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Cancer, a pressing global health challenge, is characterized by its rapid onset and high mortality rates. Conventional treatment methods prove insufficient in achieving the desired therapeutic outcomes, underscoring the critical need to identify an effective and safe approach for cancer treatment. In this study, a copper-doped nanoparticle known as Cu2+-DOX@ZIF-90 is designed by incorporating copper(II) (Cu(II)) and encapsulating doxorubicin (DOX) within ZIF-90. Leveraging the elevated ATP levels in cancer cells relative to normal cells, Cu2+-DOX@ZIF-90 undergoes intracellular degradation, leading to the release of DOX and Cu(II). DOX, a traditional chemotherapy drug for clinical use, induces apoptosis in cancer cells. Cu(II) interacts with glutathione (GSH) to generate Cu(I), catalyzing H2O2 to produce ˙OH, thereby prompting apoptosis in cancer cells. Concurrently, the reduction of GSH enhances the therapeutic effect of chemodynamic therapy (CDT). Furthermore, Cu(II) triggers the aggregation of lipoylated mitochondrial proteins, leading to the formation of DLAT oligomers and ultimately promoting cuproptosis in cancer cells. In vivo experimental findings demonstrate that Cu2+-DOX@ZIF-90 does not cause damage to normal tissues and organs in tumor-bearing mice, with a notable tumor inhibition rate of 86.18%. This synergistic approach, combining chemotherapy, CDT, and cuproptosis, holds significant promise for the effective and safe treatment of cancer. [ABSTRACT FROM AUTHOR]

ETV6::ABL1 is a rare fusion gene that found in MPN, ALL, and AML. It has a complex and diverse formation mechanism due to the reciprocal orientations of the ETV6 and ABL1 genes relative to the centromeres. NPM1 is frequently mutated in adult AML, often accompanied by FLT3-ITD, which suggests molecular synergisms in AML pathogenesis. Previous reports on ETV6::ABL1 mostly focus on FLT3-ITD. In this study, we present a case of AML with ETV6::ABL1, along with NPM1 and FLT3-ITD. The patient showed a rapid increase in primitive cells at the initial stage, along with the presence of immature granulocytes and erythrocytes. Through cytogenetic analysis, fluorescence in situ hybridization (FISH), and RNA-seq, we elucidated the mechanism behind the formation of the ETV6::ABL1 fusion gene. Despite conventional chemotherapy failure and rapid tumor proliferation, we attempted to add FLT3 inhibitor sorafenib to the treatment, along with chemotherapy bridging to haploidentical transplantation. After haplo-HSCT, a combination of sorafenib and dasatinib was administered as maintenance therapy. The patient achieved complete remission (CR) and maintained it for 11 months. The intricate genetic landscape observed in this case presents diagnostic dilemmas and therapeutic challenges, emphasizing the importance of a comprehensive understanding of its implications for disease classification, risk stratification, and treatment selection. [ABSTRACT FROM AUTHOR]

