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Abstract Background Malformation of cortical development (MCD) is a common cause of intractable epilepsy in children. In this study, the effectiveness of frontal lobe epilepsy (FLE) surgery in children with intractable epilepsy due to MCD was assessed and its prognostic factors were studied. Methods Seventy-six patients with intractable FLE who received epilepsy surgery between January 2016 and March 2018 in Peking University First Hospital were recruited in this study. All the resected brain tissues were demonstrated to be MCD. All patients were followed up for at least 3 years. The clinical data and prognosis were analyzed retrospectively. Univariate and multivariate analyses were performed to investigate the correlations between clinical variables and prognostic outcome (Engel classification). Results Sixty (78.9%) patients had Engel class I postoperative outcome. The mean age at surgery was 6.00 ± 4.24 years. Sixty-six patients (86.8%) had daily seizures, 40.2% of the patients had epileptic spasm, and 33% of the patients had extensive interictal EEG abnormalities, which, however, could not provide any helpful information for localizing epileptogenic zones. About 29% of the patients had normal MRI findings even by experienced radiologists, and 26% of the patients had epileptogenic lesion involving adjacent lobes. There was a significant correlation between acute postoperative seizure (APOS) and prognosis (P

Abstract Background Zuojin formula, a traditional Chinese medicine, comprises Coptis chinensis and Evodia rutaecarpa. In our previous study, the total alkaloid extract from Zuojin formula (TAZF) showed potent and improved efficacy. However, its safety and toxicokinetics remain unknown. The objective of this study was to evaluate the safety of repeated administrations of TAZF and investigate the internal exposure of the main components and its relationship with toxic symptoms. Methods Sprague–Dawley rats were orally administered TAZF at 0.4, 1.2 and 3.7 g/kg for 28 days, which was followed by a 14-day recovery period. The toxic effects were evaluated weekly by assessing body weight changes, food intake, blood biochemistry and haematological indices, organ weights and histological changes. A total of eight components were detected, including berberine, coptisine, epiberberine, palmatine, jatrorrhizine, columbamine, evodiamine, and rutaecarpine. The toxicokinetic profiles of the eight components were investigated after single and repeated administrations. Linear mixed effect models were applied to analyse the associations between internal exposure and toxic symptoms. Network pharmacology analysis was applied to explore the potential toxic mechanisms. Results Compared with the vehicle group, the rats in the low- and medium-dose groups did not show noticeable abnormal changes, while rats in the high-dose group exhibited inhibition of weight gain, a slight reduction in food consumption, abdominal bloating and atrophy of the splenic white pulp during drug administration. The concentration of berberine in plasma was the highest among all compounds. Epiberberine was found to be associated with the inhibition of weight gain. Network pharmacology analysis suggested that the alkaloids might cause abdominal bloating by affecting the proliferation of smooth muscle cells. The benchmark dose lower confidence limits (based on body weight inhibition) of TAZF were 1.27 g/kg (male) and 1.91 g/kg (female). Conclusions TAZF has no notable liver or kidney toxicity but carries risks of gastrointestinal and immune toxicity at high doses. Alkaloids from Coptis chinensis are the main plasma components related to the toxic effects of TAZF.

Abstract Background Melanoma is the most malignant skin tumor and is difficult to cure with the alternative treatments of chemotherapy, biotherapy, and immunotherapy. Our previous study showed that triptolide (TP) exhibited powerful tumoricidal activity against melanoma. However, the clinical potential of TP is plagued by its poor aqueous solubility, short half-life, and biotoxicity. Therefore, developing an ideal vehicle to efficiently load TP and achieving targeted delivery to melanoma is a prospective approach for making full use of its antitumor efficacy. Results We applied exosome (Exo) derived from human umbilical cord mesenchymal stromal cells (hUCMSCs) and engineered them exogenously with a cyclic peptide, arginine-glycine-aspartate (cRGD), to encapsulate TP to establish a bionic-targeted drug delivery system (cRGD-Exo/TP), achieving synergism and toxicity reduction. The average size of cRGD-Exo/TP was 157.34 ± 6.21 nm, with a high drug loading of 10.76 ± 1.21%. The in vitro antitumor results showed that the designed Exo delivery platform could be effectively taken up by targeted cells and performed significantly in antiproliferation, anti-invasion, and proapoptotic activities in A375 cells via the caspase cascade and mitochondrial pathways and cell cycle alteration. Furthermore, the biodistribution and pharmacokinetics results demonstrated that cRGD-Exo/TP possessed superior tumor targetability and prolonged the half-life of TP. Notably, cRGD-Exo/TP significantly inhibited tumor growth and extended survival time with negligible systemic toxicity in tumor-bearing mice. Conclusion The results indicated that the functionalized Exo platform provides a promising strategy for targeted therapy of malignant melanoma. Graphical Abstract

IntroductionClear cell renal cell carcinoma (ccRCC) is the most prevalent type of urological carcinoma. Although targeted therapy and immunotherapy are usually employed, they often result in primary and acquired resistance. There is currently a lack of dependable biomarkers that can accurately anticipate the prognosis of ccRCC. Recent research has indicated the critical role of neutrophil extracellular traps (NETs) in the development, metastasis, and immune evasion of cancer. The aim of this study was to explore the value of NETs in the development and prognosis of ccRCC.MethodsClinical features and genetic expression information of ccRCC patients were acquired from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and E-MTAB-1980 database. NETs-related gene set were obtained from previous studies. A NETs-related gene signature was constructed based on TCGA data and validated using ICGC and E-MTAB-1980 databases. Furthermore, the immune microenvironment and responsiveness to anticancer medications in ccRCC patients with varying levels of NETs risks were investigated.ResultsA total of 31 NET-related genes were differently expressed between normal kidney and ccRCC tissues. 17 out of 31 were significantly associated with overall survival. After LASSO Cox regression analysis, nine NETs-related genes were enrolled to construct the NETs prognosis signature, and all the ccRCC patients from TCGA were divided into low and high risk group. This signature demonstrated excellent performance in predicting the overall survival of TCGA patients as well as the validation ICGC and E-MTAB-1980 patients. Additionally, the NETs signature was significantly correlated with immune infiltration and drug sensitivity.ConclusionsThe NETs signature established by the current study has prognostic significance in ccRCC, and may serve as a useful biomarker for patient stratification and treatment decisions. Further validation and clinical studies are required to fully translate these findings into clinical practice.

IntroductionObsessive-compulsive symptoms is a common psychological phenomenon among early adulthood college students, which are closely related to their parents’ parenting styles. Theoretical and some empirical studies have suggested the mediating role of perfectionism in this process, but this has not been confirmed, and the binary perspective of positive-negative perfectionism has not been addressed in this issue.MethodsThis study aimed to investigate the mediating role of perfectionism in the relationship between parenting styles and obsessive-compulsive symptoms among college students. A total of 661 college students participated in this study.ResultsNegative perfectionism mediated the relationship between negative parenting style and obsessive-compulsive symptoms among college students. Negative parenting style predicted obsessive-compulsive symptoms through its positive predictive effect on negative perfectionism. However, the mediating effect of positive perfectionism was not significant in this process.DiscussionThis study provides further evidence of the mechanisms underlying the occurrence of obsessive-compulsive symptoms, and offers new ideas for interventions for OCD.

