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1.
Int Immunopharmacol ; 140: 112843, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39098224

ABSTRACT

Neutrophils and macrophages confine pathogens by entrapping them in extracellular traps (ETs) through activating TLR9 function. However, plasmodial parasites secreted TatD-like DNases (TatD) to counteract ETs-mediated immune clearance. We found that TLR9 mutant mice increased susceptibility to rodent malaria, suggesting TLR9 is a key protein for host defense. We found that the proportion of neutrophils and macrophages in response to plasmodial parasite infection in the TLR9 mutant mice was significantly reduced compared to that of the WT mice. Importantly, PbTatD can directly bind to the surface TLR9 (sTLR9) on macrophages, which blocking the phosphorylation of mitogen-activated protein kinase and nuclear factor-κB, negatively regulated the signaling of ETs formation by both macrophages and neutrophils. Such, P. berghei TatD is a parasite virulence factor that can inhibit the proliferation of macrophages and neutrophils through directly binding to TLR9 receptors on the cell surface, thereby blocking the activation of the downstream MyD88-NF-kB pathways.

2.
Se Pu ; 42(8): 773-782, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39086246

ABSTRACT

A method based on a dual-channel gas chromatograph equipped with three columns and three detectors was established for the determination of individual components in finished motor gasoline. The gasoline samples were separately introduced into the two injection ports of the chromatograph using two autosamplers. The components of the sample introduced into the first injection port (channel 1) were separated on a nonpolar PONA column (50 m×0.20 mm×0.5 µm) for gasoline analysis and detected by an flame ionization detector (FID). The components of the sample introduced into the second injection port (channel 2) were separated on another PONA column. Oxygenates (e.g., ethers and alcohols), other unconventional and prohibited additives that would co-elute with the hydrocarbons (e.g., methylal, dimethyl carbonate, sec-butyl acetate, and anilines), and some difficult-to-separate hydrocarbon pairs (e.g., 2,3,3-trimethylpentane and toluene) eluted from the PONA column and entered a DM-624 column (30 m×0.25 mm×1.4 µm) to achieve further separation according to the switch timetable using the Deans switch procedure and detected by an FID. The peak of 3-methylpentane, a common component in gasoline samples, also entered the DM-624 column by the Deans switch procedure for calculation purposes. The peak areas of target components on the PONA column in channel 1 were calculated using the peak areas on the DM-624 column as well as those of 3-methylpentane on both the DM-624 and PONA columns in channel 1 with a calibration factor between the two channels. The peak areas of co-eluted components were obtained by subtracting the calculated peak areas of the target components from those of the co-eluted peaks. The mass percentages of the individual components were calculated according to the normalization method using all peak areas on the PONA column in channel 1 with relative response factors. The mass percentages of the oxygenates, anilines, and individual hydrocarbons were determined, and the group-type distribution was calculated according to the carbon number. Separation and quantitation interferences between the additives and hydrocarbons were eliminated using this procedure. Twenty oxygenates and unconventional additives, each with a mass percentage of approximately 3%, were added to a real motor gasoline-92 sample and analyzed using the proposed method. The recoveries of the target components were between 90.1% and 118.2% with relative standard deviations (RSDs) between 0.2% and 5.1% (n=6). The analysis of a real ethanol-gasoline sample showed that the RSDs of contents of most components was less than 3% (n=6). Because the heart-cut of peaks using Deans switch technique requires the precise repeatability of retention times, the retention-time repeatability of components on the PONA column in channel 2 was investigated over an extended period of time after thousands of runs of real-sample analysis. The retention times of the same component in several randomly selected motor gasoline-92 samples varied from 0.01 to 0.03 min, indicating that the proper timetable for the Deans switch remained stable for two years. The precise repeatability of retention times was achieved owing to the high precision of the electric pneumatic control of the chromatograph and the stability of the column used. Real finished motor gasoline samples with different octane numbers (gasoline-92, gasoline-95, and ethanol gasoline-95) were analyzed using the developed method, and the results acquired were consistent with those of standard methods (GB/T 30519-2016, NB/SH/T 0663-2014, and SH/T 0693-2000). If some unconventional additives (such as methylal) were added to gasoline samples, the contents of these unconventional additives could also be detected, which means one run of the proposed method could provide results corresponding to three or four runs of different standard methods. The acquisition of information on the individual components of finished motor gasoline will assist in research on precise gasoline blending.

