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1.
Biosens Bioelectron ; 266: 116727, 2024 Dec 15.
Article in English | MEDLINE | ID: mdl-39232433

ABSTRACT

The isolation and identification of pathogenic bacteria from a variety of samples are critical for controlling bacterial infection-related health problems. The conventional methods, such as plate counting and polymerase chain reaction-based approaches, tend to be time-consuming and reliant on specific instruments, severely limiting the effective identification of these pathogens. In this study, we employed the specificity of the cell wall-binding (CBD) domain of the Staphylococcus aureus bacteriophage 80 alpha (80α) endolysin towards the host bacteria for isolation. Amidase 3-CBD conjugated magnetic beads successfully isolated as few as 1 × 102 CFU/mL of S. aureus cells from milk, blood, and saliva. The cell wall hydrolyzing activity of 80α endolysin promoted the genomic DNA extraction efficiency by 12.7 folds on average, compared to the commercial bacterial genomic DNA extraction kit. Then, recombinase polymerase amplification (RPA) was exploited to amplify the nuc gene of S. aureus from the extracted DNA at 37 °C for 30 min. The RPA product activated Cas12a endonuclease activity to cleave fluorescently labeled ssDNA probes. We then converted the generated signal into a fluorescent readout, detectable by either the naked eye or a portable, self-assembled instrument with ultrasensitivity. The entire procedure, from isolation to identification, can be completed within 2 h. The simplicity and sensitivity of the method developed in this study make it of great application value in S. aureus detection, especially in areas with limited resource supply.


Subject(s)
Biosensing Techniques , Endopeptidases , Staphylococcus aureus , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/virology , Biosensing Techniques/methods , Endopeptidases/chemistry , Endopeptidases/isolation & purification , Endopeptidases/genetics , Bacteriophages/chemistry , Bacteriophages/genetics , Bacteriophages/isolation & purification , Humans , Staphylococcus Phages/genetics , Staphylococcus Phages/chemistry , Staphylococcus Phages/isolation & purification , Animals , Nucleic Acid Amplification Techniques/methods , Staphylococcal Infections/microbiology , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , Micrococcal Nuclease/chemistry , Micrococcal Nuclease/metabolism , Micrococcal Nuclease/genetics , Viral Proteins/chemistry , Viral Proteins/metabolism
3.
Med Sci Monit ; 30: e944916, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39233395

ABSTRACT

BACKGROUND This study aimed to compare the hemodynamic changes and the occurrence of oropharyngeal complications among patients undergoing tracheal intubation with an ordinary laryngoscope, video laryngoscope, and rigid video laryngoscope under general anesthesia. MATERIAL AND METHODS Patients undergoing elective tracheal intubation under general anesthesia were prospectively enrolled as study subjects. Hemodynamic indicators such as diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR), as well as the incidences of oropharyngeal complications, including dental injury, oral mucosal injury, hoarseness, sore throat, and dysphagia, were observed in the patients of 3 groups (group A: ordinary laryngoscope, group B: video laryngoscope, group C: rigid video laryngoscope). Observations were made after anesthesia induction (T0), immediately after tracheal intubation (T1), and at 5 min after intubation (T2). RESULTS The HR at T1 in group A was significantly higher than in groups B and C (P<0.05). However, the difference in the number of tracheal intubations was statistically significant among the 3 groups (P<0.05); group C exhibited the highest first-time success rate of tracheal intubation (95%), whereas group A had the highest failure rate (5%). Significant differences were also noted in the incidences of oral mucosal injury and sore throat among the groups (P<0.05), with the highest incidence in group A and the lowest in group C. CONCLUSIONS Compared with the ordinary laryngoscope, tracheal intubation using a video or rigid video laryngoscope results in milder hemodynamic impacts and fewer intubation-related complications. The rigid video laryngoscope may be safer and more effective.


