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BACKGROUND: Colorectal cancer (CRC) has always been one of the most common malignant tumors in the world. Whether the factors related to the diagnosis and risk of CRC can be found from the existing peripheral blood routine indicators. METHODS: The relevant data of patients with colorectal diseases in our hospital of about ten years were collected, the differences among the biomarkers in serum were analyzed, the risk factors were analyzed by logistic regression, the ROC was drawn, and the diagnostic efficacy was evaluated. RESULTS: Colorectal malignancies and benign diseases in AST, GGT, LDH, D-BIL, ALB, ALP, AchE, CR, TP, PA, RDW, LMR, NMR, TC, TG, HDL-C, CA19-9, CEA, Cyfra21-1, and Fer have statistical differences (p < 0.05). ALB, PLR, CEA, Fer, NLR, TP, GGT, and Cyfra21-1 in different malignant tumor types have statistical differences (p < 0.05). When CEA increased by 1, the risk of colorectal cancer increased by 45.7%. When AchE and HDL-C increased by 1, the risk of colorectal cancer decreased by 32% and 66.8%. Compared with other blood groups, blood group AB colorectal cancer patients had a shallower tumor invasion (p = 0.047). HDL-C were significantly weakly-correlated with tumor size (p < 0.05, |r| < 0.4). CEA, AchE, and HDL-C were combined diagnosed; the sensitivity, PPV, and accuracy were 94.35%, 95.43%, 90.77%, respectively. CONCLUSIONS: The occurrence and development of colorectal cancer is the result of multi-factors, and the combined detection of multi-indicators has positive significance for the diagnosis, pathological stage, and prevention of CRC.
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Biomarcadores Tumorais , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Estudos Retrospectivos , Biomarcadores Tumorais/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Adulto , Curva ROC , Antígeno Carcinoembrionário/sangueRESUMO
Ammonia (NH3) is regarded as an essential hydrogen storage material in the new energy field, and plasma-electrocatalytic synthesis of NH3 (PESA) is an alternative to the traditional Haber-Bosch process. Here, a bifunctional catalyst CoOOH/CF is proposed to enhance the PESA process. Benefiting from the efficient activation of O2 by CoOOH/CF, NOx - yield rate can reach the highest value of 171.90 mmol h-1 to date. Additionally, CoOOH holds a more negative d-band center, thereby exhibiting weaker adsorption toward NO*, lowering the energy barrier for the rate determining step, resulting in a high NH3 yield rate (302.55 mg h-1 cm-2 at -0.8 V) with ampere-level NH3 current density (2.86 A cm-2 at -0.8 V) and nearly 100% Faraday efficiency (FE, 99.8% at -0.6 V). Moreover, CoOOH/CF achieves an excellent 4.54 g h-1 NH3 yield rate with 97.9% FE in an enlarged electrolyzer, demonstrating the feasibility of PESA on a large scale.
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BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D) is a functional bowel disease with diarrhea, and can be associated with common spleen deficiency syndrome of the prevelent traditional Chinese medicine (TCM) syndrome. Fecal microbiota transplantation (FMT) could help treating IBS-D, but may provide variable effects. Our study evaluated the efficacy of TCM- shenling Baizhu decoction and FMT in treating IBS-D with spleen deficiency syndrome, with significant implications on gut microbiome and serum metabolites. METHODS: The new borne rats were procured from SPF facility and separated as healthy (1 group) and IBS-D model ( 3 groups) rats were prepared articially using mother's separation and senna leaf treatment. 2 groups of IBS-D models were further treated with TCM- shenling Baizhu decoction and FMT. The efficacy was evaluated by defecation frequency, bristol stool score, and intestinal tight junction proteins (occludin-1 and claudin-1) expression. Microbiomic analysis was conducted using 16 S rRNA sequencing and bioinformatics tools. Metabolomics were detected in sera of rats by LC-MS and annotated by using KEGG database. RESULTS: Significant increment in occludin-1 and claudin-1 protein expression alleviated the diarrheal severity in IBS-D rats (P < 0.05) after treatment with FMT and TCM. FMT and TCM altered the gut microbiota and regulated the tryptophan metabolism, steroid hormone biosynthesis and glycerophospholipid metabolism of IBS-D rats with spleen deficiency syndrome.The microbial abundance were changed in each case e.g., Monoglobus, Dubosiella, and Akkermansia and othe metabolic profiles. CONCLUSION: FMT and TCM treatment improved the intestinal barrier function by regulating gut microbiota and improved metabolic pathways in IBS-D with spleen deficiency syndrome.
