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1.
J Environ Manage ; 366: 121775, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38991343

ABSTRACT

Grazing exclusion (GE), as an effective strategy for revitalizing degraded grasslands, possesses the potential to increase ecosystem respiration (Re) and significantly influence the capacity of grassland soils to sequester carbon. However, our current grasp of Re dynamics in response to varying durations of GE, particularly in the context of precipitation fluctuations, remains incomplete. To fill this knowledge gap, we conducted a monitoring of Re over a 40-year GE chronosequence within Inner Mongolia temperate typical steppe across two distinct hydrologically years. Overall, Re exhibited a gradual saturation curve and an increasing trend with the duration of GE in the wet year of 2021 and the normal precipitation year of 2022, respectively. The variance primarily stemmed from relatively higher microbial biomass carbon observed in the short-term GE during 2022 in contrast to 2021. Moreover, the impacts of GE on the sensitivities of Re to moisture and temperature were intricately tied to precipitation patterns. increasing significantly with prolonged GE duration in 2022 but not in 2021. Our study highlights the intricate interplay between GE duration, precipitation variability, and Re dynamics. This deeper understanding enhances our ability to predict and manage carbon cycling within typical steppe in Inner Mongolia, offering invaluable insights for effective restoration strategies and climate change mitigation.

2.
J Hazard Mater ; 476: 134741, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38991640

ABSTRACT

Exposure to environmental BaP or its metabolite BPDE causes trophoblast cell dysfunctions to induce miscarriage (abnormal early embryo loss), which might be generally regulated by lncRNAs. IL1B, a critical inflammatory cytokine, is closely associated with adverse pregnancy outcomes. However, whether IL1B might cause dysfunctions of BaP/BPDE-exposed trophoblast cells to induce miscarriage, as well as its specific epigenetic regulatory mechanisms, is completely unexplored. In this study, we find that BPDE-DNA adducts, trophoblast cell dysfunctions, and miscarriage are closely associated. Moreover, we also identify a novel lnc-HZ06 and IL1B, both of which are highly expressed in BPDE-exposed trophoblast cells, in villous tissues of recurrent miscarriage patients, and in placental tissues of BaP-exposed mice with miscarriage. Both lnc-HZ06 and IL1B suppress trophoblast cell migration/invasion and increase apoptosis. In mechanism, lnc-HZ06 promotes STAT4-mediated IL1B mRNA transcription, enhances IL1B mRNA stability by promoting the formation of METTL3/HuR/IL1B mRNA ternary complex, and finally up-regulates IL1B expression levels. BPDE exposure promotes TBP-mediated lnc-HZ06 transcription, and thus up-regulates IL1B levels. Knockdown of either murine lnc-hz06 (which down-regulates Il1b levels) or murine Il1b could alleviate miscarriage in BaP-exposed mice. Collectively, this study not only discovers novel biological mechanisms and pathogenesis of unexplained miscarriage but also provides novel potential targets for treatment against BaP/BPDE-induced miscarriage.

3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(6): 664-668, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38991970

ABSTRACT

Resveratrol is a polyphenolic plant extract with many biological activities such as anti-inflammation and anti-oxidative stress. Vascular endothelial cell (VEC) is the main sites for maintaining normal vascular permeability and participating in vasomotor regulation and substance exchange. VEC injury plays a key role in various diseases or pathological processes such as cardiovascular disease, chronic inflammation and sepsis. Studies have shown that resveratrol protects VEC and reduces endothelial damage by regulating nitric oxide (NO) and its related enzymes, reducing oxidative stress and inhibiting apoptosis, thereby exerting beneficial effects.


