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1.
Sci Total Environ ; : 174345, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960174

ABSTRACT

Seaweed cultivation can inhibit the occurrence of red tides. However, how seaweed aquaculture interactions with harmful algal blooms will be affected by the increasing occurrence and intensity of marine heatwaves (MHWs) is unknown. In this study, we run both monoculture and coculture systems to investigate the effects of a simulated heatwave on the competition of the economically important macroalga Gracilariopsis lemaneiformis against the harmful bloom diatom Skeletonema costatum. Coculture with G. lemaneiformis led to a growth decrease in S. costatum. Growth and photosynthetic activity (Fv/Fm) of G. lemaneiformis was greatly reduced by the heatwave treatment, and did not recover even after one week. Growth and photosynthetic activity of S. costatum was also reduced by the heatwave in coculture, but returned to normal during the recovery period. S. costatum also responded to the stressful environment by forming aggregates. Metabolomic analysis suggests that the negative effects on S. costatum were related to an allelochemical release from G. lemaneiformis. These findings show that MHWs may enhance the competitive advantages of S. costatum against G. lemaneiformis, leading to more severe harmful algal blooms in future extreme weather scenarios.

2.
World J Clin Cases ; 12(16): 2745-2750, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38899299

ABSTRACT

BACKGROUND: By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries, doctors can more accurately identify fetal intrauterine distress, as well as assess its severity, so that timely interventions can be implemented to safeguard the health and safety of the fetus. AIM: To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress. METHODS: Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups (n = 50 each), according to the presence or absence of intrauterine distress. The ultrasound hemodynamic parameters of the uterine artery (UtA), fetal middle cerebral artery (MCA), and umbilical artery (UmA) were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups. RESULTS: Comparison of ultrasonic hemodynamic parameters, resistance index (RI), pulsatility index (PI), and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity (S/D), revealed higher values of fetal MCA, PI, and S/D of UmA in pregnant women with UtA compared to controls (P < 0.05), while there was no difference between the two groups in terms of RI (P < 0.05) The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group (66.7%) than in the control group (90.0%), and neonatal weight (2675.5 ± 27.6 g) was lower than in the control group (3117.5 ± 31.2 g). Further, cesarean section rate was higher in the observation group (70.0%) than in the control group (11.7%), and preterm labor rate was higher in the observation group (40.0%) than in the control group (10.0%). The incidence of fetal distress, neonatal growth restriction and neonatal asphyxia were also higher in the observation group (all P < 0.05). CONCLUSION: Fetal MCA, UmA, and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy, which suggests that clinical attention should be paid to them, and monitoring should be strengthened to provide guidance for clinical intervention.

3.
Front Neurol ; 15: 1385546, 2024.
Article in English | MEDLINE | ID: mdl-38854963

ABSTRACT

Rationale/Aim: Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke in Asia and is significantly associated with stroke recurrence. The Balloon angiopLasty for intracranial Atherosclerotic minor Stroke/TIA (BLAST) study aims to evaluate the safety and effectiveness of early submaximal balloon angioplasty (SBA) combined with standard medical therapy vs. standard medical therapy alone in patients with minor stroke or transient ischemic attack (TIA) due to ICAS. Methods: The BLAST study is a multicenter prospective cohort study which will enroll patients with minor stroke or TIA due to symptomatic ICAS within 1 week of symptom onset from 20 centers in China. Eligible patients will receive either SBA with standard medical therapy or standard medical therapy alone based on the decision of the patient or legal representative. Participants will be followed up for 1 year. Study outcomes: The primary outcome is a composite of stroke or death within 30 days or ischemic stroke in the culprit artery territory from 30 days to 1 year. Secondary outcomes include stroke or death within 30 days, ischemic stroke in the culprit artery territory from 30 days to 1 year, restenosis rate of the culprit artery at 1 year, and neurological improvement at 90 days (assessed by mRS score). Safety outcomes include intracranial hemorrhage within 30 days and endovascular complications. Sample size estimate: According to previous studies, the incidence of the composite clinical outcomes is 15% in the group receiving medical therapy alone. We assumed the incidence would decrease to 5% in the SBA combined with the medical therapy group. The target sample size is 416 patients (208 per group), with 90% power and 5% type I error, allowing for a 10% loss to follow-up. Implications: The BLAST study will provide evidence regarding whether early SBA can reduce stroke recurrence and mortality in patients with minor stroke/TIA due to ICAS compared with medical therapy alone.Clinical trial registration:Clinicaltrials.gov, NCT06014723.

