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This study investigates the impact of various molecular weights (MWs) of fulvic acid (FA) on maize growth, grain yield, and nutrient uptake under different nitrogen levels (NLs). A 2 × 3 balanced design was employed, with high (0.2 g N/kg) and low (0.05 g N/kg) NLs, and three FA MW ranges (W1 ≤ 3 000 D, 3 000 < W2 ≤ 10 000 D, W3 > 10 000 D) were applied at 25 mg/kg in soil. Significant interactions between NLs and FA MWs were observed in chlorophyll a/b ratio, nitrate reductase and glutamate dehydrogenase activities, nitrogen content, and nitrogen uptake efficiency. Overall, under different NLs, FA application reduced chlorophyll a/b ratio, increased nitrogen metabolism enzyme activities, promoted maize growth, and thereby improved grain yield and nitrogen fertiliser uptake efficiency. Additionally, the promotion effect of low MW FA on these indicators outweighed that of high MW FA, yet the latter exhibited a more pronounced effect on increasing grain nitrogen concentration. Structural equation model analysis revealed direct effects of chlorophyll content, nitrogen accumulation, nitrogen uptake efficiency, NLs and FA MWs on maize grain yield, with FA MWs negatively impacting yield.

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation and lipid peroxidation, ferroptosis has been implicated in the progression of various skin conditions, including psoriasis, photosensitive dermatitis, and melanoma. This review provides an in-depth analysis of the molecular mechanisms underlying ferroptosis and compares its cellular effects with other forms of cell death in the context of skin health and disease. We systematically examine the role of ferroptosis in five specific skin diseases, including ichthyosis, psoriasis, polymorphous light eruption (PMLE), vitiligo, and melanoma, detailing its influence on disease pathogenesis and progression. Moreover, we explore the current clinical landscape of ferroptosis-targeted therapies, discussing their potential in managing and treating skin diseases. Our aim is to shed light on the therapeutic potential of modulating ferroptosis in skin disease research and practice.

IntroductionGraft failure (GF) or poor graft function (PGF) remain critical obstacles in haploidentical hematopoietic stem cell transplantation (haplo-HSCT), especially in recipients with HLA antibodies. Here, we performed a retrospective cohort study to investigate the efficacy and safety of the use of unrelated umbilical cord blood stem cells (UCBs) as a third-party adjuvant infusion in patients with HLA-antibodies undergoing haplo-HSCT.MethodsA total of 90 patients were divided into three groups: 17 patients in Group A (with positive HLA antibodies and who received UCB infusion), 36 patients in Group B (with positive HLA antibodies without UCB infusion), and 37 patients in Group C (without HLA antibody or UCB infusion).ResultsThe median age of patients included in Groups A, B, and C was 43 (IQR, 27 - 49.5), 33 (IQR, 20 - 48.75), and 30 (IQR, 18 - 46.5) years, respectively. All but one patient in Group B achieved granulocyte recovery within 28 days after transplantation. The median time to granulocyte engraftment were all 12 days for patients in Groups A, B, and C, respectively. All the patients in Group A achieved 100% donor chimerism without UCB engraftment. There were no significant differences in granulocyte or platelet engraftment time between the three groups. There were 1, 5, and 0 patients in Groups A, B, and C, respectively, who developed PGF. The cumulative incidence rates for any grade of acute graft-versus-host disease (aGVHD) were comparable among the three groups. Patients in Group B presented a greater incidence of cGVHD than did those in Group A (P = 0.002) and Group C (P = 0.006). Patients in Group A presented more limited and milder cGVHD than those in Group C (P < 0.0001). The 1-year relapse-free survival (RFS) was 70.6% (95% CI, 0.47 - 0.87), 55.6% (95% CI, 0.40 - 0.70), and 77.9% (95% CI, 0.63 - 0.89) in Groups A, B, and C, respectively.DiscussionOur results indicated that patients who were positive for HLA antibodies were at a greater risk of developing GF/PGF. Co-infusion with UCBs was safe and improved engraftment, cGVHD, and improved the 1-year RFS to some extent.

IntroductionCisplatin is a widely used chemotherapeutic agent prescribed to treat solid tumors. However, its clinical application is limited because of cisplatin- induced nephrotoxicity. A known complication of cisplatin is acute kidney injury (AKI). Deletion polymorphisms of GSTM1 and GSTT1, members of the glutathione S-transferase family, are common in humans and are presumed to be associated with various kidney diseases. However, the specific roles and mechanisms of GSTM1 and GSTT1 in cisplatin induced AKI remain unclear.MethodsTo investigate the roles of GSTM1 and GSTT1 in cisplatin-induced AKI, we generated GSTM1 and GSTT1 knockout mice using CRISPR-Cas9 technology and assessed their kidney function under normal physiological conditions and cisplatin treatment. Using ELISA kits, we measured the levels of oxidative DNA and protein damage, along with MDA, SOD, GSH, and the GSH/GSSG ratio in wild-type and GSTM1/GSTT1 knockout mice following cisplatin treatment. Additionally, oxidative stress levels and the expression of ferroptosis-related proteins in kidney tissues were examined through Western blotting, qPCR, immunohistochemistry, and immunofluorescence techniques.ResultsHere, we found that GSTT1 and GSTM1 were downregulated in the renal tubular cells of AKI patients and cisplatin-treated mice. Compared with WT mice, Gstm1/Gstt1-DKO mice were phenotypically normal but developed more severe kidney dysfunction and exhibited increased ROS levels and severe ferroptosis after injecting cisplatin.DiscussionOur study revealed that GSTM1 and GSTT1 can protect renal tubular cells against cisplatin-induced nephrotoxicity and ferroptosis, and genetic screening for GSTM1 and GSTT1 polymorphisms can help determine a standard cisplatin dose for cancer patients undergoing chemotherapy.

ABSTRACTAnalysis of transcription factors and chromatin modifications at the genome-wide level provides insights into gene regulatory processes, such as transcription, cell differentiation and cellular response. Chromatin immunoprecipitation is the most popular and powerful approach for mapping chromatin, and other enzyme-tethering techniques have recently become available for living cells. Among these, Cleavage Under Targets and Tagmentation (CUT&Tag) is a relatively novel chromatin profiling method that has rapidly gained popularity in the field of epigenetics since 2019. It has also been widely adapted to map chromatin modifications and TFs in different species, illustrating the association of these chromatin epitopes with various physiological and pathological processes. Scalable single-cell CUT&Tag can be combined with distinct platforms to distinguish cellular identity, epigenetic features and even spatial chromatin profiling. In addition, CUT&Tag has been developed as a strategy for joint profiling of the epigenome, transcriptome or proteome on the same sample. In this review, we will mainly consolidate the applications of CUT&Tag and its derivatives on different platforms, give a detailed explanation of the pros and cons of this technique as well as the potential development trends and applications in the future.