Subject(s)
Endothelial Cells , Nitric Oxide , Resveratrol , Stilbenes , Resveratrol/pharmacology , Humans , Endothelial Cells/drug effects , Stilbenes/pharmacology , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Apoptosis/drug effects
4.
Int J Biol Macromol ; : 133778, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992541

ABSTRACT

Pickering emulsions with good freeze-thaw stability are essential in frozen food applications. This study developed a high freeze-thaw stabilized soy protein isolate (SPI)-maltose (M) Pickering emulsion and applied it to frozen doughs to investigate and reveal its impacts on the processing properties of the frozen dough. The results showed that after the freeze-thaw cycle, with a volume ratio of 1:2 of SPI to M, the appropriate amount of M changed the structure of SPI. This resulted in the Pickering emulsion prepared by the SPI exhibiting the least droplet coalescence and the best freeze-thaw stability. The results of dough rheological properties, textural properties, and binding capacity with water demonstrated that Pickering emulsions effectively inhibited the loss of gluten protein network structure in the dough after freeze treatment and increased the binding capacity of gluten proteins with starch and water in the dough. The best results were obtained with the incorporation of 3 % SPI-M high freeze-thaw stability, where the amount of bound water following three freeze-thaw cycles was 4.27 times higher than in doughs without Pickering emulsion. Overall, this study is significant for enhancing the freeze-thaw stability of Pickering emulsions stabilized by proteins and providing a new application route for Pickering emulsions.

5.
Angew Chem Int Ed Engl ; : e202409693, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38993073

ABSTRACT

The photoelectrochemical reduction of nitrate to ammonia (PEC NO3RR) has emerged as a promising pathway for facilitating the natural nitrogen cycle. The PEC NO3RR can lower the reduction potential needed for ammonia synthesis through photogenerated voltage, showcasing the significant potential for merging abundant solar energy with sustainable nitrogen fixation. However, it is influenced by the selective photocathodes with poor carrier kinetics, low catalytic selectivity, and ammonia yields. There are few reports on suitable photoelectrodes owning efficient charge transport on PEC NO3RR at low overpotentials. Herein, we rationally constructed the CuSn alloy co-catalysts on the antimony sulfides with a highly selective PEC ammonia and an ultra-low onset potential (0.62 VRHE). CuSn/TiO2/Sb2S3 achieved an ammonia faradic efficiency of 97.82% at a low applied potential of 0.4 VRHE, and an ammonia yield of 16.96 µmol h-1 cm-2 at 0 VRHE under one sun illumination. Dynamics experiments and theoretical calculations have demonstrated that CuSn/TiO2/Sb2S3 has an enhanced charge separation and transfer efficiency, facilitating photogenerated electrons to participate in PEC NO3RR quickly. Meanwhile, moderate NO2* adsorption on this photocathode optimizes the catalytic activity and increases the NH4+ yield. This work opens an avenue for designing sulfide-based photocathodes for the efficient route of solar-to-ammonia conversion.

6.
Adv Sci (Weinh) ; : e2307254, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946659

ABSTRACT

The rational construction of efficient hypoxia-tolerant nanocatalysts capable of generating singlet oxygen (1O2) without external stimuli is of great importance for tumor therapy. Herein, uniformly dispersed and favorable biosafety profile graphitic carbon nitride quantum dots immobilized with Fe-N4 moieties modulated by axial O atom (denoted as O-Fe-N4) are developed for converting H2O2 into 1O2 via Russell reaction, without introducing external energy. Notably, O-Fe-N4 performs two interconnected catalytic properties: glutathione oxidase-mimic activity to provide substrate for subsequent 1O2 generation, avoiding the blunting anticancer efficacy by glutathione. The O-Fe-N4 catalyst demonstrates a specific activity of 79.58 U mg-1 at pH 6.2, outperforming the most reported Fe-N4 catalysts. Density functional theory calculations demonstrate that the axial O atom can effectively modulate the relative position and electron affinity between Fe and N, lowering the activation energy, strengthening the selectivity, and thus facilitating the Russell-type reaction. The gratifying enzymatic activity stemming from the well-defined Fe-N/O structure can inhibit tumor proliferation by efficiently downregulating glutathione peroxidase 4 activity and inducing lipid peroxidation. Altogether, the O-Fe-N4 catalyst not only represents an efficient platform for self-cascaded catalysis to address the limitations of 1O2-involved cancer treatment but also provides a paradigm to enhance the performance of the Fe-N4 catalyst.

