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The incidence of neurotrophic tyrosine kinase receptor (NTRK) fusion uterine sarcoma is extremely low, and reports have been mostly focused on cases localized to the cervix. So far, only 4 cases have been reported of the uterine corpus. In this study, we reported a case of NTRK fusion corpus sarcoma. This study aimed to expand the morphologic spectrum of this tumor, which showed adenosarcoma-like features not previously described. The tumor was confined to the uterine corpus, polypoid growth, comprised predominantly of a fascicular proliferation of spindle cells, entrapping benign endometrial glands, and exhibited a pseudo-biphasic growth pattern. The tumor showed coexpression of S-100, CD34, and pan-Trk by immunohistochemistry, DNA-sequencing identified TPR-NTRK1 gene fusion and AKT1(E17K) mutation. Four cases of NTRK fusion corpus sarcoma were reviewed. The clinicopathologic features, immunohistochemical phenotype, molecular testing, and prognosis of 5 cases including this one were summarized and analyzed. Most cases exhibited an infiltrative g rowth pattern and showed mild or moderate cytologic atypia. The potential for these tumors to be misclassified as uterine adenosarcoma or other uterine mesenchymal tumors. The diagnosis relies on pan-Trk, S-100, CD34 immunohistochemistry, and molecular testing. Surgical resection is the mainstay of treatment for most patients. Distinguishing these tumors from morphologic mimics is significant because patients with advanced-stage disease may be treated with TRK inhibitors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cognition, behaviours and social environment are associated with Clonorchis sinensis infection, a prevalent liver fluke disease in China. This study aimed to use social cognitive theory (SCT) to investigate these three aspects and their interaction in an endemic area., Methods: We conducted three semi-structured focus group discussions in Da'ao town, Jiangmen city, Guangdong Province, China. Thematic analysis was used to extract themes., Results: Twenty-four people were interviewed. The participants exhibited inadequate knowledge about C. sinensis infection and were unaware of the health risks. Although some have reduced their consumption of raw fish, some continue to consume it frequently. Compared with stopping eating raw fish, receiving tests and taking medicines were easier behaviours to adopt. Guided by the SCT, we considered the reciprocal determinism between people and the social environment as the basis of the persistent raw fish consumption behaviour. While the social environment could influence the cognition and behaviours of people, people also can reshape the social environment. Based on the reciprocal determinism, we proposed an integrated intervention framework., Conclusions: Our study unveiled a reciprocal determinism between the cognition, behaviours and social environment related to C. sinensis infection in high-endemic areas of China, providing insights for establishing control strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Bone defect healing is a multi-factorial process involving the inflammatory microenvironment, bone regeneration and the formation of blood vessels, and remains a great challenge in clinical practice. Combined use of three-dimensional (3D)-printed scaffolds and bioactive factors is an emerging strategy for the treatment of bone defects. Scaffolds can be printed using 3D cryogenic printing technology to create a microarchitecture similar to trabecular bone. Melatonin (MT) has attracted attention in recent years as an excellent factor for promoting cell viability and tissue repair. In this study, porous scaffolds were prepared by cryogenic printing with poly(lactic-co-glycolic acid) and ultralong hydroxyapatite nanowires. The hierarchical pore size distribution of the scaffolds was evaluated by scanning electron microscopy (SEM) and micro-computed tomography (micro-CT). Sleep-inspired small extracellular vesicles (MT-sEVs) were then obtained from MT-stimulated cells and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)-inorganic pyrophosphate (DSPE-PEG-PPi) was used to modify the membrane of MT-sEVs to obtain PPi-MT-sEVs. RNA sequencing was performed to explore the potential mechanisms. The results demonstrated that PPi-MT-sEVs not only enhanced cell proliferation, migration and angiogenesis, but also regulated the osteogenic/adipogenic fate determination and M1/M2 macrophage polarization switch in vitro. PPi-MT-sEVs were used to coat scaffolds, enabled by the capacity of PPi to bind to hydroxyapatite, and computational simulations were used to analyze the interfacial bonding of PPi and hydroxyapatite. The macrophage phenotype-modulating and osteogenesis-angiogenesis coupling effects were evaluated in vivo. In summary, this study suggests that the combination of hierarchical porous scaffolds and PPi-MT-sEVs could be a promising candidate for the clinical treatment of bone defects., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval was granted by the Ethics Committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. All animal experiments were approved by the Animal Care Committee of Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and followed the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The bioaccumulation of heavy metals due to metallurgical and smelting activities threatens human health. Although microbial-induced carbonate/phosphate precipitation (MICP/MIPP) technology has been applied to heavy metal remediation, the relative merits of MICP and MIPP, especially under extreme pH environments, have not yet been documented. In this study, Sporosarcina pasteurii (SP)-based MICP and Bacillus megaterium (BM)-based MIPP were applied to immobilize lead (Pb) in aqueous solution and loess soil. The results showed that the BM retained a strong phosphorolysis ability when under strongly acidic conditions, while the ureolysis ability of SP approached zero. Furthermore, the bioprecipitates obtained under BM-based MIPP had a denser appearance, presumably due to the enrichment of calcite and apatite crystals. The results also showed that Pb immobilization was achieved through bacterial adsorption, the chelate function of sodium glycerophosphate (SGP), large organic matter complexation, and biomineralization through the MICP/MIPP mechanism. Under SP-based MICP, SP and large organic matter immobilized Pb 2+ at rates of 17.6 % and 31.7 %, respectively, while under BM-based MIPP, BM, organic matter, and SGP immobilized Pb 2+ at rates of 21.5 %, 23.4 %, and 48.5 % respectively. The MICP and MIPP mechanisms dominated Pb immobilization at rates of 78.6 % and 99.6 %, respectively., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study investigated the enhancing effects of soil treatment with ethylene diamine tetraacetic acid (EDTA) and oxalic acid (OA) on the remediation of Cr(VI) contaminated soil by Datura stramonium L. A greenhouse pot experiment was conducted, where Cr(VI) contaminated soil was treated with 100 mg/kg Cr(VI) and varying concentrations of EDTA (5 and 10 mmol/kg) and OA (5 and 10 mmol/kg). The effects of these soil treatments on biomass, chlorophyll content, antioxidant enzyme activities, and Cr(VI) enrichment and translocation efficiency of D. stramonium were evaluated. The results showed that added OA to soil significantly increased the biomass and chlorophyll content of D. stramonium. The addition of 10 mmol/kg of OA to soil increased the plant biomass by 67.16 % and chlorophyll b content by 40.01 %. In addition, OA soil treatment significantly enhanced the activities of superoxide dismutase (SOD) by 6.36 %, peroxidase (POD) by 163.13 %, catalase (CAT) by 36.92 %, and ascorbate peroxidase (APX) by 32.12 %, which effectively alleviated the oxidative stress induced by Cr(VI). In contrast, soil treatment with a high concentration of EDTA (10 mmol/kg) significantly reduced plant biomass and chlorophyll content, although it increased the biological concentration factor (BCF) of the stem and leaf, as well as the translocation factor (TF). In conclusion, appropriate amounts of EDTA and OA added to soil can enhance the phytoremediation efficiency of D. stramonium grown in Cr(VI) contaminated soil, with OA added to soil being more effective than addition of EDTA. This study revealed the potential mechanisms of chelating agents EDTA and OA in enhancing the phytoremediation of Cr(VI) contaminated soil by D. stramonium, providing a scientific basis for further optimization of phytoremediation techniques., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cong Shi reports financial support was provided by National Natural Science Foundation of China. Cong Shi reports financial support was provided by National Forestry and Grassland Administration. Cong Shi reports financial support was provided by Tianjin Agriculture and Rural Committee. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Repairing osteochondral defects necessitates the intricate reestablishment of the microenvironment. The cartilage layer consists of a porous gelatin methacryloyl hydrogel (PGelMA) covalently crosslinked with the chondroinductive peptide CK2.1 via a "linker" acrylate-PEG-N-hydroxysuccinimide (AC-PEG-NHS). This layer is optimized for remodeling the senescent microenvironment in the cartilage region, thereby establishing a regenerative microenvironment that supports chondrogenesis. For the bone layer, silk fibroin methacryloyl (SilMA) is coated onto a three dimensional (3D)-printed 45S5 bioactive glass scaffold (BG scaffold). The "exercise hormone" N-lactoyl-phenylalanine (Lac-Phe) is loaded onto the SilMA, endowing it with diversified functions to regulate the osteogenic microenvironment. Systematic analysis in vitro reveals that PGelMA-CK2.1 shifts the microenvironment from a pro-inflammatory into an anti-inflammatory condition, and alleviates cellular senescence, thus modifying the cartilage microenvironment to improve the recruitment, proliferation and chondral differentiation of bone marrow mesenchymal stem cells (BMSCs). The scaffold bone layer enhances microvascular endothelial cell proliferation, migration, and angiogenic activities, which, couple with increased BMSC recruitment and regulatory mechanisms directing BMSC differentiation, favor a shift in the "osteogenesis-adipogenesis" balance toward enhanced osteogenesis. In vivo, it is found that this biphasic biomimetic scaffold favors simultaneous dual tissue regeneration. This approach facilitates the development of bioactive regenerative scaffolds and holds great potential for clinical application., (© 2024 Wiley‐VCH GmbH.)

