Neuronal double-stranded DNA accumulation induced by DNase II deficiency drives tau phosphorylation and neurodegeneration.

BACKGROUND: Deoxyribonuclease 2 (DNase II) plays a key role in clearing cytoplasmic double-stranded DNA (dsDNA). Deficiency of DNase II leads to DNA accumulation in the cytoplasm. Persistent dsDNA in neurons is an early pathological hallmark of senescence and neurodegenerative diseases including Alzheimer's disease (AD). However, it is not clear how DNase II and neuronal cytoplasmic dsDNA influence neuropathogenesis. Tau hyperphosphorylation is a key factor for the pathogenesis of AD. The effect of DNase II and neuronal cytoplasmic dsDNA on neuronal tau hyperphosphorylation remains unclarified. METHODS: The levels of neuronal DNase II and dsDNA in WT and Tau-P301S mice of different ages were measured by immunohistochemistry and immunolabeling, and the levels of DNase II in the plasma of AD patients were measured by ELISA. To investigate the impact of DNase II on tauopathy, the levels of phosphorylated tau, phosphokinase, phosphatase, synaptic proteins, gliosis and proinflammatory cytokines in the brains of neuronal DNase II-deficient WT mice, neuronal DNase II-deficient Tau-P301S mice and neuronal DNase II-overexpressing Tau-P301S mice were evaluated by immunolabeling, immunoblotting or ELISA. Cognitive performance was determined using the Morris water maze test, Y-maze test, novel object recognition test and open field test. RESULTS: The levels of DNase II were significantly decreased in the brains and the plasma of AD patients. DNase II also decreased age-dependently in the neurons of WT and Tau-P301S mice, along with increased dsDNA accumulation in the cytoplasm. The DNA accumulation induced by neuronal DNase II deficiency drove tau phosphorylation by upregulating cyclin-dependent-like kinase-5 (CDK5) and calcium/calmodulin activated protein kinase II (CaMKII) and downregulating phosphatase protein phosphatase 2A (PP2A). Moreover, DNase II knockdown induced and significantly exacerbated neuron loss, neuroinflammation and cognitive deficits in WT and Tau-P301S mice, respectively, while overexpression of neuronal DNase II exhibited therapeutic benefits. CONCLUSIONS: DNase II deficiency and cytoplasmic dsDNA accumulation can initiate tau phosphorylation, suggesting DNase II as a potential therapeutic target for tau-associated disorders.

Real-world effectiveness and safety of recombinant human endostatin plus PD-1 inhibitors and chemotherapy as first-line treatment for EGFR/ALK-negative, advanced or metastatic non-small cell lung cancer.

BACKGROUND: This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. CONCLUSIONS: Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.

Machine learning prediction model for gray-level co-occurrence matrix features of synchronous liver metastasis in colorectal cancer.

BACKGROUND: Synchronous liver metastasis (SLM) is a significant contributor to morbidity in colorectal cancer (CRC). There are no effective predictive device integration algorithms to predict adverse SLM events during the diagnosis of CRC. AIM: To explore the risk factors for SLM in CRC and construct a visual prediction model based on gray-level co-occurrence matrix (GLCM) features collected from magnetic resonance imaging (MRI). METHODS: Our study retrospectively enrolled 392 patients with CRC from Yichang Central People's Hospital from January 2015 to May 2023. Patients were randomly divided into a training and validation group (3:7). The clinical parameters and GLCM features extracted from MRI were included as candidate variables. The prediction model was constructed using a generalized linear regression model, random forest model (RFM), and artificial neural network model. Receiver operating characteristic curves and decision curves were used to evaluate the prediction model. RESULTS: Among the 392 patients, 48 had SLM (12.24%). We obtained fourteen GLCM imaging data for variable screening of SLM prediction models. Inverse difference, mean sum, sum entropy, sum variance, sum of squares, energy, and difference variance were listed as candidate variables, and the prediction efficiency (area under the curve) of the subsequent RFM in the training set and internal validation set was 0.917 [95% confidence interval (95%CI): 0.866-0.968] and 0.09 (95%CI: 0.858-0.960), respectively. CONCLUSION: A predictive model combining GLCM image features with machine learning can predict SLM in CRC. This model can assist clinicians in making timely and personalized clinical decisions.