Subject(s)
Anesthesia, General , Heart Rate , Hemodynamics , Intubation, Intratracheal , Laryngoscopes , Laryngoscopy , Humans , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/methods , Laryngoscopes/adverse effects , Anesthesia, General/adverse effects , Anesthesia, General/methods , Male , Female , Hemodynamics/physiology , Middle Aged , Adult , Heart Rate/physiology , Laryngoscopy/methods , Laryngoscopy/adverse effects , Oropharynx , Blood Pressure/physiology , Prospective Studies , Video Recording/methods , Aged , Pharyngitis/etiology , Pharyngitis/physiopathology
4.
Talanta ; 279: 126639, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39094531

ABSTRACT

In this paper, an ultra-small-sized CuOx/GDYO nanozyme in situ grown on ITO glass was rationally synthesized from mixed precursors of graphdiyne oxide (GDYO) and copper based infinite coordination polymer (Cu-ICP, consisting of Cu ions and two organic ligands 3,5-di-tert-butylcatechol and 1,4-bis(imidazole-1-ylmethyl)benzene) via mild and simple electrochemical strategy. On one hand, the preferential electro-reduction of Cu-ICP enabled the formation of ultra-small CuOx with Cu(I) as the main component and avoided the loss of oxygen-containing functional groups and defects on the surface of GDYO; on the other hand, GDYO can also serve as electroless reductive species to facilitate the electrochemical deposition of CuOx and turn itself to a higher oxidation state with more exposed functional groups and defects. This one-stone-two-birds electrochemical strategy empowered CuOx/GDYO nanozyme with superior peroxidase-mimicking activity and robust anchoring stability on ITO glass, thus enabled further exploration of the portable device with availability for point-of-use applications. Based on the organophosphorus pesticides (OPs) blocked acetylcholinesterase (AChE) activity, the competitive redox reaction was regulated to initiate the chromogenic reaction of 3,3',5,5'-tetramethylbenzidine (TMB) catalyzed by CuOx/GDYO peroxidase-like nanozyme, which laid out a foundation for the detection of OPs (with chlorpyrifos as an example). With a detection of limit low to 0.57 nM, the OPs residues during agricultural production can be directly monitored by the portable device we developed.


Subject(s)
Colorimetry , Copper , Electrochemical Techniques , Pesticides , Colorimetry/methods , Copper/chemistry , Pesticides/analysis , Pesticides/chemistry , Electrochemical Techniques/methods , Graphite/chemistry , Limit of Detection , Peroxidase/metabolism , Peroxidase/chemistry , Nanostructures/chemistry , Acetylcholinesterase/metabolism , Acetylcholinesterase/chemistry , Organophosphates/chemistry , Organophosphates/analysis , Benzidines/chemistry
5.
Drug Des Devel Ther ; 18: 3329-3336, 2024.
Article in English | MEDLINE | ID: mdl-39100225

ABSTRACT

Background: This study explored the effects of different doses of remimazolam tosilate (RT) and propofol combined with remifentanil anesthesia on hemodynamic and inflammatory responses in patients undergoing laparoscopic surgery. Subjects and Methods: Ninety patients with a BMI of less than 35 kg/m², classified as ASA II-III and scheduled for laparoscopic surgery, were enrolled in this study. Patients were divided into three groups: low-dose RT group (A), high-dose RT group (B), and propofol group (C). The changes in hemodynamic indices such as SBP, DBP, HR, MAP, and inflammatory response indices such as IL-6, SAA, CRP, and PCT, along with extubation time and doses of sufentanil, remifentanil, urapidil, and phenylephrine, were compared among the three groups. Results: There were no statistically significant differences in extubation time, doses of sufentanil and remifentanil, or the usage rates and average doses of urapidil and phenylephrine between the three groups. The average dose of phenylephrine in group A was lower than in group B and group C, with a statistically significant difference. There were no statistically significant differences among the groups in SBP, DBP, HR, and MAP from T0 to T2, nor in IL-6, SAA, CRP, or PCT levels. Conclusion: Using RT for induction and maintenance of anesthesia in laparoscopic surgery ensures stable hemodynamic and inflammatory responses in patients. Low-dose RT may reduce the usage rate and dose of vasopressors such as phenylephrine during surgery.