4.
J Med Chem ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38920289

ABSTRACT

Developing therapies for the activated B-cell like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL) remains an area of unmet medical need. A subset of ABC DLBCL tumors is driven by activating mutations in myeloid differentiation primary response protein 88 (MYD88), which lead to constitutive activation of interleukin-1 receptor associated kinase 4 (IRAK4) and cellular proliferation. IRAK4 signaling is driven by its catalytic and scaffolding functions, necessitating complete removal of this protein and its escape mechanisms for complete therapeutic suppression. Herein, we describe the identification and characterization of a dual-functioning molecule, KT-413 and show it efficiently degrades IRAK4 and the transcription factors Ikaros and Aiolos. KT-413 achieves concurrent degradation of these proteins by functioning as both a heterobifunctional degrader and a molecular glue. Based on the demonstrated activity and safety of KT-413 in preclinical studies, a phase 1 clinical trial in B-cell lymphomas, including MYD88 mutant ABC DLBCL, is currently underway.

5.
Sci Adv ; 10(12): eadk8331, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38507478

ABSTRACT

Appendage regeneration relies on the formation of blastema, a heterogeneous cellular structure formed at the injury site. However, little is known about the early injury-activated signaling pathways that trigger blastema formation during appendage regeneration. Here, we provide compelling evidence that the extracellular signal-regulated kinase (ERK)-activated casein kinase 2 (CK-2), which has not been previously implicated in appendage regeneration, triggers blastema formation during leg regeneration in the American cockroach, Periplaneta americana. After amputation, CK-2 undergoes rapid activation through ERK-induced phosphorylation within blastema cells. RNAi knockdown of CK-2 severely impairs blastema formation by repressing cell proliferation through down-regulating mitosis-related genes. Evolutionarily, the regenerative role of CK-2 is conserved in zebrafish caudal fin regeneration via promoting blastema cell proliferation. Together, we find and demonstrate that the ERK-activated CK-2 triggers blastema formation in both cockroach and zebrafish, helping explore initiation factors during appendage regeneration.


Subject(s)
Regeneration , Zebrafish , Animals , Zebrafish/metabolism , Regeneration/genetics , Wound Healing , Signal Transduction/genetics , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism
6.
J Sci Food Agric ; 104(7): 4145-4156, 2024 May.
Article in English | MEDLINE | ID: mdl-38294322

ABSTRACT

BACKGROUND: Wheat is one of the key ingredients used to make Chinese liquor, and its saccharification power and protein content directly affect the quality of the liquor. In pursuit of a non-destructive assessment of wheat components and the optimization of raw material proportions in liquor, this study introduces a precise predictive model that integrates hyperspectral imaging (HSI) with stacked ensemble learning (SEL). RESULTS: This study extracted hyperspectral information from 14 different varieties of wheat and employed various algorithms for preprocessing. It was observed that multiplicative scatter correction (MSC) emerged as the most effective spectral preprocessing method. The feature wavelengths were extracted from the preprocessed spectral data using three different feature extraction methods. Then, single models (support vector machine (SVM), backpropagation neural network (BPNN), random forest (RF), and gradient boosting tree (XGBoost)) and a SEL model were developed to compare the prediction accuracies of the SEL model and the single models based on the full-band spectral data and the characteristic wavelengths. The findings indicate that the MSC-competitive adaptive reweighted sampling-SEL model demonstrated the highest prediction accuracy, with Rp 2 (test set-determined coefficient) values of 0.9308 and 0.9939 for predicting the saccharification power and protein content and root mean square error of the test set values of 0.0081 U and 0.0116 g kg-1, respectively. CONCLUSION: The predictive model established in this study, integrating HSI and SEL models, accurately detected wheat saccharification power and protein content. This validation underscores the practical potential of the SEL model and holds significant importance for non-destructive component analysis of raw materials used in liquor. © 2024 Society of Chemical Industry.