Biochar alleviates inhibition effects of humic acid on anaerobic digestion: Insights to performances and mechanisms.

To recover methane from waste activated sludge through anaerobic digestion (AD) is one promising alternative to achieve carbon neutrality for wastewater treatment plants. However, humic acids (HAs) are one of the major compositions in waste activated sludge, and their accumulation performs inhibition effects on AD. This study investigated the potentials of biochar (BC) in alleviating inhibition effects of HAs on AD. Results showed that although the accumulated HAs reduced methane yield by 9.37% compared to control, the highest methane yield, 132.6 mL CH4/g VSS, was obtained after adding BC, which was 45.9% higher than that in HA group. Mechanism analysis showed that BC promoted the activities of hydrolase such as protease and α-glucosidase, which were 69.7% and 29.7% higher than those in HA group, respectively. The conversion of short-chain fatty acids was accelerated. In addition, the evolutions of electroactive microorganisms like Clostridium_sensu_stricto_13 and Methanosaeta were consistent with the activitiies of electron transfer and the contents of cytochrome c. Furthermore, parts of HAs rather than all of them were adsorbed by BC, and the remaining free HAs and BC formed synergistic effects on methanogenesis, then both CO2 reduction and acetoclastic methanogenesis pathways were improved. The findings may provide some solutions to alleviate inhibition effects of HAs on AD.

The interaction between physical activity and ambient particulate matters on cognitive function among Chinese community-dwelling older adults.

BACKGROUND: The interaction between physical activity (PA) and ambient particulate matters (PMs) on cognition is rarely investigated. Our study aimed to assess the interactions of PA and PMs on cognitive function in older adults. METHODS: Our study comprised 3937 Chinese community-dwelling older adults. Cognition was evaluated using the Mini-Mental State Examination. PA information was gathered using the International Physical Activity Questionnaire. The data of PMs were obtained from China High Air Pollutants (CHAP). Linear regressions model and interaction plots were applied to assess and visualize the interaction of PA and PMs on cognition, respectively. Bayesian kernel machine regression (BKMR) method was employed to visualize discernible thresholds for the interaction. RESULTS: PMs were negatively associated with MMSE scores (PM1: ß = -0.40, 95 % CI: -0.58, -0.28; PM2.5: ß = -0.46, 95 % CI: -0.64, -0.29; PM10: ß = -0.44, 95 % CI: -0.61, -0.26), and PA was positively affiliated with MMSE scores (ß = 0.18, 95 % CI: -0.01, 0.38). Interaction plots and BKMR demonstrated that adverse connotations of PMs with MMSE increased with the elevated PA levels, and the positive associations of PA with MMSE scores were attenuated by increased PMs (all Pinteraction < 0.20). Discernible thresholds for the interaction between PMs and PA on MMSE were found. CONCLUSIONS: Our findings suggest that PA should not be taken at higher PMs concentrations, and that low level of PA could be performed in PMs polluted environment to improve cognitive function. Further experimental and cohort researches are required to reproduce our discovery.

Characterizing sector-oriented roadside exposure to ultrafine particles (PM0.1) via machine learning models: Implications of covariates influences on sectors variability.