3.
BMC Gastroenterol ; 24(1): 263, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138423

ABSTRACT

BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC). Mucinous adenocarcinoma (MAC) is a potential poor prognosis subgroup of rectal cancer. However, the predictive value of MAC in NCRT treatment of LARC is controversial. METHODS: A comprehensive literature search of PubMed, Embase, and the Cochrane Library was performed. All studies examining the effect of MAC on CRT response in LARC were included. Outcomes of MAC were compared with non-specific adenocarcinoma (AC) by using random-effects methods. Data were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The main outcomes were the rates of pathological complete response (pCR), tumor and nodal down-staging, positive resection margin rate, local recurrence, and overall mortality. RESULTS: Fifteen studies containing comparative data on outcomes in a total of 9,238 patients receiving NCRT for LARC were eligible for inclusion. MAC had a reduced rate of pCR (OR, 0.38; 95% CI, 0.18-0.78) and tumor down-staging (OR, 0.31; 95% CI, 0.22-0.44) following NCRT compared with AC. MAC did not significantly affect nodal down-staging (OR, 0.42; 95% CI, 0.16-1.12) after NCRT. CONCLUSION: MAC of LARC was found to be a negative predictor of response to NCRT with lower rates of pCR and tumor down-staging for LARC. The nodal down-staging of MAC was relatively lower than that of AC, although the differences were not statistically significant.


Subject(s)
Adenocarcinoma, Mucinous , Neoadjuvant Therapy , Rectal Neoplasms , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/mortality , Humans , Adenocarcinoma, Mucinous/therapy , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/mortality , Neoplasm Staging , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Neoplasm Recurrence, Local , Prognosis , Treatment Outcome , Chemoradiotherapy , Chemoradiotherapy, Adjuvant , Margins of Excision
4.
Nat Commun ; 15(1): 5550, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956014

ABSTRACT

Oocyte in vitro maturation is a technique in assisted reproductive technology. Thousands of genes show abnormally high expression in in vitro maturated metaphase II (MII) oocytes compared to those matured in vivo in bovines, mice, and humans. The mechanisms underlying this phenomenon are poorly understood. Here, we use poly(A) inclusive RNA isoform sequencing (PAIso-seq) for profiling the transcriptome-wide poly(A) tails in both in vivo and in vitro matured mouse and human oocytes. Our results demonstrate that the observed increase in maternal mRNA abundance is caused by impaired deadenylation in in vitro MII oocytes. Moreover, the cytoplasmic polyadenylation of dormant Btg4 and Cnot7 mRNAs, which encode key components of deadenylation machinery, is impaired in in vitro MII oocytes, contributing to reduced translation of these deadenylase machinery components and subsequently impaired global maternal mRNA deadenylation. Our findings highlight impaired maternal mRNA deadenylation as a distinct molecular defect in in vitro MII oocytes.


Subject(s)
Oocytes , Polyadenylation , Oocytes/metabolism , Animals , Humans , Female , Mice , Poly A/metabolism , In Vitro Oocyte Maturation Techniques , RNA, Messenger/metabolism , RNA, Messenger/genetics , Transcriptome , RNA, Messenger, Stored/metabolism , RNA, Messenger, Stored/genetics , Metaphase , Exoribonucleases , Repressor Proteins , Cell Cycle Proteins
5.
Rev Sci Instrum ; 95(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-39016701

ABSTRACT

Microwave reflectometry is an invaluable diagnostic tool for measuring electron density profiles in large fusion devices. Density fluctuations near the plasma cutoff layer, particularly those that are time-varying on the timescale of the reflectometry measurement, can result in distortions in phase and/or amplitude of the reflected waveform, which present challenges to the accuracy of the reconstructed profile. The ultra-short pulse reflectometry (USPR) technique eliminates the time-varying issue in that reflectometry data are collected on a nanosecond timescale, essentially freezing the fluctuations in place. An X-mode dedicated 32-channel USPR system has been developed and installed on the EAST, covering the operation frequency range from 52 to 92 GHz. This system enables high-resolution density profile measurements in the plasma pedestal and scrape-off layer, with resolutions reaching 5 mm and 1 µs, respectively. Laboratory testing of the system performance has been conducted, demonstrating the potential of the USPR technique to provide accurate and high-temporal-resolution density profiles in challenging plasma environments.