Subject(s)
Benzodiazepines , Dose-Response Relationship, Drug , Hemodynamics , Inflammation , Laparoscopy , Propofol , Humans , Hemodynamics/drug effects , Male , Female , Propofol/administration & dosage , Propofol/pharmacology , Adult , Middle Aged , Inflammation/drug therapy , Benzodiazepines/administration & dosage , Benzodiazepines/pharmacology , Remifentanil/administration & dosage , Remifentanil/pharmacology , Anesthetics, Intravenous/administration & dosage , Anesthetics, Intravenous/pharmacology , Young Adult
6.
Ann Hematol ; 103(9): 3691-3699, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39073588

ABSTRACT

The prognosis of primary plasma cell leukemia (pPCL) is poor, and the relevant prognostic factors are incompletely understood. We aimed to explore the prognostic factors and develop a validated prognostic prediction model for pPCL patients in the new era. This multicenter retrospective study was conducted across 16 hospitals in China. Cox proportional hazards regression analysis was used to develop a prediction model. The predictive performance of the model was assessed using multiple metrics. Internal validation was conducted using bootstrap resampling. A total of 102 pPCL patients were included in this study, and 57 (55.9%) were male. The 12-month, 24-month, and 36-month OS rates for pPCL patients were 75.4%, 58.3%, and 47.6%, respectively. An overall survival prognostic nomogram for pPCL patients was established by integrating independent prognostic factors, including age, B2MG, and del17p. The nomogram exhibited good performance, with a C-index of 0.720 (95% CI 0.642-0.797) and an AUC of 0.653. Bootstrap validation yielded a C-index of 0.721 (95% CI 0.629-0.787) and an AUC of 0.653 (95% CI 0.546-0.759), indicating a relatively good fit of the calibration curve. A nomogram incorporating age, B2MG grade, and del17p were developed and validated to accurately and consistently predict the prognosis of pPCL patients.


Subject(s)
Leukemia, Plasma Cell , Nomograms , Humans , Retrospective Studies , Male , Middle Aged , Female , Leukemia, Plasma Cell/mortality , Leukemia, Plasma Cell/diagnosis , Leukemia, Plasma Cell/therapy , Leukemia, Plasma Cell/drug therapy , Aged , Prognosis , Adult , Survival Rate , Aged, 80 and over , China/epidemiology
7.
Talanta ; 278: 126512, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38970964

ABSTRACT

The tetracycline (TC) residue in water environment has caused serious public safety issue. Thus, efficient sensing of TC is highly desirable for environmental protection. Herein, biomass-derived nitrogen-doped carbon dots (N-CDs) synthesized from natural Ophiopogon japonicus f. nanus (O. japonicus) were used for TC detection. The unique solvent synergism efficiently enhanced detection sensitivity, and the detailed sensing mechanism was deeply investigated. The blue fluorescence of N-CDs was quenched by TC via static quenching and inner filter effect. Moreover, the enhancement of green fluorescence from deprotonated TC was firstly proposed and sufficiently verified. The solvent effect of N-methyl pyrrolidone (NMP) and the fluorescence resonance energy transfer (FRET) with N-CDs achieved an instantaneous enhancement of the green emission by 64-fold. Accordingly, a ratiometric fluorescence method was constructed for rapid and sensitive sensing of TC with a low detection limit of 6.3 nM within 60 s. The synergistic effect of N-CDs and solvent assistance significantly improved the sensitivity by 7-fold compared to that in water. Remarkably, the biomass-derived N-CDs displayed low cost, good solubility, and desired stability. The deep insights into the synergism with solvent can provide prospects for the utilization of biomass-based materials and broaden the development of advanced sensors with promising applications.


Subject(s)
Biomass , Carbon , Pyrrolidinones , Quantum Dots , Solvents , Tetracycline , Water Pollutants, Chemical , Pyrrolidinones/chemistry , Pyrrolidinones/analysis , Carbon/chemistry , Quantum Dots/chemistry , Solvents/chemistry , Water Pollutants, Chemical/analysis , Tetracycline/analysis , Tetracycline/chemistry , Limit of Detection , Fluorescence Resonance Energy Transfer/methods , Spectrometry, Fluorescence/methods
8.
Ecotoxicol Environ Saf ; 271: 116002, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38277972

ABSTRACT

Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.