Ultrafine particles (UFPs; PM0.1) possess intensified health risk due to their smaller size and unique spatial variability. One of major emission sources for UFPs is vehicle exhaust, which varies based on the traffic composition in each type of roadside sector. The current challenge of epidemiological UFPs study is limited characterization ability due to expensive instruments. This study assessed the UFPs particle number concentrations (UFPs PNC) exposure dose for typical healthy adults and children at three different roadside sectors, including industrial roadside (IN), residential roadside (RS), and urban background (UB). Furthermore, this study also developed and utilized machine learning (ML) algorithms that could accurately characterize the UFPs exposure dose and explain the covariates effects on the model outputs, representing the intra-urban variability of UFPs between sectors. It was found that the average inhaled UFPs dose for healthy adults and children during off-peak season (warm period) were 1.71 ± 0.19 × 1010; 1.28 ± 0.22 × 1010; 1.09 ± 0.18 × 1010 #/hour and 1.33 ± 0.15 × 1010; 0.99 ± 0.17 × 1010; 0.86 ± 0.14 × 1010 #/hour at IN, RS, UB. Inhaled UFPs were mainly deposited in tracheobronchial (TB) respiratory fraction for adults (67.7%) and in alveoli (ALV) fraction for children (67.5%). Among three ML algorithms implemented in this study, XGBoost possessed the highest UFPs PNC exposure dose estimation performances with R2 = 0.965; 0.959; 0.929 & RMSE = 0.79 × 108; 0.54 × 108; 0.15 × 105 #/hour at IN, RS, and UB which then followed by multiple linear regression (MLR), and random forest (RF). Furthermore, SHAP analysis from the XGBoost model has successfully pointed out the spatial variability of each roadside sector by quantifying the approximated contributions of covariates to the model's output. Findings in this study highlighted the potential use of ML models as an alternative for preliminary particle exposure source apportionment.

Green Synthesis of Polyurethane Sponge-Grafted Calcium Alginate with Carbon Ink Aerogel with High Water Vapor Harvesting Capacity for Solar-Driven All-Weather Atmospheric Water Harvesting.

Atmospheric water harvesting (AWH) technology is a new strategy for alleviating freshwater scarcity. Adsorbent materials with high hygroscopicity and high photothermal conversion efficiency are the key to AWH technology. Hence, in this study, a simple and large-scale preparation for a hygroscopic compound of polyurethane (PU) sponge-grafted calcium alginate (CA) with carbon ink (SCAC) was developed. The PU sponge in the SCAC aerogel acts as a substrate, CA as a moisture adsorber, and carbon ink as a light adsorber. The SCAC aerogel exhibits excellent water absorption of 0.555-1.40 g·g-1 within a wide range of relative humidity (40-80%) at 25 °C. The SCAC aerogel could release adsorbed water driven by solar energy, and more than 92.17% of the adsorbed water could be rapidly released over a wide solar intensity range of 1.0-2.0 sun. In an outdoor experiment, 57.517 g of SCAC was able to collect 32.8 g of clean water in 6 h, and the water quality meets the drinking water standards set by the World Health Organization. This study suggests a new approach to design promising AWH materials and infers the potential practical application of SCAC aerogel-based adsorbents.

Anaerobic membrane bioreactors for municipal wastewater: Progress in resource and energy recovery improvement approaches.

Anaerobic membrane bioreactor (AnMBR) offer promise in municipal wastewater treatment, with potential benefits including high-quality effluent, energy recovery, sludge reduction, and mitigating greenhouse gas emissions. However, AnMBR face hurdles like membrane fouling, low energy recovery, etc. In light of net-zero carbon target and circular economy strategy, this work sought to evaluate novel AnMBR configurations, focusing on performance, fouling mitigation, net-energy generation, and nutrients-enhancing integrated configurations, such as forward osmosis (FO), membrane distillation (MD), bioelectrochemical systems (BES), membrane photobioreactor (MPBR), and partial nitrification-anammox (PN/A). In addition, we highlight the essential role of AnMBR in advancing the circular economy and propose ideas for the water-energy-climate nexus. While AnMBR has made significant progress, challenges, such as fouling and cost-effectiveness persist. Overall, the use of novel configurations and energy recovery strategies can further improve the sustainability and efficiency of AnMBR systems, making them a promising technology for future sustainable municipal wastewater treatment.

Characteristics and risk differences of different tumor sizes on distant metastases of pancreatic neuroendocrine tumors: A retrospective study in the SEER database.