Summary: Probiotics play essential roles in immune modulation. Combining probiotics with cancer vaccines potentially can achieve a synergistic effect. To maximize the efficacy of probiotics, proper probiotics formulation is necessary. Herein, Lactobacillus rhamnosus and Bifidobacterium longum are coated with lipid membrane to achieve the goal of losing less activity and bettering colonization in colon. In the subcutaneous transplanted colon cancer mouse model, probiotics formulation showed potent preventive and therapeutic efficacy, and the efficacy could be further improved by combining with cancer nanovaccines. Probiotics formulation can perform as immune adjuvants to enhance the innate immune response or as in-situ cancer vaccines. In the study of preventing chemical-induced orthotopic colon cancer model, probiotics formulation alone efficiently reduced tumor number in colon and the efficacy is improved by combining with cancer nanovaccines. All in all, the studies demonstrated that probiotics formulation can assist to maximize the efficacy of cancer nanovaccines.

Introduction: The middle and lower reaches of the Yangtze River basin (hereafter MLYRB) are one of the most important wintering grounds for waterbirds along the East Asian-Australasian Flyway (EAAF). Climate change and human activities have greatly altered the habitats of waterbirds in this region.Methods: The potential distribution of suitable habitats for the Siberian crane (Grus leucogeranus) in the MLYRB was projected using Maximum Entropy Models (MaxEnt) and three Global Climate Models (GCMs). Additionally, estimations for temperature and precipitation before 2060 were made using CMIP6 multi-model and multi-scenario data.Results: 1) the MaxEnt model was highly applicable (AUC = 0.939) for analyzing the suitable habitat distribution and climatic suitability of Siberian cranes in the study area; 2) Precipitation of the driest quarter and altitude were the main factors affecting the potential suitable habitat distribution of Siberian cranes, accounting for 40% of the total contribution rate each; 3) The climatically suitable areas for the distribution of suitable habitats of Siberian cranes in the study area was mainly concentrated in parts of Poyang Lake, Dongting Lake, Taihu Lake, and the mainstream of the Yangtze River; 4) In the BCC-CSM2-MR, CanESM5, and CNRM-CM6-1 models, the suitable habitat area for Siberian cranes is expected to decrease under different SSP scenarios from 2021 to 2060 compared to 1970–2000.Discussion: The BCC-CSM2-MR model’s SSP2-4.5 scenario shows the most significant decline in the suitable habitat area for Siberian cranes, with a maximum decrease of approximately 35.7%, followed by a maximum decrease of about 26.2% and 16.4% under the CNRM-CM6-1 and CanESM5 models’ SSP2-4.5 scenario, respectively. In general, the suitable habitat areas for Siberian cranes are projected to decline, indicating the need for comprehensive evaluation and uncertainty research using more models.

IntroductionIn the world, the incidence of breast cancer has surpassed that of lung cancer, and it has become the first malignant tumor among women. Triple-negative breast cancer (TNBC) shows an extremely heterogeneous malignancy toward high recurrence, metastasis, and mortality, but there is a lack of effective targeted therapy. It is urgent to develop novel molecular targets in the occurrence and therapeutics for TNBC, and novel therapeutic strategies to block the recurrence and metastasis of TNBC.MethodsIn this study, CTSL (cathepsin L) expression in tissues and adjacent tissues of TNBC patients was monitored by immunohistochemistry and western blots. The correlations between CTSL expressions and clinicopathological characteristics in the patient tissues for TNBC were analyzed. Cell proliferation, migration, and invasion assay were also performed when over-expressed or knocked-down CTSL.ResultsWe found that the level of CTSL in TNBC is significantly higher than that in the matched adjacent tissues, and associated with differentiated degree, TNM Stage, tumor size, and lymph node metastatic status in TNBC patients. The high level of CTSL was correlated with a short RFS (p

Because of its excellent stress resistance and forage quality, the forage bermudagrass hybrid population had attracted the attention of scientific researchers in recent years. Studying its diversity could promote the breeding of desirable varieties. The variability in agronomic traits including fresh weight, dry weight, ash content, crude protein content, crude fat, phosphorus content, and relative feed value for 56 bermudagrass was investigated using Wrangler as an experimental reference. Grey correlation analysis and cluster analysis were employed to screen bermudagrass with high yield and superior quality. WCF-34 had the highest 2-year fresh weight (109,773.3 kg/ha), WCF-37 had the highest 2-year dry weight (31,951.6 kg/ha), WCF-24 had the lowest Ash content (7.46%), WCF-26 had the highest crude protein content (16.27%), WCF-27 had the highest curde fat content (3.58%), WCF-13 had the highest P content (0.45%), and WCF-42 had the highest relative feed value (95.32). Combining the results of grey relational analysis and cluster analysis, WCF-42, WCF-34, WCF-38, WCF-37, and WCF-40 were selected as high-quality bermudagrass. Through comprehensive analysis of the agronomic characters of bermudagrass, five bermudagrass were selected, the outcomes of this study would provide a theoretical basis for the breeding and genetic enhancement of bermudagrass.

Aims and backgroundHepatic hydrothorax, which presents as an unexplained pleural effusion, is one of the important complications in patients with end-stage cirrhosis. It has a significant correlation with prognosis and mortality. The aim of this clinical study was to detect the risk factors for hepatic hydrothorax in patients with cirrhosis and to better understand potentially life-threatening complications.MethodsRetrospectively, 978 cirrhotic patients who were hospitalized at the Shandong Public Health Clinical Center from 2013 to 2021 were involved in this study. They were divided into the observation group and the control group based on the presence of hepatic hydrothorax. The epidemiological, clinical, laboratory, and radiological characteristics of the patients were collected and analyzed. ROC curves were used to evaluate the forecasting ability of the candidate model. Furthermore, 487 cases in the experimental group were divided into left, right, and bilateral groups, and the data were analyzed.ResultsThe patients in the observation group had a higher proportion of upper gastrointestinal bleeding (UGIB), a history of spleen surgery, and a higher model for end-stage liver disease (MELD) scores compared with the control group. The width of the portal vein (PVW) (P = 0.022), prothrombin activity (PTA) (P = 0.012), D-dimer (P = 0.010), immunoglobulin G (IgG) (P = 0.007), high-density lipoprotein cholesterol (HDL) (P = 0.022), and the MELD score were significantly associated with the occurrence of the hepatic hydrothorax. The AUC of the candidate model was 0.805 (P < 0.001, 95% CI = 0.758–0.851). Portal vein thrombosis was more common in bilateral pleural effusion compared with the left and right sides (P = 0.018).ConclusionThe occurrence of hepatic hydrothorax has a close relationship with lower HDL, PTA, and higher PVW, D-dimer, IgG, and MELD scores. Portal vein thrombosis is more common in cirrhotic patients with bilateral pleural effusion compared to those with unilateral pleural effusion.

