resistance to oxidative and osmotic stresses were also seriously compromised in mrt4 mutants. Overall, our study clarified the role of SsMRT4 in S. sclerotiorum, providing new insights into ribosome assembly in regulating pathogenicity and resistance to environmental stresses of fungi.