Subject(s)
Electronic Nicotine Delivery Systems , Glycerol , Male , Female , Rats , Animals , Glycerol/toxicity , Glycerol/analysis , Vegetables , Multiomics , Proteomics , Propylene Glycol/toxicity , Propylene Glycol/analysis , Solvents , Aerosols/analysis
9.
Hortic Res ; 11(1): uhad238, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38222823

ABSTRACT

As two of the most abundant post-translational modifications, phosphorylation and ubiquitination play a significant role in modulating plant-pathogen interactions and increasing evidence indicates their crosstalk in plant immunity. Rose (Rosa sp.) is one of the most important ornamental plants and can be seriously infected by Botrytis cinerea. Here, integrated proteomics analysis was performed to detect global proteome, phosphorylation, and ubiquitination changes in rose upon B. cinerea infection and investigate the possible phosphorylation and ubiquitination crosstalk. A total of 6165 proteins, 11 774 phosphorylation and 10 582 ubiquitination sites, and 77 phosphorylation and 13 ubiquitination motifs were identified. Botrytis cinerea infection resulted in 169 up-regulated and 122 down-regulated proteins, 291 up-regulated and 404 down-regulated phosphorylation sites, and 250 up-regulated and 634 down-regulated ubiquitination sites. There were 12 up-regulated PR10 proteins and half of them also showed reduced ubiquitination. A lot of kinases probably involved in plant pattern-triggered immunity signaling were up-regulated phosphoproteins. Noticeably, numerous kinases and ubiquitination-related proteins also showed a significant change in ubiquitination and phosphorylation, respectively. A cross-comparison of phosphoproteome and ubiquitylome indicated that both of two post-translational modifications of 104 proteins were dynamically regulated, and many putative pattern-triggered immunity signaling components in the plant plasma membrane were co-regulated. Moreover, five selected proteins, including four PR10 proteins and a plasma membrane aquaporin, were proven to be involved in rose resistance to B. cinerea. Our study provides insights into the molecular mechanisms underlying rose resistance to B. cinerea and also increases the database of phosphorylation and ubiquitination sites in plants.

11.
Angew Chem Int Ed Engl ; 62(52): e202316495, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-37948070

ABSTRACT

Non-fullerene acceptors have shown great promise for organic solar cells (OSCs). However, challenges in achieving high efficiency molecular system with conformational unicity and effective molecular stacking remain. In this study, we present a new design of non-fused tetrathiophene acceptor R4T-1 via employing the encapsulation of tetrathiophene with macrocyclic ring. The single crystal structure analysis reveals that cyclic alkyl side chains can perfectly encapsulate the central part of molecule and generate a conformational stable and planar molecular backbone. Whereas, the control 4T-5 without the encapsulation restriction displays cis- and twisted conformation. As a result, R4T-1 based OSCs achieved an outstanding power conversion efficiency (PCE) exceeding 15.10 % with a high short-circuit current density (Jsc ) of 25.48 mA/cm2 , which is significantly improved by ≈30 % in relative to that of the control. Our findings demonstrate that the macrocyclic encapsulation strategy could assist fully non-fused electron acceptors (FNEAs) to achieve a high photovoltaic performance and pave a new way for FNEAs design.

12.
Eur J Med Chem ; 262: 115915, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37948955

ABSTRACT

Inhibition of PI3K and histone deacetylase (HDAC) activity simultaneously using a single molecule appears to be a promising approach for cancer treatment. Current PI3K/HDAC dual inhibitors commonly use hydroxamate moiety as zinc binding group, which lack HDAC isoform selectivity and have potential genotoxicity. In this study, a novel series of benzamide-based PI3K/HDAC dual inhibitors were rationally designed and synthesized. Representative compound PH14 showed potent inhibitory activity toward PI3Kα and HDAC3, with IC50 values of 20.3 nM and 24.5 nM, respectively. This was further supported by the blockage of AKT phosphorylation and an increase in acetylated histone H3 levels in Western blot study. The advantage of simultaneously targeting PI3Kα and HDAC is not only reflected in the significant antiproliferative activity, but also in its ability to promote the apoptosis in Jeko-1 cells. Moreover, PH14 had weak inhibitory effects on CYP450 enzymes and hERG. In the pharmacokinetic study, the administration of 1 mg/kg of PH14 the administration of 1 mg/kg of PH14 resulted in a t1/2 of 10 h and an AUC (0-∞) of 2772 h ng/mL. Our study may provide ideas for the further development of novel HDAC/PI3K dual inhibitors.


