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1.
Heliyon ; 10(11): e31549, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38828349

ABSTRACT

Background: There is no standard consensus on the optimal number of cycles of neoadjuvant immunotherapy prior to surgery for patients with locoregionally advanced non-small cell lung cancer (NSCLC). We carried out a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy with different treatment cycles in order to provide valuable information for clinical decision-making. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were systematically searched before May 2023. The included studies were categorized based on different treatment cycles of neoadjuvant immunotherapy to assess their respective efficacy and safety in patients with resectable NSCLC. Results: Incorporating data from 29 studies with 1331 patients, we found major pathological response rates of 43 % (95%CI, 34-52 %) with two cycles and 33 % (95%CI, 22-45 %) with three cycles of neoadjuvant immunotherapy. Radiological response rates were 39 % (95%CI, 28-50 %) and 56 % (95%CI, 44-68 %) for two and three cycles, respectively, with higher incidence rates of severe adverse events (SAEs) in the three-cycle group (32 %; 95%CI, 21-50 %). Despite similar rates of R0 resection between two and three cycles, the latter showed a slightly higher surgical delay rate (1 % vs. 7 %). Neoadjuvant treatment modes significantly affected outcomes, with the combination of immunotherapy and chemotherapy demonstrating superiority in improving pathological and radiological response rates, while the incidence of SAEs in patients receiving combination therapy remained within an acceptable range (23 %; 95%CI, 15-35 %). However, regardless of the treatment mode administered, an increase in the number of treatment cycles did not result in substantial improvement in pathological response rates. Conclusion: There are clear advantages of combining immunotherapy and chemotherapy in neoadjuvant settings. Increasing the number of cycles of neoadjuvant immunotherapy from two to three primarily may not substantially improve the overall efficacy, while increasing the risk of adverse events. Further analysis of the outcomes of four cycles of neoadjuvant immunotherapy is necessary.

2.
Nat Commun ; 15(1): 3904, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724502

ABSTRACT

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.


Subject(s)
Cell Proliferation , Diabetes Mellitus, Experimental , Extracellular Vesicles , Fibroblasts , Keratinocytes , RNA, Circular , Wound Healing , Animals , Extracellular Vesicles/metabolism , Extracellular Vesicles/transplantation , Wound Healing/drug effects , Humans , Male , Mice , Rats , Fibroblasts/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Keratinocytes/metabolism , Cell Movement , Skin/metabolism , Hyaluronan Receptors/metabolism , Hyaluronan Receptors/genetics , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Mice, Inbred C57BL , Disease Models, Animal , Rats, Sprague-Dawley , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics
3.
Cells ; 13(9)2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38727274

ABSTRACT

α-Synuclein (α-syn) can form oligomers, protofibrils, and fibrils, which are associated with the pathogenesis of Parkinson's disease and other synucleinopathies. Both the lipid peroxidation product 4-oxo-2-nonenal (ONE) and agitation can induce aggregation of α-syn and phosphorylated α-syn. Thus, clarification of the characteristics of different α-syn species could help to select suitable aggregates for diagnosis and elucidate the pathogenesis of diseases. Here, we characterized ONE-induced wild-type (WT) α-syn aggregates (OW), ONE-induced phosphorylated α-syn (p-α-syn) aggregates (OP), agitation-induced α-syn preformed fibrils (PFF), and agitation-induced p-α-syn preformed fibrils (pPFF). Thioflavin T (ThT) dying demonstrated that OW and OP had fewer fibrils than the PFF and pPFF. Transmission electron microscopy revealed that the lengths of PFF and pPFF were similar, but the diameters differed. OW and OP had more compact structures than PFF and pPFF. Aggregation of p-α-syn was significantly faster than WT α-syn. Furthermore, OW and OP were more sodium dodecyl sulfate-stable and proteinase K-resistant, suggesting greater stability and compactness, while aggregates of PFF and pPFF were more sensitive to proteinase K treatment. Both ONE- and agitation-induced aggregates were cytotoxic when added exogenously to SH-SY5Y cells with increasing incubation times, but the agitation-induced aggregates caused cell toxicity in a shorter time and more p-α-syn inclusions. Similarly, p-proteins were more cytotoxic than non-p-proteins. Finally, all four aggregates were used as standard antigens to establish sandwich enzyme-linked immunosorbent assay (ELISA). The results showed that the recognition efficiency of OW and OP was more sensitive than that of PFF and pPFF. The OW- and OP-specific ELISA for detection of p-α-syn and α-syn in plasma samples of Thy1-α-syn transgenic mice showed that the content of aggregates could reflect the extent of disease. ONE and agitation induced the formation of α-syn aggregates with distinct biophysical properties and biomedical applications.