A near-infrared fluorescent probe (TX-P) for detecting peroxynitrite is constructed. The probe has a near-infrared emission (725 nm), large Stokes shift (125 nm) and excellent sensitivity and selectivity. In addition, TX-P can be used to visualize ONOO− in living cells, image ONOO− in paw edema mice and evaluate anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Background: Rodents are recognized as the hosts of many vector-borne bacteria and protozoan parasites and play an important role in their transmission and maintenance. Intensive studies have focused on their infections in vectors, especially in ticks, however, vector-borne bacterial and protozoan infections in rodents are poorly understood although human cases presenting with fever may due to their infection have been found. Methods: From May to October 2019, 192 wild rodents were trapped in wild environment of Guangxi Province, and the spleen samples were collected to reveal the presence of vector-borne bacterial and protozoan infections in them. The microorganisms in rodents were identified by detecting their DNA using (semi-)nested PCR. All the PCR products of the expected size were subjected to sequencing, and then analyzed by BLASTn. Furthermore, all the recovered sequences were subjected to nucleotide identity and phylogenetic analyses. Results: As a result, 192 rodents representing seven species were captured, and Bandicota indica were the dominant species, followed by Rattus andamanensis. Based on the (semi-)nested PCR, our results suggested that Anaplasma bovis, Anaplasma capra, Anaplasma ovis, Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis", "Candidatus E. hainanensis", "Candidatus E. zunyiensis", three uncultured Ehrlichia spp., Bartonella coopersplainsensis, Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella silvatica, two uncultured Bartonella spp., Babesia microti and diverse Hepatozoon were identified in six rodent species. More importantly, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are zoonotic pathogens except Anaplasma bovis and Anaplasma ovis with zoonotic potential. Furthermore, dual infection was observed between different microorganisms, and the most common type of co-infection is between "Ca. N. mikurensis" and other microorganisms. Additionally, potential novel Bartonella species and Hepatozoon species demonstrated the presence of more diverse rodent-associated Bartonella and Hepatozoon. Conclusions: The results in this work indicated great genetic diversity of vector-borne infections in wild rodents, and highlighted the potential risk of human pathogens transmitted from rodents to humans through vectors. Author summary: Rodents are the important hosts of many pathogens, especially vector-borne pathogens, and can harbor and transmit them to humans and cause diseases. In China, little information is known about the infection of vector-borne pathogens in rodents although the rodent species are very diverse. In this study, seven wild rodent species were collected to identify the genetic diversity of vector-borne bacteria and protozoan. Interestingly, diverse vector-borne microorganisms, including four Anaplasma, five Ehrlichia, "Candidatus Neoehrlichia mikurensis", six Bartonella, Babesia microti and diverse Hepatozoon were identified in six rodent species. Furthermore, two potential novel Bartonella species were detected. All these data suggested great genetic diversity of vector-borne pathogens infections in rodents. Of them, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are pathogenic to humans except A. bovis and A. ovis with zoonotic potential, suggesting significant risks to local human population. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to identify the risk factors for postoperative delirium (POD) in elderly patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). Methods: Elderly patients undergoing elective heart valve surgery with CPB in The First Affiliated Hospital of Wenzhou Medical University between March 2022 and March 2023 were selected for this investigation. They were divided into a POD group and a non-POD group. Their baseline information was collected and recorded, and the patients were subjected to neurocognitive function assessment using the Mini-Mental State Examination and the Montreal Cognitive Assessment scales before surgery. We also recorded their intraoperative indicators such as duration of surgery, duration of CPB, duration of aortic cross-clamp, blood transfusion, and postoperative indicators such as duration of mechanical ventilation, postoperative 24-hour drainage volume, and pain score. Regional cerebral oxygen saturation was monitored intraoperatively by near-infrared spectroscopy based INVOS5100C Regional Oximeter. Patients were assessed for the occurrence of POD using Confusion Assessment Method for the Intensive Care Unit, and logistic regression analysis of risk factors for POD was performed. Results: The study finally included 132 patients, with 47 patients in the POD group and 85 ones in the non-POD group. There were no significant differences in baseline information and preoperative indicators between the two groups. However, marked differences were identified in duration of surgery, duration of CPB, duration of aortic cross-clamp, duration of postoperative mechanical ventilation, postoperative length of stay in cardiac intensive care unit, postoperative length of hospital stay, intraoperative blood transfusion, postoperative pain score, and postoperative 24-hour drainage volume between the two groups (p < 0.05). Additionally, the two groups had significant differences in rScO2 at each intraoperative time point and in the difference of rScO2 from baseline at each intraoperative time point (p < 0.05). Multivariate logistic regression analysis showed that duration of surgery > 285 min (OR, 1.021 [95% CI, 1.008–1.035]; p = 0.002), duration of postoperative mechanical ventilation > 23.5 h (OR, 6.210 [95% CI, 1.619–23.815]; p = 0.008), and postoperative CCU stay > 3.5 d (OR, 3.927 [95% CI, 1.046–14.735]; p = 0.043) were independent risk factors of the occurrence of POD while change of rScO2 at T1>50.5 (OR, 0.832 [95% CI 0.736–0.941]; p = 0.003) was a protective factor for POD. Conclusion: Duration of surgery duration of postoperative mechanical ventilation and postoperative CCU stay are risk factors for POD while change of rScO2 at T1 is a protective factor for POD in elderly patients undergoing heart valve surgery with CPB. [ABSTRACT FROM AUTHOR]