7.
Front Microbiol ; 15: 1418556, 2024.
Article in English | MEDLINE | ID: mdl-38946910

ABSTRACT

Introduction: This study aimed to explore the anti-oxidative and anti-inflammatory properties of Lactococcus lactis subsp. lactis HFY14 (LLSLHFY14) and investigate its effects on the intestinal barrier, cranial nerve, and motor function in mice treated with antibiotics. Methods: Mice were administered an antibiotic mixture (neomycin 5 mg/mL, vancomycin 25 mg/mL, amphotericin B 0.1 mg/mL, ampicillin 10 mg/mL, metronidazole file 5 mg/mL, and lipopolysaccharide 1.5 µg/mL) intraperitoneally, and oxidative stress and inflammatory markers in the serum and brain tissues, and liver index were measured. H&E staining was performed to detect pathological alterations in brain tissues. The expression of intestinal-barrier-related genes and that of genes involved in inflammatory pathways in the brain were detected using polymerase chain reaction (PCR). Results: LLSLHFY14 administration extended the weight-loaded swimming and running times of mice and decreased the liver index. Moreover, the levels of malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) in the serum and brain tissue were reduced, whereas those of superoxide dismutase (SOD), glutathione (GSH), and interleukin-10 (IL-10) were elevated. Elevated brain expression of the protein kinase B (AKT)/cAMP-response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF)/extracellular signal-regulated kinase 1 (ERK1) pathway, decreased brain expression of the IL-6 gene, and elevated cecum expression of zonula occludens-1 (ZO-1), occludin-1, and claudin-1 genes were noted. LLSLHFY14 supplementation significantly increased Bacteroidetes expression but decreased Firmicutes expression, thus increasing the Bacteroidetes/Firmicutes ratio. Discussion: Overall, LLSLHFY14 supplementation ameliorated antibiotic-induced oxidative stress and inflammation in the mouse central nervous system, intestinal barrier dysfunction, and increased motor function, thus confirming its potential application as probiotics.

8.
Heliyon ; 10(11): e31638, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38947479

ABSTRACT

Hydroxyapatite (HAp) coatings currently have limited therapeutic applications because they lack anti-infection, osteoinductivity, and poor mechanical characteristics. On the titanium substrate, electrochemical deposition (ECD) was used to construct the strontium (Sr)-featuring hydroxyapatite (HAp)/graphene oxides (GO)/linezolid (LZ) nanomaterial coated with antibacterial and drug delivery properties. The newly fabricated nanomaterials were confirmed by X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) analysis and morphological features were examined by scanning electron microscope (SEM) analysis. The results reveal multiple nucleation sites for SrHAp/GO/LZ composite coatings due to oxygen-comprising moieties on the 2D surface of GO. It was shown to be favorable for osteoblast proliferation and differentiation. The elastic modulus and hardness of LZ nanocomposite with SrHAp/GO/LZ coatings were increased by 67 % and 121 %, respectively. An initial 5 h burst of LZ release from the SrHAp/GO/LZ coating was followed by 14 h of gradual release, owing to LZ's physical and chemical adsorption. The SrHAp/GO/LZ coating effectively inhibited both S. epidermidis and S. aureus, and the inhibition lasted for three days, as demonstrated by the inhibition zone and colony count assays. When MG-63 cells are coated with SrHAp/GO/LZ composite coating, their adhesion, proliferation, and differentiation greatly improve when coated with pure titanium. A novel surface engineering nanomaterial for treating and preventing osteoporotic bone defects, SrHAp/GO/LZ, was shown to have high mechanical characteristics, superior antibacterial abilities, and osteoinductivity.

9.
J Transl Med ; 22(1): 613, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956649

ABSTRACT

BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.


Subject(s)
Antigens, CD19 , Fever , Immunotherapy, Adoptive , Humans , Female , Male , Middle Aged , Immunotherapy, Adoptive/methods , Adult , Antigens, CD19/metabolism , Infections/blood , Aged , ROC Curve , Young Adult , Retrospective Studies
10.
Ital J Pediatr ; 50(1): 124, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956688

ABSTRACT

BACKGROUND: Addison's disease and X-linked adrenoleukodystrophy (X-ALD) (Addison's-only) are two diseases that need to be identified. Addison's disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison's-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison's disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD. METHODS: We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics. RESULTS: Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison's disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394-2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison's-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum. CONCLUSIONS: Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison's disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison's-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.