Given the unique charm of dipole chemistry, intercepting N-O=C dipoles precisely generated by designed processes to develop novel reactivity has become a seminal challenge. The polar fragmentation of 1,3,2-dioxazolidine species generated through the radical addition of excited nitro(hetero)arenes to alkenes represents a significantly underappreciated mechanism for generating N-O=C dipoles. Herein, we present a photoinduced Bartoli indole synthesis by the oxidative cleavage of alkenes with nitro(hetero)arenes. Various indoles and azaindoles are constructed through the multi-step spontaneous rearrangement of carbonyl imine intermediates generated by the polar fragmentation of 1,3,2-dioxazolidine species. Mechanism studies and DFT calculations support that the reaction involves radical cycloaddition, ozonolysis-type cycloreversion, intramolecular H-shift of carbonyl imines, and 3,3-sigmatropic shift of O-Alkenyl hydroxylamines, etc. The implementation of continuous- flow photochemistry, in particular, significantly enhances efficiency, thereby overcoming obstacles to the commercialization process., (© 2024 Wiley-VCH GmbH.)

The stereoconvergent synthesis of a single stereoisomer from E / Z -olefin mixtures remains one of the foremost challenges in organic synthesis. Herein, we describe a nickel-catalyzed stereoconvergent cross-coupling between E - and Z -mixed monofluoroalkenes and alkenyl electrophiles, which allows the construction of C(sp 2 )-C(sp 2 ) bonds. This defluorinative transformation offers facile access to various 1,3-dienes with E -selectivity and good functional group tolerance. Preliminary mechanistic studies indicate that the reaction most likely proceeds through a migratory insertion/β-F elimination/isomerization process.

Background: Cancer is one of the most serious threats to human health worldwide. Conventional treatments such as surgery and chemotherapy are associated with some drawbacks. In recent years, traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians, and has become an indispensable part of the comprehensive treatment for gastric cancer., Aim: To investigate the mechanism of Xiaojianzhong decoction (XJZ) in the treatment of gastric cancer (GC) by utilizing network pharmacology and experimental validation, so as to provide a theoretical basis for later experimental research., Methods: We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics. Subsequently, we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8, apoptosis, cell cycle, and clone formation assays. Additionally, we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins., Results: XJZ mainly regulates IL6 , PTGS2 , CCL2 , MMP9 , MMP2 , HMOX1 , and other target genes and pathways in cancer to treat GC. The inhibition of cell viability, the increase of apoptosis, the blockage of the cell cycle at the G0/G1 phase, and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment. In addition, XJZ induced a decrease in the mRNA expression of IL6 , PTGS2 , MMP9 , MMP2 , and CCL2 , and an increase in the mRNA expression of HOMX1 . XJZ significantly inhibited the expression of IL6, PTGS2, MMP9, MMP2, and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein., Conclusion: XJZ exerts therapeutic effects against GC through multiple components, multiple targets, and multiple pathways. Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The synthesis of medicinally interesting aryldifluoromethylated compounds has drawn significant research attention in recent years. Herein, we report an unprecedented iron-mediated process for the selective defluorination of trifluoromethylarenes to achieve the 1,2-difluoroalkylthiolation of alkenes. Preliminary mechanistic studies revealed that thiolate anion, trifluoromethylarene, and iron cation could form an electron donor-acceptor (EDA) complex, which induced selective defluorination and then difunctionalization of alkenes to obtain aryldifluoromethylated products. The generated aryldifluoromethylated compounds make it difficult to form an EDA complex again, thus avoiding excessive defluorination. This conversion has concise and ambient reaction conditions and provides an alternative solution for obtaining difluorobenzylic intermediates.

Background: Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN)., Methods: A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated., Results: The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group ( P  = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P  = 0.031). Kaplan-Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group ( P  = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P  < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival., Conclusions: Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To study the factors affecting the prognosis of patients with intrauterine adhesions (IUAs) after transcervical resection of adhesions (TCRA), analyze the reproductive outcome, and guide prognostic improvements., Design: Prospective study., Patients: Our study included 292 patients diagnosed with IUAs who underwent follow-up office hysteroscopy at Shenyang Women's and Children's Hospital between June 2018 and June 2022., Interventions: Patients were divided into case (52 patients whose hysteroscopy results indicated the presence of IUAs) and nocase (240 patients whose uterine cavity had returned to normal shape without obvious adhesion) groups on the basis of the results of a 2-month follow-up hysteroscopy following TCRA. Clinical data were collected and compared with various influencing factors, and the combined effect of these factors was assessed using multifactorial logistic regression analysis. A nomogram prediction model was constructed and internally validated on the basis of multifactorial analysis., Main Outcome Measures: Intrauterine re-adhesion was observed at a 2-month follow-up after TCRA., Results: Postoperative re-adhesion occurred in 52 of 292 patients with IUAs. Multifactorial binary logistic regression analysis showed that IUA barrier gel reapplication 5 days after TCRA was a protective factor. In contrast, the preoperative American Fertility Society scores demonstrated that severe IUAs and chronic endometritis were risk factors. The results of the multifactorial analysis were used to build a nomogram model, and the area under the curve value of the nomogram model for predicting postoperative recurrence was 0.914 (95% confidence interval: 0.864-0.956). The bootstrap method was subsequently used to resample 1,000 times for internal validation. The results showed that the internal validation C-index was 0.9135, and the calibration and ideal curves were well-matched., Conclusion: The prognosis of patients with IUAs after TCRA is related to the severity of preoperative IUAs, presence of chronic endometritis, and IUA barrier gel reapplication 5 days after TCRA. Therefore, clinicians should monitor patients using targeted data to reduce recurrence risk after TCRA and improve the prognosis of patients with IUAs., Competing Interests: Declaration of Interests J.Z. has nothing to disclose. C.S. has nothing to disclose. J.S. has nothing to disclose. J.N. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripheral lymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear., Methods: A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models., Results: MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender ( P = 0.030), lower HB (<10 g/dl, P = 0.029), higher BM blast (>5%, P < 0.0001), higher-risk IPSS-R cytogenetic ( P = 0.032) and lower NK percent ( P < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS., Conclusion: Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Gong and Shi.)