Subject(s)
Hyperspectral Imaging , Triticum , Algorithms , Neural Networks, Computer , Support Vector Machine , Least-Squares Analysis
7.
China Pharmacy ; (12): 925-930, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1016713

ABSTRACT

OBJECTIVE To prepare tetrandrine (TET)-loaded chitosan(CS)-stearic acid (SA) nano micelles modified with folic acid (FA)( FA-CS-SA/TET nano micelles), characterize them and study the anti-inflammatory effect in vitro. METHODS FA- CS-SA/TET nano micelles were prepared by ultrasonic method; the preparation technology was optimized by orthogonal test and validation test was also performed with the mass ratio of FA-CS-SA to TET, ultrasound power and ultrasound times as the factors, using the comprehensive score of entrapment efficiency (EE), drug loading (DL) and particle size as evaluation index. FA-CS-SA/ TET nano micelles prepared by the optimal technology were characterized, and their release performance in vitro was investigated. RAW264.7 cells were used as subjects to investigate their anti-inflammatory activity in vitro. RESULTS The optimal preparation technology included that the mass ratio of FA-CS-SA to TET was 2∶1, ultrasonic power was 200 W, and the ultrasonic frequency was 200 times. The parameters of FA-CS-SA/TET nano micelles prepared by optimized technology included that EE was (98.86± 0.30)%, DL was (28.57±0.34)%, the average particle size was (227.0±9.4) nm, polydispersity index was 0.42±0.04, and the Zeta potential was(12.6±2.3)mV, respectively. The nano micelles were uniform in appearance and round in shape. The nano micelles were released quickly in 0.5% sodium dodecyl sulfate solution, with a cumulative release rate of (79.49±3.43)% within 72 hours, and its anti-inflammatory effect was stronger than that of TET raw materials. CONCLUSIONS FA-CS-SA/TET nano micelles are prepared successfully in the study, with good drug loading performance, uniform particle size, and good in vitro anti-inflammatory activity.

8.
Zhongguo Zhen Jiu ; 43(12): 1363-1369, 2023 Dec 12.
Article in English, Chinese | MEDLINE | ID: mdl-38092533

ABSTRACT

Acupuncture-moxibustion is remarkably effective on encephalopathy, but its mechanism is unclear. With the continuous development of imaging technology, the in vivo brain imaging technology has been used increasingly in life science research and it also becomes a more effective tool for the basic research of acupuncture-moxibustion in treatment of encephalopathy. The paper summarizes the application of its technology in the basic research of acupuncture-moxibustion for encephalopathy and the characteristics of imaging, as well as the advantages and shortcomings. It is anticipated that the references may be provided for the basic research of acupuncture-moxibustion in treatment of encephalopathy and be conductive to the modernization of acupuncture-moxibustion.