Epoxy resins, known for their excellent properties, are widely used thermosetting resins, but their tendency towards brittle fracture limits their applications. This study addresses this issue by preparing graphene oxide via the Hummer method, modifying it with hyperbranched polyamide ester, and reducing it with hydrazine hydrate to obtain functionalized graphene. This functionalized graphene improves compatibility with epoxy resin. Using a novel two-phase extraction method, different ratios of functionalized graphene/epoxy composites were prepared and tested for mechanical properties and thermal stability. The results showed significant improvements: the tensile strength of composites with 0.1 wt% functionalized graphene increased by 77% over pure epoxy resin, flexural strength by 56%, and glass transition temperature by 50°C. These enhancements, attributed to the improved compatibility between graphene and epoxy resin, demonstrate the potential of functionalized graphene to mitigate the brittleness of epoxy resins, expanding their application potential.

Genetic mutations in TP53 contribute to human malignancies through various means. To date, there have been a variety of therapeutic strategies targeting p53, including gene therapy to restore normal p53 function, mutant p53 rescue, inhibiting the MDM2-p53 interaction, p53-based vaccines, and a number of other approaches. This review focuses on the functions of TP53 and discusses the aberrant roles of mutant p53 in various types of cancer. Recombinant human p53 adenovirus, trademarked as Gendicine, which is the first anti-tumor gene therapy drug, has made tremendous progress in cancer gene therapy. We herein discuss the biological mechanisms by which Gendicine exerts its effects and describe the clinical responses reported in clinical trials. Notably, the clinical studies suggest that the combination of Gendicine with chemotherapy and/or radiotherapy may produce more pronounced efficacy in slowing tumor growth and progression than gene therapy/chemotherapy alone. Finally, we summarize the methods of administration of recombinant human p53 adenovirus for different cancer types to provide a reference for future clinical trials.

Abstract Field observations in sedimentation and erosion-prone areas indicate that most natural sand deposits may contain a certain amount of non-plastic fines and are often under anisotropic stress conditions. A series of triaxial compression tests were performed on clean and silty sand with fines content f c ranging from 0 to 20% at an initial mean effective stress of p 0′ = 100 kPa and varying consolidation conditions to understand the impact of initial stress anisotropy on undrained shear behavior. The results indicate that the state parameter ψ is a superior predictor for characterizing the responses of sand-fines mixtures compared to the global void ratio and relative density. A comparison of the behavior of clean and silty sand with a constant ψ (= − 0.03) confirms that the sample with 10% f c exhibits the strongest dilation and greatest shear resistance, irrespective of the consolidation conditions. It is also demonstrated that the initial stress anisotropy with a comparably higher static stress ratio η s typically diminishes the shear strength of mixtures. However, the influence of initial stress anisotropy on soil stiffness is not unilateral. The sample consolidated to a negative η s is stiffer than that under isotropic consolidation, while the presence of a positive η s leads to a decrease in the secant Young's modulus.

Abstract The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.

Objective: The effect of three coating agents, namely chitosan, sodium alginate, and carrageenan, on the color protection and preservation of peeled ginger was investigated to screen the best combination of color protection coating for scraped ginger to inhibit the browning of scraped ginger during processing. Methods: Based on a single-factor test, three color protectors, namely chitosan, sodium alginate, and carrageenan, were selected as independent variables and the browning degree was used as the response value, and the Box-Behnken central combination experiment and response surface analysis were used to investigate the effects of the interaction of independent variables on the browning of scraped ginger. The optimum composite color protection coating process for the inhibition of browning of peeled ginger was determined. Results: The optimum formulation of the composite coating agent was 1.399% chitosan, 1.783% sodium alginate and 1.311% carrageenan. The browning of scraped ginger stored for 15 days under this color protection condition was 0.232, which was close to the response surface prediction (2.230). The measured curcumin content was 1.62%, total flavonoid content was 1.83%, total phenolic content 53.88 μg/g, weight loss 0.89% and DPPH free radical scavenging capacity 442.21 μg Trolox/g, all had significantly different compared with the control (P

Cropland acidification seriously restricts sustainable agricultural development. The main purpose of this study was to determine whether deeper tilling could alleviate topsoil acidification to improve the quality of arable land. A soil column incubation experiment simulating tillage depths (10 cm, 30 cm and 50 cm) and lime addition was conducted to determine their effects on soil acidification improvement. The changes in soil pH, exchangeable acidity, ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3−-N), available phosphorus (AP), and microbial phospholipid fatty acids (PLFA) were analyzed. Tillage depth, lime application, and their interaction all had significant impacts on soil pH. T50 (simulated tillage depth of 50 cm) and T50+Lime (simulated tillage depth of 50 cm plus lime) treatments significantly increased the topsoil pH from 5.41 to 6.35 and 7.12, respectively. T50 treatment significantly reduced the soil exchangeable acid content compared to the T10 treatment. The nutrient accumulation along soil column indicated that the T50 and T50+Lime treatments significantly increased NO3−-N and AP content in the >30–50 cm soil layer. Compared with T30, NO3−-N accumulation in the >30–50 cm soil layers of T50 and T50+Lime treatments was 6.62 and 7.93 times higher, respectively. The accumulation of AP in the >30–50 cm soil layers of the T50 and T50+Lime treatments was 1.33 and 1.54 times higher than in the T30 treatment, respectively. These findings imply tillage up to 50 cm without exogenous materials could be a potential measure to reduce topsoil acidification and increase nutrition availability of >30–50 cm soil layers. Tillage of up to 30 cm combined with lime application confers greater benefits, which would particularly impact crops with shallow root systems. Subsequent field experiments will be conducted to further investigate the efficacy of these strategies in enhancing crop yield.

