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The middle Eocene climatic optimum (MECO, ca. ~42 Ma) is a key time period for understanding Cenozoic cooling of the global climate. Still, midlatitude terrestrial records of climate evolution during MECO epoch are rare. In this study, continuous high-resolution record of shale sediments in mid-Eocene Shahejie Formation (MES shales) in the Bohai Bay Basin were performed with major-element and wavelet analysis. The midlatitude paleoweathering and paleoclimatic evolution during MECO epoch were analyzed in this study. The MES shales experienced weak-moderate paleoweathering under a subtropical monsoon paleoclimate with mean annual temperature of 8.3-12.9 °C and mean annual precipitation of 685-1100 mm/yr. The MES shales record a mixed provenance involving intermediate igneous rocks, and low compositional maturity. The nutrient-rich environment led to enrichment in organic matter in the MES shales. Wavelet analysis revealed good periodicity about the paleoclimate and weathering during MECO epoch. In the stage I of MES shales depositional process, the paleolake was high in nutrients, and the MES shales experienced high chemical weathering due to a relatively warmer and more humid climate. In contrast, the climate in stage II was relatively cold and dry, and the maturity of the MES shales was relatively high during this stage, suggesting a relatively stable tectonic background. This work provides more terrestrial records of MECO epoch for midlatitude region, and is benefit for better understanding of the palaeoenvironment when MES shales formed. The implication of organic matters enrichment in this study is meaningful for the shale oil/gas exploration in Nanpu Sag. [ABSTRACT FROM AUTHOR]

Abstract With climate change and anthropic influence on the coastal ecosystems, mangrove ecosystems are disappearing at an alarming rate. Accordingly, it becomes important to track, study, record and store the mangrove microbial community considering their ecological importance and potential for biotechnological applications. Here, we provide information on mangrove fungal community composition and diversity in mangrove ecosystems with different plant species and from various locations differing in relation to anthropic influences. We describe twelve newly assembled genomes, including four chromosomal-level genomes of fungal isolates from the mangrove ecosystems coupled with functional annotations. We envisage that these data will be of value for future studies including comparative genome analysis and large-scale temporal and/or spatial research to elucidate the potential mechanisms by which mangrove fungal communities assemble and evolve. We further anticipate that the genomes represent valuable resources for bioprospecting related to industrial or clinical uses.

Abstract To evaluate the diagnostic accuracy of matrix-assisted laser desorption ionization time-of-flight mass spectrometry based on nucleotide (nucleotide MALDI-TOF MS) on bronchoalveolar lavage fluid (BALF) from suspected pulmonary tuberculosis (PTB) patients. A retrospective study was conducted on suspected PTB patients (total of 960) admitted to Chongqing Public Health Medical Center between May 2021 and January 2022. The sensitivity, specificity, positive predictive value, negative predictive value (NPV) and area under the curve values of nucleotide MALDI-TOF MS as well as smear microscopy, Mycobacterium Growth Indicator Tube 960 culture (MGIT culture), and Xpert MTB/RIF were calculated and compared. Total of 343 presumed PTB cases were enrolled. Overall, using the clinical diagnosis as reference, the sensitivity and NPV of nucleotide MALDI-TOF MS was 71.5% and 43.1%, respectively, significantly higher than smear microscopy (22.6%, 23.2%), MGIT culture (40.6%, 18.9%), Xpert MTB/RIF (40.8%, 27.9%). Furthermore, nucleotide MALDI-TOF MS also outperformed over Xpert MTB/RIF and MGIT culture on smear-negative BALFs. Approximately 50% and 30% of patients benefited from nucleotide MALDI-TOF MS compared with smear and MGIT culture or Xpert MTB/RIF, respectively. This study demonstrated that the analysis of BALF with nucleotide MALDI-TOF MS provided an accurate and promising tool for the early diagnosis of PTB.