Subject(s)
Acupuncture Therapy , Acupuncture , Brain Diseases , Moxibustion , Humans , Brain Diseases/diagnostic imaging , Brain Diseases/therapy , Neuroimaging
9.
Front Oncol ; 13: 1276524, 2023.
Article in English | MEDLINE | ID: mdl-37936612

ABSTRACT

Objective: To analyze the clinical and ultrasonic characteristics of breast sclerosing adenosis (SA) and invasive ductal carcinoma (IDC), and construct a predictive nomogram for SA. Materials and methods: A total of 865 patients were recruited at the Second Hospital of Shandong University from January 2016 to November 2022. All patients underwent routine breast ultrasound examinations before surgery, and the diagnosis was confirmed by histopathological examination following the operation. Ultrasonic features were recorded using the Breast Imaging Data and Reporting System (BI-RADS). Of the 865 patients, 203 (252 nodules) were diagnosed as SA and 662 (731 nodules) as IDC. They were randomly divided into a training set and a validation set at a ratio of 6:4. Lastly, the difference in clinical characteristics and ultrasonic features were comparatively analyzed. Result: There was a statistically significant difference in multiple clinical and ultrasonic features between SA and IDC (P<0.05). As age and lesion size increased, the probability of SA significantly decreased, with a cut-off value of 36 years old and 10 mm, respectively. In the logistic regression analysis of the training set, age, nodule size, menopausal status, clinical symptoms, palpability of lesions, margins, internal echo, color Doppler flow imaging (CDFI) grading, and resistance index (RI) were statistically significant (P<0.05). These indicators were included in the static and dynamic nomogram model, which showed high predictive performance, calibration and clinical value in both the training and validation sets. Conclusion: SA should be suspected in asymptomatic young women, especially those younger than 36 years of age, who present with small-size lesions (especially less than 10 mm) with distinct margins, homogeneous internal echo, and lack of blood supply. The nomogram model can provide a more convenient tool for clinicians.

10.
Nat Commun ; 14(1): 7281, 2023 11 10.
Article in English | MEDLINE | ID: mdl-37949857

ABSTRACT

AAA+ proteases degrade intracellular proteins in a highly specific manner. E. coli ClpXP, for example, relies on a C-terminal ssrA tag or other terminal degron sequences to recognize proteins, which are then unfolded by ClpX and subsequently translocated through its axial channel and into the degradation chamber of ClpP for proteolysis. Prior cryo-EM structures reveal that the ssrA tag initially binds to a ClpX conformation in which the axial channel is closed by a pore-2 loop. Here, we show that substrate-free ClpXP has a nearly identical closed-channel conformation. We destabilize this closed-channel conformation by deleting residues from the ClpX pore-2 loop. Strikingly, open-channel ClpXP variants degrade non-native proteins lacking degrons faster than the parental enzymes in vitro but degraded GFP-ssrA more slowly. When expressed in E. coli, these open channel variants behave similarly to the wild-type enzyme in assays of filamentation and phage-Mu plating but resulted in reduced growth phenotypes at elevated temperatures or when cells were exposed to sub-lethal antibiotic concentrations. Thus, channel closure is an important determinant of ClpXP degradation specificity.


Subject(s)
Escherichia coli Proteins , Escherichia coli , Humans , ATPases Associated with Diverse Cellular Activities/genetics , ATPases Associated with Diverse Cellular Activities/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Escherichia coli Proteins/metabolism , Adenosine Triphosphatases/metabolism , Endopeptidase Clp/metabolism , Proteolysis , Translocation, Genetic
11.
J Virol ; 97(11): e0106723, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37855618

ABSTRACT

IMPORTANCE: Many plant viruses are transmitted by insect vectors in a circulative manner. For efficient transmission, the entry of the virus from vector hemolymph into the primary salivary gland (PSG) is a step of paramount importance. Yet, vector components mediating virus entry into PSG remain barely characterized. Here, we demonstrate the role of clathrin-mediated endocytosis and early endosomes in begomovirus entry into whitefly PSG. Our findings unravel the key components involved in begomovirus transport within the whitefly body and transmission by their whitefly vectors and provide novel clues for blocking begomovirus transmission.