The decreased antioxidant capacity in the retinal pigment epithelium (RPE) is the hallmark of retinal degenerative diseases including age-related macular degeneration (AMD). Nevertheless, the exact regulatory mechanisms underlying the pathogenesis of retinal degenerations remain largely unknown. Here we show in mice that deficiencies in Dapl1, a susceptibility gene for human AMD, impair the antioxidant capacity of the RPE and lead to age-related retinal degeneration in the 18-month-old mice homozygous for a partial deletion of Dapl1. Dapl1-deficiency is associated with a reduction of the RPE's antioxidant capacity, and experimental re-expression of Dapl1 reverses this reduction and protects the retina from oxidative damage. Mechanistically, DAPL1 directly binds the transcription factor E2F4 and inhibits the expression of MYC, leading to upregulation of the transcription factor MITF and its targets NRF2 and PGC1α, both of which regulate the RPE's antioxidant function. When MITF is experimentally overexpressed in the RPE of DAPL1 deficient mice, antioxidation is restored and retinas are protected from degeneration. These findings suggest that the DAPL1-MITF axis functions as a novel regulator of the antioxidant defense system of the RPE and may play a critical role in the pathogenesis of age-related retinal degenerative diseases.

Abstract The development of vision bionic systems is indispensable for the perception, memory, and processing of optical signals, which promotes the exploration of efficient visual perception systems. In this work, a simple and novel two‐terminal optoelectronic memristor based on the CuAlAgCr/TiO2/W (CTW) structure is prepared, where the CuAlAgCr high‐entropy alloys are employed as the top electrode for the first time. Before annealing, the CTW optoelectronic memristor exhibited fascinating performance, including uniformly distributed operating voltage, reliable data retention, and a higher switching ratio. Moreover, the optoelectronic memristor can be reversibly switched between volatile and nonvolatile memories by adjusting compliance currents. The CTW optoelectronic memristor annealed in air exhibits various artificial synaptic functions, such as short‐term memory, optical learning, and forgetting behavior under the illumination of the laser. The photo‐response current is increased from nano‐ampere to micro‐ampere level. Furthermore, a logic function unit based on CTW optoelectronic memristor is proposed, which realizes “AND” operation. Furthermore, first‐principles calculations of the CTW structure are performed to describe the influence of photocarriers on the barrier height at the CuAlAgCr‐TiO2 interface, revealing the working mechanism of the CTW optoelectronic memristor. This work has greatly facilitated the development of optically operated artificial synaptic devices and vision bionic systems.

IntroductionUrine metabolomics has been a promising technique in the liquid biopsy of urothelial cancer (UC). The comparison of upper tract urothelial cancer (UTUC), lower tract urothelial cancer (BCa), and healthy controls (HCs) need to be performed to find related biomarkers. MethodsIn our investigation, urine samples from 35 UTUCs, 44 BCas, and 53 gender- and age-matched HCs were analyzed using liquid chromatography-high resolution mass spectrometry (LC-HRMS). In different groups, the differential metabolites and the disturbed metabolism pathways were explored. Transcriptomics and urine metabolomics are combined to identify the probably disturbed gene in BCa. ResultsWith an area under the curve (AUC) of 0.815, the panel consisting of prostaglandin I2, 5-methyldeoxycytidine, 2,6-dimethylheptanoyl carnitine, and deoxyinosine was able to discriminate UC from HCs. With an AUC of 0.845, the validation group also demonstrated strong predictive ability. UTUC and BCa without hematuria could be distinguished using the panel of 5'-methylthioadenosine, L-beta-aspartyl-L-serine, dehydroepiandrosterone sulfate, and N'-formylkynurenine (AUC=0.858). The metabolite panel comprising aspartyl-methionine, 7-methylinosine, and alpha-CEHC glucuronide could discriminate UTUC from BCa with hematuria with an AUC of 0.83. Fatty acid biosynthesis, purine metabolism, tryptophan metabolism, pentose and glucuronate interconversions, and arachidonic acid metabolism were dysregulated when comparing UC with HCs. PTGIS and BCHE, the genes related to the metabolism of prostaglandin I2 and myristic acid respectively, were significantly associated with the survival of BCa. DiscussionNot only could LC-HRMS urine metabolomic investigations distinguish UC from HCs, but they could also identify UTUC from BCa. Additionally, urine metabolomics combined with transcriptomics can find out the potential aberrant genes in the metabolism.

MYB98 is a key regulator of the genetic network behind pollen tube attraction toward the female gametophyte. MYB98 is specifically expressed in the synergid cells (SCs), a female gametophyte component cells specialized for pollen tube attraction. However, it had not been clear how exactly MYB98 achieves this specific expression pattern. In the current study, we have determined that a normal SC-specific expression of MYB98 is dependent on a 16-bp-long cis-regulatory element, CATTTACACATTAAAA, freshly named as the “Synergid-specificActivationElement ofMYB98” (SaeM). An 84 bp fragment harboring SaeM in the middle was sufficient to drive exclusively SC-specific expression. The element was present in a significantly large proportion of SC-specific gene promoters and in the promoter of MYB98 homologous genes in the Brassicaceae (pMYB98s). Significance of such family-wide SaeM-like element conservation in exclusive SC-specific expression was confirmed by the Arabidopsis-like activation feature of Brassica oleracea–derived pMYB98 and absence of such feature of pMYB98 derived from a non-Brassicaceae member Prunus persica. Additionally, the yeast-one-hybrid assay showed that the SaeM can be recognized by ANTHOCYANINLESS2 (ANL2) and DAP-seq data further suggested for additional three ANL2 homologs targeting the similar cis-element. Overall, our study has concluded that SaeM plays a crucial role in driving exclusively SC-specific expression of MYB98 and strongly suggests for the involvement of ANL2 and its homologs in its dynamic regulation in planta. Future study on the transcription factors is expected to shed more light on the mechanism behind the process.

Accurate simulation of the battery thermoelectric coupling characteristics is the key to the thermal design and thermal management. As the electrically connected component between the battery electrodes, the heat production and heat transfer of the busbars have a significant impact on the battery thermoelectric behavior. A small number of battery thermal management studies have begun to model busbars recently, but the thickness, length, and material of the busbars are diverse. There is a lack of perfect simulation analysis and optimization methods. There is an urgent need to conduct in-depth research on the influence of characteristic parameters of the busbars on the battery thermoelectric behavior. Based on the MSMD-NTGK model, this paper investigates the influence of the thickness, length, and material of the busbars on the battery thermoelectric behavior without considering the economic cost and differences in the battery structure design. In this paper, a simulation analysis method and an ideal improvement solution for the design of the busbars are proposed. This paper compares the changes in the battery thermal behavior before and after the improvement of the busbars under the constant-rate discharge process, FTP75 condition, NEDC condition and WLTC condition respectively. This study can improve the realism of the battery thermal behavior simulation, provide a reliable simulation analysis method and reference basis for the industrial design and optimization of the busbars, and further improve the reliability of the subsequent battery thermal management simulation.

O/W emulsions stabilized by polyphenol/amylose (AM) complexes with several polyphenol/AM mass ratios and different polyphenols (gallic acid (GA), epigallocatechin gallate (EGCG) and tannic acid (TA)) were prepared by a high-intensity ultrasound emulsification technique. The effect of the pyrogallol group number of polyphenols and the mass ratio of polyphenols/AM on polyphenol/AM complexes and emulsions was studied. The soluble and/or insoluble complexes gradually formed upon adding polyphenols into the AM system. However, insoluble complexes were not formed in the GA/AM systems because GA has only one pyrogallol group. In addition, the hydrophobicity of AM could also be improved by forming polyphenol/AM complexes. The emulsion size decreased with increasing pyrogallol group number on the polyphenol molecules at a fixed ratio, and the size could also be controlled by the polyphenol/AM ratio. Moreover, all emulsions presented various degrees of creaming, which was restrained by decreasing emulsion size or the formation of a thick complex network. The complex network was enhanced by increasing the ratio or pyrogallol group number on the polyphenol molecules, which was because the increasing number of complexes was adsorbed onto the interface. Altogether, compared to GA/AM and EGCG/AM, the TA/AM complex emulsifier had the best hydrophobicity and emulsifying properties, and the TA/AM emulsion had the best emulsion stability.