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Diarreia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Medicina Tradicional Chinesa , Metabolômica , Animais , Síndrome do Intestino Irritável/terapia , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , Diarreia/microbiologia , Diarreia/terapia , Diarreia/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Esplenopatias/terapia , Esplenopatias/microbiologia , Esplenopatias/tratamento farmacológico , Masculino , RNA Ribossômico 16S/genética , Fezes/microbiologia , Baço/microbiologia , Baço/metabolismoRESUMO
Mitochondrial DNA G-quadruplexes (mtDNA G4s) play potential regulatory roles in mitochondrial functions. Fluorescent probes for imaging mtDNA G4s may provide useful information to unveil their regulating dynamics and functions. However, the existing probes for mtDNA G4s still exhibit short absorption and emission wavelengths and limited sensitivity. Here, we develop a new isaindigotone-derived near-infrared (NIR) fluorogenic probe for imaging mtDNA G4s in live cells and in vivo. Different fluorescent probes are engineered by conjugating the isaindigotone scaffold with varying electron-donating groups. It is shown that the probe ISAP using dimethylaminophenyl as the electron-donating group exhibits near-infrared absorption/emission and a high fluorescence activation fold in response to G4s. Molecular docking simulations reveal that ISAP binds to c-Myc G4 via multiple π-π stacking and hydrogen-bond interaction. Cellular studies show that ISAP exhibits an excellent mitochondrial targeting ability and allows specific imaging of mtDNA G4s. We further employed ISAP to image the dynamics of mtDNA G4s under glycolysis and oxidative stresses in live cells. Its capability to mtDNA G4s in vivo is showcased using a tumor-bearing mice model. This probe may serve as a useful tool to image mtDNA G4s and interrogate their biological roles in living systems.
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BACKGROUND: Familial hypercholesterolemia (FH) is a common monogenic autosomal dominant disorder, primarily mainly caused by pathogenic mutations in the low-density lipoprotein receptor (LDLR) gene. Through phenotypic-genetic linkage analysis, two LDLR pathogenic mutations were identified in FH families: c.G1027A (p.Gly343Ser) and c.G1879A (p.Ala627Thr). MATERIALS AND METHODS: Whole exome sequencing was conducted on the proband with familial hypercholesterolemia to identify the target gene and screen for potential pathogenic mutations. The suspicious responsible mutation sites in 14 family members were analyzed using Sanger sequencing to assess genotype-phenotype correlations. Mutant and wild type plasmids were constructed and transfected into HEK293T cells to evaluate LDLR mRNA and protein expression. In parallel, bioinformatics tools were employed to predict structural and functional changes in the mutant LDLR. RESULTS: Immunofluorescence analysis revealed no significant difference in the intracellular localization of the p.Gly343Ser mutation, whereas protein expression of the p.Ala627Thr mutation was decreased and predominantly localized in the cytoplasm. Western blotting has showed that protein expression levels of the mutant variants were markedly declined in both cell lysates and supernatants. Enzyme linked immunosorbent assay has demonstrated that LDLR protein levels in the supernatant of cell culture medium was not significant different from those of the wild-type group. However, LDLR protein levels in the cell lysate of both the Gly343Ser and Ala627Thr variants groups were significantly lower than those in the wild-type group. Bioinformatic predictions further suggested that these mutations may affect post-translational modifications of the protein, providing additional insight into the mechanisms underlying the observed reduction in protein expression. CONCLUSIONS: In this study, we identified two heterozygous pathogenic variants in the LDLR gene, c.G1027A (p.Gly343Ser) and c.G1879A (p.Ala627Thr), in a family with familial hypercholesterolemia. We also conducted preliminary investigations into the mechanisms by which these mutations contribute to disease pathology.