Diabetic nephropathy (DN) is a severe complication of prolonged diabetes, impacting millions worldwide with an increasing incidence. This study investigates the role of tribbles pseudokinase 3 (TRIB3), a protein implicated in the progression of DN, focusing on its mechanisms underlying glomerular damage. Through analysis of the Gene Expression Omnibus (GEO) database, we identified TRIB, among differentially expressed genes (DEGs) in streptozotocin (STZ)-treated C57BL/6J mice. Both in vitro and in vivo experiments were conducted to examine the effects of TRIB3 inhibition on high glucose (HG)-induced damage in podocytes and DN mouse models. The results demonstrated that TRIB3 inhibition reduced inflammatory responses and extracellular matrix (ECM) production inMPC5 cells, mediated by the downregulation of DNA damage-inducible transcript 3 (DDIT3) - a critical regulator of proinflammatory cytokine secretion and ECM synthesis. Inhibiting TRIB3 decreased inflammatory factors and ECM deposition in diabetic mice in vivo, confirming its pivotal role in DN pathogenesis. These findings indicate that TRIB3 and its interaction with DDIT3 contribute significantly to DN by promoting inflammatory cascades and ECM accumulation, presenting potential therapeutic targets for managing the disease.

Antimicrobial peptides (AMPs) from natural sources represent promising candidates for novel antimicrobial agents instead of antibiotics in aquaculture. Moricin, a family of AMPs from Lepidoptera, has shown bactericidal activity against both gram-positive and gram-negative bacteria. However, it remains uncertain whether these peptides possess antimicrobial activity against Vibrio pathogens affecting various aquatic animals, including sea cucumbers. In this study, we investigated five moricin-like peptides (MLPs) from Antheraea pernyi (Anpe) and identified Anpe-MLP1 as a new member of the moricin family through bioinformatics analysis. Anpe-MLP1 was heterologously expressed using the AnpeNPV bacmid system and purified from A. pernyi pupae. Our findings revealed that recombinant Anpe-MLP1 (rAnpe-MLP1) exhibited antimicrobial activity against gram-positive Staphylococcus aureus (S. aureus ATCC 6538 P), gram-negative Escherichia coli (E. coli ATCC 25922) and three Vibrio species. Moreover, both in vitro and in vivo assays showed that rAnpe-MLP1 effectively inhibited wild-type Vibrio fluvialis infections in the sea cucumber (Apostichopus japonicus). These results suggest that Anpe-MLP1 holds great potential as a novel anti-infective agent and provide valuable insights for its future application in aquaculture.

Abstract Background Gastropoda, the largest class within the phylum Mollusca, houses diverse gut microbiota, and some gastropods serve as intermediate hosts for parasites. Studies have revealed that gut bacteria in gastropods are associated with various biological aspects, such as growth, immunity and host–parasite interactions. Here, we summarize our current knowledge of gastropod gut microbiomes and highlight future research priorities and perspectives. Methods A literature search was undertaken using PubMed, Web of Science and CNKI for the articles on the gut microbiota of gastropods until December 31, 2022. We retrieved a total of 166 articles and identified 73 eligible articles for inclusion in this review based on the inclusion and exclusion criteria. Results Our analysis encompassed freshwater, seawater and land snails, with a specific focus on parasite-transmitting gastropods. We found that most studies on gastropod gut microbiota have primarily utilized 16S rRNA gene sequencing to analyze microbial composition, rather than employing metagenomic, metatranscriptomic, or metabolomic approaches. This comprehensive review provided an overview of the parasites carried by snail species in the context of gut microbiota studies. We presented the gut microbial trends, a comprehensive summary of the diversity and composition, influencing factors, and potential functions of gastropod gut microbiota. Additionally, we discussed the potential applications, research gaps and future perspectives of gut microbiomes in parasite-transmitting gastropods. Furthermore, several strategies for enhancing our comprehension of gut microbiomes in snails were also discussed. Conclusions This review comprehensively summarizes the current knowledge on the composition, potential function, influencing factors, potential applications, limitations, and challenges of gut microbiomes in gastropods, with a specific emphasis on parasite-transmitting gastropods. These findings provide important insights for future studies aiming to understand the potential role of gastropod gut microbiota in controlling snail populations and snail-borne diseases. Graphical abstract

The early and accurate mapping of winter canola is essential in predicting crop yield, assessing agricultural disasters, and responding to food price fluctuations. Although some methods have been proposed to map the winter canola at the flowering or later stages, mapping winter canola planting areas at the early stage is still challenging, due to the insufficient understanding of the multi-source remote sensing features sensitive for winter canola mapping. The objective of this study was to evaluate the potential of using the combination of optical and synthetic aperture radar (SAR) data for mapping winter canola at the early stage. We assessed the contributions of spectral features, backscatter coefficients, and textural features, derived from Sentinel-2 and Sentinel-1 SAR images, for mapping winter canola at early stages. Random forest (RF) and support vector machine (SVM) classification models were built to map winter canola based on early-stage images and field samples in 2017 and then the best model was applied to corresponding satellite data in 2018–2022. The following results were obtained: (1) The red edge and near-infrared-related spectral features were most important for the mapping of early-stage winter canola, followed by VV (vertical transmission, vertical reception), DVI (Difference vegetation index), and GOSAVI (Green Optimized Soil Adjusted Vegetation Index); (2) based on Sentinel-1 and Sentinel-2 data, winter canola could be mapped as early as 130 days prior to ripening (i.e., early overwinter stage), with the F-score over 0.85 and the OA (Overall Accuracy) over 81%; (3) adding Sentinel-1 could improve the OA by about 2–4% and the F-score by about 1–2%; and (4) based on the classifier transfer approach, the F-scores of winter canola mapping in 2018–2022 varied between 0.75 and 0.97, and the OAs ranged from 79% to 86%. This study demonstrates the potential of early-stage winter canola mapping using the combination of Sentinel-2 and Sentinel-1 images, which could enable the large-scale early mapping of canola and provide valuable information for stakeholders and decision makers.

With the swift progress of the electronics industry, discarded circuit boards have become an important source of non-degradable waste. In this work, discarded epoxy resin was collected as a precursor to prepare activated carbon (AC) through stepwise carbonization/activation methods. The rough carbon materials with a certain graphite and amorphous structure reveal the multiple oxygen-containing groups on their surface. In the process of studying the adsorption of methyl orange by activated carbon, it is found that the adsorption is in accordance with the quasi-secondary kinetic model, and equilibrium adsorption amounts can reach 41.051 mg/g. The adsorption isotherm of AC is more in line with the Langmuir model, and the saturation adsorption amount at three different temperatures is 23.137 mg/g, 30.358 mg/g, and 37.202 mg/g, respectively. The enthalpy (ΔH) is 17.30 KJ/mol in the adsorption process, which indicates that is a physical process with heat-absorbing capabilities. This work is of great significance with regard to the recycling of waste to reduce pollution and in terms of gaining economic benefits.