Background: Multiple myeloma cancer stem cells (MMSC) have been considered as the leading cause of multiple myeloma (MM) drug resistance and eventual relapse, microRNAs (miRNAs) collectively participate in the progression of MM. However, the pathogenesis of miR-138 in MMSC is still not fully understood., Objective: The intention of this study was to investigate the mechanism and role of miR-138 in multiple myeloma., Method: Bone marrow samples and peripheral blood from patients and normal controls were collected. Use Magnet-based Cancer Stem Cell Isolation Kit to separate and extract MMSC. Real-time quantitative PCR (RT-qPCR) was carried out to determine mRNA level. Western blot was applied to detect protein levels. MTT and flow cytometry were conducted to examine the proliferation and apoptosis of MMSC. Finally, dual-luciferase reporter gene assays were performed to confirm that paired box 5 (PAX5) is a direct target for miR-138., Results: Compared with normal group, the expression of miR-138 in patients was significantly up-regulated, and the expression of miR-138 was in a negative correlation with PAX5. Additionally, downregulated miR-138 facilitated the apoptosis and inhibited the proliferation of MMSC in vitro and in vivo. Downregulated miR-138 moderated the expression of PAX5, Bcl-2, Bax, and Caspase-3. PAX5 was a direct target of miR-138., Conclusion: Taken together, miR-138 plays a carcinogenic role in MM, and miR-138 adjusted the proliferation and apoptosis of MMSC by targeting PAX5. miR-138 has the probability of becoming a new medicinal target for the treatment of MM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This paper presents a digital edge neuromorphic spiking neural network (SNN) processor chip for a variety of edge intelligent cognitive applications. This processor allows high-speed, high-accuracy and fully on-chip spike-timing-based multi-layer SNN learning. It is characteristic of hierarchical multi-core architecture, event-driven processing paradigm, meta-crossbar for efficient spike communication, and hybrid and reconfigurable parallelism. A prototype chip occupying an active silicon area of 7.2 mm 2 was fabricated using a 65-nm 1P9M CMOS process. when running a 256-256-256-256-200 4-layer fully-connected SNN on downscaled 16 × 16 MNIST images. it typically achieved a high-speed throughput of 802 and 2270 frames/s for on-chip learning and inference, respectively, with a relatively low power dissipation of around 61 mW at a 100 MHz clock rate under a 1.0V core power supply, Our on-chip learning results in comparably high visual recognition accuracies of 96.06%, 83.38%, 84.53%, 99.22% and 100% on the MNIST, Fashion-MNIST, ETH-80, Yale-10 and ORL-10 datasets, respectively. In addition, we have successfully applied our neuromorphic chip to demonstrate high-resolution satellite cloud image segmentation and non-visual tasks including olfactory classification and textural news categorization. These results indicate that our neuromorphic chip is suitable for various intelligent edge systems under restricted cost, energy and latency budgets while requiring in-situ self-adaptative learning capability.

Background: Yigong San (YGS) is a representative prescription for the treatment of digestive disorders, which has been used in clinic for more than 1000 years. However, the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear., Aim: To explore the mechanism of YGS anti-gastric cancer and immune regulation., Methods: Firstly, collect the active ingredients and targets of YGS, and the differentially expressed genes of gastric cancer. Secondly, constructed a protein-protein interaction network between the targets of drugs and diseases, and screened hub genes. Then the clinical relevance, mutation and repair, tumor microenvironment and drug sensitivity of the hub gene were analyzed. Finally, molecular docking was used to verify the binding ability of YGS active ingredient and hub genes., Results: Firstly, obtained 55 common targets of gastric cancer and YGS. The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6, EGFR, MMP2, MMP9 and TGFB1 as the hub genes. The 5 hub genes were involved in gastric carcinogenesis, staging, typing and prognosis, and their mutations promote gastric cancer progression. Finally, molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets., Conclusion: YGS has the effect of anti-gastric cancer and immune regulation., Competing Interests: Conflict-of-interest statement: All authors declare no financial or commercial conflict of interest for this manuscript., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The SARS-CoV-2 virus is responsible for the human disease known as COVID-19. This virus is capable of generating a spectrum of infections ranging from moderate to severe. Serum apolipoprotein E (ApoE) inhibits inflammation by preserving immune regulatory function. Nonetheless, the relationship between serum ApoE and clinical prognosis in omicron remains elusive. A cohort of 231 patients was observed for 65 days, with death as the primary outcome. Based on their ApoE levels, the patients were categorized into patients with elevated ApoE levels and those with lower ApoE levels. To do statistical comparisons, the log-rank test was utilized, and the Kaplan-Meier method was utilized to estimate survival rates. Cox hazard models, both univariate and multivariate, were employed to examine the prognostic relevance. According to our research, omicron had significantly greater ApoE levels. In mild-to-moderate and severe cases, the study identified a statistically significant variation in ApoE levels. Additionally, there was a drop in overall survival that is statistically significant (OS, p < 0.0001) for patients with greater ApoE levels. Multiple Cox proportional hazards regression analysis indicates that an elevated ApoE level was determined to be an adverse and independent prognostic factor of OS in patients with omicron. Taken together, our study found that the level of serum ApoE at the time of initial diagnosis was substantially connected to the severity and prognosis of omicron. Consequently, we propose that ApoE might be a poor prognostic factor in individuals afflicted with the omicron variant., (© 2024 Wiley Periodicals LLC.)

Period circadian regulator 3 (PER3) functions as a tumor suppressor in various cancers. However, the role of PER3 in multiple myeloma (MM) has not been reported yet. Through this study, we aimed to investigate the potential role of PER3 in MM and the underlying mechanisms. RT-qPCR and western blotting were used to determine the mRNA and protein expression levels of PER3. Glyoxylate reductase 1 homolog (GLYR1) was predicted to be a transcription factor of PER3. The binding sites of GLYR1 on the promoter region of PER3 were analyzed using UCSC and confirmed using luciferase and chromatin immunoprecipitation assays. Viability, apoptosis, and metathesis were determined using CCK-8, colony formation, TUNEL, and transwell assays. We found that PER3 expression decreased in MM. Low PER3 levels may predict poor survival rates; PER3 overexpression suppresses the viability and migration of MM cells and promotes apoptosis. Moreover, GLYR1 transcriptionally activates PER3, and the knockdown of PER3 alleviates the effects of GLYR1 and induces its malignant behavior in MM cells. To conclude, GLYR1 upregulates PER3 and suppresses the aggressive behavior of MM cells, suggesting that GLYR1/PER3 signaling may be a potential therapeutic target for MM., Competing Interests: Declaration of competing interest The authors declared that they have none conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

C-C σ-bond cleavage and reconstruction is a significant tool for structural modification in synthetic chemistry but it remains a formidable challenge to perform on unstrained skeletons. Herein, we describe a radical addition-enabled C-C σ-bond cleavage/reconstruction reaction of unstrained allyl ketones to access various functional indanones bearing a benzylic quaternary center. The synthetic utility of this method has been showcased by the first total synthesis of carexane L, an indanone-based natural product.