Since the last IAEA-FEC in 2021, significant progress on the development of long pulse steady state scenario and its related key physics and technologies have been achieved, including the reproducible 403 s long-pulse steady-state H-mode plasma with pure radio frequency (RF) power heating. A thousand-second time scale (∼1056 s) fully non-inductive plasma with high injected energy up to 1.73 GJ has also been achieved. The EAST operational regime of high β _P has been significantly extended ( H _98y2 > 1.3, β _P ∼ 4.0, β _N ∼ 2.4 and n _e / n _GW ∼ 1.0) using RF and neutral beam injection (NBI). The full edge localized mode suppression using the n = 4 resonant magnetic perturbations has been achieved in ITER-like standard type-I ELMy H-mode plasmas with q _95 ≈ 3.1 on EAST, extrapolating favorably to the ITER baseline scenario. The sustained large ELM control and stable partial detachment have been achieved with Ne seeding. The underlying physics of plasma-beta effect for error field penetration, where toroidal effect dominates, is disclosed by comparing the results in cylindrical theory and MARS-Q simulation in EAST. Breakdown and plasma initiation at low toroidal electric fields (

The gut microbiome’s imbalance has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), yet the contribution of the gut mycobiome remains largely unclear. This study delineates the gut mycobiome profile in PAH and examines its interplay with the bacterial microbiome alterations. Fecal samples from monocrotaline-induced PAH rats and matched controls were subjected to internal transcribed spacer 1 (ITS1) sequencing for fungal community assessment and 16S ribosomal RNA (rRNA) gene sequencing for bacterial community characterization. Comparative analysis revealed no significant disparities in the overall mycobiome diversity between the PAH and control groups. However, taxonomic profiling identified differential mycobiome compositions, with the PAH group exhibiting a significant enrichment of genera such as Wallemia, unidentified_Branch02, Postia, Malassezia, Epicoccum, Cercospora, and Alternaria. Conversely, genera Xeromyces, unidentified_Plectosphaerellaceae, and Monilia were more abundant in the controls. Correlations of Malassezia and Wallemia abundance with hemodynamic parameters were observed. Indications of bidirectional fungal–bacterial community interactions were also noted. This investigation reveals distinct gut mycobiome alterations in PAH, which are intricately associated with concurrent bacterial microbiome changes, suggesting a possible contributory role of gut fungi in PAH pathophysiology. These findings underscore the potential for novel gut mycobiome-targeted therapeutic interventions in PAH management.

Breakdown characteristics play an important role in silicon carbide (SiC) power devices; however, the wide bandgap of SiC poses a challenge for numerical simulation of breakdown characteristics. In this work, a self-developed simulator employing a novel numerical processing method to prevent convergence issues, based on semi-classical transport models and including several kinds of mobility, generation and recombination models, is used to investigate the performance and breakdown characteristics of 4H-SiC MOSFETs in high-power applications. Good agreement between our simulator and an experiment and commercial TCAD was achieved. The simulator has good stability and convergence and can be used as a powerful tool to design and optimize semiconductor devices. Further, the breakdown characteristics are evaluated with different factors, including lattice temperature, device structure and doping profiles. Our results show that the doping profile plays the most important role in the breakdown voltage, followed by the device structure, while the impact of lattice temperature is found to be minimal.

A high-yield 3-methylthiopropanol (3-Met) yeast Y1402 was obtained from sesame-flavored Daqu, and it was identified as Saccharomycopsis fibuligera. S. fibuligera Y1402 showed a broad range of growth temperatures and pH, as well as the maximum tolerance to glucose, NaCl, nicotine, and 3-Met at 50% (w/w), 15% (w/v), 1.2 g/L, and 18 g/L, respectively. After optimization using single-factor experiments, a Plackett–Burman design, a steepest ascent test, and a Box–Behnken design, the 3-Met yield reached 4.03 g/L by S. fibuligera Y1402 under the following optimal conditions: glucose concentration of 40 g/L, yeast extract concentration of 0.63 g/L, Tween 80 concentration of 2 g/L, L-methionine concentration of 5 g/L, liquid volume of 25 mL/250 mL, initial pH of 5.3, fermentation temperature of 32 °C, inoculum size of 0.8%, shaking speed of 210 rpm, and fermentation time of 54 h. The fermentation was scaled up to a 3 L fermenter under the optimized conditions, and the yield of 3-Met reached 0.71 g/L. Additionally, an aroma analysis revealed that the flavor substances produced by S. fibuligera Y1402 in sorghum hydrolysate medium was mainly composed of compounds with floral, sweet, creamy, roasted nut, and clove-like aromas. Therefore, S. fibuligera has great potential for application in the brewing of Baijiu and other fermented foods.

Root knot nematodes cause serious damage to global agricultural production annually. Given that traditional chemical fumigant nematicides are harmful to non-target organisms and the environment, the development of biocontrol strategies has attracted significant attention in recent years. In this study, it was found that the Bacillus thuringiensis Berliner strain NBIN-863 exhibits strong fumigant nematicidal activity and has a high attraction effect on Meloidogyne incognita (Kofoid and White) Chitwood. Four volatile organic compounds (VOCs) produced by NBIN-863 were identified using solid-phase microextraction and gas chromatography–mass spectrometry. The nematicidal activity of four VOCs, namely, N-methylformamide, propenamide, 3-(methylthio)propionic acid, and phenylmalonic acid, was detected. Among these compounds, 3-(methylthio)propionic acid exhibited the highest direct contact nematicidal activity against M. incognita, with an LC50 value of 6.27 μg/mL at 24 h. In the fumigant bioassay, the mortality rate of M. incognita treated with 1 mg/mL of 3-(methylthio)propionic acid for 24 h increased to 69.93%. Furthermore, 3-(methylthio)propionic acid also exhibited an inhibitory effect on the egg-hatching of M. incognita. Using chemotaxis assays, it was determined that 3-(methylthio)propionic acid was highly attractive to M. incognita. In pot experiments, the application of 3-(methylthio)propionic acid resulted in a reduction in gall numbers, decreasing the number of galls per gram of tomato root from 97.58 to 6.97. Additionally, the root length and plant height of the treated plants showed significant increases in comparison with the control group. The current study suggests that 3-(methylthio)propionic acid is a novel nematicidal virulence factor of B. thuringiensis. Our research provides evidence for the potential use of NBIN-863 or its VOCs in biocontrol against root knot nematodes.

Soy molasses is rich in oligosaccharides like sucrose, stachyose, and raffinose, with stachyose and raffinose being functional oligosaccharides. Harnessing soy molasses for the production of functional soy oligosaccharides (FSO) can significantly elevate its value. Biological purification, a method leveraging the selective utilization of different carbon sources by microorganisms, allows for the specific removal of sucrose from soy molasses while preserving stachyose and raffinose, thereby increasing the FSO content. This research identified a yeast named YT312 with strong purification capabilities for soy molasses and optimized the purification conditions. The study revealed that yeast YT312 was Wickerhamomyces anomalus, exhibiting a broad range of growth temperatures and pH levels alongside a high tolerance to glucose, sucrose, and NaCl. Through single-factor and orthogonal experiments, it was established that under specific conditions—0.375% inoculum size, 30 °C fermentation temperature, 150 rpm shaking speed, 10-fold dilution ratio, pH of 7, and 12 h of fermentation—sucrose was completely removed from soy molasses, while functional raffinose and stachyose were retained at rates of 96.1% and 90.2%, respectively. Consequently, W. anomalus YT312 displayed exceptional characteristics for the biological purification of soy molasses and the production of FSO.