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Hiperlipoproteinemia Tipo II , Mutação , Linhagem , Receptores de LDL , Humanos , Receptores de LDL/genética , Hiperlipoproteinemia Tipo II/genética , Feminino , Masculino , Células HEK293 , Adulto , Pessoa de Meia-Idade , Sequenciamento do ExomaRESUMO
Sodium ion batteries (SIBs) are promising postlithium battery technologies with high safety and low cost. However, their development is hampered by complicated electrode material preparation and unsatisfactory sodium storage performance. Here, a bismuth/N-doped carbon nanosheets (Bi/N-CNSs) composite featuring a quasi-array structure (alternated porous Bi layers and N-CNSs) with hierarchical Bi distribution (large particles of â¼35 nm in Bi layers and ultrafine Bi of â¼8 nm on N-CNSs) is prepared. Bi/N-CNSs delivers an ultralong-lifespan of 26000 cycles at 5 A g-1 and prominent rate capability of 91.5% capacity retention at 100 A g-1. Even at -40 °C, it exhibits a high rate capability of 161 mAh g-1 at 5 A g-1. Notably, the involved preparation method is characterized by a high yield of 14.53 g in a single laboratory batch, which can be further scaled up, and such a method can also be extended to synthesize other metallic-based materials.
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OBJECTIVES: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. METHODS: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. RESULTS: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). CONCLUSIONS: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.
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5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase , Suplementos Nutricionais , Ácido Fólico , Comunicação Interventricular , Humanos , Ácido Fólico/administração & dosagem , Feminino , Comunicação Interventricular/genética , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Estudos de Casos e Controles , Lactente , Adulto , Gravidez , Polimorfismo Genético , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The understanding of cellular energy metabolism activation by engineered scaffolds remains limited, posing challenges for therapeutic applications in tissue regeneration. This study presents biosynthesized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] and its major degradation product, 3-hydroxybutyrate (3HB), as endogenous bioenergetic fuels that augment cellular anabolism, thereby facilitating the progression of human bone marrow-derived mesenchymal stem cells (hBMSCs) towards osteoblastogenesis. Our research demonstrated that 3HB markedly boosts in vitro ATP production, elevating mitochondrial membrane potential and capillary-like tube formation. Additionally, it raises citrate levels in the tricarboxylic acid (TCA) cycle, facilitating the synthesis of citrate-containing apatite during hBMSCs osteogenesis. Furthermore, 3HB administration significantly increased bone mass in rats with osteoporosis induced by ovariectomy. The findings also showed that P(3HB-co-4HB) scaffold substantially enhances long-term vascularized bone regeneration in rat cranial defect models. These findings reveal a previously unknown role of 3HB in promoting osteogenesis of hBMSCs and highlight the metabolic activation of P(3HB-co-4HB) scaffold for bone regeneration.
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BACKGROUND: Thoracoscopic-guided thoracic paravertebral nerve block (TG-TPVB) and thoracoscopic-guided intercostal nerve block (TG-INB) are two postoperative analgesia technology for thoracic surgery. This study aims to compared the analgesic effect of TG-TPVB and TG-INB after uniportal video-asssited thoracic surgery (UniVATS). METHODS: Fifty-eight patients were randomly allocated to the TG-TPVB group and the TG-INB group. The surgical time of nerve block, the visual analog scale (VAS) scores, the consumption of sufentanil and the number of patient-controlled intravenous analgesic (PCIA) presses within 24 h after surgery, the incidence of adverse reactions were compared between the two groups. RESULTS: The VAS scores were significantly lower during rest and coughing at 2, 6, 12, and 24 h in the TG-TPVB group than in the TG-INB group (P < 0.05). The consumption of sufentanil and the number of PCIA presses within 24 h after surgery were significantly lower in the TG-TPVB group than in the TG-INB group (P < 0.001).The surgical time of nerve block was significantly shorter in the TG-TPVB group than in the TG-INB group (P < 0.001). The incidence of bleeding at the puncture point was lower in the TG-TPVB group than that in the TG-INB group (P < 0.05). CONCLUSION: TG-TPVB demonstrated superior acute pain relieve after uniVATS, shorter surgical time and non-inferior adverse effects than TG-INB.