Subject(s)
Antineoplastic Agents , Lymphoma , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Apoptosis , Cell Line, Tumor , Cell Proliferation , Histone Deacetylase Inhibitors/pharmacology , Histone Deacetylase Inhibitors/chemistry , Phosphatidylinositol 3-Kinases/metabolism , Structure-Activity Relationship , Benzamides/chemistry , Benzamides/pharmacology
13.
J Int Med Res ; 51(8): 3000605231197069, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37666219

ABSTRACT

Postoperative intractable hiccups slow patient recovery and generate multiple adverse effects, highlighting the importance of investigating the pathogenesis and terminating the hiccups in a timely manner. At present, medical and physical therapies account for the main treatments. We encountered a case in which postoperative intractable hiccups after biliary T-tube drainage removal ceased with the application of an ultrasound-guided block of the unilateral phrenic nerve and stellate ganglion. No complications developed, and the therapeutic effect was remarkable. To our knowledge, this approach has not been reported to date. Simultaneously blocking the phrenic nerve and stellate ganglion may be a treatment option for intractable hiccups.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Hiccup , Humans , Phrenic Nerve/surgery , Hiccup/etiology , Hiccup/therapy , Stellate Ganglion/surgery , Drainage
14.
Drug Dev Ind Pharm ; 49(10): 628-636, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37751149

ABSTRACT

OBJECTIVE: This study aimed to investigate the transport capability of nicotine across Calu-3 cell monolayer in various nicotine forms, including nicotine freebase, nicotine salts, and flavored e-liquids with nicotine benzoate. SIGNIFICANCE: Nicotine is rapidly absorbed from the respiratory system into systemic circulation during e-cigarettes use. However, the mechanism of nicotine transport in the lung has not been well understood yet. This study may offer critical biological evidence and have implications for the use and regulation of e-cigarettes. METHODS: The viability of Calu-3 cells after administration of nicotine freebase, nicotine salts and representative e-liquid were evaluated using the MTT assay, and the integrity of the Calu-3 cell monolayer was evaluated by transepithelial electrical resistance measurement and morphological analysis. Further, the nicotine transport capacity across the Calu-3 cell monolayer in various formulations of nicotine was investigated by analysis of nicotine transport amount. RESULTS: The findings indicated that nicotine transport occurred passively and was time-dependent across the Calu-3cell monolayer. In addition, the nicotine transport was influenced by the type of nicotine salts and their respective pH value. The nicotine benzoate exhibited the highest apparent permeability coefficient (Papp), and higher nicotine-to-benzoic acid ratios led to higher Papp values. The addition of flavors to e-liquid resulted in increased Papp values, with the most significant increment being observed in tobacco-flavored e-liquid. CONCLUSIONS: In summary, the transport capability of nicotine across the Calu-3 cell monolayer was influenced by the pH values of nicotine salts and flavor additives in e-liquids.


Subject(s)
Electronic Nicotine Delivery Systems , Nicotine , Nicotine/pharmacology , Salts , Lung , Flavoring Agents , Benzoates
15.
Hum Vaccin Immunother ; 19(2): 2241309, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37519009

ABSTRACT

Persistent infection with high-risk human papillomavirus (HR-HPV) is a known pathogenic factor of cervical cancer. To develop scientific guidance for cervical cancer screening and HPV vaccination, we analyzed HPV genotypes in Suzhou City, China. This study utilized data from the cervical cancer screening project in Suzhou from 2016 to 2021. A total of 444,471 female residents who voluntarily underwent HPV testing were included in the study. The overall HR-HPV prevalence was 10.2%. The three most common HR-HPV genotypes were HPV52 (2.81%), HPV58 (1.64%), and HPV16 (1.46%). The rate of HPV infection increased with age. Having a junior school education or higher was a protective factor compared to having an education level below junior school. The overall HPV infection rate showed a downwards trend from 2016 to 2021. HPV16 exhibited the fastest annual decline rate, followed by HPV18. As the severity of cervical intraepithelial neoplasia increases, the detection rate of HPV infection significantly increased. In conclusion, in addition to cervical cancer screening, it is important to pay attention to health promotion and education for low-educated women aged 45-59. Considering the distribution of HPV genotypes, prioritizing the administration of high-valency HPV vaccines to local seventh-grade female students is recommended.


Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/pathology , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Human Papillomavirus Viruses , Prevalence , Early Detection of Cancer , Genotype , Papillomaviridae/genetics , China/epidemiology , Human papillomavirus 16/genetics
16.
World J Clin Cases ; 11(10): 2160-2167, 2023 Apr 06.
Article in English | MEDLINE | ID: mdl-37122525

ABSTRACT

The stellate ganglion (SG), as a type of sympathetic ganglion, consists of the sixth and seventh cervical vertebrae and the first thoracic sympathetic ganglia. SG block (SGB) is a minimally invasive injection that aims to inject low-concentration local anesthetics to induce a broad sympathetic blocking effect near the SG. There have been no changes and progress in the clinical application of SGB since the 1830s due to several potential risks, including hematoma from blood vessel injury, hoarseness from recurrent laryngeal nerve injury, and cardiopulmonary arrest. The feasibility and safety of SGB have greatly improved since the appearance of ultrasound-guided SGB. In recent years, SGB has been widely applied in the field of non-anesthesiology sedation, with significant therapeutic effects on pain, immunological diseases, somnipathy, psychological disorders, arrhythmias, and endocrine diseases. The present study reviews the present application of SGB in clinical practice.

17.
J Phys Chem Lett ; 14(20): 4842-4849, 2023 May 25.
Article in English | MEDLINE | ID: mdl-37194946

ABSTRACT

DNA alkylating agents are widely used in anticancer pharmacology. Although shown to induce cross-linking and/or methylation of DNA, how they affect the mechanical properties of DNA and activity of DNA enzymes remains to be elucidated. Here, we perform single-molecule optical tweezer experiments on DNA treated with alkylating agents, including melphalan, cisplatin, and dacarbazine. While all three drugs induce a significant increase of overstretching force and a reduction of hysteresis, suggesting stabilization of DNA against shearing forces, their effects on elasticity of DNA were quite different, with the largest change in persistence length induced by cisplatin. Furthermore, we find that these alkylating-agent-induced changes on DNA have different effects on processivity of DNA polymerase, with melphalan and cisplatin showing significantly reduced activity and dacarbazine showing little effect. Overall, our results provide new insights into the effects for these alkylating agents, which could potentially facilitate a better design of related drugs.


Subject(s)
Alkylating Agents , Melphalan , Alkylating Agents/pharmacology , Melphalan/pharmacology , Cisplatin , Antineoplastic Agents, Alkylating/pharmacology , Dacarbazine , DNA , Spectrum Analysis
18.
Article in English | MEDLINE | ID: mdl-37080813

ABSTRACT

BACKGROUND: Gallbladder carcinoma (GBC) is highly malignant, and its early diagnosis remains difficult. This study aimed to develop a deep learning model based on contrast-enhanced computed tomography (CT) images to assist radiologists in identifying GBC. METHODS: We retrospectively enrolled 278 patients with gallbladder lesions (> 10 mm) who underwent contrast-enhanced CT and cholecystectomy and divided them into the training (n = 194) and validation (n = 84) datasets. The deep learning model was developed based on ResNet50 network. Radiomics and clinical models were built based on support vector machine (SVM) method. We comprehensively compared the performance of deep learning, radiomics, clinical models, and three radiologists. RESULTS: Three radiomics features including LoG_3.0 gray-level size zone matrix zone variance, HHL first-order kurtosis, and LHL gray-level co-occurrence matrix dependence variance were significantly different between benign gallbladder lesions and GBC, and were selected for developing radiomics model. Multivariate regression analysis revealed that age ≥ 65 years [odds ratios (OR) = 4.4, 95% confidence interval (CI): 2.1-9.1, P < 0.001], lesion size (OR = 2.6, 95% CI: 1.6-4.1, P < 0.001), and CA-19-9 > 37 U/mL (OR = 4.0, 95% CI: 1.6-10.0, P = 0.003) were significant clinical risk factors of GBC. The deep learning model achieved the area under the receiver operating characteristic curve (AUC) values of 0.864 (95% CI: 0.814-0.915) and 0.857 (95% CI: 0.773-0.942) in the training and validation datasets, which were comparable with radiomics, clinical models and three radiologists. The sensitivity of deep learning model was the highest both in the training [90% (95% CI: 82%-96%)] and validation [85% (95% CI: 68%-95%)] datasets. CONCLUSIONS: The deep learning model may be a useful tool for radiologists to distinguish between GBC and benign gallbladder lesions.