Abstract Background Approximately 25–30% of patients with acute myeloid leukemia (AML) have FMS-like receptor tyrosine kinase-3 (FLT3) mutations that contribute to disease progression and poor prognosis. Prolonged exposure to FLT3 tyrosine kinase inhibitors (TKIs) often results in limited clinical responses due to diverse compensatory survival signals. Therefore, there is an urgent need to elucidate the mechanisms underlying FLT3 TKI resistance. Dysregulated sphingolipid metabolism frequently contributes to cancer progression and a poor therapeutic response. However, its relationship with TKI sensitivity in FLT3-mutated AML remains unknown. Thus, we aimed to assess mechanisms of FLT3 TKI resistance in AML. Methods We performed lipidomics profiling, RNA-seq, qRT-PCR, and enzyme-linked immunosorbent assays to determine potential drivers of sorafenib resistance. FLT3 signaling was inhibited by sorafenib or quizartinib, and SPHK1 was inhibited by using an antagonist or via knockdown. Cell growth and apoptosis were assessed in FLT3-mutated and wild-type AML cell lines via Cell counting kit-8, PI staining, and Annexin-V/7AAD assays. Western blotting and immunofluorescence assays were employed to explore the underlying molecular mechanisms through rescue experiments using SPHK1 overexpression and exogenous S1P, as well as inhibitors of S1P2, β-catenin, PP2A, and GSK3β. Xenograft murine model, patient samples, and publicly available data were analyzed to corroborate our in vitro results. Results We demonstrate that long-term sorafenib treatment upregulates SPHK1/sphingosine-1-phosphate (S1P) signaling, which in turn positively modulates β-catenin signaling to counteract TKI-mediated suppression of FLT3-mutated AML cells via the S1P2 receptor. Genetic or pharmacological inhibition of SPHK1 potently enhanced the TKI-mediated inhibition of proliferation and apoptosis induction in FLT3-mutated AML cells in vitro. SPHK1 knockdown enhanced sorafenib efficacy and improved survival of AML-xenografted mice. Mechanistically, targeting the SPHK1/S1P/S1P2 signaling synergizes with FLT3 TKIs to inhibit β-catenin activity by activating the protein phosphatase 2 A (PP2A)-glycogen synthase kinase 3β (GSK3β) pathway. Conclusions These findings establish the sphingolipid metabolic enzyme SPHK1 as a regulator of TKI sensitivity and suggest that combining SPHK1 inhibition with TKIs could be an effective approach for treating FLT3-mutated AML.

[Objective] To analyze the differences in volatile components between three kinds of dried L. edoeds. [Methods] Three different drying methods (hot air drying, radio frequency-hot air drying, vacuum freeze drying) were used to determine the volatile substances in L. edoeds by gas chromatogi-ion migration spectrometry (GC-IMS), and the differences of volatile substances in L. edoeds were analyzed according to fingerprint and PCA. [Results] The main volatile components of dried L. edoeds were aldehydes, alcohols, ketones and acids. There were significant differences in the characteristic volatile organic substances of dried L. edoeds in three different drying methods, the contents of aldehyde and alcohol were hot air drying > radio frequency-hot air drying > VD. Fingerprint analysis showed that compared with vacuum freeze drying, hot air drying and radio frequency-hot air drying could significantly improve the fruity flavor of L. edoeds. PCA analysis showed that the contribution rate of PC1 and PC2 was 61% and 29%, respectively, and the cumulative contribution rate reached 90.0%. Hot air drying and radio frequency-hot air drying had high similarity in the flavor composition of L. edoeds. [Conclusion] GC-IMS can realize differential and rapid analysis and identification of volatile flavor components of L. edoeds produced by three drying methods, and provide theoretical reference for high-quality drying of L. edoeds and its product identification.

Abstract Background Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis. Methods In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure. Results We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods. Conclusions This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis. Graphical Abstract

This paper substantiates a theoretical approach to the integral study of various directions of Russian poetics associated with the new concept of the “Russian School of European Poetics” or “Russian School of Poetics,” which is distinguished by its pioneering modernization of European classical poetics at the turn of the 20th century and its cross-cultural development and expansion in the 1960s and the 1970s. Four questions are also discussed: firstly, why do Western scholars prefer to develop modern Russian theory of literature into “Theory”? Secondly, how to identify the main line of modern Russian poetics from its genetic origin to maturity? Third, why was the modernization of European poetics initiated in Russia? Fourth, what specific characteristics are found in the Russian school of Poetics in the state of “overflowing” of poetics in Western countries? The author of the present paper believes that an attempt to reconstruct the Russian school of poetics can serve as a valuable research example for the revival of Chinese traditional culture, including the ancient poetics of China, in the form of modernization.