The objective of this study was to examine the impacts of the combing of Agrocybe aegerita polysaccharides (AAPS) with Bifidobacterium lactis Bb-12 (Bb-12) on antioxidant activity, anti-aging properties, and modulation of gut microbiota. The results demonstrated that the AAPS and Bb-12 complex significantly increased the average lifespan of male and female Drosophila melanogaster under natural aging conditions (p < 0.05), with an improvement of 8.42% and 9.79%, respectively. Additionally, the complex enhanced their climbing ability and increased antioxidant enzyme activity, protecting them from oxidative damage induced by H2O2. In D-galactose induced aging mice, the addition of AAPS and Bb-12 resulted in significantly increase in antioxidant enzyme activity, regulation of aging-related biomarker levels, changed gut microbiota diversity, restoration of microbial structure, and increased abundance of beneficial bacteria, particularly lactobacilli, in the intestines. These findings suggested that the complex of AAPS and Bb-12 had the potential to serve as a dietary supplement against organism aging and oxidative stress.

Based on the unit life and death technology, the dynamic evolution process of soil loss is considered, and a pipe-soil nonlinear coupling model of buried pipelines passing through the collapse area is constructed. The analysis shows that after the third layer of soil is lost, the existence of the “pipe-soil separation” phenomenon can be confirmed, which then supplements the assumption that “pipe-soil is always in contact” in the elastic foundation beam theory. Calculation of settlement deformation of buried pipelines It needs to be divided into two stages: cooperative deformation and non-cooperative deformation. Taking the settlement prediction of buried pipelines as the goal, the particle swarm algorithm (PSO) was used to optimize the number of neurons, Dropout, and Batch-size in the long short-term memory network (LSTM) structure. The optimization results were 60, 0.001, and 100, respectively. The PSO-LSTM model proposed in this article can accurately describe the dynamic evolution process of buried pipelines and has better prediction accuracy than the modified Gaussian curve method and LSTM neural network model. The use of this model can provide a reference for safety risk management, disaster early warning, and intelligent monitoring when buried pipelines suffer from soil collapse disasters.

Dietary risk has always been a major risk factor for colorectal cancer (CRC). However, the contribution of dietary risk factors to CRC at the level of region, gender, and age has not been fully characterized. Based on the Global Burden of Disease (GBD) 2019 study, the death rates, age-standardized mortality rates (ASDRs), and estimated annual percentage changes (EAPCs) were calculated to assess the trends of CRC attributable to dietary risk factors over the past 30 years. Globally, the death cases of CRC increased to 1,085,797 in 2019, and the number of deaths attributed to dietary risk factors increased to 365,752 in 2019, representing approximately one-third of all CRC-related fatalities. Overall, the ASDR attributable to dietary risks was 4.61 per 100,000 in 2019, with a slight downward trend (EAPC = −0.29). Notably, there is a rising trend in early-onset colorectal cancer mortality associated with dietary factors. To alleviate CRC burdens, it is recommended to elevate the intake of whole grains, milk, calcium, and fiber while reducing consumption of red and processed meats. The results will improve the understanding, and provide guidance on the diet of CRC in different regions, gender, and age groups worldwide.

The structural stability of silt foundations, particularly sensitive to moisture content, can be severely compromised by recurring wetting and drying processes. This not only threatens the foundational integrity but also raises grave concerns about the long-term safety of major civil engineering endeavors. Addressing this critical issue, our study delves into the transformative effects of reclaimed polyester fiber on subgrade silt exposed to such environmental stressors. Through rigorous wet–dry cycle tests on this enhanced soil, we evaluate shifts in shear strength across varying confining pressures. We also dissect the interplay between average pore diameter, particle distribution, and morphology in influencing the soil’s microstructural responses to these cycles. A detailed analysis traces the structural damage timeline in the treated soil, elucidating the intertwined micro–macro dynamics driving strength reduction. Key discoveries indicate a notably non-linear trajectory of shear strength degradation, marked by distinct phases of rapid, subdued, and stabilized strength attrition. Alterations within the micropores induce a rise in both their count and size, ultimately diminishing the total volume proportion of the reinforced soil. Intriguingly, particle distribution is directly tied to the wet–dry cycle frequency, while the fractal dimension of soil particles consistently wanes. This research identifies cement hydrolysis and pore expansion as the dominant culprits behind the observed macroscopic strength degradation due to incessant wet–dry cycles. These revelations hold profound implications for risk management and infrastructural strategizing in areas dominated by silt foundations.

Flexible and effective methods for oil–water separation are crucial for reducing pollutant emissions and safeguarding water and fuel resources. In recent years, there has been growing interest in fundamental research and engineering applications related to water and fuel purification, especially oil–water separation. To date, filter materials with special wetting characteristics have been widely used in oil–water separation. Nanostructured materials are one of the most attractive candidates for next-generation oil–water separation. This review systematically summarizes the mechanisms and current status of oil–water separation using nanostructured materials. Basically, this can be achieved by using nanostructured materials with specific wettability and nanostructures. Here, we provide a detailed discussion of two general approaches and their filtration mechanisms: (1) the selective filtration technique, based on specific surface wettability, which allows only oil or water to penetrate while blocking impurities; (2) the absorption technique, employing porous sponges, fibers, or aerogels, which selectively absorbs impure oil or water droplets. Furthermore, the main failure modes are discussed in this review. The purposes of this article are: (1) to summarize the methods of oil–water separation by nanotechnology; (2) to raise the level of environmental protection consciousness of water pollution by using nanotechnology; (3) to tease out the features of different approaches and provide a pivotal theoretical basis to optimize the performance of filtering materials. Several approaches for oil and water separation are compared. Furthermore, the principle and application scope of each method are introduced.

A simple water soaking treatment significantly weakened the strong covalent metal-support interaction between the atomically dispersed Pt and CoFe2O4, which leads to an enhanced activity towards methane combustions by 55 times. This work highlights the critical role of altering the coordination structure of single-atom active sites and provides a new strategy to modulate metal-support interaction regulation.

Adenosine is a metabolite produced abundantly in the tumor microenvironment, dampening immune response in inflamed tissues via adenosine A2A receptor (A2AR) which is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Therefore, blocking adenosine signaling pathway is of potential to promote anti-tumor immunity. This review briefly introduces adenosine signaling pathway, describes its role in regulating tumor immunity and highlights A2AR blockade in cancer therapy. Prospective anti-tumor activity of adenosine/A2AR inhibition has been revealed by preclinical data, and a number of clinical trials of A2AR antagonists are under way. Primary results from clinical trials suggest that A2AR antagonists are well tolerated in cancer patients and are effective both as monotherapy and in combination with other therapies. In the future, finding predictive biomarkers are critical to identify patients most likely to benefit from adenosine pathway blockade, and further researches are needed to rationally combine A2AR antagonists with other anti-tumor therapies.