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Nervos Intercostais , Bloqueio Nervoso , Dor Pós-Operatória , Cirurgia Torácica Vídeoassistida , Humanos , Feminino , Masculino , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Pessoa de Meia-Idade , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Estudos Prospectivos , Seguimentos , Idoso , Prognóstico , Adulto , Toracoscopia/métodos , Toracoscopia/efeitos adversos , Medição da DorRESUMO
The active ingredients most commonly employed in sunscreens are compounds containing one or two aromatic rings. Lignin is the most abundant renewable aromatic polymer that has the potential to yield low molecular weight aromatic chemicals when strategically depolymerized. Here, the UV absorbance of a series of monomeric and dimeric lignin model compounds (LMCs) were studied. Specifically, vanillin and ferulic acid demonstrated good absorption in the UVB (280-320 nm) range, while the 5-5 dimer showed efficient absorption in the UVA (320-400 nm) range. Based on this, vanillin, ferulic acid and 5-5 dimer were mixed in pairs and dispersed in the oily isoeugenol to prepare LMC hybrid dispersions. Subsequently, demethylated lignin (DL) was synthesized and used to encapsulate the LMC hybrid dispersions via ultrasonic cavitation to prepare DL-based nano-capsules (DLNCs). The DLNCs were used as the only active ingredient in sunscreens, whose sun protection factor (SPF) value could be up to 55 with a dosage of 10 wt%. Due to anti-photolysis property of DL, the SPF value of DLNCs-based sunscreens increased initially and maintained >8 h under UV irradiation. Additionally, the prepared DLNCs exhibited excellent anti-permeability, antioxidant capacity and biocompatibility, making them a potential substitute for conventional petroleum-based sunscreen agents.
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Inter-metalloid clusters in Zintl chemistry have been extensively studied due to their unique electronic structures and potential applications. In this work, we explored a series of actinide endohedral inter-metalloid clusters of the group 15 elements [An@Bi12]4- (An = Th-U) and [An@Sb12]4- using density functional theory (DFT). [Th@Bi12]4- and [U@Bi12]4- exhibit Cs symmetry, while [Pa@Bi12]4- and [An@Sb12]4- (An = Th-U) have C1 structures. Bonding analyses such as bond order, molecular orbitals (MO) and quantum theory of atoms in molecules (QTAIM) show covalent An-Bi/An-Sb bonding in the clusters. All these clusters are highly stable according to the studied formation reactions and may be accessible experimentally. Compared with [An@Bi12]4-, [An@Sb12]4- possesses stronger bonding interactions, mainly arising from the higher electrostatic interaction energy. For clusters with the same group 15 elements, the bonding interactions increase gradually from Th to U, which is mainly determined by the covalent interactions of An-Bi/An-Sb bonding. This work is expected to provide potential avenues for the construction of robust inter-metalloid clusters of the group 15 elements.
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CONTEXT: Revealing the mechanism of intermolecular interactions in dinitroamine ammonium (ADN)-based liquid propellants and exploring the reasons for their performance changes, multi-perspective interaction analyses of ADN and ADN-water (H2O)-methanol (CH3OH) solutions have been conducted via theoretical methods. The band structure, density of states (DOS), surface electrostatic potential (ESP), Hirshfeld surface, reduced density gradient (RDG), AIM topological analysis, and detonation performance were studied and the results showed that both the ADN and ADN-H2O-CH3OH solutions had hydrogen bonds and van der Waals interactions. By introducing the small molecules H2O and CH3OH, the detonation performance of the ADN-H2O-CH3OH solution slightly decreased, but its sensitivity also decreased. Overall, the comprehensive performance of the ADN-H2O-CH3OH solution has improved, and the application range has expanded. These results are helpful for obtaining a deeper understanding of ADN-based liquid propellants at the atomic level and contribute to the development of new liquid propellants. METHODS: The ADN and ADN-H2O-CH3OH solutions were constructed by Amorphous cell module and optimized via GGA with PBE methods in the Dmol3 module of the Materials Studio, and their electronic properties were calculated. Hirshfeld surfaces were generated with CrystalExplorer 3.0. A topological analysis of a variety of molecular clusters was performed via QTAIM. The QTAIM and RDG analyses in this work were generated by Multiwfn 3.0.