6.
Int J Mol Sci ; 25(13)2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39000399

ABSTRACT

Histiocytic sarcoma (HS) is an extremely rare but aggressive hematopoietic malignancy, and the prognosis has been reported to be rather unfavorable with a median overall survival of merely 6 months. We presented a 58-year-old female patient complaining of abdominal pain and fever, who was admitted to our institution in September 2021. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scan showed enlargement of generalized multiple lymph nodes. Subsequently, laparoscopic retroperitoneal lesion biopsy and bone marrow aspiration were performed. The pathological findings indicated the diagnosis of HS concurrent with follicular lymphoma. The immunohistochemistry (IHC) staining of the tumor lesion revealed a high expression of CD38 and PD-L1 proteins. Furthermore, KRAS gene mutation was identified by means of next-generation sequencing. The patient exhibited poor treatment response to both first- and second-line cytotoxic chemotherapies. Therefore, she underwent six cycles of Daratumumab (anti-CD38 monoclonal antibody), Pazopanib (multi-target receptor tyrosine kinases inhibitor) combined with third-line chemotherapy, followed by involved-site radiotherapy and maintenance therapy with the PD-1 inhibitor Tislelizumab. Long-term partial remission was finally achieved after multi-modality treatment. Duration of remission and overall survival reached 22 and 32 months, respectively. Our case indicated that immuno-targeted treatment coupled with chemotherapy and radiotherapy might constitute a potential therapeutic option for HS.


Subject(s)
Histiocytic Sarcoma , Lymphoma, Follicular , Humans , Female , Lymphoma, Follicular/drug therapy , Lymphoma, Follicular/therapy , Lymphoma, Follicular/pathology , Middle Aged , Histiocytic Sarcoma/drug therapy , Histiocytic Sarcoma/pathology , Histiocytic Sarcoma/therapy , Positron Emission Tomography Computed Tomography , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Remission Induction
7.
ESC Heart Fail ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38984376

ABSTRACT

AIMS: Improvement in left ventricular ejection fraction (impEF) often presents in contemporary acute myocardial infarction (AMI) patients. New-onset atrial fibrillation (NOAF) during AMI is an important predictor of subsequential heart failure (HF), while its impact on the trajectory of post-MI left ventricular ejection fraction (LVEF) and prognostic implication in patients with and without impEF remains undetermined. We aimed to investigate the prognostic impacts of NOAF in AMI patients with and without impEF. METHODS AND RESULTS: Consecutive AMI patients without a prior history of AF between February 2014 and March 2018 with baseline LVEF ≤ 40% and had ≥1 LVEF measurement after baseline were included. ImpEF was defined as a baseline LVEF ≤ 40% and a re-evaluation showed both LVEF > 40% and an absolute increase of LVEF ≥ 10%. Persistently reduced EF (prEF) was defined as the second measurement of LVEF either ≤40% or an absolute increase of LVEF < 10%. The primary endpoint was a major adverse cardiac event (MACE) that was composed of cardiovascular death and HF hospitalization. Cox regression analysis and competing risk analysis were performed to assess the association of post-MI NOAF with MACE. Among 293 patients (mean age: 66.6 ± 11.3 years, 79.2% of males), 145 (49.5%) had impEF and 67 (22.9%) developed NOAF. Higher heart rate (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.73-0.97; P = 0.015), prior MI (OR: 0.25, 95% CI: 0.09-0.69; P = 0.008), and STEMI (OR: 0.40, 95% CI: 0.21-0.77; P = 0.006) were independent predictors of post-MI impEF. Within up to 5 years of follow-up, there were 22 (15.2%) and 53 (35.8%) MACE in patients with impEF and prEF, respectively. NOAF was an independent predictor of MACE in patients with impEF (hazard ratio [HR]: 7.34, 95% CI: 2.49-21.59; P < 0.001) but not in those with prEF (HR: 0.78, 95% CI: 0.39-1.55; P = 0.483) after multivariable adjustment. Similar results were obtained when accounting for the competing risk of all-cause death (subdistribution HR and 95% CIs in impEF and prEF were 6.47 [2.32-18.09] and 0.79 [0.39-1.61], respectively). CONCLUSIONS: The NOAF was associated with an increased risk of cardiovascular outcomes in AMI patients with impEF.