Context: Patients with differentiated thyroid cancer (DTC) with distant metastasis (DM) are usually not recognized as radioactive iodine (RAI)-refractory DTC in a timely manner. The elucidation of genetic features related to RAI uptake patterns may shed light on the early recognition of RAI-refractory DTC., Objective: This work aimed to elucidate the underlying molecular features behind different RAI uptake patterns., Methods: A total of 214 patients with DM-DTC were retrospectively included in the analysis. RAI uptake patterns were defined as initially RAI refractory (I-RAIR) and initially RAI avid (I-RAIA) according to the first post-treatment scan, then I-RAIA was further divided into continually RAIA (C-RAIA), partly RAIR (P-RAIR), and gradually RAIR (G-RAIR) according to subsequent scans. The molecular subtype groups-BRAFV600E mutated, RAS mutated, fusions, and others-were classified according to main driver genes status., Results: BRAF, TERT promoter, and TP53 mutations are more frequently detected in the I-RAIR pattern while RET fusions and RAS mutations are more frequent in the I-RAIA pattern. A late-hit mutation including TERT, TP53, or PIK3CA is more common in I-RAIR than that in I-RAIA (50.0% vs 26.9%, P = .001), particularly for those with RAS mutations in the I-RAIR group, always accompanied by TERT promoter. Isolated RET fusions accounts for 10% of I-RAIR. When compared among driver gene groups, BRAFV600E-mutated tumors have a higher rate of the I-RAIR pattern (64.4%) than RAS-mutated (4.5%, P < .001) and fusion-positive (20.7%, P < .001) tumors. In I-RAIA subgroups, BRAFV600E-mutated tumors have lower prevalence of the C-RAIA pattern than those with RAS mutation or fusions., Conclusion: Patients with the I-RAIR pattern predominantly featured mutations of the BRAF and/or TERT promoter, of which RAS mutations were usually accompanied by late-hit mutations, while fusions mostly occurred alone., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model., Methods: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment., Results: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4 + T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8 + T cells (P<0.01 or P<0.05)., Conclusion: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Vascular dementia (VaD) represents a severe cognitive dysfunction syndrome closed linked to cardiovascular function. In the present study, we assessed the potential of Xinshubao tablet (XSB), a traditional Chinese prescription widely used for cardiovascular diseases, to mitigate neuropathological damage in a mouse model of VaD and elucidated the underlying mechanisms. Our findings revealed that oral administration of XSB rescued the cardiac dysfunction resulting from bilateral common carotid artery stenosis (BCAS), improved the cerebral blood flow (CBF) and cognitive function, reduced white matter injury, inhibited excessive microglial and astrocytic activation, stimulated hippocampal neurogenesis, and reduced neural apoptosis in the brains of BCAS mice. Mechanistically, RNA-seq analysis indicated that XSB treatment was significantly associated with neuroinflammation, vasculature development, and synaptic transmission, which were further confirmed by q-PCR assays. Western blot results revealed that XSB treatment hindered the nuclear translocation of nuclear factor-κB (NF-κB), thereby suppressing the NF-κB signaling pathway. These results collectively demonstrated that XSB could ameliorate cognitive dysfunction caused by BCAS through regulating CBF, reducing white matter lesions, suppressing glial activation, promoting neurogenesis, and mitigating neuroinflammation. Notably, the NF-κB signaling pathway emerged as a pivotal player in this mechanism., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Phenolic compounds are industrially versatile chemicals, also the most ubiquitous pollutants. Recently, biosynthesis and biodegradation of phenols has attracted increasing attention, while phenols' toxicity is a major issue. Here, we evolved phloroglucinol-tolerant Escherichia coli strains via adaptive evolution, and three mutations (ΔsodB, ΔclpX and fetAB overexpression) prove of great assistance in the tolerance improvement. We discover that phloroglucinol complexes with iron and promotes the generation of hydroxyl radicals in Fenton reaction, which leads to reducing power depletion, lipid peroxidation, and ferroptosis-like cell death of E. coli. Besides phloroglucinol, various phenols can trigger ferroptosis-like death in diverse organisms, from bacteria to mammalian cells. Furthermore, repressing this ferroptosis-like death improves phloroglucinol production and phenol degradation by corresponding strains respectively, showing great application potential in microbial degradation or production of desired phenolic compounds, and phloroglucinol-induced ferroptosis suppresses tumor growth in mice, indicating phloroglucinol as a promising drug for cancer treatment., (© 2024. The Author(s).)

Background: Pachymic acid (PA) is derived from Poria cocos. PA has a variety of pharmacological and inhibitory effects on various tumors. However, the mechanism of action of PA in gastric cancer (GC) remains unclear., Aim: To investigate the mechanism of PA in treating GC via the combination of network pharmacology and experimental verification., Methods: The GeneCards and OMIM databases were used to derive the GC targets, while the Pharm Mapper database provided the PA targets. Utilizing the STRING database, a protein-protein interaction network was constructed and core targets were screened. The analyses of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis were conducted, and molecular docking and clinical correlation analyses were performed on the core targets. Ultimately, the network pharmacology findings were validated through in vitro cell assays, encompassing assessments of cell viability, apoptosis, cell cycle, cloning, and western blot analysis., Results: According to network pharmacology analysis, the core targets were screened, and the PI3K/AKT signaling pathway is likely to be the mechanism by which PA effectively treats GC, according to KEGG enrichment analysis. The experimental findings showed that PA could control PI3K/AKT signaling to prevent GC cell proliferation, induce apoptosis, and pause the cell cycle., Conclusion: Network pharmacology demonstrated that PA could treat GC by controlling a variety of signaling pathways and acting on a variety of targets. This has also been supported by in vitro cell studies, which serve as benchmarks for further research., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Musashi-2 (MSI2), implicated in the oncogenesis and propagation of a broad array of malignancies, inclusive of certain leukemia, remains a nascent field of study within the context of acute lymphoblastic leukemia (ALL). Using lentiviral transfection, ALL cells with stable MSI2 knockdown were engineered. A suite of analytic techniques - a CCK-8 assay, flow cytometry, qRT-PCR, and western blotting - were employed to evaluate cellular proliferation, cell cycle arrest, and apoptosis and to confirm differential gene expression. The suppression of MSI2 expression yielded significant results: inhibition of cell proliferation, G0/G1 cell cycle arrest, and induced apoptosis in ALL cell lines. Furthermore, it was noted that MSI2 inhibition heightened the responsiveness of ALL cells to dexamethasone. Significantly, the depletion of MSI2 prompted the translocation of GR from the cytoplasm to the nucleus upon dexamethasone treatment, consequently leading to enhanced sensitivity. Additionally, the FOXO1/4 signaling pathway contributed to the biological effects of ALL cells evoked by MSI2 silencing. Our study offers novel insight into the inhibitory effects of MSI2 suppression on ALL cells, positing MSI2 as a promising therapeutic target in the treatment of ALL., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Spiking neural networks (SNNs) have garnered significant attention due to their computational patterns resembling biological neural networks. However, when it comes to deep SNNs, how to focus on critical information effectively and achieve a balanced feature transformation both temporally and spatially becomes a critical challenge. To address these challenges, our research is centered around two aspects: structure and strategy. Structurally, we optimize the leaky integrate-and-fire (LIF) neuron to enable the leakage coefficient to be learnable, thus making it better suited for contemporary applications. Furthermore, the self-attention mechanism is introduced at the initial time step to ensure improved focus and processing. Strategically, we propose a new normalization method anchored on the learnable leakage coefficient (LLC) and introduce a local loss signal strategy to enhance the SNN's training efficiency and adaptability. The effectiveness and performance of our proposed methods are validated on the MNIST, FashionMNIST, and CIFAR-10 datasets. Experimental results show that our model presents a superior, high-accuracy performance in just eight time steps. In summary, our research provides fresh insights into the structure and strategy of SNNs, paving the way for their efficient and robust application in practical scenarios.