Abstract Nicotinamide adenine dinucleotide (NAD) is the core of cellular energy metabolism. NAMPT, Sirtuins, PARP, CD38, and other molecules in this classic metabolic pathway affect many key cellular functions and are closely related to the occurrence and development of many diseases. In recent years, several studies have found that these molecules can regulate cell energy metabolism, promote the release of related cytokines, induce the expression of neoantigens, change the tumor immune microenvironment (TIME), and then play an anticancer role. Drugs targeting these molecules are under development or approved for clinical use. Although there are some side effects and drug resistance, the discovery of novel drugs, the development of combination therapies, and the application of new technologies provide solutions to these challenges and improve efficacy. This review presents the mechanisms of action of NAD pathway-related molecules in tumor immunity, advances in drug research, combination therapies, and some new technology-related therapies.

Abstract Inorganic nitrate production is critical in atmospheric chemistry that reflects the oxidation capacity and the acidity of the atmosphere. Here we use the oxygen anomaly of nitrate (Δ17O( $$\rm{NO}_{3}^{-}$$ NO 3 − )) in high-time-resolved (3 h) aerosols to explore the chemical mechanisms of nitrate evolution in fine particles during the winter in Nanjing, a megacity of China. The continuous Δ17O( $$\rm{NO}_{3}^{-}$$ NO 3 − ) observation suggested the dominance of nocturnal chemistry (NO3 + HC/H2O and N2O5 + H2O/Cl−) in nitrate formation in the wintertime. Significant diurnal variations of nitrate formation pathways were found. The contribution of nocturnal chemistry increased at night and peaked (72%) at midnight. Particularly, nocturnal pathways became more important for the formation of nitrate in the process of air pollution aggravation. In contrast, the contribution of daytime chemistry (NO2 + OH/H2O) increased with the sunrise and showed a highest fraction (48%) around noon. The hydrolysis of N2O5 on particle surfaces played an important role in the daytime nitrate production on haze days. In addition, the reaction of NO2 with OH radicals was found to dominate the nitrate production after nitrate chemistry was reset by the precipitation events. These results suggest the importance of high-time-resolved observations of Δ17O( $$\rm{NO}_{3}^{-}$$ NO 3 − ) for exploring dynamic variations in reactive nitrogen chemistry.

Abstract Background Coronary heart disease (CHD) is one of the most common causes of morbidity and mortality in type 2 diabetes mellitus (T2DM). Oxidative stress is one of the important contributors to the pathogenesis of CHD. Sestrin2 is a stress-induced antioxidant protein that plays a important role in T2DM and CHD. However, the relationship between serum Sestrin2 levels and T2DM with CHD remains unclear. Aim This study aimed to investigate the relationship between serum Sestrin2 levels and CHD in patients with type 2 diabetes. Methods A total of 70 T2DM patients with CHD and 69 T2DM patients were enrolled in this study. Clinical features and metabolic indices were identified. Serum Sestrin2 was measured by ELISA. Results Serum Sestrin2 levels in T2DM-CHD groups were significantly lower compared with the T2DM group (11.17 (9.79, 13.14) ng/mL vs 9.46 (8.34, 10.91) ng/mL). Bivariate correlation analysis revealed that serum Sestrin2 levels were negatively correlated with age (r = − 0.256, P = 0.002), BMI (r = − 0.206, P = 0.015), FBG (r = − 0.261, P = 0.002) and Tyg index (r = − 0.207, P

Angarotipula is a small genus of Tipulidae with only fourteen described species in the world and seven known species in China.Here, one new species is added to the fauna of Sichuan. The life history of Angarotipula laetipennis (Alexander, 1935) is presented and the morphologies of all stages are described.

Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored. Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) target genes, including fibroblast growth factor (FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2E1 and to serve as PPARα agonists, thus explaining how CYP2E1 deficiency causes hepatic PPARα activation through increasing cellular levels of endogenous PPARα agonists. Translationally, a CYP2E1 inhibitor was found to activate the PPARα–FGF21–beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Ppara-null mice. The present results establish a metabolic crosstalk between PPARα and CYP2E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism.

More sensitive and specific non-invasive biomarkers are desired for early detection of cancer. Here, the authors show a protein signature in the urine that increases sensitivity for colorectal cancer detection when combined with fecal immunochemical tests and corrects diagnosis in some fecal immunochemical tests-negative patients.

Abstract 2D ferroelectrics provide great promise for future electronics owing to their unique properties at 2D limit. Although simple perovskite oxides (such as BaTiO3 and PbTiO3) are an important target for 2D ferroelectrics, controlled synthesis of 2D nanosheets still remains a challenge. Here, this issue is addressed by using a new chemical protocol; unilamellar Ti0.87O2 nanosheets can serve as templates, guiding the solvothermal synthesis of 2D BaTiO3 nanosheets with a molecularly thin thickness (< 3 nm). Raman spectroscopy, second‐harmonic generation, and transmission electron microscopy characterizations suggest the formation of tetragonal ferroelectric BaTiO3 nanosheets. Based on piezoresponse force microscopy, BaTiO3 nanosheets exhibit a clear ferroelectric response with a high Curie temperature (≈100 °C) even down to 1.8 nm thickness. This study provides new opportunities to investigate perovskite ferroelectrics with the critical thickness.

It is daunting to determine the etiology of rapidly progressive dementia (RPD), which includes metabolic, neoplastic, infectious, autoimmune, neurodegenerative and other conditions. Herein, we illustrate an unusual case of a patient primarily exhibiting RPD, overlapping sleep dysfunction, psychosis and abnormal movement, which was finally defined as anti-IgLON5 disease, a novel and rare autoimmune encephalopathy. Furthermore, we longitudinally described his cognitive and psychological performance in detail, and determined that early initiation of immunotherapy in this patient did not result in a good outcome. These data highlight anti-IgLON5 disease as a possible differential diagnosis in patients with RPD.

Summary: Neoadjuvant therapy (NAT) is currently recommended to patients with human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) that typically exhibit a poor prognosis. The tumor immune microenvironment profoundly affects the efficacy of NAT. However, the correlation between tumor-infiltrating lymphocytes or their specific subpopulations and the response to NAT in HER2+ BC remains largely unknown. In our study, the immune infiltration status of 295 patients was classified as “immune-rich” or “immune-poor” phenotypes. The “immune-rich” phenotype was significantly positively related to pathological complete response (pCR). Ten genes were correlated with both pCR and the immune phenotype based on the results of spline and logistic regression. We constructed a generalized non-linear model combining linear and non-linear gene effects and successfully validated its predictive power using an internal and external validation set (AUC = 0.819, 0.797; respectively) and a clinical set (accuracy = 0.75).

Ampelopsis Michx. (Vitaceae) contains more than 30 species and is discontinuously distributed in Eurasia, North America, and Central America. China hosts an abundance of Ampelopsis species. Until now, fossil records of Ampelopsis have been reported only from the Paleocene to the Pleistocene of Europe, the Eocene to the Pliocene of Asia, and the Eocene to the Miocene of North America. Although Ampelopsis is abundant and widespread in China today, no fossils of Ampelopsis have so far been found there, except for fossil seed from the Upper Miocene of Yunnan. In this study, a fossil seed of Ampelopsis japonica (Thunb.) Makino was recovered from the Upper Pleistocene of the Maoming Basin, Guangdong province. It is the first Ampelopsis fossil found in South China. This finding shows that Ampelopsis was distributed in the low latitudes of South China in the Late Pleistocene. Global cooling during the last glaciation might have led to the southward spread of the genus to the low-latitude areas of South China. According to the structural characteristics of our fossil, it is speculated that the aborted ovule, which is common in the fruits of extant Ampelopsis, existed in this genus in the Late Pleistocene.