19.
Anal Chem ; 95(15): 6261-6270, 2023 Apr 18.
Article in English | MEDLINE | ID: mdl-37013351

ABSTRACT

In this work, by fully exploring the stimulus response of the guest-functionalized infinite coordination polymers (ICPs), a double-ratio colorimetric and fluorometric dual mode assay and multi-responsive coffee ring chips for point-of-use analysis of phosphate ions (Pi) were proposed. First, the complex host-guest interactions were rationally designed to obtain Au/Lum/RhB@Ag-DMcT ICPs. The composite ICPs exhibited a purple-blue color resulted from the modulated localized surface plasmon resonance (LSPR) of the Au core, and a blue fluorescence color stemmed from the unique aggregation-induced-emission (AIE) of Luminol (Lum) and the aggregation-caused-quenching (ACQ) of rhodamine B (RhB). With the presence of Pi, the host-guest interactions of the shell within Au/Lum/RhB@Ag-DMcT ICPs were interrupted to release Au core, Lum, and RhB in a dispersed state. Consequently, the color of the solution changed to purple-red (the mixed color of the Au core and RhB guest), and the fluorescence color turned to orange-red (AIE of Lum decreased, while the ACQ of RhB recovered). This constituted the sensing mechanism for dual-mode Pi assay with the double ratiometric response. Second, during the stimulus response, the surface wettability/size/amount of Au/Lum/RhB@Ag-DMcT ICPs simultaneously altered. These changes were reflected in the form of the coffee ring deposition pattern variances on the glass substrate and served as signal readouts for the exploration of multi-responsive coffee ring chips for the first time. Quantitative Pi detection with high accuracy and reliability in real samples was thereby realized, which offered an opportunity for the point-of-use analysis of Pi in resources-limited areas in a high-throughput fashion.

20.
Mol Biotechnol ; 65(8): 1263-1274, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36507941

ABSTRACT

Members of the MEX3 (muscle excess 3) family, uniquely characterised as mRNA binding proteins, play emerging roles in the post-transcriptional regulation of programmed biological processes, including tumour cell death and immune mechanisms, and have been shown to be involved in a variety of diseases. However, the role of MEX3 in non-small cell lung cancer (NSCLC) has not been fully elucidated. In this study, we found no significant changes in the sequence and copy number of the MEX3 gene through analysis using the COSMIC database, revealing its stability during malignancy development. Its expression in NSCLC was examined using the Oncomine™ database, and the prognosis of each member gene was analysed by Kaplan-Meier. The results showed that overexpression of MEX3A, MEX3B, MEX3C and MEX3D was associated with significantly worse OS in patients with LUAD, while overexpression of MEX3D was also associated with significantly worse OS in patients with LUSC. Afterwards, we applied the Tumour Immunology Estimation Resource (TIMER) tool to assess the correlation between different MEX3 and infiltrative immune cell infiltration. Ultimately, we found that most MEX3 members were highly expressed in NSCLC, with high expression suggesting poor prognosis and correlating with immune cell infiltration. The complexity and heterogeneity of NSCLC was understood through MEX3, setting the framework for the prognostic impact of MEX3 in NSCLC patients and the development of new targeted therapeutic strategies in the future.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , RNA, Messenger , RNA-Binding Proteins/genetics , Phosphoproteins
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