8.
Cancer Sci ; 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39073190

ABSTRACT

Osteosarcoma, recognized for its aggressiveness and resistance to chemotherapy, notably doxorubicin, poses significant treatment challenges. This comprehensive study investigated the CXCR4-CARM1-YAP signaling axis and its pivotal function in controlling aerobic glycolysis, which plays a crucial role in doxorubicin resistance. Detailed analysis of Dox-resistant 143b/MG63-DoxR cells has uncovered the overexpression of CXCR4. Utilizing a combination of molecular biology techniques including gene silencing, aerobic glycolysis assays such as Seahorse experiments, RNA sequencing, and immunofluorescence staining. The study provides insight into the mechanistic pathways involved. Results demonstrated that disrupting CXCR4 expression sensitizes cells to doxorubicin-induced apoptosis and alters glycolytic activity. Further RNA sequencing revealed that CARM1 modulated this effect through its influence on glycolysis, with immunofluorescence of clinical samples confirming the overexpression of CXCR4 and CARM1 in drug-resistant tumors. Chromatin immunoprecipitation studies further highlighted the role of CARM1, showing it to be regulated by methylation at the H3R17 site, which in turn affected YAP expression. Crucially, in vivo experiments illustrated that CARM1 overexpression could counteract the tumor growth suppression that resulted from CXCR4 inhibition. These insights revealed the intricate mechanisms at play in osteosarcoma resistance to doxorubicin and pointed toward potential new therapeutic strategies that could target this metabolic and signaling network to overcome drug resistance and improve patient outcomes.

9.
Digit Health ; 10: 20552076241260557, 2024.
Article in English | MEDLINE | ID: mdl-38882253

ABSTRACT

Background: Left ventricular opacification (LVO) improves the accuracy of left ventricular ejection fraction (LVEF) by enhancing the visualization of the endocardium. Manual delineation of the endocardium by sonographers has observer variability. Artificial intelligence (AI) has the potential to improve the reproducibility of LVO to assess LVEF. Objectives: The aim was to develop an AI model and evaluate the feasibility and reproducibility of LVO in the assessment of LVEF. Methods: This retrospective study included 1305 echocardiography of 797 patients who had LVO at the Department of Ultrasound Medicine, Union Hospital, Huazhong University of Science and Technology from 2013 to 2021. The AI model was developed by 5-fold cross validation. The validation datasets included 50 patients prospectively collected in our center and 42 patients retrospectively collected in the external institution. To evaluate the differences between LV function determined by AI and sonographers, the median absolute error (MAE), spearman correlation coefficient, and intraclass correlation coefficient (ICC) were calculated. Results: In LVO, the MAE of LVEF between AI and manual measurements was 2.6% in the development cohort, 2.5% in the internal validation cohort, and 2.7% in the external validation cohort. Compared with two-dimensional echocardiography (2DE), the left ventricular (LV) volumes and LVEF of LVO measured by AI correlated significantly with manual measurements. AI model provided excellent reliability for the LV parameters of LVO (ICC > 0.95). Conclusions: AI-assisted LVO enables more accurate identification of the LV endocardium and reduces observer variability, providing a more reliable way for assessing LV function.

10.
Proc Natl Acad Sci U S A ; 121(25): e2316615121, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38861602

ABSTRACT

Many cancer-driving protein targets remain undruggable due to a lack of binding molecular scaffolds. In this regard, octahedral metal complexes with unique and versatile three-dimensional structures have rarely been explored as inhibitors of undruggable protein targets. Here, we describe antitumor iridium(III) pyridinium-N-heterocyclic carbene complex 1a, which profoundly reduces the viability of lung and breast cancer cells as well as cancer patient-derived organoids at low micromolar concentrations. Compound 1a effectively inhibits the growth of non-small-cell lung cancer and triple-negative breast cancer xenograft tumors, impedes the metastatic spread of breast cancer cells, and can be modified into an antibody-drug conjugate payload to achieve precise tumor delivery in mice. Identified by thermal proteome profiling, an important molecular target of 1a in cellulo is Girdin, a multifunctional adaptor protein that is overexpressed in cancer cells and unequivocally serves as a signaling hub for multiple pivotal oncogenic pathways. However, specific small-molecule inhibitors of Girdin have not yet been developed. Notably, 1a exhibits high binding affinity to Girdin with a Kd of 1.3 µM and targets the Girdin-linked EGFR/AKT/mTOR/STAT3 cancer-driving pathway, inhibiting cancer cell proliferation and metastatic activity. Our study reveals a potent Girdin-targeting anticancer compound and demonstrates that octahedral metal complexes constitute an untapped library of small-molecule inhibitors that can fit into the ligand-binding pockets of key oncoproteins.