BackgroundBiomarkers of different stages and grades of bladder cancer (BC) are important in clinical work. The objective of our study was to investigate new biomarkers of early-stage BC with liquid chromatography-high resolution mass spectrometry (LC-HRMS) using serum samples.MethodsA total of 215 cases were included in our study, including 109 healthy adults as the control group and 106 non-muscle invasive bladder cancer (NMIBC) patients as the NMIBC group. Serum samples were collected from BC patients in the early stage, called NMIBC, and healthy people before surgery. We used LC-HRMS to distinguish the NMIBC group from the control group and the low-grade NMIBC group from the control group.ResultsAn apparent difference between the NMIBC group and the control group was visualized by unsupervised principal component analysis (PCA). Metabolite panels for 16-hydroxy-10-oxohexadecanoic acid, PGF2a ethanolamide, sulfoglycolithocholate, and threoninyl-alanine were used to distinguish the two groups. The area under the curve (AUC) of the panels was 0.985, and the sensitivity and specificity were 98.63% and 98.59%, respectively. To distinguish the low-grade NMIBC group from the control group, serum metabolic profiling differences between the low-grade NMIBC group and control group samples were also analyzed. Metabolite panels of L-octanoylcarnitine, PGF2a ethanolamide, and threoninyl-alanine showed good discrimination performance. The AUC of the panels was 0.999, and the sensitivity and specificity were 97.8% and 100%, respectively.ConclusionMetabolomics analysis of serum samples can distinguish the NMIBC group from the control group, particularly the early-stage low-grade NMIBC group.

ObjectiveTo analyse the surgical outcomes of pediatric patients with Lennox-Gastaut syndrome (LGS) secondary to viral encephalitis.MethodsWe retrospectively analyzed the data of four patients with LGS secondary to viral encephalitis who underwent surgery at the pediatric epilepsy center of Peking University First Hospital from January 2014 to December 2019. Preoperative evaluations included a detailed history, long-term video electroencephalography (VEEG), brain magnetic resonance imaging (MRI), positron emission tomography (PET) and a neuropsychological test. All patients were followed up at 1, 3, and 6 months and then yearly. The surgical outcome was evaluated according to the Engel classification.ResultsAmong the four children, the surgeries were right temporo-parieto-occipital disconnection (case 1), corpus callosotomy (case 2), left temporo-parieto-occipital disconnection (case 3), and left temporal lobectomy (case 4). The pathology was gliosis secondary to viral encephalitis. The median follow-up time was 4 years (3–5 years). At the last follow-up, one case had Engel I, two cases had Engel III, and one case had Engel IV.ConclusionsPreliminary observations shows that surgical treatment may be challenging for patients with LGS secondary to viral encephalitis. However, suitable surgical candidacy and approaches have a significant impact on the prognosis of the patients.

Aim: To profile the plasma proteomics and metabolomics of patients with renal cysts, sporadic angiomyolipoma (S-AML) and tuberous sclerosis complex related angiomyolipoma (TSC-RAML) before and after everolimus treatment, and to find potential diagnostic and prognostic biomarkers as well as reveal the underlying mechanism of TSC tumorigenesis.Materials and Methods: We retrospectively measured the plasma proteins and metabolites from November 2016 to November 2017 in a cohort of pre-treatment and post-treatment TSC-RAML patients and compared them with renal cyst and S-AML patients by ultra-performance liquid chromatography-mass spectrometer (UPLC-MS). The tumor reduction rates of TSC-RAML were assessed and correlated with the plasma protein and metabolite levels. In addition, functional analysis based on differentially expressed molecules was performed to reveal the underlying mechanisms.Results: Eighty-five patients with one hundred and ten plasma samples were enrolled in our study. Multiple proteins and metabolites, such as pre-melanosome protein (PMEL) and S-adenosylmethionine (SAM), demonstrated both diagnostic and prognostic effects. Functional analysis revealed many dysregulated pathways, including angiogenesis synthesis, smooth muscle proliferation and migration, amino acid metabolism and glycerophospholipid metabolism.Conclusion: The plasma proteomics and metabolomics pattern of TSC-RAML was clearly different from that of other renal tumors, and the differentially expressed plasma molecules could be used as prognostic and diagnostic biomarkers. The dysregulated pathways, such as angiogenesis and amino acid metabolism, may shed new light on the treatment of TSC-RAML.

Karst caves are usually considered as natural laboratories to study pristine microbiomes in subsurface biosphere. However, effects of the increasingly detected nitrate in underground karst ecosystem due to the acid rain impact on microbiota and their functions in subsurface karst caves have remained largely unknown. In this study, samples of weathered rocks and sediments were collected from the Chang Cave, Hubei province and subjected to high-throughput sequencing of 16S rRNA genes. The results showed that nitrate significantly impacted bacterial compositions, interactions, and functions in different habitats. Bacterial communities clustered according to their habitats with distinguished indicator groups identified for each individual habitat. Nitrate shaped the overall bacterial communities across two habitats with a contribution of 27.2%, whereas the pH and TOC, respectively, structured bacterial communities in weathered rocks and sediments. Alpha and beta diversities of bacterial communities increased with nitrate concentration in both habitats, with nitrate directly affecting alpha diversity in sediments, but indirectly on weathered rocks by lowering pH. Nitrate impacted more on bacterial communities in weathered rocks at the genus level than in sediments because more genera significantly correlated with nitrate concentration in weathered rocks. Diverse keystone taxa involved in nitrogen cycling were identified in the co-occurrence networks such as nitrate reducers, ammonium-oxidizers, and N2-fixers. Tax4Fun2 analysis further confirmed the dominance of genes involved in nitrogen cycling. Genes of methane metabolism and carbon fixation were also dominant. The dominance of dissimilatory and assimilatory nitrate reduction in nitrogen cycling substantiated nitrate impact on bacterial functions. Our results for the first time revealed the impact of nitrate on subsurface karst ecosystem in terms of bacterial compositions, interactions, and functions, providing an important reference for further deciphering the disturbance of human activities on the subsurface biosphere.

Underwater image enhancement is a fundamental requirement in the field of underwater vision. Along with the development of deep learning, underwater image enhancement has made remarkable progress. However, most deep learning-based enhancement methods are computationally expensive, restricting their application in real-time large-size underwater image processing. Furthermore, GAN-based methods tend to generate spatially inconsistent styles that decrease the enhanced image quality. We propose a novel efficiency model, FSpiral-GAN, based on a generative adversarial framework for large-size underwater image enhancement to solve these problems. We design our model with equal upsampling blocks (EUBs), equal downsampling blocks (EDBs) and lightweight residual channel attention blocks (RCABs), effectively simplifying the network structure and solving the spatial inconsistency problem. Enhancement experiments on many real underwater datasets demonstrate our model's advanced performance and improved efficiency.