Subject(s)
Aldehydes , Protein Aggregates , alpha-Synuclein , alpha-Synuclein/metabolism , alpha-Synuclein/chemistry , Aldehydes/metabolism , Phosphorylation , Humans , Animals , Mice , Cell Line, Tumor , Parkinson Disease/metabolism , Parkinson Disease/pathology , Biophysical Phenomena
4.
Front Plant Sci ; 15: 1377269, 2024.
Article in English | MEDLINE | ID: mdl-38812735

ABSTRACT

The application of autonomous navigation technology of electric crawler tractors is an important link in the development of intelligent greenhouses. Aiming at the characteristics of enclosed and narrow space and uneven ground potholes in greenhouse planting, to improve the intelligence level of greenhouse electric crawler tractors, this paper develops a navigation system of electric crawler tractors for the greenhouse planting environment based on LiDAR technology. The navigation hardware system consists of five modules: the information perception module, the control module, the communication module, the motion module, and the power module. The software system is composed of three layers: the application layer, the data processing layer, and the execution layer. The developed navigation system uses LiDAR, Inertial Measurement Unit (IMU) and wheel speed sensor to sense the greenhouse environment and the crawler tractor's information, employs the Gmapping algorithm to build the greenhouse environment map, and utilizes the adaptive Monte Carlo positioning algorithm for positioning. The simulation test of different global path planning algorithms in Matlab shows that the A* algorithm obtains the optimal overall global path. In the scene of map 5, the path planned by the A* algorithm is the most significant, and the number of inflection points is reduced by 40.00% and 87.50%, respectively; meanwhile, the path length is the same as that of the Dijkstra algorithm, but the runtime is reduced by 68.87% and 81.49%, respectively; compared with the RRT algorithm, the path length is reduced by 7.27%. Therefore, the A* algorithm and the Dynamic Window Approach (DWA) method are used for tractor navigation and obstacle avoidance, which ensures global path optimality while also achieving effective local path planning for obstacle avoidance. The test results suggest that the maximum lateral deviation of the built map is 6 cm, and the maximum longitudinal deviation is 16 cm, which meets the requirement of map accuracy. Additionally, the results of the navigation accuracy test indicate that the maximum lateral deviation of navigation is less than 13 cm, the average lateral deviation is less than 7 cm, and the standard lateral deviation is less than 8 cm. The maximum heading deviation is less than 14°, the average heading deviation is less than 7°, and the standard deviation is less than 8°. These results show that the developed navigation system meets the navigation accuracy requirements of electric crawler tractors in the greenhouse environment.

5.
Chem Commun (Camb) ; 60(45): 5832-5835, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38747248

ABSTRACT

We report an electron-insulating layer of Li2O nanoparticles passivating a Li-rich Li-Cu-Zn ternary alloy as an advanced Li anode. The insulating layer ensures Li deposition below the top protective layer and inhibits side reactions effectively. Additionally, the ternary alloy framework offers superior lithiophilicity and robust mechanical stability. Galvanostatic measurements demonstrate a prolonged lifespan of symmetric cells for over 1200 h at 1 mA cm-2 and 1 mA h cm-2.

6.
Cancer Med ; 13(9): e7218, 2024 May.
Article in English | MEDLINE | ID: mdl-38733169

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising immunotherapy approach, but glioblastoma clinical trials have not yielded satisfactory results. OBJECTIVE: To screen glioblastoma patients who may benefit from immunotherapy. METHODS: Eighty-one patients receiving anti-PD1/PD-L1 treatment from a large-scale clinical trial and 364 patients without immunotherapy from The Cancer Genome Atlas (TCGA) were included. Patients in the ICI-treated cohort were divided into responders and nonresponders according to overall survival (OS), and the most critical responder-relevant features were screened using random forest (RF). We constructed an artificial neural network (ANN) model and verified its predictive value with immunotherapy response and OS. RESULTS: We defined two groups of ICI-treated glioblastoma patients with large differences in survival benefits as nonresponders (OS ≤6 months, n = 18) and responders (OS ≥17 months, n = 8). No differentially mutated genes were observed between responders and nonresponders. We performed RF analysis to select the most critical responder-relevant features and developed an ANN with 20 input variables, five hidden neurons and one output neuron. Receiver operating characteristic analysis and the DeLong test demonstrated that the ANN had the best performance in predicting responders, with an AUC of 0.97. Survival analysis indicated that ANN-predicted responders had significantly better OS rates than nonresponders. CONCLUSION: The 20-gene panel developed by the ANN could be a promising biomarker for predicting immunotherapy response and prognostic benefits in ICI-treated GBM patients and may guide oncologists to accurately select potential responders for the preferential use of ICIs.