BACKGROUND: The rate of distant metastasis in patients with pancreatic neuroendocrine tumors (PNETs) is 20%-50% at the time of initial diagnosis. However, whether tumor size can predict distant metastasis for PNETs remains unknown up to date. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) population-based data to collect 6089 patients with PNETs from 2010 to 2019. The optimal cut-off point of tumor size to predict distant metastasis was calculated by Youden's index. Multivariate logistic regression analysis was used to figure out the association between tumor size and distant metastasis patterns. RESULTS: The most common metastatic site was liver (27.2%), followed by bone (3.0%), lung (2.3%) and brain (0.4%). Based on an optimal cut-off value of tumor size (25.5 mm) for predicting distant metastasis determined by Youden's index, patients were categorized into groups of tumor size < 25.5 mm and ≥ 25.5 mm. Multivariate logistic regression analyses showed that, compared with < 25.5 mm, tumor size ≥ 25.5 mm was an independent risk predictor of overall distant metastasis [odds ratio (OR) = 4.491, 95% confidence interval (CI): 3.724-5.416, P < 0.001] and liver metastasis (OR = 4.686, 95% CI: 3.886-5.651, P < 0.001). CONCLUSIONS: Tumor size ≥ 25.5 mm was significantly associated with more overall distant and liver metastases. Timely identification of distant metastasis for tumor size ≥ 25.5 mm may provide survival benefit for timely and precise treatment.

Inhibition of Mettl3 ameliorates osteoblastic senescence by mitigating m6A modifications on Slc1a5 via Igf2bp2-dependent mechanisms.

Age-related osteoporosis is characterized by a marked decrease in the number of osteoblasts, which has been partly attributed to the senescence of cells of the osteoblastic lineage. Epigenetic studies have provided new insights into the mechanisms of current osteoporosis treatments and bone repair pathophysiology. N6-methyladenosine (m6A) is a novel transcript modification that plays a major role in cellular senescence and is essential for skeletal development and internal environmental stability. Bioinformatics analysis revealed that the expression of the m6A reading protein Igf2bp2 was significantly higher in osteoporosis patients. However, the role of Igf2bp2 in osteoblast senescence has not been elucidated. In this study, we found that Igf2bp2 levels are increased in ageing osteoblasts induced by multiple repetition and H2O2. Increasing Igf2bp2 expression promotes osteoblast senescence by increasing the stability of Slc1a5 mRNA and inhibiting cell cycle progression. Additionally, Mettl3 was identified as Slc1a5 m6A-methylated protein with increased m6A modification. The knockdown of Mettl3 in osteoblasts inhibits the reduction of senescence, whereas the overexpression of Mettl3 promotes the senescence of osteoblasts. We found that administering Cpd-564, a specific inhibitor of Mettl3, induced increased bone mass and decreased bone marrow fat accumulation in aged rats. Notably, in an OVX rat model, Igf2bp2 small interfering RNA delivery also induced an increase in bone mass and decreased fat accumulation in the bone marrow. In conclusion, our study demonstrated that the Mettl3/Igf2bp2-Slc1a5 axis plays a key role in the promotion of osteoblast senescence and age-related bone loss.

Merging DNA Repair with Bioorthogonal Conjugation Enables Accessible and Versatile Asymmetric DNA Catalysis.

Optimizing catalysts through high-throughput screening for asymmetric catalysis is challenging due to the difficulty associated with assembling a library of catalyst analogues in a timely fashion. Here, we repurpose DNA excision repair and integrate it with bioorthogonal conjugation to construct a diverse array of DNA hybrid catalysts for highly accessible and high-throughput asymmetric DNA catalysis, enabling a dramatically expedited catalyst optimization process, superior reactivity and selectivity, as well as the first atroposelective DNA catalysis. The bioorthogonality of this conjugation strategy ensures exceptional tolerance toward diverse functional groups, thereby facilitating the facile construction of 44 DNA hybrid catalysts bearing various unprotected functional groups. This unique feature holds the potential to enable catalytic modalities in asymmetric DNA catalysis that were previously deemed unattainable.

Placenta-Related Parameters at Delivery in Relation to Folic Acid Supplementation in Different Pregnancies.