Datura stramonium is an invasive herb of the family Solanaceae from Mexico and has been invading seriously in China. The effects of invasive plants on the functional traits of native plants and the stoichiometric characteristics of soil carbon, nitrogen and phosphorus in different habitats were explored by taking the invasive plant D. stramonium and coexisting native plants as the research object. The species, quantity and height of plants in sample plots in farmland, wasteland and roadside habitats were investigated and the specific leaf area (SLA), leaf carbon content (C), nitrogen content (N), carbon-to-nitrogen ratio (C:N), construction cost (CC mass ) and stoichiometric characteristics of soil carbon (C), nitrogen (N) and phosphorus (P) were analyzed. The results showed that compared with the noninvaded area, the species and quantity of native plants decreased in the invaded area, and SLA and leaf N showed a decreasing trend. The plant height of native plants in the invaded area of the farmland and wasteland decreased by 23.19% and 15.26%, respectively, while the height of native plants along the roadside increased by 95.91%. The leaf C:N ratio of native plants in the invaded area along the roadside significantly increased by 54.07%. The plant height and leaf N of D. stramonium in the three habitats were higher than those of the native plants. The soil N in the invaded area of the three habitats increased, with the soil N in the farmland increasing by 21.05%, in the wasteland increasing by 9.82% and along the roadside significantly increasing by 46.85%. The soil carbon-to-phosphorus ratio (C:P) in the three habitats showed an increasing trend. The soil C:P ratio in the farmland increased by 62.45%, in the wasteland it increased by 11.91% and along the roadside it significantly increased by 71.14%. These results showed that invasion by D. stramonium has a great effect on the local ecosystem, and it has a high ability to capture resources. D. stramonium can improve its own competitiveness by enhancing invasiveness by changing the functional traits of native plants and the stoichiometric characteristics of soil C, N and P, which may be the reason for its invasive success.

Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors., Competing Interests: Conflict-of-interest statement: The authors declare having no conflict of interests for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Glucose-6-phosphate dehydrogenases (G6PDs) are essential regulators of cellular redox. Hydrogen sulfide (H 2 S) is a small gasotransmitter that improves plant adaptation to stress; however, its role in regulating G6PD oligomerization to resist oxidative stress remains unknown in plants. Persulfidation of cytosolic G6PDs was analyzed by mass spectrometry (MS). The structural change model of AtG6PD6 homooligomer was built by chemical cross-linking coupled with mass spectrometry (CXMS). We isolated AtG6PD6 C159A and SlG6PDC C155A transgenic lines to confirm the in vivo function of persulfidated sites with the g6pd5,6 background. Persulfidation occurs at Arabidopsis G6PD6 Cystine (Cys)159 and tomato G6PDC Cys155, leading to alterations of spatial distance between lysine (K)491-K475 from 42.0 Å to 10.3 Å within the G6PD tetramer. The structural alteration occurs in the structural NADP + binding domain, which governs the stability of G6PD homooligomer. Persulfidation enhances G6PD oligomerization, thereby increasing substrate affinity. Under high salt stress, cytosolic G6PDs activity was inhibited due to oxidative modifications. Persulfidation protects these specific sites and prevents oxidative damage. In summary, H 2 S-mediated persulfidation promotes cytosolic G6PD activity by altering homotetrameric structure. The cytosolic G6PD adaptive regulation with two kinds of protein modifications at the atomic and molecular levels is critical for the cellular stress response., (© 2023 The Authors New Phytologist © 2023 New Phytologist Foundation.)

Competing Interests: The authors report no conflicts of interest.

Background: Gastric cancer (GC) is one of the most common cancer types worldwide, and its prevention and treatment methods have garnered much attention. As the active ingredient of licorice, 18β-glycyrrhetinic acid (18β-GRA) has a variety of pharmacological effects. The aim of this study was to explore the effective target of 18β-GRA in the treatment of GC, in order to provide effective ideas for the clinical prevention and treatment of GC., Aim: To investigate the mechanism of 18β-GRA in inhibiting cell proliferation and promoting autophagy flux in GC cells., Methods: Whole transcriptomic analyses were used to analyze and screen differentially expressed microRNAs (miRNAs) in GC cells after 18β-GRA intervention. Lentivirus-transfected GC cells and the Cell Counting Kit-8 were used to detect cell proliferation ability, cell colony formation ability was detected by the clone formation assay, and flow cytometry was used to detect the cell cycle and apoptosis. A nude mouse transplantation tumor model of GC cells was constructed to verify the effect of miR-328-3p overexpression on the tumorigenicity of GC cells. Tumor tissue morphology was observed by hematoxylin and eosin staining, and microtubule-associated protein light chain 3 (LC3) expression was detected by immunohistochemistry. TransmiR, STRING, and miRWalk databases were used to predict the relationship between miR-328-3p and signal transducer and activator of transcription 3 (STAT3)-related information. Expression of STAT3 mRNA and miR-328-3p was detected by quantitative polymerase chain reaction (qPCR) and the expression levels of STAT3, phosphorylated STAT3 (p-STAT3), and LC3 were detected by western blot analysis. The targeted relationship between miR-328-3p and STAT3 was detected using the dual-luciferase reporter gene system. AGS cells were infected with monomeric red fluorescent protein-green fluorescent protein-LC3 adenovirus double label. LC3 was labeled and autophagy flow was observed under a confocal laser microscope., Results: The expression of miR-328-3p was significantly upregulated after 18β-GRA intervention in AGS cells ( P = 4.51E-06). Overexpression of miR-328-3p inhibited GC cell proliferation and colony formation ability, arrested the cell cycle in the G0/G1 phase, promoted cell apoptosis, and inhibited the growth of subcutaneous tumors in BALB/c nude mice ( P < 0.01). No obvious necrosis was observed in the tumor tissue in the negative control group (no drug intervention or lentivirus transfection) and vector group (the blank vector for lentivirus transfection), and more cells were loose and necrotic in the miR-328-3p group. Bioinformatics tools predicted that miR-328-3p has a targeting relationship with STAT3, and STAT3 was closely related to autophagy markers such as p62. After overexpressing miR-328-3p, the expression level of STAT3 mRNA was significantly decreased ( P < 0.01) and p-STAT3 was downregulated ( P < 0.05). The dual-luciferase reporter gene assay showed that the luciferase activity of miR-328-3p and STAT3 3' untranslated regions of the wild-type reporter vector group was significantly decreased ( P < 0.001). Overexpressed miR-328-3p combined with bafilomycin A 1 (Baf A 1 ) was used to detect the expression of LC3 II. Compared with the vector group, the expression level of LC3 II in the overexpressed miR-328-3p group was downregulated ( P < 0.05), and compared with the Baf A 1 group, the expression level of LC3 II in the overexpressed miR-328-3p + Baf A 1 group was upregulated ( P < 0.01). The expression of LC3 II was detected after intervention of 18β-GRA in GC cells, and the results were consistent with the results of miR-328-3p overexpression ( P < 0.05). Additional studies showed that 18β-GRA promoted autophagy flow by promoting autophagosome synthesis ( P < 0.001). qPCR showed that the expression of STAT3 mRNA was downregulated after drug intervention ( P < 0.05). Western blot analysis showed that the expression levels of STAT3 and p-STAT3 were significantly downregulated after drug intervention ( P < 0.05)., Conclusion: 18β-GRA promotes the synthesis of autophagosomes and inhibits GC cell proliferation by regulating the miR-328-3p/STAT3 signaling pathway., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The devastating coronavirus disease of 2019 (COVID-2019) epidemic has been declared a public health emergency, resulting in a worldwide pandemic. The omicron variety is the most common epidemic mutant strain in the globe. Serum beta-2 microglobulin (β2-MG) is associated with endothelial cell injury and has value in monitoring the progression of inflammation in infected individuals. Nonetheless, the potential functions of β2-MG in omicron remain elusive., Methods: To investigate the prognostic value of serum β2-MG levels at diagnosis, we retrospectively analyzed a cohort of 240 people with omicron. Over the course of 65 days, all patients were monitored, and death was the primary outcome. Patients were allocated to two groups: those with high and low β2-MG levels. The Kaplan-Meier method was used to examine OS, and the log-rank test was used to compare them. Univariate and multivariate Cox hazard models were used to determine the prognostic significance., Results: Our results revealed that β2-MG was significantly elevated in omicron. β2-MG levels in severe patients were higher than in mild-to-moderate patients, and the difference was statistically significant. Timely, interleukin-6 (IL-6) and interleukin-10 (IL-10) were observed to be significantly increased in individuals exhibiting elevated levels of β2-MG. In addition, patients exhibiting elevated levels of β2-MG demonstrated a statistically significant decrease in overall survival (OS, P < 0.0001). An elevated β2-MG level (≥4.72 mg/l) was found to be an independent, adverse prognostic factor for OS in omicron patients, according to multivariate Cox proportional hazards regression analysis ( P = 0.001)., Conclusion: Serum β2-MG level at initial diagnosis was significantly correlated with omicron severity and prognosis. Thus, we propose that β2-MG may be an independent poor additional prognostic factor in patients with omicron., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gong, Ma, Zhu, Ge, Xie, Tao and Shi.)