Subject(s)
Begomovirus , Endocytosis , Hemiptera , Animals , Begomovirus/physiology , Clathrin/metabolism , Endosomes , Hemiptera/metabolism , Hemiptera/virology , Plant Diseases , Salivary Glands/metabolism , Salivary Glands/virology
12.
Front Pharmacol ; 14: 1184754, 2023.
Article in English | MEDLINE | ID: mdl-37701026

ABSTRACT

Goals: To explore factors associated with inadequate gastric preparation for MCE. Background: Factors associated with inadequate gastric preparation for magnetically controlled capsule endoscopy (MCE) remains unclear. Study: Data of patients who underwent MCE from June 2021 to July 2022 were prospectively collected. The gastric cleanliness score (GCS) of the six stomach regions (gastric cardia, fundus, body, angulus, antrum, and pylorus) was recorded. Patients with GCS score ≥18 were defined as the adequate preparation. Factors related to inadequate gastric preparation were analyzed using a logistic regression model with estimated odds ratios (OR). Results: The mean GCS score of 211 patients was 17.01 ± 2.82. In the multivariable analysis, proton pump inhibitor (PPI) use (OR 3.57; 95% CI 1.69-7.95; p < 0.01) and premedication time after administering simethicone <30 min (OR 2.86; 95% CI 1.10-7.39; p = 0.03) were independent risk factors for inadequate gastric preparation. Comparing the gastric cleanliness of different locations, the median GCS of the lower stomach [10.00, IQR (9.50, 11.00)] was significantly higher than that of the upper stomach [7.00, IQR (6.00, 8.00)] (p <0.001). Conclusion: PPI use and inadequate premedication time (<30 min) may reduce the quality of gastric preparation for MCE. The type, dose, duration of medication, and discontinuation time of PPIs was well worth further exploration. Appropriate control of the type and time of premedication may be the key to improving overall gastric cleanliness.

13.
Anal Methods ; 15(38): 5050-5062, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37740377

ABSTRACT

Obtaining a comprehensive understanding of ore grade information is of significant importance for evaluating the value of ore. However, the real-time detection of multicomponent grade needs more effective online methods. This study proposes a novel approach utilizing hyperspectral imaging (HSI) to evaluate the grade information of nine major ilmenite components by integrating spectral and spatial data. Four multivariate input-output models were developed to mitigate variable interference to predict each component's grade. The results demonstrated that the backpropagation neural network (BPNN) model built from iPLS-VCPA-IRIV feature selection spectral data worked best (RP2 = 0.9935, RMSEP = 0.1364, RPD = 12.8986, and RPIQ = 21.4871, with a computational time of approximately 0.8 s). Furthermore, applying the best optimal combination algorithm for multicomponent grade inversion yielded highly accurate results, in which 97% of the component inversion residuals were less than 1. This investigation affirms that HSI enables rapid and accurate prediction and inversion of the multicomponent grade of ilmenite, thereby presenting a promising alternative to online analysis in the mineral field.

14.
Harmful Algae ; 127: 102467, 2023 08.
Article in English | MEDLINE | ID: mdl-37544669

ABSTRACT

Along the west coast of the United States, highly toxic Pseudo-nitzschia blooms have been associated with two contrasting regional phenomena: seasonal upwelling and marine heatwaves. While upwelling delivers cool water rich in pCO2 and an abundance of macronutrients to the upper water column, marine heatwaves instead lead to warmer surface waters, low pCO2, and reduced nutrient availability. Understanding Pseudo-nitzschia dynamics under these two conditions is important for bloom forecasting and coastal management, yet the mechanisms driving toxic bloom formation during contrasting upwelling vs. heatwave conditions remain poorly understood. To gain a better understanding of what drives Pseudo-nitzschia australis growth and toxicity during these events, multiple-driver scenario or 'cluster' experiments were conducted using temperature, pCO2, and nutrient levels reflecting conditions during upwelling (13 °C, 900 ppm pCO2, replete nutrients) and two intensities of marine heatwaves (19 °C or 20.5 °C, 250 ppm pCO2, reduced macronutrients). While P. australis grew equally well under both heatwave and upwelling conditions, similar to what has been observed in the natural environment, cells were only toxic in the upwelling treatment. We also conducted single-driver experiments to gain a mechanistic understanding of which drivers most impact P. australis growth and toxicity. These experiments indicated that nitrogen concentration and N:P ratio were likely the drivers that most influenced domoic acid production, while the impacts of temperature or pCO2 concentration were less pronounced. Together, these experiments may help to provide both mechanistic and holistic perspectives on toxic P. australis blooms in the dynamic and changing coastal ocean, where cells interact simultaneously with multiple altered environmental variables.