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This study addresses the relationship between platelet count and 30-day in-hospital mortality in End-Stage Kidney Disease (ESRD) patients in the intensive care unit (ICU), a topic with limited existing evidence. Utilizing data from the US eICU-CRD v2.0 database (2014-2015), a retrospective cohort study was conducted involving 3700 ICU ESRD patients. We employed binary logistic regression, smooth curve fitting, and subgroup analyses to explore the association between platelet count and 30-day in-hospital mortality. The 30-day in-hospital mortality rate was 13.27% (491/3700), with a median platelet count of 188 × 109/L. After adjusting for covariates, we observed a relationship between platelet count and 30-day in-hospital mortality (OR = 0.98, 95% CI 0.97, 0.99). Subgroup analyses supported these findings. More importantly, a nonlinear association was detected, with an inflection point at 222 × 109/L. The effect sizes (OR) on the left and right sides of the inflection point were 0.94 (0.92, 0.96) and 1.03 (1.00, 1.05), respectively. The most significant finding of this study is the revelation of a nonlinear relationship between baseline platelet count and 30-day in-hospital mortality in ICU patients with ESRD. This discovery explicitly suggests that when ESRD patients are admitted to the ICU, a platelet level closer to 222 × 109/L may predict a lower 30-day in-hospital mortality risk.
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Mortalidade Hospitalar , Unidades de Terapia Intensiva , Falência Renal Crônica , Humanos , Contagem de Plaquetas , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Feminino , Estudos Retrospectivos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/sangue , Pessoa de Meia-Idade , IdosoRESUMO
A protein modification strategy was developed based on a thiol-yne click reaction using an electron-deficient yne reagent. This approach demonstrated exceptional selectivity towards thiols and exhibited rapid kinetics, resulting in conjugates with superior acid stability. The conjugation of IgG with an indole-derived fluorophore was achieved for the imaging of PD-L1 in cancer cells.
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Química Click , Elétrons , Compostos de Sulfidrila , Compostos de Sulfidrila/química , Humanos , Corantes Fluorescentes/química , Imunoglobulina G/química , Antígeno B7-H1/química , Antígeno B7-H1/metabolismo , Indóis/química , Indóis/síntese química , Alcinos/química , Linhagem Celular Tumoral , Estrutura MolecularRESUMO
Microplastics (MPs) have emerged as a pervasive environmental pollutant of global concern. Their detection within the human placenta and fetal organs has prompted apprehension regarding the potential hazards of MPs during early organogenesis. The kidney, a vital multifunctional organ, is susceptible to damage from MPs in adulthood. However, the precise adverse effects of MP exposure on human nephrogenesis remain ambiguous due to the absence of a suitable model. Here, we explore the potential impact of MPs on early kidney development utilizing human kidney organoids in vitro. Human kidney organoids were subjected to polystyrene-MPs (PS-MPs, 1 µm) during the nephron progenitor cell (NPC) stage, a critical phase in early kidney development and patterning. We delineate the effects of PS-MPs on various stages of nephrogenesis, including NPC, renal vesicle, and comma-shaped body, through sequential examination of kidney organoids. PS-MPs were observed to adhere to the surface of cells during the NPC stage and accumulate within glomerulus-like structures within kidney organoids. Moreover, both short- and long-term exposure to PS-MPs resulted in diminished organoid size and aberrant nephron structure. PS-MP exposure heightened reactive oxygen species (ROS) production, leading to NPC apoptosis during early kidney development. Increased apoptosis, diminished cell viability, and NPC reduction likely contribute to the observed organoid size reduction under PS-MP treatment. Transcriptomic analysis at both NPC and endpoint stages revealed downregulation of Notch signaling, resulting in compromised proximal and distal tubular structures, thereby disrupting normal nephron patterning following PS-MP exposure. Our findings highlight the significant disruptive impact of PS-MPs on human kidney development, offering new insights into the mechanisms underlying PS-MP-induced nephron toxicity.