Background: Mycoheterotrophs, acquiring organic carbon and other nutrients from mycorrhizal fungi, have evolved repeatedly with substantial plastid genome (plastome) variations. To date, the fine-scale evolution of mycoheterotrophic plastomes at the intraspecific level is not well-characterized. A few studies have revealed unexpected plastome divergence among species complex members, possibly driven by various biotic/abiotic factors. To illustrate evolutionary mechanisms underlying such divergence, we analyzed plastome features and molecular evolution of 15 plastomes of Neottia listeroides complex from different forest habitats. Results: These 15 samples of Neottia listeroides complex split into three clades according to their habitats approximately 6 million years ago: Pine Clade, including ten samples from pine-broadleaf mixed forests, Fir Clade, including four samples from alpine fir forests and Fir-willow Clade with one sample. Compared with those of Pine Clade members, plastomes of Fir Clade members show smaller size and higher substitution rates. Plastome size, substitution rates, loss and retention of plastid-encoded genes are clade-specific. We propose to recognized six species in N. listeroides complex and slightly modify the path of plastome degradation. Conclusions: Our results provide insight into the evolutionary dynamics and discrepancy of closely related mycoheterotrophic orchid lineages at a high phylogenetic resolution. [ABSTRACT FROM AUTHOR]

Layered BiCuXO (X = S, Se, and Te) compounds attract much attention recently because of their superior thermoelectric properties. However, the major shortcoming of these compounds is the relatively large electrical resistance. Exploring the mechanism of electrical scattering of BiCuXO can give some hints on how to optimize their electrical conductivity. Here, we compared electrical and magnetotransport properties of degenerate semiconductor BiCuXO. These compounds show metallic electrical properties, and the in-plane resistivity is linearly dependent on the temperature at the high-temperature regime (>150 K). The magnetoresistance of these compounds is approximately quadratically dependent on the square of magnetic field B, and magnetoresistance decreases from 10%–16% to 0.5% when the temperature is increased from 2 to 300 K. The Hall measurements substantiate that the electrical carriers of BiCuXO are holes, which perhaps come from Bi vacancies. The electron-optical-phonon interaction is the major mechanism of electron scattering when the temperature is higher than 80 K. Analyzing the linear coefficient ρxx-T of BiCuXO (X = S, Se, and Te) suggests that the averaged electron-phonon interaction of BiCuSO is nearly six times larger than that of BiCuSeO/BiCuTeO. Based on the Thomas-Fermi model, compared with BiCuSO, the weak electron-phonon interaction in BiCuSeO/BiCuTeO could be attributed to a highly screened Coulomb interaction between electrons and ions. This work may be useful to optimize the electrical properties of BiCuXO to satisfy the requirement of thermoelectric materials. [ABSTRACT FROM AUTHOR]