Background: Ozone can enhance the expression of some growth factors (GFs) in platelet rich plasma (PRP), recent study showed oxygen-rich PRP (ozonized PRP) have better therapeutic effects on bone and joint diseases. PRP injection has been widely used in the treatment of facial rejuvenation, but the efficacy of sufficient oxygen-rich PRP in facial rejuvenation has not been studied. Objective: Firstly, we examined whether ozone treatment can increase the concentration of GFs of PRP in vitro. And then a variety of subjective and objective detection methods were used to evaluate the effect of sufficient(10–12 mL each time for the injection of face and neck) oxygen-rich (ozonized PRP) PRP injection in facial rejuvenation by follow-up for 6 months. At last, we investigated the satisfaction, side effects and pain score of the treatment through a questionnaire survey. Methods: The concentration of main GFs in PRP treated with different dose of ozone in vitro was measured by ELISA. Clinical picture, the collagen thickness of dermis by reflectance confocal microscope(RCM), skin conditions (including spots, ultraviolet (UV) spots, brown spots, red area, pores, wrinkles, texture and porphyrin) by VISIA were collected before treatment and each month follow-up visit after treatment until 6-month follow-up period was finished. Patients’ satisfaction, side effects and pain score were collected at the end of follow-up period. Results: PRP treated by high-dose ozone (57 μg/mL, ozone/PRP volume ratio:1/1) in vitro showed a significant increase in endothelial growth factor (EGF) and transforming growth factor-β (TGF-β) compared to baseline(P

Background Bendamustine–rituximab (BR) therapy stands out as a promising alternative for elderly patients with diffuse large B-cell lymphoma (DLBCL), demonstrating notable efficacy when conventional regimens pose challenges. Despite its clinical success, the intricate mechanisms underlying BR therapy have remained elusive.Methods DLBCL cell lines were used to investigate the mechanism of BR therapy in vitro. RNA-seq and Western blot were used to explore the target pathways of BR therapy. STING was knocked out using Crispr-cas9 and inhibited using H-151 to investigate its role in BR therapy. Bulk RNA-seq and single-cell RNA-seq data from patients were analyzed to investigate the association between STING and pyroptosis pathways, validated using STING downregulated cells. Flow cytometry, transwell experiments and co-culture experiments were performed to investigate the inflammatory phenotype of DLBCL cells after BR treatment and its effect on T-cell recruitment and activation.Results This study elucidates that BR elicits direct tumoricidal effects by promoting apoptosis and inducing cell cycle arrest. The synergistic impact with rituximab is further potentiated by complement addition, demonstrating the pivotal role of in vivo antibody-dependent cellular cytotoxicity. Moreover, our investigation reveals that, through a cGAS–STING-dependent pathway, prolonged exposure to BR induces pyroptosis in DLBCL cells. Activation of the cGAS–STING pathway by BR therapy triggers the release of inflammatory factors and upregulates major histocompatibility complex molecules, shaping an immunologically hot tumor microenvironment.Conclusions This unique dual influence not only directly targets DLBCL cells but also engages the patient’s immune system, paving the way for innovative combination therapies. The study provides comprehensive insights into the multifaceted actions of BR in DLBCL, offering a foundation for refined and personalized treatment strategies in elderly patients.

Introduction: Vitiligo is a common acquired depigmenting dermatosis resulting from a loss of epidermal melanocytes. The academic attention to vitiligo has gradually increased over the past two decades. Objective: We aimed to explore the current research structure and trends of vitiligo. Methods: Publications about vitiligo from the Web of Science Core Collection (WoSCC) database were searched. VOSviewer, CiteSpace, GraphPad Prism 8, ArcGIS, and Charticulator were implemented for data description and visual analysis. Results: A total of 3,037 publications authored by 10,993 individuals from 2,753 institutions across 88 countries/regions were collected. These publications were published in 616 journals and cited a total of 39,433 references. China was the most productive country. Cairo University and Ezzedine Khaled were the most prolific institution and author, respectively. Additionally, the British Journal of Dermatology stood out as the journal with the highest number of publications. According to the analysis of keywords and references, “quality of life,” “depression,” and “validation” were hotspots in terms of clinical characteristics, while “prevalence”, “comorbidity,” “association,” and “immunotherapy” gained more research interest with respect to epidemiology and genetics. The frontiers of pathogenesis focused on “unfolded protein response,” “migration,” “biomarkers,” and “CXCL10.” As far as treatment is concerned, there was increasing attention to “janus kinase inhibitor,” “fractional carbon dioxide laser,” “platelet-rich plasma,” and “5-fluorouracil.” Conclusion: The bibliometric analysis elucidates the foundational knowledge structure on research forces and unveiled the hotspots and frontiers, aiding researchers in gaining a deeper comprehension of the future development trends in the field of vitiligo.