Subject(s)
Antineoplastic Agents , Iridium , Methane , Animals , Humans , Mice , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Iridium/chemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Methane/analogs & derivatives , Methane/chemistry , Methane/pharmacology , Microfilament Proteins/metabolism , Neoplasm Metastasis , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Xenograft Model Antitumor Assays , Male
11.
Nat Commun ; 15(1): 4913, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38851821

ABSTRACT

Host immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection.


Subject(s)
Malaria, Falciparum , Mice, Inbred C57BL , Mice, Knockout , Neutrophils , Superoxide Dismutase , Animals , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Humans , Mice , Neutrophils/immunology , Malaria, Falciparum/immunology , Malaria, Falciparum/parasitology , Immunity, Cellular , T-Lymphocytes/immunology , Plasmodium falciparum/immunology , Female , Host-Parasite Interactions/immunology , Host-Parasite Interactions/genetics , Interferon-gamma/metabolism , Interferon-gamma/immunology , Male , Immunity, Innate , Interleukin-2/metabolism , Interleukin-2/immunology , Interleukin-2/genetics , Parasitemia/immunology
12.
Diagnostics (Basel) ; 14(12)2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38928720

ABSTRACT

Heart transplantation (HT) is the mainstream therapy for end-stage heart disease. However, the cardiac graft function can be affected by several factors. It is important to monitor HT patients for signs of graft dysfunction. Transthoracic echocardiography is a simple, first-line, and non-invasive method for the assessment of cardiac function. The emerging speckle-tracking echocardiography (STE) could quickly and easily provide additive information over traditional echocardiography. STE longitudinal deformation parameters are markers of early impairment of ventricular function. Although once called the "forgotten ventricle", right ventricular (RV) assessment has gained attention in recent years. This review highlights the potentially favorable role of STE in assessing RV systolic function in clinically well HT patients.

13.
Toxicon ; 245: 107788, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38823652

ABSTRACT

Ginkgo biloba L. is a valuable plant, which can be used for medicine, food and ornamental purposes. Despite the above benefits, the components of ginkgolic acids (GA) in ginkgo are considered to cause allergies, embryotoxicity, liver damage and some other adverse reactions. However, the mechanism of GA induced liver injury is still unclear. In this study, we developed an acute liver injury model induced by GA in mice, and investigated the mechanism of GA induced liver injury from the perspectives of oxidative stress, steatosis, apoptosis, and immune response. Intraperitoneal injection of GA (400 mg/kg) can cause liver damage. The levels of serum transaminase, oxidation and triglycerides were increased, liver fibrosis, hepatocyte apoptosis, G2/M phase arrest of the hepatic cell cycle and monocyte infiltration in the liver were detected in GA-treated mice. Flow cytometry analysis of cells separated from the spleen showed that the proportion of Th1 and Th17 cells were increased, and the proportion of Th2 cells were decreased in GA-treated mice. The rise in Th1/Th2 ratio and Th17 cell ratio usually cause inflammatory problems. At the same time, cleaved Caspase-8 and Caspase-3 were detected in hepatocytes, indicating that GA may induce apoptosis through FADD pathway. Although GA is capable of causing the above problems, the inflammation and damage in liver tissue are not severe and there are certain individual differences. Our study reveals the potential hepatotoxicity of GA in ginkgo and its mechanism of action, providing a new perspective for the intervention and prevention of ginkgo toxicity.