Phytoremediation is a facile strategy to remove environmental heavy metals by using metal-accumulating plants from the rhizosphere environment. However, its efficiency is frequently compromised by the weak activity of rhizosphere microbiomes. This study developed a magnetic nanoparticle-assisted root colonization technique of synthetic functional bacteria to regulate rhizosphere microbiome composition for enhanced phytoremediation of heavy metals. The iron oxide magnetic nanoparticles with the size of 15-20 nm were synthesized and grafted by chitosan, a natural bacterium-binding polymer. The synthetic Escherichia coli SynEc2, which highly exposed an artificial heavy metal-capturing protein, was then introduced with the magnetic nanoparticles to bind the Eichhornia crassipes plants. Confocal microscopy, scanning electron microscopy, and microbiome analysis revealed that the grafted magnetic nanoparticles strongly promoted colonization of the synthetic bacteria on the plant roots, leading to remarkable change of rhizosphere microbiome composition, with the increase in the abundance of Enterobacteriaceae, Moraxellaceae, and Sphingomonadaceae. Histological staining and biochemical analysis further showed that the combination of SynEc2 and the magnetic nanoparticles protected the plants from heavy metal-induced tissue damage, and increased plant weights from 29 g to 40 g. Consequently, the plants with the assistance of synthetic bacteria and the magnetic nanoparticles in combination exhibited much higher heavy metal-removing capacity than the plants treated by the synthetic bacteria or the magnetic nanoparticles alone, leading to the decrease in the heavy metal levels from 3 mg/L to 0.128 mg/L for cadmium, and to 0.032 mg/L for lead. This study provided a novel strategy to remodel rhizosphere microbiome of metal-accumulating plants by integrating synthetic microbes and nanomaterials for improving the efficiency of phytoremediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The interaction between invasive plants and soil microbial communities is critical for plant establishment. However, little is known about the assembly and co-occurrence patterns of fungal communities in the rhizosphere soil of Amaranthus palmeri . The soil fungal communities and co-occurrence networks were investigated in 22 invaded patches and 22 native patches using high-throughput Illumina sequencing. Despite having little effect on alpha diversity, plant invasion significantly altered the composition of the soil fungal community (ANOSIM, p < 0.05). Fungal taxa associated with plant invasion were identified using linear discriminant analysis effect size (LEfSe). In the rhizosphere soil of A. palmeri , Basidiomycota was significantly enriched, while Ascomycota and Glomeromycota were significantly reduced when compared to native plants. At the genus level, the invasion of A. palmeri dramatically increased the abundance of beneficial fungi and potential antagonists such as Dioszegia , Tilletiopsis , Colacogloea , and Chaetomium , while it significantly decreased the abundance of pathogenic fungi such as Alternaria and Phaeosphaeria . Plant invasion reduced the average degree and average path length, and increased the modularity value, resulting in a less complex but more effective and stable network. Our findings improved the knowledge of the soil fungal communities, network co-occurrence patterns, and keystone taxa in A. palmeri -invaded ecosystems.

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Plant invasion can profoundly alter ecosystem processes driven by microorganisms. The fundamental mechanisms linking microbial communities, functional genes, and edaphic characteristics in invaded ecosystems are, nevertheless, poorly understood., Methods: Here, soil microbial communities and functions were determined across 22 Amaranthus palmeri (A. palmeri) invaded patches by pairwise 22 native patches located in the Jing-Jin-Ji region of China using high-throughput amplicon sequencing and quantitative microbial element cycling technologies., Results: As a result, the composition and structure of rhizosphere soil bacterial communities differed significantly between invasive and native plants according to principal coordinate analysis. A. palmeri soils exhibited higher abundance of Bacteroidetes and Nitrospirae, and lower abundance of Actinobacteria than native soils. Additionally, compared to native rhizosphere soils, A. palmeri harbored a much more complex functional gene network with higher edge numbers, average degree, and average clustering coefficient, as well as lower network distance and diameter. Furthermore, the five keystone taxa identified in A. palmeri rhizosphere soils belonged to the orders of Longimicrobiales, Kineosporiales, Armatimonadales, Rhizobiales and Myxococcales, whereas Sphingomonadales and Gemmatimonadales predominated in the native rhizosphere soils. Moreover, random forest model revealed that keystone taxa were more important indicators of soil functional attributes than edaphic variables in both A. palmeri and native rhizosphere soils. For edaphic variables, only ammonium nitrogen was a significant predictor of soil functional potentials in A. palmeri invaded ecosystems. We also found keystone taxa in A. palmeri rhizosphere soils had strong and positive correlations with functional genes compared to native soils., Discussion: Our study highlighted the importance of keystone taxa as a driver of soil functioning in invaded ecosystem., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Shi, Li, Wang, Qiu and Shi.)

Spiking neural networks (SNNs) have attracted intensive attention due to the efficient event-driven computing paradigm. Among SNN training methods, the ANN-to-SNN conversion is usually regarded to achieve state-of-the-art recognition accuracies. However, many existing ANN-to-SNN techniques impose lengthy post-conversion steps like threshold balancing and weight renormalization, to compensate for the inherent behavioral discrepancy between artificial and spiking neurons. In addition, they require a long temporal window to encode and process as many spikes as possible to better approximate the real-valued ANN neurons, leading to a high inference latency. To overcome these challenges, we propose a calcium-gated bipolar leaky integrate and fire (Ca-LIF) spiking neuron model to better approximate the functions of the ReLU neurons widely adopted in ANNs. We also propose a quantization-aware training (QAT)-based framework leveraging an off-the-shelf QAT toolkit for easy ANN-to-SNN conversion, which directly exports the learned ANN weights to SNNs requiring no post-conversion processing. We benchmarked our method on typical deep network structures with varying time-step lengths from 8 to 128. Compared to other research, our converted SNNs reported competitively high-accuracy performance, while enjoying relatively short inference time steps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, He, Wang, Wang, Zhong, Yu, Wang, Tian and Shi.)

Background: This study aims to investigate the prognostic significance of transthyretin in newly diagnosed myelodysplastic syndromes (MDS)., Methods: The clinical, laboratory, and follow-up data of 280 newly diagnosed patients with MDS were collected. The relationship between serum transthyretin levels and overall survival (OS) and leukemia-free survival (LFS) were analyzed by Kaplan-Meier analysis and Cox Regression Model., Result: In the MDS cohort, there were 121 cases in the low transthyretin group and 159 cases in the normal transthyretin group. MDS patients with decreased transthyretin had a higher risk score on the Revised International Prognostic Scoring System (IPSS-R) ( p  = 0.004) and on the molecular IPSS (IPSS-M) ( p  = 0.005), a higher frequency of TP53 mutation ( p  < 0.0001), a shorter OS ( p  < 0.0001) and LFS (p < 0.0001). Multivariate analyses showed that higher IPSS-R and IPSS-M score were adverse factors for OS ( p  = 0.008 and p  = 0.015, respectively) and LFS ( p  = 0.024 and p  = 0.005, respectively). Mutations of TP53 and NRAS were also poor factors for LFS ( p  = 0.034 and p  = 0.018, respectively). Notably, decreased transthyretin was an independent adverse predictor for OS ( p  = 0.009, HR = 0.097, 95%CI, 0.017-0.561) but not for LFS ( p  = 0.167) when IPSS-R was included in the Cox regression model and an independent poor one for OS ( p  = 0.033, HR = 0.267, 95%CI, 0.080-0.898) and LFS ( p  = 0.024, HR = 0.290, 95%CI, 0.099-0.848) while IPSS-M involved., Conclusion: The results indicate that decreased transthyretin could be an independent adverse prognostic factor in patients with MDS and may provide a supplement to IPSS-R and IPSS-M., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Niu, Chen, Wu, Zou, Shi, Wu, Zhang, Wu, Zhang, Yan, Sheng, Lv, Ouyang, Chen and Mu.)