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Células-Tronco Pluripotentes Induzidas , Rim , Microplásticos , Organoides , Humanos , Organoides/efeitos dos fármacos , Rim/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Microplásticos/toxicidade , Organogênese/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Néfrons/efeitos dos fármacos , Poluentes Ambientais/toxicidadeRESUMO
The ability to precisely control the function of nucleic acids plays an important role in biosensing and biomedicine. In recent years, novel strategies employing biological, physical, and chemical triggers have been developed to modulate the function of nucleic acids spatiotemporally. These approaches commonly involve the incorporation of stimuli-responsive groups onto nucleic acids to block their functions until triggers-induced decaging restore activity. These inventive strategies deepen our comprehension of nucleic acid molecules' dynamic behavior and provide new techniques for precise disease diagnosis and treatment. Focusing on the spatiotemporal regulation of nucleic acid molecules through the chemical caging-decaging strategy, we here present an overview of the innovative triggered control mechanisms and accentuate their implications across the fields of chemical biology, biomedicine, and biosensing.
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Wasp venom injections from wasp stings can damage several organs, most commonly the kidneys. Despite literature evidence, wasp sting-induced acute kidney injury (AKI) is rare and involves complex pathophysiological processes. While acute tubular necrosis (ATN) is the most prevalent histological result of wasp sting-induced AKI, uncommon combinations of chronic renal lesions have been described, alerting us to the patient's underlying illness. We report a 55-year-old hypertensive patient with unknown renal function who got AKI following multiple wasp stings. His renal function had not improved after continuous hemodialysis and plasma exchange; therefore, a kidney biopsy was performed. The pathology revealed that in addition to ATN, his kidney's distinguishing feature was a mix of chronic interstitial renal disease and chronic glomerulosclerosis. We think that his current renal pathological results were caused by hypertension in addition to wasp venom.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is classified under fibrotic interstitial pneumonia, characterized by a chronic and progressive course. The predominant clinical features of IPF include dyspnea and pulmonary dysfunction. AIM: To assess the effects of pirfenidone in the early treatment of IPF on lung function in patients. METHODS: A retrospective analysis was performed on 113 patients with IPF who were treated in our hospital from November 2017 to January 2023. These patients were divided into two groups: control group (n = 53) and observation group (n = 60). In the control group, patients received routine therapy in combination with methylprednisolone tablets, while those in the observation group received routine therapy together with pirfenidone. After applying these distinct treatment approaches to the two groups, we assessed several parameters, including the overall effectiveness of clinical therapy, the occurrence of adverse reactions (e.g., nausea, vomiting, and anorexia), symptom severity scores, pulmonary function index levels, inflammatory marker levels, and the 6-min walk distance before and after treatment in both groups. RESULTS: The observation group exhibited significantly higher rates than the control group after therapy, with a clear distinction (P < 0.05). After treatment, the observation group experienced significantly fewer adverse reactions than the control group, with a noticeable difference (P < 0.05). When analyzing the symptom severity scores between the two groups of patients after treatment, the observation group had significantly lower scores than the control group, with a distinct difference (P < 0.05). When comparing the pulmonary function index levels between the two groups of patients after therapy, the observation group displayed significantly higher levels than the control group, with a noticeable difference (P < 0.05). Evaluating the inflammatory marker data (C-reactive protein, interleukin-2 [IL-2], and IL-8) between the two groups of patients after therapy, the observation group exhibited significantly lower levels than the control group, with significant disparities (P < 0.05). Comparison of the 6-min walking distance data between the two groups of patients after treatment showed that the observation group achieved significantly greater distances than the control group, with a marked difference (P < 0.05). CONCLUSION: Prompt initiation of pirfenidone treatment in individuals diagnosed with IPF can enhance pulmonary function, elevate inflammatory factor levels, and increase the distance covered in the 6-min walk test. This intervention is conducive to effectively decreasing the occurrence of adverse reactions in patients.