Subject(s)
ATP Binding Cassette Transporter, Subfamily D, Member 1 , Adrenoleukodystrophy , Humans , Adrenoleukodystrophy/diagnosis , Adrenoleukodystrophy/genetics , Male , Retrospective Studies , ATP Binding Cassette Transporter, Subfamily D, Member 1/genetics , Child , Diagnostic Errors , Magnetic Resonance Imaging , Addison Disease/diagnosis , Addison Disease/genetics
11.
Stem Cell Res Ther ; 15(1): 196, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956734

ABSTRACT

Over the past decade, we have witnessed the development of cell transplantation as a new strategy for repairing spinal cord injury (SCI). However, due to the complexity of the central nervous system (CNS), achieving successful clinical translation remains a significant challenge. Human umbilical cord mesenchymal stem cells (hUMSCs) possess distinct advantages, such as easy collection, lack of ethical concerns, high self-renewal ability, multilineage differentiation potential, and immunomodulatory properties. hUMSCs are promising for regenerating the injured spinal cord to a significant extent. At the same time, for advancing SCI treatment, the appropriate benefit and risk evaluation methods play a pivotal role in determining the clinical applicability of treatment plans. Hence, this study discusses the advantages and risks of hUMSCs in SCI treatment across four dimensions-comprehensive evaluation of motor and sensory function, imaging, electrophysiology, and autonomic nervous system (ANS) function-aiming to improve the rationality of relevant clinical research and the feasibility of clinical translation.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Spinal Cord Injuries , Umbilical Cord , Humans , Spinal Cord Injuries/therapy , Mesenchymal Stem Cell Transplantation/methods , Umbilical Cord/cytology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/cytology , Risk Assessment , Cell Differentiation , Animals
12.
J Am Chem Soc ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963753

ABSTRACT

Converting dilute CO2 source into value-added chemicals and fuels is a promising route to reduce fossil fuel consumption and greenhouse gas emission, but integrating electrocatalysis with CO2 capture still faced marked challenges. Herein, we show that a self-healing metal-organic macrocycle functionalized as an electrochemical catalyst to selectively produce methane from flue gas and air with the lowest applied potential so far (0.06 V vs reversible hydrogen electrode, RHE) through an enzymatic activation fashion. The capsule emulates the enzyme' pocket to abstract one in situ-formed CO2-adduct molecule with the commercial amino alcohols, forming an easy-to-reduce substrate-involving clathrate to combine the CO2 capture with electroreduction for a thorough CO2 reduction. We find that the self-healing system exhibited enzymatic kinetics for the first time with the Michaelis-Menten mechanism in the electrochemical reduction of CO2 and maintained a methane Faraday efficiency (FE) of 74.24% with a selectivity of over 99% for continuous operation over 200 h. A consecutive working lab at 50 mA·cm-2, in an eleven-for-one (10 h working and 1 h healing) electrolysis manner, gives a methane turnover number (TON) of more than 10,000 within 100 h. The integrated electrolysis with CO2 capture facilitates the thorough reduction of flue gas (ca. 13.0% of CO2) and first time of air (ca. 400 ppm of CO2 to 42.7 mL CH4 from 1.0 m3 air). The new self-healing strategy of molecular electrocatalyst with an enzymatic activation manner and anodic shifting of the applied potentials provided a departure from the existing electrochemical catalytic techniques.