Objectives: To study new biomarkers for the early diagnosis of retinopathy of prematurity (ROP) by analyzing the differences in blood metabolites based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and metabolomics., Methods: Dried blood spots were collected from 21 infants with ROP (ROP group) and 21 infants without ROP (non-ROP group) who were hospitalized in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2013 to December 2016. LC-MS/MS was used to measure the metabolites, and orthogonal partial least squares-discriminant analysis was used to search for differentially expressed metabolites and biomarkers., Results: There was a significant difference in blood metabolic profiles between the ROP and non-ROP groups. The pattern recognition analysis, Score-plot, and weight analysis obtained 10 amino acids with a relatively large difference. Further statistical analysis showed that the ROP group had significant increases in blood levels of glutamic acid, leucine, aspartic acid, ornithine, and glycine compared with the non-ROP group ( P <0.05). The receiver operating characteristic curve analysis showed that glutamic acid and ornithine had the highest value in diagnosing ROP., Conclusions: Blood metabolites in preterm infants with ROP are different from those without ROP. Glutamic acid and ornithine are the metabolic markers for diagnosing ROP. LC-MS/MS combined with metabolomics analysis has a potential application value in the early identification and diagnosis of ROP.

Background: We investigated the influence of different neuromuscular blocking agents and reversal agents during anaesthesia on early removal of chest tube drainage after video-assisted thoracoscopic surgery (VATS)., Methods: This retrospective single-centre study included patients who underwent VATS after tracheal intubation under general anaesthesia. Patients received either cisatracurium and neostigmine (n=547) or rocuronium and sugammadex (n=151). Quantitative neuromuscular monitoring was used and one chest tube (size 24 Fr) was inserted. To reduce potential bias, 140 patients from each group were matched by propensity score for sex, age, body mass index and indication for VATS. Primary outcome was duration of chest tube drainage after surgery., Results: Use of rocuronium and sugammadex was associated with a shorter duration of chest tube drainage (2 [1-2] vs 2 [1-3] days; P=0.049) and a 63% reduction in delayed chest tube removal (odds ratio 0.37; 95% confidence interval [CI]: 0.20-0.67; P=0.005). This group also had a lower incidence of postoperative atelectasis (P=0.047) and consolidation (P=0.008). Each 1 h increase in the duration of anaesthesia was associated with a 1.57-fold increase in the delayed removal of the chest tube (95% CI: 1.25-1.96; P=0.005)., Conclusions: During general anaesthesia for VATS, compared with cisatracurium and neostigmine, use of rocuronium and sugammadex was associated with a significant decrease in the incidence of postoperative delayed removal of the chest tube, atelectasis, and pulmonary consolidation., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A palladium-catalyzed asymmetric C-C bond activation/carbonylation of cyclobutanones with CO has been developed. This reaction provided an efficient method for the synthesis of chiral indanones bearing a quaternary carbon stereocenter in good yields with an excellent enantiomeric ratio, exhibiting good functional group tolerance. Transformations of the products to chiral 3,4-dihydroquinolin-2(1 H )-one and 1 H -indene further demonstrated the versatility of this reaction.

Background: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients., Methods: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping., Results: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up., Conclusions: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG., Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H281 )., (Copyright © 2022 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Melanocortin-4 receptor (MC4R) plays an important role in energy balance regulation and insulin secretion. It has been demonstrated that in the pancreas, it is expressed in islet α and β cells, wherein it is significantly correlated with insulin and glucagon-like peptide-1 (GLP-1) secretion. However, the molecular mechanism by which it regulates islet function is still unclear. Therefore, in this study, our aim was to clarify the signaling and target genes involved in the regulation of insulin and GLP-1 secretion by islet MC4R. The results obtained showed that in islet cells, the expression of prohormone convertase 1/3 (PC1/3), which is correlated with islet GLP-1 and insulin secretion, increased significantly under the action of the MC4R agonist, NDP-α-MSH, but decreased under the action of the MC4R antagonist, AgRP. Additionally, we observed that to exert their regulatory functions in the islets, cAMP and β-arrestin-1 acted as important signaling mediators of MC4R, and compared with control islets, the cAMP, PKA, and β-arrestin-1 levels corresponding to NDP-α-MSH-treated islets were significantly elevated; however, in AgRP-treated islets, their levels decreased significantly. Islets treated with the PKA inhibitor, H89, and the ERK1/2 inhibitor, PD98059, also showed significant decreases in PC1/3 expression level, indicating that the cAMP and β-arrestin-1 pathways are significantly correlated with PC1/3 expression. These findings suggest that islet MC4R possibly affects PC1/3 expression via the cAMP and β-arrestin-1 pathways to regulate GLP-1 and insulin secretion. These results provide a new theoretical basis for targeting the molecular mechanism of type 2 diabetes mellitus., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gallium nitride (GaN) is a wide bandgap semiconductor with remarkable chemical and thermal stability, making it a competitive candidate for a variety of optoelectronic applications. In this study, GaN films are grown using a plasma-enhanced atomic layer deposition (PEALD) with trimethylgallium (TMG) and NH 3 plasma. The effect of substrate temperature on growth mechanism and properties of the PEALD GaN films is systematically studied. The experimental results show that the self-limiting surface chemical reactions occur in the substrate temperature range of 250-350 °C. The substrate temperature strongly affects the crystalline structure, which is nearly amorphous at below 250 °C, with (100) as the major phase at below 400 °C, and (002) dominated at higher temperatures. The X-ray photoelectron spectroscopy spectra reveals the unintentional oxygen incorporation into the films in the forms of Ga 2 O 3 and Ga-OH. The amount of Ga-O component decreases, whereas the Ga-Ga component rapidly increases at 400 and 450 °C, due to the decomposition of TMG. The substrate temperature of 350 °C with the highest amount of Ga-N bonds is, therefore, considered the optimum substrate temperature. This study is helpful for improving the quality of PEALD GaN films.

Background: Endometrial adenocarcinoma (EC) is the fifth most common cancer in women worldwide, standard treatment for EC includes hysterectomy, but it results in the loss of reproductive function. Thus, conservative treatment for these patients is strongly demanded, progestin therapy is widely accepted as the main fertility-sparing treatment for young women with endometrial hyperplasia with atypia (EHA) and well-differentiated endometrioid endometrial cancer. This trial will investigate the effectiveness of conservative treatment for obese women with early-stage EC., Method and Design: This will be an open-label, 2-armed, randomized, phase-II single-center trial of LNG-IUD plus metformin or megestrol acetate (MA) plus metformin. A total of 88 participants will be randomly assigned into 2 treatment arms in a 1:1 ratio. Clinical, laboratory, ultrasound and radiology data, will be collected at baseline, and then at 3, 6, 9, 12, 18, and 24 months. EC biomarkers will be collected at baseline. The primary aim is to determine the efficacy of a levonorgestrel-releasing intrauterine device (LNG-IUD) plus metformin, or megestrol acetate (MA) plus metformin in achieving pathological complete response (pCR) at 12 months, as well as post-treatment pregnancy outcomes and recurrence rate. The secondary aims are to predict the response to an LNG-IUD plus metformin and MA plus metformin via clinical, blood, and tissue predictive biomarkers., Conclusions: Prospective evidence for conservative treatment of EC is limited. New methods to achieve better CR rates with fewer side effects are needed. This trial will investigate the effectiveness of LNG-IUD plus metformin, and MA plus metformin, in obese women with early-stage EC, providing a non-surgical treatment option for these patients. Trial registration ChiCTR2200055624. The trial was registered at http://www.chictr.org.cn/listbycreater.aspx on January 15, 2022., (© 2022. The Author(s).)