Subject(s)
B7-H1 Antigen , Glioblastoma , Immune Checkpoint Inhibitors , Immunotherapy , Neural Networks, Computer , Programmed Cell Death 1 Receptor , Humans , Glioblastoma/drug therapy , Glioblastoma/genetics , Glioblastoma/mortality , Glioblastoma/immunology , Glioblastoma/therapy , Immune Checkpoint Inhibitors/therapeutic use , Male , Female , Immunotherapy/methods , Middle Aged , Programmed Cell Death 1 Receptor/antagonists & inhibitors , B7-H1 Antigen/antagonists & inhibitors , Biomarkers, Tumor/genetics , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Brain Neoplasms/mortality , Brain Neoplasms/immunology , Aged , Adult , Prognosis , Treatment Outcome
7.
Free Radic Biol Med ; 220: 111-124, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38697493

ABSTRACT

Hepatocellular carcinoma (HCC) is a global public health problem with increased morbidity and mortality. Agrimol B, a natural polyphenol, has been proved to be a potential anticancer drug. Our recent report showed a favorable anticancer effect of agrimol B in HCC, however, the mechanism of action remains unclear. Here, we found agrimol B inhibits the growth and proliferation of HCC cells in vitro as well as in an HCC patient-derived xenograft (PDX) model. Notably, agrimol B drives autophagy initiation and blocks autophagosome-lysosome fusion, resulting in autophagosome accumulation and autophagy arrest in HCC cells. Mechanistically, agrimol B downregulates the protein level of NADH:ubiquinone oxidoreductase core subunit S1 (NDUFS1) through caspase 3-mediated degradation, leading to mitochondrial reactive oxygen species (mROS) accumulation and autophagy arrest. NDUFS1 overexpression partially restores mROS overproduction, autophagosome accumulation, and growth inhibition induced by agrimol B, suggesting a cytotoxic role of agrimol B-induced autophagy arrest in HCC cells. Notably, agrimol B significantly enhances the sensitivity of HCC cells to sorafenib in vitro and in vivo. In conclusion, our study uncovers the anticancer mechanism of agrimol B in HCC involving the regulation of oxidative stress and autophagy, and suggests agrimol B as a potential therapeutic drug for HCC treatment.


Subject(s)
Autophagy , Carcinoma, Hepatocellular , Cell Proliferation , Liver Neoplasms , Mitochondria , Reactive Oxygen Species , Xenograft Model Antitumor Assays , Animals , Humans , Mice , Apoptosis/drug effects , Autophagosomes/metabolism , Autophagosomes/drug effects , Autophagy/drug effects , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Electron Transport Complex I/metabolism , Indoles , Liver Neoplasms/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/genetics , Mice, Nude , Mitochondria/metabolism , Mitochondria/drug effects , Mitochondria/pathology , Reactive Oxygen Species/metabolism , Sorafenib/pharmacology , Spiro Compounds
8.
Int J Biol Macromol ; 270(Pt 1): 132287, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38735601

ABSTRACT

Damage to the integrity of the preservation coating on the fruit surface will seriously affect the shelf life of the fruit. In this work, the strong hydrogen bond interaction between xanthan gum (XG) and konjac glucomannan (KGM) could form hydrogel films with self-healing properties. The introduction of gallic acid (GA) was beneficial to further improve the antioxidant activity and UV shielding performance of the composite films. Surprisingly, the mechanical properties and gas (water vapor, O2 and CO2) barrier properties of the KGM film crosslinked by XG were significantly improved. The experiment of banana preservation showed that the composite coating could effectively delay the water loss and browning of bananas, slow down the decomposition of pectin and starch in the flesh, and extend the shelf life of bananas for >6 days. Therefore, this multifunctional coating is an excellent packaging material and has a very broad application prospect in the field of food preservation.