Subject(s)
Apoptosis , Chemical and Drug Induced Liver Injury , Salicylates , Animals , Mice , Salicylates/toxicity , Apoptosis/drug effects , Ginkgo biloba , Oxidative Stress/drug effects , Cell Cycle Checkpoints/drug effects , Liver/drug effects , Liver/pathology , Male
14.
J Int Med Res ; 52(6): 3000605241258572, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38869107

ABSTRACT

We herein report a rare case of simultaneous intrauterine molar pregnancy and tubal pregnancy. A woman of childbearing age who had never been pregnant underwent an ultrasound examination 70 days after the onset of menopause. She had a history of ovulation induction. The ultrasound findings suggested a partial hydatidiform mole. She was then pathologically confirmed to have a complete hydatidiform mole after uterine suction dilation and curettage. On postoperative day 4, an ultrasound examination before discharge showed an inhomogeneous mass in the left adnexal region with mild lower abdominal pain. On postoperative day 17, the blood human chorionic gonadotropin level did not drop as expected, and a follow-up examination still indicated a mass in the left adnexal region. We were unable to rule out an ectopic hydatidiform mole. Hysteroscopy with laparoscopic exploration of the left adnexal mass and salpingotomy suggested a diagnosis of intrauterine hydatidiform mole combined with left tubal pregnancy.


Subject(s)
Hydatidiform Mole , Pregnancy, Tubal , Humans , Female , Pregnancy , Hydatidiform Mole/surgery , Hydatidiform Mole/diagnosis , Hydatidiform Mole/diagnostic imaging , Hydatidiform Mole/pathology , Pregnancy, Tubal/surgery , Pregnancy, Tubal/diagnosis , Pregnancy, Tubal/diagnostic imaging , Pregnancy, Tubal/blood , Adult , Uterine Neoplasms/surgery , Uterine Neoplasms/diagnosis , Uterine Neoplasms/diagnostic imaging , Uterine Neoplasms/pathology , Pregnancy, Heterotopic/surgery , Pregnancy, Heterotopic/diagnosis , Pregnancy, Heterotopic/diagnostic imaging , Ultrasonography
15.
J Am Chem Soc ; 146(26): 17629-17635, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38909357

ABSTRACT

The total synthesis and structural elucidation of the antimicrobial sactipeptide enteropeptin A is reported. Enteropeptin A contains a thioaminoketal group with an unassigned stereochemical configuration that is embedded in a highly unusual thiomorpholine ring. In this synthesis, a linear peptide containing a dehydroamino acid and a pendant cysteine residue is subjected to Markovnikov hydrothiolation by a dithiophosphoric acid catalyst. This cyclization reaction forms the central thiomorpholine ring found in the enteropeptins. Both diastereomers at the unassigned thioaminoketal stereocenter of enteropeptin A were prepared, and their comparison to an authentic standard allowed for the unambiguous stereochemical assignment of the natural product to be of the D configuration. This inaugural total synthesis of enteropeptin A represents the first total synthesis of a sactipeptide reported to date. Moreover, the strategy disclosed herein serves as a general platform for the synthesis of stereochemically defined thiomorpholine-containing peptides, which may enable the discovery of new cyclic peptide antibiotics.


Subject(s)
Morpholines , Stereoisomerism , Cyclization , Morpholines/chemistry , Morpholines/chemical synthesis
16.
Bioresour Technol ; 406: 131027, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38925411

ABSTRACT

In this study, the feasibility of promoting the lactic acid (LA) fermentation of food waste (FW) with iron tailings (ITs) addition was explored. The best LA yield was 0.91 g LA/g total sugar when 1 % ITs were added into the system. The mechanisms for promoting LA production were acidification alleviation effects and reduction equivalent supply of ITs. Furthermore, the addition of ITs promoted carbohydrate hydrolysis, and the carbohydrates digestibility reached 88.85 % in the 1 % ITs group. The ITs also affected the microbial communities, Lactococcus gradually replaced Streptococcus as the dominant genus, and results suggested that Lactococcus had a positive correlation with LA production and carbohydrate digestibility. Finally, the complex LAB in FW had significant effects on heavy metal removal from ITs, and the removal efficiency Cr, As, Pb, Cd, and Hg can reach 50.84 %, 26.72 %, 59.65 %, 49.75 % and 78.87 % in the 1 % ITs group, respectively.