Folic acid plays an important role in the synthesis, repair, and methylation of deoxyribonucleic acid (DNA). Currently, most studies have focused on the effects of periconceptional folic acid (FA) supplementation on fetal development, and there is still a lack of population-based research exploring the association between FA use during pregnancy and placental development. This study aimed to investigate the impacts of FA supplementation in different pregnancies on placenta-related parameters at delivery. The study included 2708 pregnant women recruited from Ma'anshan City, Anhui Province, China, between May 2013 and September 2014. Information on FA use from one month before conception to delivery was collected. Placental length, width, and thickness were measured. Multivariable logistic regression analysis was used to assess the effects of FA supplementation in different pregnancies on placenta-related parameters. Based on multiple regression analysis, propensity score weighting was adopted to enhance comparability between different FA supplementation groups. Compared with FA non-users, FA supplementation before conception was associated with increased placental width (0.241 cm, 95%CI: 0.052-0.429, p = 0.013) and increased placental surface area (6.398 cm2, 95%CI: 1.407-11.389, p = 0.012), and FA use in early/middle pregnancy was, respectively, related with increased placental thickness (0.061 cm, 95%CI: 0.004-0.117, p = 0.036; 0.066 cm, 95%CI: 0.004-0.129, p = 0.038). FA use before conception could increase placental width and area, and FA use in early/middle pregnancy could increase placental thickness. To confirm the findings, further investigations are needed.

Diagnosis of membranous nephropathy with Anti-GBM glomerulonephritis: a case series report.

BACKGROUND: The concomitant occurrence of membranous nephropathy and anti-glomerular basement (anti-GBM) disease has been previously described but is extremely rare. However, delayed recognition or misdiagnosis leads to delayed treatment, resulting in worse renal and patient outcomes. CASE PRESENTATION: We present 3 patients with rapidly progressive glomerulonephritis (RPGN), anti-GBM and serum-positive M-type phospholipase A2 receptor (anti-PLA2R) antibody. Renal biopsies revealed PLA2R-associated membranous nephropathy with anti-GBM glomerulonephritis. We analyzed the clinical and pathological characteristics and discussed that the correct diagnosis of membranous nephropathy with anti-GBM should rely on a combination of renal biopsy findings and serological testing. Despite aggressive treatment, one patient received maintenance hemodialysis, one patient progressed to CKD 3 stage, and the other patient died of cerebral infarction. CONCLUSION: The simultaneous occurrence of membranous nephropathy and anti-GBM disease is extremely rare. The correct diagnosis of membranous nephropathy with anti-GBM relies on a combination of renal biopsy findings and serological testing. Early diagnosis is needed to improve the renal dysfunction.

Trajectories of squamous cell carcinoma antigen and outcomes of patients with advanced penile cancer after chemotherapy based on paclitaxel, ifosfamid, and cisplatin regimen.

INTRODUCTION: Penile cancer (PC) is a lethal malignancy with no effective prognostic biomarker. We aim to investigate associations between trajectories of squamous cell carcinoma antigen (SCC-A) and patient outcomes after chemotherapy based on paclitaxel, ifosfamid, and cisplatin (TIP) regimen. METHODS: Consecutive AJCC staging III/IV PC patients who received TIP chemotherapy and repeated SCC-A measurements in 2014-2022 were analyzed. Latent class growth mixed (LCGM) models were employed to characterize patients' serum SCC-A trajectories. Patient survival, and clinical and pathological tumor responses were compared. Inverse probability treatment weighting was used to adjust confounding factors. RESULTS: Eighty patients were included. LCGM models identified two distinct trajectories of SCC-A: low-stable (40%; n = 32) and high-decline (60%; n = 48). Overall survival (HR [95% CI]: 3.60 [1.23-10.53], p = 0.019), progression-free survival (HR [95% CI]: 11.33 [3.19-40.3], p < 0.001), objective response rate (37.5% vs. 62.5% p = 0.028), disease control rate (60.4% vs. 96.9% p < 0.00), and pathological complete response rate (21.2% vs. 51.9%, p = 0.014) were significantly worse in the high-decline arm. CONCLUSION: PC patients' SCC-A change rate was associated with tumor response and patient survival after TIP chemotherapy. SCC-A might assist tumor monitoring after systemic therapies.

Dispersion Behavior of a Droplet Impacting a Single Fiber.