Subject(s)
Food Preservation , Mannans , Musa , Polysaccharides, Bacterial , Mannans/chemistry , Polysaccharides, Bacterial/chemistry , Musa/chemistry , Food Preservation/methods , Antioxidants/chemistry , Food Packaging/methods , Hydrogels/chemistry
9.
ACS Appl Electron Mater ; 6(3): 1530-1541, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38558951

ABSTRACT

Transition metal dichalcogenide (TMD) moiré superlattices have emerged as a significant area of study in condensed matter physics. Thanks to their superior optical properties, tunable electronic band structure, strong Coulomb interactions, and quenched electron kinetic energy, they offer exciting avenues to explore correlated quantum phenomena, topological properties, and light-matter interactions. In recent years, scanning tunneling microscopy (STM) has made significant impacts on the study of these fields by enabling intrinsic surface visualization and spectroscopic measurements with unprecedented atomic scale detail. Here, we spotlight the key findings and innovative developments in imaging and characterization of TMD heterostructures via STM, from its initial implementation on the in situ grown sample to the latest photocurrent tunneling microscopy. The evolution in sample design, progressing from a conductive to an insulating substrate, has not only expanded our control over TMD moiré superlattices but also promoted an understanding of their structures and strongly correlated properties, such as the structural reconstruction and formation of generalized two-dimensional Wigner crystal states. In addition to highlighting recent advancements, we outline upcoming challenges, suggest the direction of future research, and advocate for the versatile use of STM to further comprehend and manipulate the quantum dynamics in TMD moiré superlattices.

10.
Scand J Gastroenterol ; : 1-7, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38597576

ABSTRACT

BACKGROUND: Intramural hematoma of the small bowel is a rare yet acute gastrointestinal condition typically linked with impaired coagulation function, often posing diagnostic challenges. It is principally encountered in patients undergoing prolonged anticoagulant therapy, specifically warfarin. CASE PRESENTATION: We reported a case of intramural hematoma associated with warfarin use. The patient was admitted to hospital with abdominal pain and had received anticoagulant therapy with warfarin 2.5 mg/day for 4 years. Laboratory examination showed decreased coagulation function, abdominal CT showed obvious thickening and swelling of part of the jejunal wall, and abdominal puncture found no gastroenteric fluid or purulent fluid. We treated the patient with vitamin K and fresh frozen plasma. The patient was discharged after the recovery of coagulation function. Then we undertaook a comprehensive review of relevant case reports to extract shared clinical features and effective therapeutic strategies. CONCLUSION: Our analysis highlights that hematoma in the small intestinal wall caused by warfarin overdose often presents as sudden and intense abdominal pain, laboratory tests suggest reduced coagulation capacity, and imaging often shows thickening of the intestinal wall. Intravenous vitamin K and plasma supplementation are effective non-surgical strategies. Nevertheless, in instances of severe obstruction and unresponsive hemostasis, surgical resection of necrotic intestinal segments may be necessary. In the cases we reported, we avoided surgery by closely monitoring the coagulation function. Therefore, we suggest that identifying and correcting the impaired coagulation status of patient is essential for timely and appropriate treatment.

11.
Heliyon ; 10(7): e28401, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38586354

ABSTRACT

Background: Asthma, a principally T helper 2 (Th2) cell mediated immunological disease, is categorized into Th2-high and Th2-low endotypes. The influence of these endotypes on clinical characteristics and treatment responsiveness in asthma is yet to be completely understood. This study delves into the underlying molecular mechanisms of Th2 endotypes on asthma. Methods: Transcriptomics data of airway epithelial and corresponding clinical information were sourced from the GEO. The co-expression modules were established by WGCNA. Cytoscape was applied to construct PPI networks, and hub genes were determined via the Cytohubba plugin. Additionally, a functional enrichment analysis was conducted on the co-expressed genes from the relevant modules. The relative abundances levels of 22 different types of immune cells in asthma patients were evaluated by CIBERSORT algorithm. Results: There were 471 genes in the pink module significantly correlated with Th2 endotype. Overall, 151 DEGs were identified in the various Th2 endotypes, and 66 were obtained through intersection with the pink module. In the PPI network, the ten most important genes that regulate Th2 endotypes were selected as hub genes. In Th2-high endotype asthma, the hub genes were significantly related to γ-aminobutyric acid (GABA) pathways, indicating that hub genes can mainly regulate Th2-high endotype asthma through GABAergic system. Conclusions: The severity of asthma is influenced by different Th2 endotypes. GABAergic related hub genes may provide innovative insights for the treatment of Th2-high asthma.