esophageal cancer is one of the deadliest diseases worldwide. Due to the ineffectual screening methods referring to early diagnosis, most people have lost their chance of radical resection when diagnosed with esophageal cancer. This aim of this study was designed to evaluate the latent values of the stem signatures-associated autoantibodies (AABS) in predicting the early diagnosis, and particularly seeking the precise predictive outcomes with sensitive SOX2. We also studied the potential immunotherapeutic targets and prospective long-term prognosis predicators of esophageal cancer. The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of 203 local cases were enrolled. The TCGA databases were used to analyse distinct expression patterns and prognostic values of related genes. The TIMER database was used to explore the signatures of immune cell infiltration in related genes. The TISIDB database was used to analyse the association between related genes and immune regulators. The stem signatures-associated with antibodies of TP53, PGP9.5, SOX2, and CAGE were highly expressed in esophageal cancer and were negatively correlated with the test group, the diagnostic sensitivity of P53, SOX2, PGP9.5 and CAGE reached to 54.3%, 56.5%, 80.4% and 47.8%, respectively, and the specificity reached 77.7%, 93.6%, 76.4% and 86.6%. Especially in stage I esophageal cancer, the diagnostic sensitivity of SOX2 reached 82.4% with a specificity of 85.4%, which demonstrated good value in early diagnosis. The stem signatures-associated antibodies could be used as an effective indicator in early esophageal cancer diagnosis and could help to precisely predicate survival and prognosis. The stem signatures-associated immune-antibodies could be used as effective indicators in early diagnosis of esophageal cancer and help to precisely predicate the survival and prognosis. The potential immunotherapeutic targets referring to esophageal cancer are screened and analysed, and the high sensitivity of SOX2 in detecting early esophageal cancer will yield early and effective treatments. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Alpha-fetoprotein (AFP) is still the only serum biomarker widely used in clinical settings. However, approximately 40% of HCC patients exhibit normal AFP levels, including very early HCC and AFP-negative HCC; for these patients, serum AFP is not applicable as a biomarker of early detection. Thus, there is an urgent need to identify novel biomarkers for patients for whom disease cannot be diagnosed early. In this study, we screened and identified novel proteins in AFP-negative HCC and evaluated the feasibility of using autoantibodies to those protein to predict hepatocarcinogenesis. First, we screened and identified differentially expressed proteins between AFP-negative HCC tissue and adjacent non-tumor liver tissue using SWATH-MS proteome technology. In total, 2,506 proteins were identified with a global false discovery rate of 1%, of which 592 proteins were expressed differentially with 175 upregulated and 417 downregulated (adjusted p -value <0.05, fold-change FC ≥1.5 or ≤0.67) between the tumor and matched benign samples, including 14-3-3 zeta protein. For further serological verification, autoantibodies against 14-3-3 zeta in serum were evaluated using enzyme-linked immunosorbent, Western blotting, and indirect immunofluorescence assays. Five serial serum samples from one patient with AFP-negative HCC showed anti-14-3-3 zeta autoantibody in sera 9 months before the diagnosis of HCC, which gradually increased with an increase in the size of the nodule. Based on these findings, we detected the prevalence of serum anti-14-3-3 zeta autoantibody in liver cirrhosis (LC) patients, which is commonly considered a premalignant liver disease of HCC. We found that the prevalence of autoantibodies against 14-3-3 zeta protein was 16.1% (15/93) in LC patient sera, which was significantly higher than that in patients with chronic hepatitis (0/75, p = 0.000) and normal human sera (1/60, 1.7%, p = 0.01). Therefore, we suggest that anti-14-3-3 zeta autoantibody might be a biomarker for predicting hepatocarcinogenesis. Further follow-up and research of patients with positive autoantibodies will be continued to confirm the relationship between anti-14-3-3 zeta autoantibody and hepatocarcinogenesis. [ABSTRACT FROM AUTHOR]