The high-gravity reactor, known for its excellent mass transfer capability, plays a crucial role in the carbon capture process. The wire mesh packing serves as the core structure for enhancing mass transfer performance. Understanding the underlying dispersion mechanism requires a thorough exploration of the dynamics of droplet impact on a single fiber. This work aimed to numerically study the process of a droplet impacting a single fiber by applying the volume of fluid method. The effects of initial velocity (u0), initial diameter (D0), impact eccentric distance (e), and impact angle (θ) on the deformation evolution and dispersion characteristics of a droplet impacting a single fiber were systematically studied. Central or vertical impacts can be categorized into four main stages: splitting, merging, stretching, and breaking. Meanwhile, asynchronous breaking, sliding splitting, and oblique stages were observed during eccentric and nonvertical impacts. Subsequently, dimensionless time (t*) and the rate of increase of the gas-liquid interfacial area (η) were introduced to quantitatively analyze the dispersion characteristics postimpact. Increasing the initial velocity, reducing the droplet diameter, minimizing the impact eccentric distance, and maximizing the impact angle all contribute to enhanced dispersion performance. A correlation for the maximum increase rate of the gas-liquid interfacial area of the droplet was proposed, with errors less than ±15%. Finally, the deformation mechanism of droplet impact on a fiber was summarized by analyzing the influences of differential pressure inside and outside the liquid film, as well as gas vortices.

Associations of toxic metals and their mixture with hyperuricemia in Chinese rural older adults.

Previous studies have related single toxic metals (TMs) to hyperuricemia (HUA) among the general population, however, the association of the TM mixture with HUA, especially in older adults, remains poorly understood. We aimed to examine the relationships between individual TMs and their mixture and HUA in Chinese rural older adults. This study consisted of 2075 rural older adults aged 60 years or over. Blood concentrations of aluminum (Al), arsenic (As), barium (Ba), cadmium (Cd), cesium (Cs), gallium (Ga), mercury (Hg), lead (Pb), thallium (Tl), and uranium (U) were detected using inductively coupled plasma mass spectrometry. The associations of single TMs with HUA were assessed using logistic regression and restricted cubic spline (RCS) models, and the association of TM mixture with HUA was explored using the elastic net with environmental risk score (ENET-ERS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models, respectively. Adjusted logistic regression model showed that Cs (OR = 1.65, 95% CI 1.37-1.99) and Pb (OR = 1.46, 95% CI 1.28-1.67) were positively related to HUA, and RCS model exhibited a positive linear association of Cs and Pb with HUA. ENET-ERS and QGC models quantified a positive correlation between the TM mixture and the odds of HUA, with estimated ORs of 1.15 (95% CI 1.11-1.19) and 1.84 (95% CI 1.37-2.47), respectively, and Cs and Pb had the most weight. BKMR model demonstrated a significant linear association between the TM mixture and increased odds of HUA, with the posterior inclusion probabilities (PIPs) of both Cs and Pb being 1.00. Moreover, we observed a positive interaction between Cs and Pb on HUA. The TM mixture is associated with increased odds of HUA in rural older adults, which may mainly be driven by Cs and Pb. Subsequent studies are warranted to confirm these findings and clarify the mechanisms linking multiple TMs with HUA.

Elucidation of the Biosynthesis of Griseoluteic Acid in Streptomyces griseoluteus P510.

Phenazines are aromatic compounds with antifungal and cytotoxic activities. Phenazines incorporating phenazine 1-carboxylic acid have widespread applications in agriculture, medicine, and industry. Griseoluteic acid is a cytotoxic compound secreted by Streptomyces griseoluteus P510, displaying potential medical applications. However, the biosynthetic pathway of griseoluteic acid has not been elucidated, limiting its development and application. In this study, a conserved phenazine biosynthetic gene cluster of S. griseoluteus P510 was identified through genomic analysis. Subsequently, its was confirmed that the four essential modification enzymes SgpH, SgpI, SgpK, and SgpL convert phenazine-1,6-dicarboxylic acid into griseoluteic acid by heterologous expression in Escherichia coli. Moreover, the biosynthetic pathway of griseoluteic acid was established in Pseudomonas chlororaphis characterized by a high growth rate and synthesis efficiency of phenazines, laying the foundation for the efficient production of griseoluteic acid.