12.
World J Gastrointest Oncol ; 16(4): 1296-1308, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38660646

ABSTRACT

BACKGROUND: Preoperative knowledge of mutational status of gastrointestinal stromal tumors (GISTs) is essential to guide the individualized precision therapy. AIM: To develop a combined model that integrates clinical and contrast-enhanced computed tomography (CE-CT) features to predict gastric GISTs with specific genetic mutations, namely KIT exon 11 mutations or KIT exon 11 codons 557-558 deletions. METHODS: A total of 231 GIST patients with definitive genetic phenotypes were divided into a training dataset and a validation dataset in a 7:3 ratio. The models were constructed using selected clinical features, conventional CT features, and radiomics features extracted from abdominal CE-CT images. Three models were developed: ModelCT sign, modelCT sign + rad, and model CTsign + rad + clinic. The diagnostic performance of these models was evaluated using receiver operating characteristic (ROC) curve analysis and the Delong test. RESULTS: The ROC analyses revealed that in the training cohort, the area under the curve (AUC) values for modelCT sign, modelCT sign + rad, and modelCT sign + rad + clinic for predicting KIT exon 11 mutation were 0.743, 0.818, and 0.915, respectively. In the validation cohort, the AUC values for the same models were 0.670, 0.781, and 0.811, respectively. For predicting KIT exon 11 codons 557-558 deletions, the AUC values in the training cohort were 0.667, 0.842, and 0.720 for modelCT sign, modelCT sign + rad, and modelCT sign + rad + clinic, respectively. In the validation cohort, the AUC values for the same models were 0.610, 0.782, and 0.795, respectively. Based on the decision curve analysis, it was determined that the modelCT sign + rad + clinic had clinical significance and utility. CONCLUSION: Our findings demonstrate that the combined modelCT sign + rad + clinic effectively distinguishes GISTs with KIT exon 11 mutation and KIT exon 11 codons 557-558 deletions. This combined model has the potential to be valuable in assessing the genotype of GISTs.

13.
FEBS Lett ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664231

ABSTRACT

Mitochondria harbor the oxidative phosphorylation (OXPHOS) system to sustain cellular respiration. However, the transcriptional regulation of OXPHOS remains largely unexplored. Through the cancer genome atlas (TCGA) transcriptome analysis, transcription factor THAP domain-containing 3 (THAP3) was found to be strongly associated with OXPHOS gene expression. Mechanistically, THAP3 recruited the histone methyltransferase SET and MYND domain-containing protein 3 (SMYD3) to upregulate H3K4me3 and promote OXPHOS gene expression. The levels of THAP3 and SMYD3 were altered by metabolic cues. They collaboratively supported liver cancer cell proliferation and colony formation. In clinical human liver cancer, both of them were overexpressed. THAP3 positively correlated with OXPHOS gene expression. Together, THAP3 cooperates with SMYD3 to epigenetically upregulate cellular respiration and liver cancer cell proliferation.

14.
Vaccine ; 42(12): 3075-3083, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38584060

ABSTRACT

As the major outer membrane protein (OMP) presents in the Pasteurella multocida envelope, OmpH was frequently expressed for laboratory assessments of its immunogenicity against P. multocida infections, but the results are not good. In this study, we modified OmpH with dendritic cell targeting peptide (Depeps) and/or Salmonella FliCd flagellin, and expressed three types of recombinant proteins with the MBP tag (rDepeps-FliC-OmpH-MBP, rDepeps-OmpH-MBP, rFliC-OmpH-MBP). Assessments in mouse models revealed that vaccination with rDepeps-FliC-OmpH-MBP, rDepeps-OmpH-MBP, or rFliC-OmpH-MBP induced significant higher level of antibodies as well as IFN-γ and IL-4 in murine sera than vaccination with rOmpH-MBP (P < 0.5). Vaccination with the three modified proteins also provided increased protection (rDepeps-FliC-OmpH-MBP, 70 %; rDepeps-OmpH-MBP, 50 %; rFliC-OmpH-MBP, 60 %) against P. multocida serotype D compared to vaccination with rOmpH-MBP (30 %). In mice vaccinated with different types of modified OmpHs, a significantly decreased bacterial strains were recovered from bloods, lungs, and spleens compared to rOmpH-MBP-vaccinated mice (P < 0.5). Notably, our assessments also demonstrated that vaccination with rDepeps-FliC-OmpH-MBP provided good protection against infections caused by a heterogeneous group of P. multocida serotypes (A, B, D). Our above findings indicate that modification with DCpep and Salmonella flagellin could be used as a promising strategy to improve vaccine effectiveness.