AbstractBackground: Second primary malignancies (SPMs) account for an increasing proportion of human malignancies. We estimated the incidence, risk factors and outcomes in lymphoma survivors with SPMs.Methods: Patients diagnosed with SPMs after primary lymphoma from 2010 to 2021 were included in this study. The incidence, mortality and clinical characteristics of SPMs in our center and Surveillance, Epidemiology, and End Results database were delineated and analyzed. Standardized incidence ratio quantified second cancer risk.Results: A total of 2912 patients of lymphoma were included, 63 cases of SPM met the inclusion criteria, with the prevalence of SPMs after lymphoma was 2.16%. The male-to-female ratio of 2.32:1. The majority of these patients were older (≥60 years old, 61.90%) and previously treated with chemotherapy (68.25%). The common types among SPMs were digestive system tumors (42.86%), respiratory system tumors (20.63%) and urinary system tumors (12.70%). Additionally, cancer risks were significantly elevated after specific lymphoma though calculating the expected incidence. In terms of mortality, the diagnosis of SPMs was significantly associated with an increased risk of death over time. Moreover, although the outcome was favorable in some SPM subtypes (thyroid and breast cancer), other SPMs such as stomach and lung tumors had a dismal prognosis.Conclusion: With the improvement of medical standards, the survival of lymphoma patients has been prolonged. However, the incidence of SPM is increasing, particularly among men and older lymphoma survivors. Therefore, more attention should be invested in the SPM to further improve the prognosis of these patients.

Staphylococcus aureus (S. aureus) is an important zoonotic pathogen that causes a high incidence rate and mortality worldwide. This study investigated the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains in a tertiary A hospital in Shanxi Province, China, in order to determine the major epidemic clones as well as their antibiotic resistance and virulence characteristics. A total of 212 S. aureus strains were collected in this hospital, and were subjected to antimicrobial susceptibility testing, detection of virulence genes, resistance genes, and efflux pump genes. Among them, 38 MRSA strains were further subjected to detection of biofilm genes, assessment of biofilm formation ability, MLST, spa typing, SCCmec typing, and phylogenetic analysis. The majority of S. aureus strains came from the neonatology department, with secretions and purulent fluid being the main source of samples. The strains showed high resistance to penicillin (98.11%), erythromycin (64.62%) and clindamycin (59.91%), while being sensitive to vancomycin and linezolid. The detection rates of efflux pump genes and resistance genes were high, and there was a significant correlation between resistance gene types and phenotypes, with mecA showing a close correlation with oxacillin. The detection rates of virulence genes and the toxin gene profiles of MSSA and MRSA strains showed significant differences. And the detection rate of biofilm genes in MRSA strains was relatively high, with 13.16% of MRSA strains showing strong biofilm formation ability. The most common epidemic clone of MRSA was ST59-SCCmecIV-t437, followed by ST59-SCCmecV-t437. The former had a higher detection rate of resistance genes and a stronger biofilm formation ability, while the latter had a higher positive rate for pvl gene and stronger pathogenicity, making it more likely to cause systemic infections. Phylogenetic analysis showed that all MRSA strains in this study clustered into three major branches, with distinct differences in antibiotic resistance and virulence characteristics among the branches. ST59-MRSA strains from different species showed consistency and inter-species transmission, but there were differences among ST59-MRSA strains from different geographical locations. In general, most MSSA and MRSA strains exhibited multidrug resistance and carried multiple resistance genes, virulence genes, and biofilm formation genes, warranting further research to elucidate the mechanisms of drug resistance and pathogenesis.

As a biodegradable and flexible copolymer, poly(butyleneadipate-co-terephthalate) (PBAT) is used for packaging. However, high cost and limited properties restrict its applications. Because of the hydrophobic nature of PBAT, low mechanical properties are observed when PBAT and cellulosic fibers, which are hydrophilic, are used in blends. To increase the interfacial adhesion between cellulose and PBAT, γ-(2,3-epoxypropoxy) propytrimethoxysilane (KH560) was used as a reactive compatibilizer to modify cellulose. A one-step method was demonstrated for compounding and subsequent extrusion blowing, which is a simple and environmentally friendly approach to fabricate a series of K-Cellulose/PBAT (KH560-Cellulose/PBAT) composites. The morphology and structure of the cellulose were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectrophotometry. Meanwhile, thermal analysis of the hybrids showed an improvement of the thermal stability of the composites with increased silanized cellulose content. In addition, the barrier properties of films are measured by water vapor permeability (WVP) and oxygen permeability (OP). Finally, after addition of reactive compatibilizer KH560, there was considerable improvement with increased the cellulose content, as shown through mechanical properties testing. Therefore, the composites prepared with these enhanced properties have great potential as substitutes for traditional commodity polymers.

Type I R-M systems help establish the prokaryotic DNA methylation landscape and provide protection against invasive DNA. Here, the authors report on detailed structural and molecular mechanisms of a non-canonical type I R-M methyltransferase.

BackgroundThe incidence of non-Hodgkin’s lymphoma (NHL) has increased steadily over the past few decades. Elucidating its global burden will facilitate more effective disease management and improve patient outcomes. We explored the disease burden, risk factors, and trends in incidence and mortality in NHL globally.MethodsThe up-to-date data on age-standardized incidence and mortality rates of NHL were retrieved from the GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD) 2019, focusing on geographic disparities worldwide. We reported incidence and mortality by sex and age, along with corresponding age-standardized rates (ASRs), the average annual percentage change (AAPC), and future burden estimates to 2040.ResultsIn 2020, there were an estimated 545,000 new cases and 260,000 deaths of NHL globally. In addition, NHL resulted in 8,650,352 age-standardized DALYs in 2019 worldwide. The age-specific incidence rates varied drastically across world areas, at least 10-fold in both sexes, with the most pronounced increase trend found in Australia and New Zealand. By contrast, North African countries faced a more significant mortality burden (ASR, 3.7 per 100,000) than highly developed countries. In the past decades, the pace of increase in incidence and mortality accelerated, with the highest AAPC of 4.9 (95%CI: 3.6-6.2) and 6.8 (95%CI: 4.3-9.2) in the elderly population, respectively. Considering risk factors, obesity was positively correlated with age-standardized incidence rates (P< 0.001). And North America was the high-risk region for DALYs due to the high body mass index in 2019. Regarding demographic change, NHL incident cases are projected to rise to approximately 778,000 by 2040.ConclusionIn this pooled analysis, we provided evidence for the growing incidence trends in NHL, particularly among women, older adults, obese populations, and HIV-infected people. And the marked increase in the older population is still a public health issue that requires more attention. Future efforts should be directed at cultivating health awareness and formulating effective and locally tailored cancer prevention strategies, especially in most developing countries.