Background: The basement membranes (BMs) are involved in tumor progression, while few comprehensive analyses to date are performed on the role of BM-related gene signatures in lung adenocarcinoma (LUAD). Thus, we aimed to develop a novel prognostic model in LUAD based on BMs-related gene profiling.Methods: The LUAD BMs-related gene profiling and corresponding clinicopathological data were obtained from the basement membrane BASE, The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) databases. The Cox regression and least absolute shrinkage and selection operator (LASSO) methods were used to construct a BMs-based risk signature. The concordance index (C-index), receiver operating characteristic (ROC), and calibration curves were generated to evaluate the nomogram. The GSE72094 dataset was used to validate prediction of the signature. The differences in functional enrichment, immune infiltration, and drug sensitivity analyses were compared based on risk score.Results: In TCGA training cohort, 10 BMs-related genes were found, (e.g., ACAN, ADAMTS15, ADAMTS8, BCAN, etc). The signal signature based on these 10 genes was categorized into high- and low-risk groups regarding survival differences (p < 0.001). Multivariable analysis showed that the signature of combined 10 BMs-related genes was an independent prognostic predictor. Such a prognostic value of BMs-based signature in validation cohort of the GSE72094 were further verified. The GEO verification, C-index, and ROC curve showed that the nomogram had accurate prediction performance. The functional analysis suggested that BMs were mainly enriched in extracellular matrix-receptor (ECM-receptor) interaction. Moreover, the BMs-based model was correlated with immune checkpoint.Conclusion: This study identified BMs-based risk signature genes and demonstrated their ability to predict prognosis and guide personalized treatment of patients with LUAD.

Objectives Whether KMT2A-PTD has a prognostic impact on patients with acute myeloid leukaemia (AML) is controversial. Therefore, we conducted a meta-analysis to assess the prognostic value of KMT2A-PTD in patients with AML.Methods Eligibility criteria: we included studies concerning the prognostic value of KMT2A-PTD in patients with AML.Information sources: Eligible studies were identified from PubMed, Embase, Medline, Web of Science, Cochrane Library and Chinese Biomedical Database. The systematic search date was 19 December 2020.Risk of bias: Sensitivity analysis was used to evaluate the stability and reliability of the combined results. Begg’s and Egger’s tests were used to assess the publication biases of studies.Synthesis of results: We calculated the pooled HRs and their 95% CIs for overall survival (OS) and event-free survival (EFS) by Stata V.12 software.Results Included studies: 18 studies covering 6499 patients were included.Synthesis of results: KMT2A-PTD conferred shorter OS in total population (HR=1.30, 95% CI 1.09 to 1.51). In the subgroup analysis, KMT2A-PTD also resulted in shorter OS in karyotypically normal AML patients (HR=2.72, 95% CI 1.83 to 3.61) and old AML patients (HR=1.93, 95% CI 1.44 to 2.42). KMT2A-PTD indicated no prognostic impact on EFS in total population (HR=1.26, 95% CI 0.86 to 1.66). However, in the sensitivity analysis, KMT2A-PTD resulted in poor EFS (HR=1.34, 95% CI 1.04 to 1.64) when deleting the study with a relatively obvious effect on the combined HR. In the subgroup analysis, KMT2A-PTD was associated with poor EFS in old AML patients (HR=1.64, 95% CI 1.25 to 2.03).Conclusion The findings indicated that KMT2A-PTD had an adverse impact on the prognosis of patients with AML in the total population, and the conclusion can also be applied to some subgroups including karyotypically normal AML and old AML patients. KMT2A-PTD may be a promising genetic biomarker in patients with AML in the future.Trial registration number CRD42021227185.

Endoplasmic reticulum stress (ERS)-related autophagy is involved in the occurrence and development of ulcerative colitis (UC). Therefore, regulating ERS-related autophagy is a potential therapeutic target for the treatment of UC. Jianpi-Qingchang (JPQC) decoction, consisting of nine Chinese herbal medicines, is used to treat patients with UC. However, its mechanism of action has not been completely elucidated. Here, we aimed to reveal the therapeutic effects and mechanisms of JPQC in UC. We established a colitis model using dextran sulfate sodium (DSS) and an ERS model using thapsigargin (Tg) and administered JPQC. We systematically examined ERS-related autophagy associated protein expression, inflammatory cytokines, apoptotic cells, and autophagic flux. Moreover, the cellular ultrastructure was observed via transmission electron microscopy (TEM). We found that JPQC reduced disease activity index (DAI) scores, counteracted colonic tissue damage, decreased the number of autophagosomes, inhibited proinflammatory cytokines, enhanced anti-inflammatory cytokines, and dampened ERS-related autophagy associated protein gene expression.

Mutations in the plant homeodomain-like finger protein 6 (PHF6) gene are strongly associated with acute myeloid (AML) and T-cell acute lymphoblastic leukemia (T-ALL). In this study, we demonstrated that PHF6 can bind to H3K9me3 and H3K27me1 on the nucleolar chromatin and recruit histone methyltransferase SUV39H1 to the rDNA locus. The deletion of PHF6 caused a decrease in the recruitment of SUV39H1 to rDNA gene loci, resulting in a reduction in the level of H3K9me3 and the promotion of rDNA transcription. The knockdown of either SUV39H1 or PHF6 significantly attenuated the effects of increase in H3K9me3 and suppressed the transcription of rDNA induced by the overexpression of the other interacting partner, thereby establishing an interdependent relationship between PHF6 and SUV39H1 in their control of rRNA transcription. The PHF6 clinical mutants significantly impaired the ability to bind and recruit SUV39H1 to the rDNA loci, resulting in an increase in rDNA transcription activity, the proliferation of in vitro leukemia cells, and the growth of in vivo mouse xenografts. Importantly, significantly elevated levels of pre-rRNA were observed in clinical AML patients who possessed a mutated version of PHF6. The specific rDNA transcription inhibitor CX5461 significantly reduced the resistance of U937 AML cells deficient in PHF6 to cytarabine, the drug that is most commonly used to treat AML. Collectively, we revealed a novel molecular mechanism by which PHF6 recruits methyltransferase SUV39H1 to the nucleolar region in leukemia and provided a potential therapeutic target for PHF6-mutant leukemia.

Abstract Aims and background IFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1β. However, the role of IFI16 in regulating the immune response to viruses in Hepatitis B Virus-Associated Glomerulonephritis (HBV-GN), especially in sensing hepatitis B virus (HBV), has not been determined. In this study, we investigated the inflammatory role of IFI16 in HBV-GN. Methods A total 75 kidney tissue including 50 HBV-GN and 25 chronic glomerulonephritis (CCN) were collected to determine the expression of IFI16, Caspase-1 and IL-1β using immunohistochemistry (IHC), then the correlation between them was analyzed. In vitro, the primary human glomerular mesangial (HGM) cells and HEK-293 T cell lines were used in this study. The cell lines were both co-transfected with HBVDNA and overexpression or silencing IFI16. Quantitative Real-time PCR and western blotting were used to determine the expression of IFI16, Caspase-1 and IL-1β. Results IFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and positively correlated with HBVDNA,caspase-1 and IL-1β expression in HBV-GN. Meanwhile, over expression of IFI16 increased caspase-1 and IL-1β expression in HBV-infected HGM and HEK-293 T cell lines, knockdown of IFI16 mRNA by siRNA resulted in downregulation of the caspase-1 and IL-1β expression in both cell lines. Conclusions The elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for researching the pathogenesis of HBV-GN.