Subject(s)
Diatoms , Kainic Acid/toxicity , Water , Environment
15.
Frontline Gastroenterol ; 14(4): 350-351, 2023.
Article in English | MEDLINE | ID: mdl-37409335
16.
Sheng Li Xue Bao ; 75(3): 360-368, 2023 Jun 25.
Article in Chinese | MEDLINE | ID: mdl-37340645

ABSTRACT

This study aims to explore the auditory response characteristics of the thalamic reticular nucleus (TRN) in awake mice during auditory information processing, so as to deepen the understanding of TRN and explore its role in the auditory system. By in vivo electrophysiological single cell attached recording of TRN neurons in 18 SPF C57BL/6J mice, we observed the responses of 314 recorded neurons to two kinds of auditory stimuli, noise and tone, applied to mice. The results showed that TRN received projections from layer six of the primary auditory cortex (A1). Among 314 TRN neurons, 56.05% responded silently, 21.02% responded only to noise and 22.93% responded to both noise and tone. The neurons with noise response can be divided into three patterns according to their response time: onset, sustain and long-lasting, accounting for 73.19%, 14.49% and 12.32%, respectively. The response threshold of the sustain pattern neurons was lower than those of the other two types. Under noise stimulation, compared with A1 layer six, TRN neurons showed unstable auditory response (P < 0.001), higher spontaneous firing rate (P < 0.001), and longer response latency (P < 0.001). Under tone stimulation, TRN's response continuity was poor, and the frequency tuning was greatly different from that of A1 layer six (P < 0.001), but their sensitivity to tone was similar (P > 0.05), and TRN's tone response threshold was much higher than that of A1 layer six (P < 0.001). The above results demonstrate that TRN mainly undertakes the task of information transmission in the auditory system. The noise response of TRN is more extensive than the tone response. Generally, TRN prefers high-intensity acoustic stimulation.


Subject(s)
Auditory Pathways , Wakefulness , Rats , Mice , Animals , Auditory Pathways/physiology , Rats, Wistar , Mice, Inbred C57BL , Thalamus/physiology
17.
Cancer Med ; 12(13): 13991-14003, 2023 07.
Article in English | MEDLINE | ID: mdl-37211956

ABSTRACT

BACKGROUND: KRT80 is a human epithelial intermediate filament type II gene; its expression product is a component of intracellular intermediate filaments (IFs) and is involved in the assembly of the cytoskeleton. There is evidence that IFs form a dense network mainly in the perinuclear area, but they can also reach the cortex. They are essential for mechanical cushioning of cells, organelle positioning, cell apoptosis, migration, adhesion, and interactions with other cytoskeletal components. Humans possess 54 functional keratin genes, and KRT80 is one of the more unique genes. It is widely expressed in almost all epithelial cells, although it is structurally more similar to type II hair keratins than to type II epithelial keratins. AIM: In this review, we summarize the basic facts about the keratin family and KRT80, the essential role of KRT80 in neoplasms, and its potential as a therapeutic target. We hope that this review will inspire researchers to at least partially focus on this area. RESULT: In many neoplastic diseases, the high expression status of KRT80 and its role in regulating the biological functions of cancer cells have been well established. KRT80 can effectively enhance the proliferation, invasiveness and migration of cancer cells. However, the effects of KRT80 on prognosis and clinically relevant indices in patients with various cancers have not been extensively studied, and even opposite conclusions have been reached in different studies of the same cancer. Based on this, we should add more clinically relevant studies to clarify the prospect of clinical application of KRT80. Many researchers have made great progress in studying the mechanism of action of KRT80. However, their studies should be extended to more cancers to find common regulators and signaling pathways of KRT80 in different cancers. KRT80 may have far-reaching effects on the human body, and this marker may play a crucial role in the function of cancer cells and the prognosis of cancer patients, so it has a promising future in the field of neoplasms. CONCLUSION: In neoplastic diseases, KRT80 is overexpressed in many cancers and plays an essential role in promoting proliferation, migration, invasiveness and poor prognosis. The mechanisms of KRT80 functions in cancer have been partially elucidated, suggesting that KRT80 is a potentially useful cancer therapeutic target. However, more systematic, in-depth and comprehensive studies are still needed in this field.