Oligosaccharides are important functional active components of Lycium barbarum L. (LBL, “Goji”) fruits, but their metabolic mechanisms are not yet clear. In this study, we firstly investigated the changes in the content of oligosaccharides in LBL at different stages (S1–S5), and found that it mainly accumulated at S3 and S4. Secondly, the structural characteristics of LBL oligosaccharide (LBO) were studied by GC-MS and FT-IR. Thirdly, using iTRAQ proteomics analysis, we identified 135 differentially expressed proteins associated with oligosaccharide metabolism, which is mainly accomplished through the collaboration of a range of key enzymes. At S1 and S2, oligosaccharide synthesis was achieved mainly through photosynthesis, and changes in anabolism were mainly associated with the expression of sucrose synthase, sucrose phosphate synthase and hexokinase. Oligosaccharide accumulation was achieved through starch and polysaccharide metabolism and cellulose catabolism at S3 and S4, where the enzymes associated with changes in oligosaccharide anabolism included glycosylase, β-fructosidase and glucan endonuclease. This report will provide a theoretical basis for further elucidating the mechanisms of oligosaccharide anabolism during the growth and development of LBL.

Highlights Satisfactory p-ASA degradation was achieved in a wide pH range. Simultaneous removal of p-ASA and the released arsenic was achieved in biochar supported MnFe2O4/persulfate system. Generation abundant reactive oxygen species via redox cycles between Mn and Fe.

Abstract Background Cisplatin, the alkylating agent of platinum(II) (Pt(II)), is the most common antitumor drug in clinic; however, it has many side effects, therefore it is higly desired to develop low toxicity platinum(IV) (Pt(IV)) drugs. Multi-omics analysis, as a powerful tool, has been frequently employed for the mechanism study of a certain therapy at the molecular level, which might be helpful for elucidating the mechanism of platinum drugs and facilitating their clinical application. Methods Strating form cisplatin, a hydrophobic Pt(IV) prodrug (CisPt(IV)) with two hydrophobic aliphatic chains was synthesized, and further encapsulated with a drug carrier, human serum albumin (HSA), to form nanoparticles, namely AbPlatin(IV). The anticancer effect of AbPlatin(IV) was investigated in vitro and in vivo. Moreover, transcriptomics, metabolomics and lipidomics were performed to explore the mechanism of AbPlatin(IV). Results Compared with cisplatin, Abplatin(IV) exhibited better tumor-targeting effect and greater tumor inhibition rate. Lipidomics study showed that Abplatin(IV) might induce the changes of BEL-7404 cell membrane, and cause the disorder of glycerophospholipids and sphingolipids. In addition, transcriptomics and metabolomics study showed that Abplatin(IV) significantly disturbed the purine metabolism pathway. Conclusions This research highlighted the development of Abplatin(IV) and the use of multi-omics for the mechanism elucidation of prodrug, which is the key to the clinical translation of prodrug. Graphical Abstract

A magnetic adsorbent based on a C-nanofiber (Fe3O4@C–NFs) nanocomposite was synthesized using a simple one-pot co-precipitation method. The characterized results showed that the obtained C–nanofiber–coated magnetic nanoparticles had many attractive features such as a large specific surface area and a highly interwoven and branched mesoporous structure, as well as distinguished magnetism. The nanocomposite was then used as an adsorbent in the magnetic solid phase extraction (MSPE) of four typical tetracyclines (oxytetracycline, tetracycline, chlortetracycline, and doxycycline) in aquatic products. The TCs in the extract were determined using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). Experimental variables of MSPE, including the sorbent amount, pH condition, adsorption and desorption time, and desorption solvent, were investigated and optimized systematically. The method validation indicated that the developed method showed good linearity (R2 > 0.995) in the range of 1.0–200 ng/mL. The average recoveries at the spiked levels ranged from 90.7% to 102.7% with intra-day and inter-day relative standard deviations (RSDs, n = 6) ranging from 3.72% to 8.17% and 4.20% to 9.69%, respectively. The limit of detection (LOD) and limit of quantification (LOQ) for the four kinds of TCs were 0.7 μg/kg and 2.0 μg/kg, respectively. Finally, MSPE based on C-nanofiber-coated magnetic nanoparticles was successfully applied to TC analysis in real aquatic products (grass carp, large yellow croaker, snakehead, mandarin fish, Penaeus vannamei, swimming crab, etc.). Compared with traditional extraction methods, the proposed method for TC analysis in aquatic products is more sensitive, effective, recyclable, and environmentally friendly.

The storage quality and microbiome analysis of pickled swimming crabs (Portunus trituberculatus) stored at 20 and 4 °C were investigated. It showed that samples stored at 4 °C had a longer shelf life, lower total viable count (TVC), pH, and total volatile base nitrogen (TVB-N) contents than those stored at 20 °C. The biogenic amine (BA) results demonstrated that tyramine (tyr), putrescine (put), and cadaverine (cad) were the dominant amines in all samples, and samples stored at 4 °C had lower BA contents. A microbiome analysis indicated that a salt–alcohol water mixture significantly inhibited the growth of Tenericutes. Firmicutes, Proteobacteria, Bacteroidetes, Acidobacteria, Actinobacteria, and Cyanobacteria were the dominant bacteria of stored pickled crabs, and storage at 4 °C significantly inhibited the growth of dominant bacteria, more than that of 20 °C. In conclusion, 4 °C storage guaranteed the quality of samples by inhibiting changes in biochemical properties and the growth of dominant bacteria, thereby prolonging its shelf life.

Breast cancer is one of the most common female diseases, posing a great threat to women’s health, and breast ultrasound imaging is a common method for breast cancer diagnosis. In recent years, U-Net and its variants have dominated the medical image segmentation field with their excellent performance. However, the existing U-type segmentation networks have the following problems: (1) the design of the feature extractor is complicated, and the calculation difficulty is increased; (2) the skip connection operation simply combines the features of the encoder and the decoder, without considering both spatial and channel dimensions; (3) during the downsampling phase, the pooling operation results in the loss of feature information. To address the above deficiencies, this paper proposes a breast tumor segmentation network, RMAU-Net, that combines residual depthwise separable convolution and a multi-scale channel attention gate. Specifically, we designed the RDw block, which has a simple structure and a larger sensory field, to overcome the localization problem of convolutional operations. Meanwhile, the MCAG module is designed to correct the low-level features in both spatial and channel dimensions and assist the high-level features to recover the up-sampling and pinpoint non-regular breast tumor features. In addition, this paper used the Patch Merging operation instead of the pooling method to prevent the loss of breast ultrasound image information. Experiments were conducted on two breast ultrasound datasets, Dataset B and BUSI, and the results show that the method in this paper has superior segmentation performance and better generalization.