Porosity and pore structure evolution during the weathering of black shale.

Pore type and pore structure evolves systematically across continuous black shale weathering profile. However, the extend and process of pore structure change is still an enigma. In this study, we try to unveil the pore structure evolution during weathering process through studying Cambrian Hetang shales in southern China. Fourteen shale samples, from protolith zone (PZ), fractured and weathered shale zone (FWZ), and saprolite zone (SZ), were collected to elucidate how porosity and pore structure develop during black shale weathering under subtropical condition. Through low pressure argon (Ar) gas adsorption (LP-ArGA), high pressure mercury intrusion (HPMI), nuclear magnetic resonance(NMR) and field emission scanning electron microscope (FESEM) observation, the results reveal significant differences in physical properties and pore structures among the PZ, FWZ, and SZ samples. Specifically, compared to PZ, FWZ and SZ samples are characterized by higher clay mineral content, lower organic matter (OM), and the absence of carbonates and pyrite. Total porosity, determined through HPMI and NMR, exhibits a gradual increase from PZ (6.70 % and 6.41 %) to FWZ (20.47 % and 13.45 %) and SZ (23.22 % and 12.48 %). Ar adsorption isotherms indicate a change in pore type from predominantly ink-bottle and slit-shaped in the PZ to mainly slit-shaped in FWZ and SZ. Integrated analysis of LP-ArGA, HPMI, NMR and SEM observation suggests a substantial decrease in the contribution of micropores to total pore volume (PV) and a concurrent increase in larger pores (meso-macropores) with the increase of weathering intensity. This results in smoother surfaces of micro-transition pores but rougher surfaces of macropores. Changes in mineralogy composition during weathering play a crucial role in influencing pore structure of shales and further accelerating the release and migration of toxic elements in black shale. Our study provides the essential theoretical foundation for the remediation of soil and water environmental pollution caused by black shale weathering.

Quantitative evaluation of vertical control in orthodontic camouflage treatment for skeletal class II with hyperdivergent facial type.

BACKGROUND: In this study, we sought to quantify the influence of vertical control assisted by a temporary anchorage device (TAD) on orthodontic treatment efficacy for skeletal class II patients with a hyperdivergent facial type and probe into the critical factors of profile improvement. METHODS: A total of 36 adult patients with skeletal class II and a hyperdivergent facial type were included in this retrospective case-control study. To exclude the effect of sagittal anchorage reinforcement, the patients were divided into two groups: a maxillary maximum anchorage (MMA) group (N = 17), in which TADs were only used to help with anterior tooth retraction, and the MMA with vertical control (MMA + VC) group (N = 19), for which TADs were also used to intrude the maxillary molars and incisors. The treatment outcome was evaluated using dental, skeletal, and soft-tissue-related parameters via a cephalometric analysis and cast superimposition. RESULTS: A significant decrease in ANB (P < 0.05 for both groups), the retraction and uprighting of the maxillary and mandibular incisors, and the retraction of protruded upper and lower lips were observed in both groups. Moreover, a significant intrusion of the maxillary molars was observed via the cephalometric analysis (- 1.56 ± 1.52 mm, P < 0.05) and cast superimposition (- 2.25 ± 1.03 mm, P < 0.05) of the MMA + VC group but not the MMA group, which resulted in a remarkable decrease in the mandibular plane angle (- 1.82 ± 1.38°, P < 0.05). The Z angle (15.25 ± 5.30°, P < 0.05) and Chin thickness (- 0.97 ± 0.45°, P < 0.05) also improved dramatically in the MMA + VC group, indicating a better profile and a relaxed mentalis. Multivariate regression showed that the improvement in the soft tissue was closely related to the counterclockwise rotation of the mandible plane (P < 0.05). CONCLUSIONS: TAD-assisted vertical control can achieve intrusion of approximately 2 mm for the upper first molars and induce mandibular counterclockwise rotation of approximately 1.8°. Moreover, it is especially important for patients without sufficient retraction of the upper incisors or a satisfactory chin shape.