Subject(s)
Neoplasms , Humans , Cytoskeleton/metabolism , Epithelial Cells/metabolism , Keratins/genetics , Keratins/metabolism , Neoplasms/genetics , Neoplasms/metabolism
18.
J Am Chem Soc ; 145(13): 7376-7389, 2023 Apr 05.
Article in English | MEDLINE | ID: mdl-36952244

ABSTRACT

Visualization of mechanochemical damages, especially for those in the molecular-scale (e.g., bond scission in polymeric materials), is of great industrial and academic significance. Herein, we report a novel strategy for in situ and real-time visualization of mechanochemical damages in hydrogels by utilizing prefluorescent probes via oxygen-relayed free-radical trapping. Double-network (DN) hydrogels that generate numerous mechanoradicals by homolytic bond scission of the brittle first network at large deformation are used as model materials. Theoretical calculation suggests that mechanoradicals generated by the damage of the first network undergo an oxygen-relayed radical-transfer process which can be detected by the prefluorescent probe through the radical-radical coupling reaction. Such an oxygen-relayed radical-trapping process of the prefluorescent probe exhibits a dramatically enhanced emission, which enables the real-time sensing and visualization of mechanochemical damages in DN hydrogels made from brittle networks of varied chemical structures. To the best of authors' knowledge, this work is the first report utilizing oxygen as a radical-relaying molecule for visualizing mechanoradical damages in polymer materials. Moreover, this new method based on the probe post-loading is simple and does not introduce any chemical structural changes in the materials, outperforming most previous methods that require chemical incorporation of mechanophores into polymer networks.

20.
Proc Natl Acad Sci U S A ; 120(6): e2219044120, 2023 02 07.
Article in English | MEDLINE | ID: mdl-36730206

ABSTRACT

Energy-dependent protein degradation by the AAA+ ClpXP protease helps maintain protein homeostasis in bacteria and eukaryotic organelles of bacterial origin. In Escherichia coli and many other proteobacteria, the SspB adaptor assists ClpXP in degrading ssrA-tagged polypeptides produced as a consequence of tmRNA-mediated ribosome rescue. By tethering these incomplete ssrA-tagged proteins to ClpXP, SspB facilitates their efficient degradation at low substrate concentrations. How this process occurs structurally is unknown. Here, we present a cryo-EM structure of the SspB adaptor bound to a GFP-ssrA substrate and to ClpXP. This structure provides evidence for simultaneous contacts of SspB and ClpX with the ssrA tag within the tethering complex, allowing direct substrate handoff concomitant with the initiation of substrate translocation. Furthermore, our structure reveals that binding of the substrate·adaptor complex induces unexpected conformational changes within the spiral structure of the AAA+ ClpX hexamer and its interaction with the ClpP tetradecamer.


Subject(s)
Carrier Proteins , Escherichia coli Proteins , ATPases Associated with Diverse Cellular Activities/genetics , ATPases Associated with Diverse Cellular Activities/metabolism , Carrier Proteins/metabolism , Escherichia coli Proteins/metabolism , Adenosine Triphosphatases/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Endopeptidase Clp/genetics , Endopeptidase Clp/metabolism , Substrate Specificity
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