Biomphalaria snails play a crucial role in the transmission of the human blood fluke Schistosoma mansoni. The gut microbiota of intermediate hosts is known to influence their physiological functions, but little is known about its composition and role in Biomphalaria snails. To gain insights into the biological characteristics of these freshwater intermediate hosts, we conducted metagenomic sequencing on Biomphalaria straminea and B. glabrata to investigate variations in their gut microbiota. This study revealed that the dominant members of the gut microbiota in B. glabrata belong to the phyla Bacteroidetes and Proteobacteria, which were also found to be the top two most abundant gut bacteria in B. straminea. We identified Firmicutes, Acidovorax and Bosea as distinctive gut microbes in B. straminea, while Aeromonas, Cloacibacterium and Chryseobacterium were found to be dependent features of the B. glabrata gut microbiota. We observed significant differences in the community structures and bacterial functions of the gut microbiota between the two host species. Notably, we found a distinctive richness of antibiotic resistance genes (ARGs) associated with various classes of antibiotics, including bacitracin, chloramphenicol, tetracycline, sulfonamide, penicillin, cephalosporin_ii and cephalosporin_i, fluoroquinolone, aminoglycoside, beta-lactam, multidrug and trimethoprim, in the digestive tracts of the snails. Furthermore, this study revealed the potential correlations between snail gut microbiota and the infection rate of S. mansoni using Spearman correlation analysis. Through metagenomic analysis, our study provided new insights into the gut microbiota of Biomphalaria snails and how it is influenced by host species, thereby enhancing our understanding of variant patterns of gut microbial communities in intermediate hosts. Our findings may contribute to future studies on gastropod–microbe interactions and may provide valuable knowledge for developing snail control strategies to combat schistosomiasis in the future.

Abstract Objective Papillary thyroid carcinoma is treated in China mostly with surgery, including total ablation, lobectomy, and lobe and isthmus resection. Therefore, whether thyroid status affects the FNA‐Tg cutoff value in the diagnosis of cervical lymph node metastasis deserves our attention. In addition, we investigated the influence of serum Tg, TSH, and TgAb on the accuracy of using FNA‐Tg for diagnosis. Methods Our retrospective analysis included 189 suspected cervical lymph nodes, and we determined whether the cutoff value of FNA‐Tg was affected by thyroid status, sTg, sTSH, and sTgAb. Results In thyroid present cases, the optimal cutoff value of FNA‐Tg was 2.3 ng/ml (sensitivity 96.2%, specificity 100%), and in the thyroid absent cases, the optimal cutoff value of FNA‐Tg was 0.7 ng/ml (sensitivity 97.6%, specificity 96.0%). Although serum Tg, TSH, and TgAb were weakly correlated with FNA‐Tg values, they did not affect the diagnostic performance of the optimal cutoff value of FNA‐Tg according to thyroid status. Conclusions The optimal cutoff value of FNA‐Tg should be selected according to the thyroid status (2.3 ng/ml for thyroid present cases and 0.7 ng/ml for thyroid absent cases) to ensure the efficient diagnosis of cervical metastatic lymph nodes of papillary thyroid carcinoma. It was determined that sTg, sTSH, and sTg‐Ab cannot influence the diagnostic performance of FNA‐Tg. The combination method of FNA‐Tg and FNAC is the most optimal choice for the diagnosis of lymph nodes metastasis.

Modulating the atomic coordination structure has emerged as a promising strategy to further improve catalytic performance. Here, the authors report an atomic Co1/NPC catalyst with unsymmetrical single Co1N3P1 sites that displays high activity and chemoselectivity for hydrogenation of functionalized nitroarenes.

Sensorineural deafness becomes an inevitable worldwide healthy problem, yet the current curative therapy is limited. Emerging evidences demonstrate mitochondrial dysfunction plays a vital role of in the pathogenesis of deafness. Reactive oxygen species (ROS)-induced mitochondrial dysfunction combined with NLRP3 inflammasome activation is involved in cochlear damage. Autophagy not only clears up undesired proteins and damaged mitochondria (mitophagy), but also eliminate excessive ROS. Appropriate enhancement of autophagy can reduce oxidative stress, inhibit cell apoptosis, and protect auditory cells. In addition, we further discuss the interplays linking ROS generation, NLRP3 inflammasome activation, and autophagy underlying the pathogenesis of deafness, including ototoxic drugs-, noise- and aging-related hearing loss.

In order to enhance tribological performance of both water-based and oil-based lubricant, the SiO2 nanoscale ionic liquid (NIL), an amphiphilic lubricant additive, was prepared by using a sulfuric acid terminated organo-silane as corona and polyether amine as canopy. Various analytical techniques were used to characterize the SiO2 NIL and stability of the nanolubricants. A ball-on-disk tribometer was adopted to investigate the lubrication enhancement of the SiO2 NIL in both water-based and oil-based lubricants. The results show that the SiO2 NIL can reduce the coefficient of friction (COF) and wear in these two lubricant groups, especially in the water-based lubricant. The lubrication mechanisms are ascribed to the polishing, ball bearing and mending effects of the SiO2 NIL.

Abstract A good method of synthesizing Ti3C2Tx (MXene) is critical for ensuring its success in practical applications, e.g., electromagnetic interference shielding, electrochemical energy storage, catalysis, sensors, and biomedicine. The main concerns focus on the moderation of the approach, yield, and product quality. Herein, a modified approach, organic solvent-assisted intercalation and collection, was developed to prepare Ti3C2Tx flakes. The new approach simultaneously solves all the concerns, featuring a low requirement for facility (centrifugation speed

Acute kidney injury (AKI), one of the most prevalent clinical diseases with a high incidence rate worldwide, is characterized by a rapid deterioration of renal function and further triggers the accumulation of metabolic waste and toxins, leading to complications and dysfunction of other organs. Multiple pathogenic factors, such as rhabdomyolysis, infection, nephrotoxic medications, and ischemia-reperfusion injury, contribute to the onset and progression of AKI. However, the detailed mechanism remains unclear. Ferroptosis, a recently identified mechanism of nonapoptotic cell death, is iron-dependent and caused by lipid peroxide accumulation in cells. A variety of studies have demonstrated that ferroptosis plays a significant role in AKI development, in contrast to other forms of cell death, such as apoptosis, necroptosis, and pyroptosis. In this review, we systemically summarized the definition, primary biochemical mechanisms, key regulators and associated pharmacological research progress of ferroptosis in AKI. We further discussed its therapeutic potential for the prevention of AKI, in the hope of providing a useful reference for further basic and clinical studies.