13.
Transl Oncol ; 47: 101950, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38964032

ABSTRACT

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a highly invasive pulmonary malignancy with an extremely poor prognosis. The results of previous studies suggest that ubiquitin-specific peptidase 9X (USP9X) contributes to the progression of numerous types of cancer. Nevertheless, there is little knowledge about the molecular mechanisms and functions of USP9X in the metastasis of PSC. METHODS: Immunohistochemistry and western blotting were used to detect USP9X expression levels in PSC tissues and cells. Wound healing, transwell, enzyme-linked immunosorbent assay (ELISA), tube formation, and aortic ring assays were used to examine the function and mechanism of USP9X in the metastasis of PSC. RESULTS: Expression of USP9X was markedly decreased and significantly correlated with metastasis and prognosis of patients with PSC. Then we revealed that USP9X protein levels were negatively associated with the levels of epithelial-mesenchymal transition (EMT) markers and the migration of PSC cells. It was confirmed that USP9X in PSC cells reduced VEGF secretion and inhibited tubule formation of human umbilical vein endothelial cells (HUVEC) in vitro. USP9X was detected to downregulate MMP9. Meanwhile, MMP9 was positively related to EMT, angiogenesis and was negatively related to immune infiltration in the public databases. USP9X was significantly negatively associated with the expression of MMP9, EMT markers, CD31, and positively associated with CD4, and CD8 in PSC tissues. CONCLUSION: The present study reveals the vital role of USP9X in regulating EMT, angiogenesis and immune infiltration and inhibiting metastasis of PSC via downregulating MMP9, which provides a new effective therapeutic target for PSC.

14.
Mol Cancer ; 23(1): 137, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970074

ABSTRACT

BACKGROUND: The outcome of hepatocellular carcinoma (HCC) is limited by its complex molecular characteristics and changeable tumor microenvironment (TME). Here we focused on elucidating the functional consequences of Maternal embryonic leucine zipper kinase (MELK) in the tumorigenesis, progression and metastasis of HCC, and exploring the effect of MELK on immune cell regulation in the TME, meanwhile clarifying the corresponding signaling networks. METHODS: Bioinformatic analysis was used to validate the prognostic value of MELK for HCC. Murine xenograft assays and HCC lung metastasis mouse model confirmed the role of MELK in tumorigenesis and metastasis in HCC. Luciferase assays, RNA sequencing, immunopurification-mass spectrometry (IP-MS) and coimmunoprecipitation (CoIP) were applied to explore the upstream regulators, downstream essential molecules and corresponding mechanisms of MELK in HCC. RESULTS: We confirmed MELK to be a reliable prognostic factor of HCC and identified MELK as an effective candidate in facilitating the tumorigenesis, progression, and metastasis of HCC; the effects of MELK depended on the targeted regulation of the upstream factor miR-505-3p and interaction with STAT3, which induced STAT3 phosphorylation and increased the expression of its target gene CCL2 in HCC. In addition, we confirmed that tumor cell-intrinsic MELK inhibition is beneficial in stimulating M1 macrophage polarization, hindering M2 macrophage polarization and inducing CD8 + T-cell recruitment, which are dependent on the alteration of CCL2 expression. Importantly, MELK inhibition amplified RT-related immune effects, thereby synergizing with RT to exert substantial antitumor effects. OTS167, an inhibitor of MELK, was also proven to effectively impair the growth and progression of HCC and exert a superior antitumor effect in combination with radiotherapy (RT). CONCLUSIONS: Altogether, our findings highlight the functional role of MELK as a promising target in molecular therapy and in the combination of RT therapy to improve antitumor effect for HCC.


Subject(s)
Carcinoma, Hepatocellular , Chemokine CCL2 , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Protein Serine-Threonine Kinases , Tumor Microenvironment , Liver Neoplasms/etiology , Liver Neoplasms/pathology , Liver Neoplasms/metabolism , Liver Neoplasms/radiotherapy , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/radiotherapy , Humans , Animals , Mice , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Chemokine CCL2/metabolism , Cell Line, Tumor , Radiation Tolerance , Prognosis , STAT3 Transcription Factor/metabolism , Xenograft Model Antitumor Assays , MicroRNAs/genetics
15.
Virol J ; 21(1): 152, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970084

ABSTRACT

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16. METHODS: In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively. RESULTS: A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes. CONCLUSION: The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China.