Subject(s)
Fermentation , Iron , Lactic Acid , Iron/metabolism , Lactic Acid/metabolism , Lactic Acid/biosynthesis , Metals, Heavy , Food , Waste Products , Hydrolysis , Hydrogen-Ion Concentration , Lactococcus/metabolism , Food Loss and Waste
17.
Small ; : e2402447, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940363

ABSTRACT

Lithium-carbon dioxide (Li-CO2) battery represents a high-energy density energy storage with excellent real-time CO2 enrichment and conversion, but its practical utilization is hampered by the development of an excellent catalytic cathode. Here, the synergistic catalytic strategy of designing CoRu bimetallic active sites achieves the electrocatalytic conversion of CO2 and the efficient decomposition of the discharge products, which in turn realizes the smooth operation of the Li-CO2 battery. Moreover, obtained support based on metal-organic frameworks precursors facilitates the convenient diffusion and adsorption of CO2, resulting in higher reaction concentration and lower mass transfer resistance. Meanwhile, the optimization of the interfacial electronic structure and the effective transfer of electrons are achieved by virtue of the strong interaction of CoRu at the support interface. As a result, the Li-CO2 cell assembled based on bimetallic CoRu active sites achieved a discharge capacity of 19,111 mA h g-1 and a steady-state discharge voltage of 2.58 V as well as a cycle life of >175 cycles at a rate of 100 mA g-1. Further experiments combined with density-functional theory calculations achieve a deeply view of the connection between cathode and electrochemical performance and pave a way for the subsequent development of advanced Li-CO2 catalytic cathodes.

18.
Research (Wash D C) ; 7: 0358, 2024.
Article in English | MEDLINE | ID: mdl-38779487

ABSTRACT

Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of "bacterioplankton ↔ biofilm", thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.

19.
Behav Sci (Basel) ; 14(5)2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38785865

ABSTRACT

Upward comparisons are prevalent in life and have a significant influence on consumer psychology and subsequent behavior. Previous research examined the effects of upward comparisons on consumption behavior, mainly focusing on behavior that evokes positive emotions (e.g., donation behavior, sustainable consumption) or behavior that evokes negative emotions (e.g., impulsive consumption, compulsive consumption) and less on behavior that evokes both negative emotions and positive emotions (i.e., counterhedonic consumption). This research examined the effect of upward comparisons on counterhedonic consumption. Five studies (N = 1111) demonstrated that upward comparison (vs. non-upward comparison) leads to counterhedonic consumption, and this effect is mediated by relative deprivation (Studies 2 and 3). In addition, this research showed that the comparison targets moderate the effects of upward comparisons on counterhedonic consumption. Specifically, when the comparison target is a friend, an upward comparison (vs. non-upward comparison) leads to counterhedonic consumption. When the comparison target is a stranger, an upward comparison (vs. non-upward comparison) has no significant influence on counterhedonic consumption (Study 5). Our findings extend the research on upward comparisons, relative deprivation, and counterhedonic consumption.

20.
Animals (Basel) ; 14(10)2024 May 16.
Article in English | MEDLINE | ID: mdl-38791701

ABSTRACT

The small intestine is important to the digestion and absorption of rumen undegradable nutrients, as well as the barrier functionality and immunological responses in ruminants. Oxidative stress induces a spectrum of pathophysiological symptoms and nutritional deficits, causing various gastrointestinal ailments. Previous studies have shown that nicotinamide (NAM) has antioxidant properties, but the potential mechanism has not been elucidated. The aim of this study was to explore the effects of NAM on hydrogen peroxide (H2O2)-induced oxidative injury in bovine intestinal epithelial cells (BIECs) and its potential mechanism. The results showed that NAM increased the cell viability and total antioxidant capacity (T-AOC) and decreased the release of lactate dehydrogenase (LDH) in BIECs challenged by H2O2. The NAM exhibited increased expression of catalase, superoxide dismutase 2, and tight junction proteins. The expression of autophagy-related proteins was increased in BIECs challenged by H2O2, and NAM significantly decreased the expression of autophagy-related proteins. When an autophagy-specific inhibitor was used, the oxidative injury in BIECs was not alleviated by NAM, and the T-AOC and the release of LDH were not affected. Collectively, these results indicated that NAM could alleviate oxidative injury in BIECs by enhancing antioxidant capacity and increasing the expression of tight junction proteins, and autophagy played a crucial role in the alleviation.

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