Background: This study was designed to detect patients with early NSCLC with tentatively using the stem signatures associated autoantibodies (AAbs), and to evaluate its latent values in the early diagnosis and precise prognosis prediction. Methods: The serum concentrations of selective antibodies were quantitated by enzyme-linked immunosorbent assay (ELISA), and a total of 458 cases were enrolled (training set = 401; validation set = 57). TCGA databases were used to analyze the distinct expressions and prognostic values of related genes. The optimal cut-off values were 11.60 U/ml for P53, 4.90 U/ml for MAGEA1, 3.85 U/ml for SOX2, and 7.05U/ml for PGP9.5. Results: We found that the stem signatures associated antibodies of MAGEA1, PGP9.5, SOX2, and TP53 exhibited high expressions in NSCLC, negatively correlating with the overall survival (OS) (P < 0.05). In the test groups, the diagnosis sensitivity of P53, PGP9.5, SOX2, and MAGEA1 reached to 21.5%, 39.0%, 50.3%, and 35.0%, respectively, and the specificity reached to 98.7%, 99.4%, 92.2%, and 97.4%. The four candidates' panel gave a sensitivity of 71.8% with a specificity of 89%. In the validation group, the detection of the four antibodies in early diagnosis of NSCLC also exhibited high specificity and sensitivity, further consolidating their potential application. Conclusions: The detection regarding stem signatures associated antibodies could be used as effective tools in early NSCLC diagnosis, but not for localized screening of cancers, and their abnormal expression was in accordance with poorer survival. [ABSTRACT FROM AUTHOR]

To evaluate prognosis of breast cancer patients, a total of 16,618 TNBC patients from SEER database were involved. High grade, unmarried status, tumor site were the main factors reduced OS in stage I. Black race, unmarried, large tumor size, and nodes metastasis would make worse prognosis in stage II. Compared with stage II, race and marital status had no significant effect on the prognosis in stage III. In stage IV, married status significantly improved the OS and DSS. Surgery and chemotherapy improve survival time in all of stages. Clinicopathological status correlated with the prognosis of patients with differentially staged TNBC. [ABSTRACT FROM AUTHOR]

Two metal–organic frameworks, {(NH2Me2)[Zn(Pycia)]}n (MOF-1) and {(NH2Me2)[Zn2(Pycia)(PBA)]}n (MOF-2), have been synthesized based on pyrazole functionalized carboxylic acid ligands for organic dye adsorption. The enlarged pore dimension of MOF-2 suggests the advantage of additional linear auxiliary ligand for the structure tuning of the MOFs. Furthermore, the anionic frameworks of the MOFs endow them with size selective adsorption toward different cationic organic dyes. [ABSTRACT FROM AUTHOR]

Extended naive Bayesian classifier (ENBC) is a general framework of NBCs, which is developed based on $$t$$ -norm based ordered weighted averaging ( $$t$$ -OWA) operator and uses the weighted summation of products of margin probabilities to determine class-conditional probability. Since ENBC was proposed in 2006, there is no such a study which tests the performances of ENBC on the real classification datasets. Thus, in this paper we conduct an experimental investigation to ENBC's generalization capability based on 44 benchmark KEEL and UCI datasets. The analysis shows that (1) ENBC is instable and its aggregation weights are sensitive to the order of training samples and (2) ENBC indeed has higher generalization capability than the existing NBCs, e.g., normal naive Bayesian and flexible naive Bayesian when its weight is properly selected. [ABSTRACT FROM AUTHOR]