Purpose: Parkinson's disease (PD) is a serious neurodegenerative disease affecting the elderly. In general, the locomotion deficit, which seriously affects the daily life of patients with PD, usually occurs at a later stage. The mask face symptom meanwhile progressively worsens. However, facial muscle disorders and changes involved in the freezing mask are unclear., Method: In this study, we recruited 35 patients with PD and 26 age- and sex-balanced controls to undergo phonation tests, while the built-in camera on the laptop recorded their facial expressions during the whole pronunciation process. Furthermore, FaceReader (version 7.0; Noldus Information Technology, Wageningen, Netherlands) was used to analyze changes in PD facial landmark movement and region movement., Results: The two-tailed Student's t -test showed that the changes in facial landmark movement among 49 landmarks were significantly lower in patients with PD than in the control group ( P < 0.05). The data on facial region movement revealed that the eyes and upper lip of patients with PD differed significantly from those in the control group., Conclusion: Patients with PD had defects in facial landmark movement and regional movement when producing a single syllable, double syllable, and multiple syllables, which may be related to reduced facial expressions in patients with PD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Zou, Yang, Mo, Guo, Zhang, Weng and Xing.)

Background: Golden leaf in autumn is a prominent feature of deciduous tree species like Ginkgo biloba L., a landscape tree widely cultivated worldwide. However, little was known about the molecular mechanisms of leaf yellowing, especially its dynamic regulatory network. Here, we performed a suite of comparative physiological and dynamic transcriptional analyses on the golden-leaf cultivar and the wild type (WT) ginkgo to investigate the underlying mechanisms of leaf yellowing across different seasons., Results: In the present study, we used the natural bud mutant cultivar with yellow leaves "Wannianjin" (YL) as materials. Physiological analysis revealed that higher ratios of chlorophyll a to chlorophyll b and carotenoid to chlorophyll b caused the leaf yellowing of YL. On the other hand, dynamic transcriptome analyses showed that genes related to chlorophyll metabolism played key a role in leaf coloration. Genes encoding non-yellow coloring 1 (NYC1), NYC1-like (NOL), and chlorophyllase (CLH) involved in the degradation of chlorophyll were up-regulated in spring. At the summer stage, down-regulated HEMA encoding glutamyl-tRNA reductase functioned in chlorophyll biosynthesis, while CLH involved in chlorophyll degradation was up-regulated, causing a lower chlorophyll accumulation. In carotenoid metabolism, genes encoding zeaxanthin epoxidase (ZEP) and 9-cis-epoxy carotenoid dioxygenase (NCED) showed significantly different expression levels in the WT and YL. Moreover, the weighted gene co-expression network analysis (WGCNA) suggested that the most associated transcriptional factor, which belongs to the AP2/ERF-ERF family, was engaged in regulating pigment metabolism. Furthermore, quantitative experiments validated the above results., Conclusions: By comparing the golden-leaf cultivar and the wide type of ginkgo across three seasons, this study not only confirm the vital role of chlorophyll in leaf coloration of YL but also provided new insights into the seasonal transcriptome landscape and co-expression network. Our novel results pinpoint candidate genes for further wet-bench experiments in tree species., (© 2022. The Author(s).)

Human brain cortex acts as a rich inspiration source for constructing efficient artificial cognitive systems. In this paper, we investigate to incorporate multiple brain-inspired computing paradigms for compact, fast and high-accuracy neuromorphic hardware implementation. We propose the TripleBrain hardware core that tightly combines three common brain-inspired factors: the spike-based processing and plasticity, the self-organizing map (SOM) mechanism and the reinforcement learning scheme, to improve object recognition accuracy and processing throughput, while keeping low resource costs. The proposed hardware core is fully event-driven to mitigate unnecessary operations, and enables various on-chip learning rules (including the proposed SOM-STDP & R-STDP rule and the R-SOM-STDP rule regarded as the two variants of our TripleBrain learning rule) with different accuracy-latency tradeoffs to satisfy user requirements. An FPGA prototype of the neuromorphic core was implemented and elaborately tested. It realized high-speed learning (1349 frame/s) and inference (2698 frame/s), and obtained comparably high recognition accuracies of 95.10%, 80.89%, 100%, 94.94%, 82.32%, 100% and 97.93% on the MNIST, ETH-80, ORL-10, Yale-10, N-MNIST, Poker-DVS and Posture-DVS datasets, respectively, while only consuming 4146 (7.59%) slices, 32 (3.56%) DSPs and 131 (24.04%) Block RAMs on a Xilinx Zynq-7045 FPGA chip. Our neuromorphic core is very attractive for real-time resource-limited edge intelligent systems.

Functional bacteria promote the efficiency of phytoremediation by enhancing plant growth and participating in decontamination. However, their activity is frequently compromised by the weakness of their interaction with plant roots. In this study, we designed the artificial protein LcGC composed of a bacterium-binding domain, a GFP fluorescence reporter, and a carbohydrate-binding domain to function as a physical contact between functional bacteria and plant roots. This protein was then expressed in an engineered yeast cell factory and extracted to assess its effect on rhizosphere microbiome composition, plant growth, and cadmium removal in a simulated phytoremediation system containing the remediation plant Lemna minor and the functional heavy metal-capturing bacteria Cupriavidus taiwanensis and Pseudomonas putida. LcGC efficiently bound bacterial cell wall components and glucan, endowing it high efficiency to bind both functional bacteria and plant roots. Scanning microscopy and microbiome analysis revealed that LcGC enhanced root recruitment and colonization of functional bacteria on the root surfaces. Furthermore, LcGC with the aid of single C. taiwanensis or of C. taiwanensis and P. putida in combination promoted plant growth, enhanced tolerance to cadmium-induced oxidative stress, and consequently improved cadmium-removing capacity of the plants, with the percent of cadmium removal reaching up to 91% for LcGC plus C. taiwanensis, and to 96% for LcGC plus C. taiwanensis and P. putida on day 7. This study provided a physical contact-based strategy to enhance the interaction between functional microbes and plant roots for efficient phytoremediation., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Myelodysplastic syndrome (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that fibrinogen (FIB) is associated with disease risk in several cancer types. Coagulation and fibrinolysis problems are widespread in MDS patients. Therefore, FIB might be one of these indicators. We thus examined the role of FIB levels in the prognosis of MDS., Methods: A cohort of 198 MDS patients were retrospectively analyzed to explore the prognostic value of the plasma FIB levels at diagnosis. Patients were divided into the high FIB group and low FIB group. The prognostic significance of FIB was determined by univariate and multivariate Cox hazard models., Results: In our cohort, the FIB levels in 198 MDS patients were higher than those in 100 healthy donors (3.9 g/L vs 2.9 g/L, P < 0.0001). MDS patients with high FIB levels had significantly shorter overall survival (OS; P = 0.001) and decreased leukemia-free survival (LFS; P = 0.036). Multivariate cox proportional hazards regression analysis indicated that, in addition to older age, gender, lower HB, poorer karyotype for OS, lower NE, and higher bone marrow blast percentage for OS and LFS, elevated FIB level was also an independent adverse prognostic factor for OS ( P = 0.045) but not for LFS ( P = 0.188)., Conclusion: Elevated FIB levels may be associated with mortality risk among MDS patients and could predict disease progress and patient prognosis. Thus, assessment of FIB levels may promote the determination of the prognosis of MDS patients., Competing Interests: The authors declare that they have no competing interests in this work., (© 2022 Shi et al.)