Epitranscriptomics has emerged as another level of epigenetic regulation similar to DNA and histone modifications. N6-methyladenosine (m6A) is one of the most prevalent and abundant posttranscriptional modifications, widely distributed in many biological species. The level of N6-methyladenosine RNA methylation is dynamically and reversibly regulated by distinct effectors including methyltransferases, demethylases, histone modification and metabolites. In addition, N6-methyladenosine RNA methylation is involved in multiple RNA metabolism pathways, such as splicing, localization, translation efficiency, stability and degradation, ultimately affecting various pathological processes, especially the oncogenic and tumor-suppressing activities. Recent studies also reveal that N6-methyladenosine modification exerts the function in immune cells and tumor immunity. In this review, we mainly focus on the regulatory mechanisms of N6-methyladenosine RNA methylation, the techniques for detecting N6-methyladenosine methylation, the role of N6-methyladenosine modification in cancer and other diseases, and the potential clinical applications.

Vertisols are clayey soils with a high potential for improving production. Therefore, understanding the impact of tillage and fertilization on soil physicochemical properties and microbial community is essential for improving the vertisols with a high montmorillonite and smectite clay content. A 3-year field experiment was conducted to compare the effects of different tillage and fertilization practices at three depths of the vertisol under the wheat–maize cropping system in the North China Plain. The experimental treatments included rotary tillage without fertilization (R-CK), rotary tillage with chemical nitrogen (N), phosphorus (P), and potassium (K) fertilization (R-NPK), R-NPK plus biochar (R-NPKB), deep tillage without fertilization (D-CK), deep tillage with chemical N, P, and K fertilization (D-NPK), and D-NPK plus biochar (D-NPKB). The results showed that D-NPKB significantly improved winter wheat and summer maize yields by 14.4 and 3.8%, respectively, compared with R-NPK. The nitrate (NO3––N) content of the deeper soil layer in D-NPKB was significantly higher than that in D-NPK. Meanwhile, biochar application increased the pH in the three layers. Compared with R-NPK, D-NPKB significantly increased the average content of available phosphorus (AP), soil organic carbon (SOC), and total nitrogen (TN) by 73.7, 18.5, and 19.0%, respectively. Meanwhile, Gaiellale, Sphingomonadaceae, and Nocardioidaceae were the predominant bacteria at the family level across all treatments, with a total relative proportion ranging from 14.1 to 23.6%. In addition, the abundance of Bacillaceae in deep tillage was 9.4% higher in the 20–30-cm soil layer than that in rotary tillage. Furthermore, the correlation analysis revealed a significant positive correlation between crop yield and chemical factors such as NO3––N and the abundances of Gaiellalea, Sphingomonadaceae, and Nocardioidaceae. The findings collectively indicated that deep tillage combined with biochar application could increase the soil nutrients and modify the bacterial structure in the deeper soil layer and therefore will be beneficial for improving the productivity of the vertisols.

The proportion of pregnant women giving birth through cesarean section is increasing annually worldwide. However, post-cesarean section scar diverticulum is a common condition that occurs and requires better surgical strategies than the methods currently used. We hypothesized that using biological lubricant topically on the incision area during C-section could be an option to minimize the scar. This water-based polyethylene glycol (PEG)/chitosan (CS) composite lubricant was prepared via ultrasonic blending. The product was characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and Raman spectroscopy. The thermal stability of the materials and their heat absorption and release during heating were analyzed using thermogravimetric analysis and differential scanning calorimetry. Tribological tests proved that the PEG/CS composite had a better lubrication effect than either the PEG or CS lubricant alone, and the cell viability experiments verified that it had good biocompatibility. Finally, application of the composite lubricant onto the backs of mice modeling full-thickness skin incisions further confirmed that the product improved both the re-epithelialization and the collagen levels of the wounded skin. In conclusion, we expect our newly formulated PEG/CS composite lubricant to be useful not only for managing post-cesarean section scar diverticulum but also for healing skin wounds in general.

Food safety is as important as ever, and the safeguards implemented to inspect and reduce pesticides, veterinary drugs, toxins, pathogens, illegal additives, and other deleterious contaminants in our food supply has helped improve human health and increase the length and quality of our lives [...]

Dysfunction of the gastrointestinal system, and to the autophagy lysososmal pathway (ALP) have been reported in Parkinson’s disease. Here the authors report epigenetic disruption of ALP related genes in the appendix of individuals with Parkinson’s disease.

Immune evasion (IEV) plays a critical role in the development and progression of colon cancer. However, studies to predict the prognosis of colon cancer via IEV-related genes are limited. Therefore, based on the 182 IEV-related genes, we used the univariate and Lasso Cox regression model to construct the IEV-related genes signature (IEVSig) of 16 prognostic IEV-related genes using the Gene Expression Omnibus and The Cancer Genome Atlas online databases. We found that IEVSig was an independent prognostic factor, and patients with high IEVSig had higher TNM stage and shorter recurrence-free survival than their counterparts. Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analyses revealed that patients with high and low IEVSig had significantly different enrichment pathways. Immune cell infiltration analysis showed that nine immune cells obviously increased in the high-IEVSig group, whereas five immune cells increased in the low-IEVSig group. Immunotherapy cohort analysis revealed that patients with high IEVSig had a higher proportion of progressive disease or stable disease after receiving immunotherapy than patients with low IEVSig. Furthermore, patients with low IEVSig had higher tumor mutation load and neoantigen burden, which indicated an improved response to immunotherapy, than patients with high IEVSig. Thus, an IEV-related prognostic signature was established to predict the prognosis of patients with colon cancer and derive a prediction marker to offer insights into therapeutic strategies.