Subject(s)
Genetic Variation , Human papillomavirus 18 , Oncogene Proteins, Viral , Papillomavirus E7 Proteins , Phylogeny , Oncogene Proteins, Viral/genetics , China , Humans , Human papillomavirus 18/genetics , Human papillomavirus 18/classification , Papillomavirus E7 Proteins/genetics , Capsid Proteins/genetics , Female , Epitopes, T-Lymphocyte/genetics , Papillomavirus Infections/virology , Repressor Proteins/genetics , Epitopes, B-Lymphocyte/genetics , DNA-Binding Proteins
16.
J Ovarian Res ; 17(1): 140, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970121

ABSTRACT

BACKGROUND: Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, effective biomarkers for accurate prediction and personalized treatment remain an urgent clinical need. METHODS: In this study, we analyzed the microbial contents of 453 ovarian serous cystadenocarcinoma and 68 adjacent non-cancerous samples. A univariate Cox regression model was used to identify microorganisms significantly associated with survival and a prognostic risk score model constructed using LASSO Cox regression analysis. Patients were subsequently categorized into high-risk and low-risk groups based on their risk scores. RESULTS: Survival analysis revealed that patients in the low-risk group had a higher overall survival rate. A nomogram was constructed for easy visualization of the prognostic model. Analysis of immune cell infiltration and immune checkpoint gene expression in both groups showed that both parameters were positively correlated with the risk level, indicating an increased immune response in higher risk groups. CONCLUSION: Our findings suggest that microbial profiles in ovarian serous cystadenocarcinoma may serve as viable clinical prognostic indicators. This study provides novel insights into the potential impact of intratumoral microbial communities on disease prognosis and opens avenues for future therapeutic interventions targeting these microorganisms.


Subject(s)
Cystadenocarcinoma, Serous , Immunotherapy , Ovarian Neoplasms , Humans , Female , Cystadenocarcinoma, Serous/immunology , Cystadenocarcinoma, Serous/mortality , Cystadenocarcinoma, Serous/pathology , Ovarian Neoplasms/immunology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/therapy , Ovarian Neoplasms/microbiology , Ovarian Neoplasms/pathology , Prognosis , Immunotherapy/methods , Middle Aged , Microbiota , Biomarkers, Tumor , Aged , Survival Analysis , Adult
17.
Article in Chinese | MEDLINE | ID: mdl-38973039

ABSTRACT

Objective:To analyze the clinical characteristics of middle ear mastoiditis combined with sigmoid sinus thrombophlebitis in children. Methods:Author retrospectively analyzed the clinical data of 6 children with middle ear mastoiditis combined with sigmoid sinus thrombophlebitis who were hospitalized in the Department of Infectious Diseases and Department of Neurology with first diagnosis of fever/headache, and subsequently underwent middle ear mastoidectomy in our department. All patients underwent comprehensive otoscopic, audiologic, imaging, and pathogenetic examinations. Clinical manifestations, pathogenetic features, treatment methods and prognosis were summarized, and the follow-up period was 3-6 months. Results:All 6 cases were first diagnosed with intracranial complications such as fever and headache in the internal medicine department. Within one month, all patients developed ear symptoms including pain, discharge, and hearing loss. Audiologic examination revealed conductive hearing loss in five cases and total deafness in one case. MRI, MRV and MRA examinations suggested that there were 6 cases of middle ear infection combined with thrombophlebitis of the ethmoid sinus, of which 3 cases had thrombus in the ethmoid sinus. 6 cases received surgical treatments: 2 cases of radical mastoidectomy+grommet Insertion, and 4 cases of radical mastoidectomy. Pathogenetic examination identified Streptococcus pneumoniae in three cases, Pseudomonas aeruginosa in one case, Enterobacter cloacae complex in one case, and no pathogens were detected in one case. Postoperative pathology was inflammatory granulation in all 6 cases. Follow-up was 3-6 months with no recurrence of intracranial and middle ear lesions on regular review. Conclusion:Children with recurrent fever, headache, and a recent history of acute and chronic otitis media should be evaluated for the possibility of sigmoid sinus thrombophlebitis, and imaging tests should be performed in a timely manner to clarify the diagnosis. Once diagnosed, surgery to remove the lesions around the ethmoid sinus, smooth drainage combined with antibiotic therapy is the most direct and effective treatment, and anticoagulation therapy is given when necessary. Timely diagnosis, multidisciplinary collaboration, and accurate timing of the management of primary foci and comorbidities are crucial to the treatment of the disease.