PIK3CA gene encodes the p110α catalytic subunit of PI3K, which regulates the PI3K/AKT/mTOR signaling pathway. PIK3CA gene mutation is one of the most common mutations in colorectal cancer (CRC), affecting about 15%–20% of CRC patients. PIK3CA gene mutation leads to the persistent activation of the PI3K/AKT/mTOR signaling pathway, which promotes the proliferation, invasion, metastasis, and drug resistance of CRC. This article provides a summary of the key detection methods for PIK3CA gene mutation, and provides an introduction to the existing colorectal cancer treatments and their practical applications in the clinic. Besides, this article summarizes the role and mechanism of PIK3CA gene mutation in the occurrence and development of CRC. It also explores the relationship between PIK3CA gene mutation and the clinical features and prognosis of CRC. This article focuses on the influence and mechanism of PIK3CA gene mutation on the targeted therapy and immunotherapy of CRC, and discusses the potential value and future direction of PIK3CA gene mutation in the personalized therapy of CRC. We aim to provide new perspectives and ideas for the precise diagnosis and treatment of CRC.

Introduction: Increasing evidence suggests that RNA modification plays a significant role in the kidney and may be an ideal target for the treatment of kidney diseases. However, the specific mechanisms underlying RNA modifications in the pathogenesis of kidney disease remain unclear. Genome-wide association studies (GWAS) have identified numerous genetic loci involved in kidney function and RNA modifications. The identification and exploration of RNA modification-related single-nucleotide polymorphisms (RNAm-SNPs) associated with kidney function can help us to comprehensively understand the underlying mechanism of kidney disease and identify potential therapeutic targets. Methods: First, we examined the association of RNAm-SNPs with eGFR. Second, we performed expression quantitative trait locus (eQTL) and protein quantitative trait locus (pQTL) analyses to explore the functions of the identified RNAm-SNPs. Finally, we evaluated the causality between RNAm-SNP-associated gene expression and circulating proteins and kidney function using a Mendelian randomization (MR) analysis. Results: A total of 252 RNA m-SNPs related to m6A, m1A, A-to-I, m5C, m7G, and m5U were identified. All these factors were significantly associated with the eGFR. A total of 119(47.22 %) RNAm-SNPs showed cis-eQTL effects in blood cells, whereas 72 (28.57 %) RNAm-SNPs showed cis-pQTL effects in plasma. 47 (18.65 %) RNAm-SNPs exhibited cis-eQTL and cis-pQTL effects. In addition, we demonstrated a causal association between RNAm-SNP-associated gene expression, circulating protein levels, and eGFR decline. Some of the identified genes and proteins have been reported to be associated with kidney diseases, such as CDK10 and SDCCAG8. Conclusions: This study reveals an association between RNAm-SNPs and kidney function. These SNPs regulate gene expression and protein levels through RNA modifications, eventually leading to kidney dysfunction. Our study provides novel insights that connect the genetic risk of kidney disease to RNA modification and suggests potential therapeutic targets for the prevention and treatment of kidney disease.

Since the p53 protein is an important promising biomarker of lung tumor and colorectal tumor, it is very essential to design a highly effective mean to monitor the degree of p53 for the early clinical analysis/therapy of the related tumors. In this work, a sandwich-type electrochemical immunosensing (SES) platform is proposed for the first time to detect p53 via synthesizing Ti3C2Tx MXene nanoribbons (Ti3C2Tx Nb) and ferrocene/gold nanoparticles (Fc/Au) respectively as the sensing substrate and signal-amplifier. The superior electrical property and large surface area of Ti3C2Tx Nb are beneficial to assemble the initial p53-antibodies (Ab1), while the synthesized Fc/Au is devoted to assemble the secondary p53 antibodies (Ab2) and gives a magnified signal. By adopting the Fc molecules as the probes, the experiments reveal the response current of Fc resulted from the SES structure increases along with the p53 increase from 1.0 to 200.0 pg mL−1. A considerable low detection limit (1.0 pg mL−1) is achieved after optimizing several key conditions, it is thus confirmed the as-proposed SES mean exhibits significant application in the detection of p53 protein and other targets.