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BACKGROUND: Prediabetes mellitus (PreDM) is a high-risk state for developing type 2 diabetes mellitus (T2DM) and often goes undiagnosed, which is closely associated with obesity and characterized by insulin resistance that urgently needs to be treated. PURPOSE: To obtain a better understanding of the biological processes associated with both "spleen-dampness" syndrome individuals and those with dysglycaemic control at its earliest stages, we performed a detailed metabolomic analysis of individuals with various early impairments in glycaemic control, the results can facilitate clinicians' decision making and benefit individuals at risk. METHODS: According to the diagnostic criteria of TCM patterns and PreDM, patients were divided into 4 groups with 20 cases, patients with syndrome of spleen deficiency with dampness encumbrance and PreDM (PDMPXSK group), patients with syndrome of dampness-heat in the spleen and PreDM (PDMSRYP group), patients with syndrome of spleen deficiency with dampness encumbrance and normal blood glucose (NDMPXSK group), and patients with syndrome of dampness-heat in the spleen and normal blood glucose (NDMSRYP group). Plasma samples from patients were collected for clinical index assessment and untargeted metabolomics using liquid chromatography-mass spectrometry. RESULTS: Among patients with the syndrome of spleen deficiency with dampness encumbrance (PXSK), those with PreDM (PDMPXSK group) had elevated levels of 2-hour post-load blood glucose (2-h PG), glycosylated hemoglobin (HbA1c), high-density lipoprotein cholesterol (HDL-C), and systolic blood pressure (SBP) than those in the normal blood glucose group (NDMPXSK group, P < 0.01). Among patients with the syndrome of dampness-heat in the spleen (SRYP), the levels of body mass index (BMI), fasting blood glucose (FBG), 2-h PG, HbA1c, and fasting insulin (FINS) were higher in the PreDM group (PDMSRYP group) than those in the normal blood glucose group (NDMSRYP group, P < 0.05). In both TCM syndromes, the plasma metabolomic profiles of PreDM patients were mainly discriminatory from the normal blood glucose controls of the same syndrome in the levels of lipid species, with the PXSK syndrome showing a more pronounced and broader spectrum of alterations than the SRYP syndrome. Changes associated with PreDM common to both syndromes included elevations in the levels of 27 metabolites which were mainly lipid species encompassing glycerophospholipids (GPs), diglycerides (DGs) and triglycerides (TGs), cholesterol and derivatives, and decreases in 5 metabolites consisting 1 DG, 1 TG, 2 N,N-dimethyl phosphatidylethanolamine (PE-NMe2) and iminoacetic acid. Correlation analysis identified significant positive correlations of 3α,7α,12α,25-Tetrahydroxy-5ß-cholestane-24-one with more than one glycaemia-related indicators, whereas DG (20:4/20:5) and PC (20:3/14:0) were positively and PC (18:1/14:0) was inversely correlated with more than one lipid profile-related indicators. Based on the value of correlation coefficient, the top three correlative pairs were TG with PC (18:1/14:0) (r = - 0.528), TG with TG (14:0/22:4/22:5) (r = 0.521) and FINS with PE-NMe (15:0/22:4) (r = 0.52). CONCLUSION: Our results revealed PreDM patients with different TCM syndromes were characterized by different clinical profiles. Common metabolite markers associated with PreDM shared by the two TCM syndromes were mainly lipid species encompassing GP, GL, cholesterol and derivatives. Our findings were in line with the current view that altered lipid metabolism is a conserved and early event of dysglycaemia. Our study also implied the possible involvement of perturbed bile acid homeostasis and dysregulated PE methylation during development of dysglycaemia.