Subject(s)
Mastoiditis , Humans , Retrospective Studies , Mastoiditis/complications , Child , Male , Female , Child, Preschool , Mastoidectomy , Sinus Thrombosis, Intracranial/complications
18.
Angew Chem Int Ed Engl ; : e202409708, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973371

ABSTRACT

Organic piezoelectric nanogenerators (PENGs) are attractive in harvesting mechanical energy for various self-powering systems. However, their practical applications are severely restricted by their low output open circuit voltage. To address this issue, herein, we prepared two two-dimensional (2D) covalent organic frameworks (COFs, CityU-13 and CityU-14), functionalized with fluorinated alkyl chains for PENGs. The piezoelectricity of both COFs was evidenced by switchable polarization, characteristic butterfly amplitude loops, phase hysteresis loops, conspicuous surface potentials and high piezoelectric coefficient value (d33). The PENGs fabricated with COFs displayed highest output open circuit voltages (60 V for CityU-13 and 50 V for CityU-14) and delivered satisfactory short circuit current with an excellent stability of over 600 seconds. The superior open circuit voltages of CityU-13 and CityU-14 rank in top 1 and 2 among all reported organic materials-based PENGs.

19.
Chem Sci ; 15(26): 9927-9948, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38966379

ABSTRACT

The ever-growing atmospheric CO2 concentration threatening the environmental sustainability of humankind makes the reduction of CO2 to chemicals or fuels an ideal solution. Two priorities are anticipated for the conversion technology, high efficiency and net carbon benefit, to ensure the mitigation of the CO2 problem both promptly and sustainably. Until now, catalytic hydrogenation or solar/electro-chemical CO2 conversion have achieved CO2 reduction promisingly while, to some extent, compromising to fulfill the two rules, and thus alternative approaches for CO2 reduction are necessary. Natural geochemical processes as abiotic CO2 reductions give hints for efficient CO2 reduction by building hydrothermal reaction systems, and this type of reaction atmosphere provides room for introducing renewable substances as reductants, which offers the possibility to achieve CO2 reduction with net carbon benefit. While the progress in CO2 reduction has been abundantly summarized, reviews on hydrothermal CO2 reduction are relatively scarce and, more importantly, few have focused on CO2 reduction with renewable reductants with the consideration of both scale of efficiency and sustainability. This review provides a fundamental and critical review of metal, biomass and polymer waste as reducing agents for hydrothermal CO2 reduction. Various products including formic acid, methanol, methane and multi-carbon chemicals can be formed, and effects of operational parameters such as temperature, batch holding time, pH value and water filing as well as detailed reaction mechanisms are illustrated. Particularly, the critical roles of high temperature and pressure water as reaction promotor and catalyst in hydrothermal CO2 conversion are discussed at the mechanistic level. More importantly, this review compares hydrothermal CO2 reduction with other methods such as catalytic hydrogenation and photo/electrocatalysis, evaluating their efficiency and potential for net carbon benefit. The aim of this review is to promote the understanding of CO2 activation under a hydrothermal environment and provide insights into the efficient and sustainable strategy of hydrothermal CO2 conversion for future fundamental research and industrial applications.

20.
Eur J Med Chem ; 276: 116633, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38968785

ABSTRACT

Influenza remains a global public health threat, and the development of new antivirals is crucial to combat emerging drug-resistant influenza strains. In this study, we report the synthesis and evaluation of a sialyl lactosyl (TS)-bovine serum albumin (BSA) conjugate as a potential multivalent inhibitor of the influenza virus. The key trisaccharide component, TS, was efficiently prepared via a chemoenzymatic approach, followed by conjugation to dibenzocyclooctyne-modified BSA via a strain-promoted azide-alkyne cycloaddition reaction. Biophysical and biochemical assays, including surface plasmon resonance, isothermal titration calorimetry, hemagglutination inhibition, and neuraminidase inhibition, demonstrated the strong binding affinity of TS-BSA to the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus as well as intact virion particles. Notably, TS-BSA exhibited potent inhibitory activity against viral entry and release, preventing cytopathic effects in cell culture. This multivalent presentation strategy highlights the potential of glycocluster-based antivirals for combating influenza and other drug-resistant viral strains.

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