To explore the quality of high-resolution CT images information in the evaluation of pulmonary nodule interface and internal structure of nodules in lung tissue, as well as the value of early diagnosis of lung cancer associated with infection, high-resolution CT images were used as the research object. Through the analysis of the computerized detection and diagnosis (Computer-Aided Diagnosis (CAD)) of lung cancer, the high-resolution CT was further explored in the process of clinical imaging doctors in the diagnosis of lung cancer, and more conditions were created for the application of medical image processing in the early diagnosis of lung cancer. The research results show that CAD can automatically and accurately complete the automatic segmentation of the lung region in the CT image by applying the automatic segmentation algorithm for a series of processing and analysis of the CT image, that is, generating high-resolution CT images. It can enhance the pulmonary nodules in CT images and improve the accuracy of lung nodule detection, which is of great value in the diagnosis of early lung cancer. CAD diagnosis of lung lesions based on high-resolution CT images is studied, which can provide reference for imaging physicians to diagnose early lung cancer. However, in the automatic identification of benign and malignant lesions in the lungs, it is necessary to further improve the analysis function of similar nodules, which will be an important step for humans in the diagnosis and treatment of diseases.

Abstract Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase belonging to class III histone deacetylases. Previous studies have shown that SIRT1 is involved in kidney physiology regulation and protects the kidney from various pathological factors. However, the underlying mechanisms behind its function have yet to be fully elucidated. In our study, we found that ablation of Sirt1 in renal interstitial cells resulted in more severe renal damage and fibrosis in unilateral ureteral obstruction (UUO) model mice. We also observed that hypoxia-inducible factor (HIF)-2α expression was increased in Sirt1 conditional knockout mice, suggesting that HIF-2α might be a substrate of SIRT1, mediating its renoprotective roles. Therefore, we bred Hif2a deficient mice and subjected them to renal trauma through UUO surgery, ultimately finding that Hif2a ablation attenuated renal fibrogenesis induced by UUO injury. Moreover, in cultured NRK-49F cells, activation of SIRT1 decreased HIF-2α and fibrotic gene expressions, and inhibition of SIRT1 stimulated HIF-2α and fibrotic gene expressions. Co-immunoprecipitation analysis revealed that SIRT1 directly interacted with and deacetylated HIF-2α. Together, our data indicate that SIRT1 plays a protective role in renal damage and fibrosis, which is likely due to inhibition of HIF-2α.

Erythromycin (ERY) is one of the most common macrolides applied in veterinary medicine to treat diseases or as a feed additive for animal growth promotion. Long-term irrational use of ERY could lead to residues in animal-derived food and the emergence of drug-resistant strains, posing potential threats to human health. In this study, a highly sensitive, specific, robust, and rapid fluorescence polarization immunoassay (FPIA) for the determination of ERY in milk has been described. Herein, to achieve high sensitivity, five tracers of ERY with different fluorescein structures were synthesized and paired with three monoclonal antibodies (mAbs). Under the optimized conditions, the combination of mAb 5B2 and tracer ERM-FITC achieved the lowest IC50 value in the FPIA with 7.39 μg/L for ERM. The established FPIA was used to detect ERY in milk, revealing a limit of detection (LOD) of 14.08 μg/L with recoveries of 96.08–107.77% and coefficients of variations (CVs) of 3.41–10.97%. The total detection time of the developed FPIA was less than 5 min from the addition of samples to the result readout. All the above results showed that the proposed FPIA in this study was a rapid, accurate, and simple method for the screening of ERY in milk samples.

The biological and clinical features of chronic lymphocytic leukemia (CLL) exhibited profound heterogeneity across Chinese and patients of predominately European descent. However, the age-related peculiarities and risk assessment of Chinese CLL patients remained ill-defined. The present study demonstrated that CLL patients were characterized by the earlier age at onset in China (median age at diagnosis: 63 years old) than in the United States (median age at diagnosis: 69 years old). Young patients from Shandong Provincial Hospital CLL database displayed prolonged overall survival than the Surveillance, Epidemiology, and End Results cohort. Furthermore, among Chinese CLL patients, young patients showed an increased relapse rate compared with elderly patients. To optimize the risk assessment of CLL patients, novel risk score models named PR-Score and HBG-Score were developed for predicting the outcomes of young and elderly CLL patients respectively. The neonatal survival prediction systems were superior to international prognostic index for CLL (CLL-IPI) and Binet stage in assessing the overall survival and progression free survival of CLL patients. The analyses highlighted refinement of risk evaluation for CLL patients in different age groups, providing insights into individualized diagnosis and treatment of CLL.

Hickory (Carya cathayensis) is a critical tree species of the genus Carya from the Juglandaceae family that contains nutrient-rich nuts. Due to large-scale soil degradation, the pests and diseases of hickory are becoming more and more serious. Thaumatin-like proteins (TLPs) are vital proteins involved in the complex defense process of plant pathogens. In this study, 40 CcTLP genes were identified genome-widely and phylogenetically grouped into three subfamilies. The sequence of CcTLPs had a conservative pattern, such as eight stable disulfide bonds, REDDD, and G-X-[GF]-X-C-X-T-[GA]-D-C-X(1,2)-G-X-(2,3)-C structure. In total, 57 cis-elements related to stress-responsive, light-responsive, phytohormone-responsive, and plant-responsive were discovered. Under salicylate (SA), methyl jasmonate (MeJA), and ethephon (ETH) treatments, the expressions of CcTLP28, CcTLP29, CcTLP30, CcTLP31, CcTLP32, CcTLP33, CcTLP37, CcTLP38, and CcTLP39 had different patterns. This is an indication that most of the TLP genes were upregulated by SA and downregulated by MeJA. Notably, seven TLP genes were significantly upregulated under the Botryosphaeria dothidea inoculation, especially CcTLP31, with an over 20-fold change. Nine genes were shown by subcellular localization analysis to be located at the plasma membrane and cytoplasm. The knowledge of the disease-resistant function of the CcTLP family in hickory is promoted by these results. A foundation reference for the molecular breeding of this plant in the future is provided by our findings.

Objective: The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision. Methods: Two time points, the summer and winter solstice, which are the longest and shortest days of the year, respectively, were selected. Male Sprague–Dawley rats that underwent a sham operation without pineal excision were included as a control group. The concentrations of 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) were determined by radioimmunoassays and enzyme-linked immunosorbent assays, respectively. Results: In the winter, the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group (P

The bacterial effector MavC can ubiquitinate the host E2 enzyme UBE2N to dampen the host immune response. Here, the authors provide mechanistic insight into this non-canonical ubiquitination machinery and reveal the structural basis for the functional differences between MavC and its close homolog MvcA.