Hollow urchin-like α-FeOOH was successfully prepared without template or surfactant, employing a facile route incorporating hydrothermal treatment with ammonium iron (III) sulphate solution. α-FeOOH was characterised by X-ray diffraction, thermal gravimetric analysis, scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM (HRTEM) and Fourier transform infrared spectroscopy. The Ostwald ripening process was believed to be the main driving force for the formation of hollow urchin-like architectures. Furthermore, the electrochemical properties of hollow urchin-like α-FeOOH were investigated by cyclic voltammetry (CV) and galvanostatic charge-discharge measurements. The CV results implied that the capacitance was mainly associated with the redox mechanism. The specific capacitance value was 88.5 F/g calculated from the discharge curve at the current density of 0.5 A·g. The hollow urchin-like α-FeOOH shows a good electrochemical performance. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) are known to promote neovascularization in ischemic diseases. Recent evidence from our group suggested that CREB-binding protein (CBP) plays an important role in thrombin-induced EPCs migration. However, whether CBP could regulate EPCs angiogenic properties is unknown. In the present study, we investigated whether CBP silencing could inhibit thrombin-induced EPCs angiogenesis. EPCs isolated from the bone marrow of Sprague-Dawley rats were cultured and identified, and then were treated by thrombin alone or combined with CBP-shRNA lentivirus. The effect of CBP silencing on EPCs proliferation was assessed using BrdU incorporation assay. Cell adhesion and tube formation were detected to evaluate the angiogenic functions. Finally, mRNA and protein expression of relevant angiogenic genes were examined by real-time PCR, western-blot, and enzyme-linked immunoassay respectively. Luciferase reporter gene assay was performed to evaluate NF-κB activity. Administration of thrombin significantly promoted EPCs proliferation and adhesion. Thrombin also increased the tube formation in Matrigel assay. However, these effects of thrombin were abolished by CBP gene silencing. CBP silencing also abrogated thrombin-induced increases of integrin β2 expression. In thrombin-induced EPCs, CBP silencing significantly decreased the secretion of VEGF, IL-6 and suppressed NF-κB activity. In conclusion, thrombin-induced EPCs proliferation, adhesion, and tube formation were inhibited by CBP silencing, indicating that CBP plays an important role in thrombin-induced EPCs neovascularization. [ABSTRACT FROM AUTHOR]

Deposition of amyloid-β peptide (Aβ) in the brain of diabetes is poorly understood. The receptor for advanced glycation end products (RAGE) at the blood-brain barrier (BBB) is critical for regulation of Aβ homeostasis in the brain. In this studies, we used streptozotocin-induced diabetic mice to observe the expression of RAGE at the BBB by Western blot and immunocytochemical analysis, and the in vivo blood-to-brain influx transport of 125I-Aβ1-40 using the permeability surface area product (PS) and brain capillary uptake. In the diabetic mice with hyperglycemia (>16.0 mmol/L) at 6 weeks, RAGE expression at the BBB was significantly upregulated, no significant changes of RAGE levels were found at 1 and 3 weeks after diabetes induction. The data of PS and brain capillary uptake for Aβ showed significant RAGE-dependent transport of Aβ across the BBB and substantial RAGE-dependent brain capillary uptake at 6 weeks after diabetes induction. We conclude that the upregulation of RAGE at the BBB contributes to cerebral Aβ deposition in the diabetes. Synapse 63:636-642, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Platanthera minor is widely distributed in East Asia. The complete circular chloroplast genome with a length of 154,430 bp possesses the typical structure, consisting of a large single copy (LSC) of 83,536 bp, a small single copy (SSC) of 17,612 bp, and two inverted repeats (IR) of 26,641 bp. The average GC content of the genome is 36.7%. The circular P. minor chloroplast genome contains 114 genes, including 80 protein-coding genes, four rRNA genes, and 30 tRNA genes. The chloroplast sequence provided a resource for analyzing genetic diversity of the Orchidaceae family. [ABSTRACT FROM AUTHOR]

A new wide‐band, low‐loss and compact vertical microstrip‐to‐microstrip transition is presented. The proposed structure consists of two quarter‐wavelength open‐circuited microstrip lines and a quarter‐wavelength open slot‐line etched on the common ground plane. The theoretical analysis based on equivalent‐circuit model reveals that the proposed transition exhibits ultra‐wide passband with three transmission poles. To effectively enhance the bandwidth, the optimised parameters are obtained by the transmission poles separations. Finally, a transition having a wide fractional bandwidth of 114% is achieved with the compact size of 8.75 mm × 4.2 mm. Predictions are well verified by measurements over a wide frequency range. [ABSTRACT FROM AUTHOR]