Subject(s)
Pasteurella Infections , Pasteurella multocida , Animals , Mice , Serogroup , Pasteurella Infections/prevention & control , Flagellin/metabolism , Bacterial Outer Membrane Proteins , Peptides/metabolism , Dendritic Cells , Bacterial Vaccines
15.
Opt Express ; 32(6): 9095-9104, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38571150

ABSTRACT

For optical interconnect applications, multi-wavelength comb sources require uniform comb spacings and high reliability at high operating temperature. Here, the high-temperature reliability measurements of a InAs quantum dot colliding pulse mode-locked (QD-CPML) laser with 100 GHz comb spacing are systematically investigated. Laser lifetime measurements are performed for over 1600 hours at 80 °C under constant stress current of 150 mA. The mean time to failure (MTTF) of the laser is approximately 38 years (336,203 hours), extracted from the threshold currents extrapolation method. The optical spectral revolutions are also monitored during the aging process, while the grids of comb laser are remarkably stable. The outstanding reliability and spectrum stability make this 100 GHz QD-CPML a promising candidate as a multi-wavelength laser source for datacom and optical I/O applications.

16.
Cell Death Dis ; 15(4): 242, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38565547

ABSTRACT

Endometrial cancer (EC) cells exhibit abnormal glucose metabolism, characterized by increased aerobic glycolysis and decreased oxidative phosphorylation. Targeting cellular glucose metabolism in these cells could be an effective therapeutic approach for EC. This study aimed to assess the roles of LIN28B, PCAT5, and IGF2BP3 in the glucose metabolism, proliferation, migration, and invasion of EC cells. LIN28B highly expressed in EC, binds and stabilizes PCAT5. PCAT5, overexpressed in EC, and its 1485-2288nt region can bind to the KH1-2 domain of IGF2BP3 to prevent MKRN2 from binding to the K294 ubiquitination site of IGF2BP3, thus stabilizing IGF2BP3. Finally, IGF2BP3 promotes the aerobic glycolysis, proliferation, migration and invasion of EC cells by stabilizing the key enzymes of glucose metabolism HK2 and PKM2. Taken together, our data reveal that the LIN28B/PCAT5/IGF2BP3 axis is critical for glucose reprogramming and malignant biological behavior in EC cells. Therefore, targeting this axis may contribute to the development of a novel therapeutic strategy for EC metabolism.


Subject(s)
Endometrial Neoplasms , Glycolysis , Female , Humans , Cell Line, Tumor , Glycolysis/genetics , Endometrial Neoplasms/genetics , Oxidative Phosphorylation , Glucose/metabolism , Cell Proliferation/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
17.
bioRxiv ; 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38659867

ABSTRACT

Uncompetitive inhibition is an effective strategy for suppressing dysregulated enzymes and their substrates, but discovery of suitable ligands depends on often-unavailable structural knowledge and serendipity. Hence, despite surging interest in mass spectrometry-based target identification, proteomic studies of substrate-dependent target engagement remain sparse. Herein, we describe the Thermal Shift Assay with ATP and RNA (TSAR) as a template for proteome-wide discovery of substrate-dependent ligand binding. Using proteomic thermal shift assays, we show that simple biochemical additives can facilitate detection of target engagement in native cell lysates. We apply our approach to rocaglates, a family of molecules that specifically clamp RNA to eukaryotic translation initiation factor 4A (eIF4A), DEAD-box helicase 3X (DDX3X), and potentially other members of the DEAD-box (DDX) family of RNA helicases. To identify unexpected interactions, we optimized a target class-specific thermal denaturation window and evaluated ATP analog and RNA probe dependencies for key rocaglate-DDX interactions. We report novel DDX targets of the rocaglate clamping spectrum, confirm that DDX3X is a common target of several widely studied analogs, and provide structural insights into divergent DDX3X affinities between synthetic rocaglates. We independently validate novel targets of high-profile rocaglates, including the clinical candidate Zotatifin (eFT226), using limited proteolysis-mass spectrometry and fluorescence polarization experiments. Taken together, our study provides a model for screening uncompetitive inhibitors using a systematic chemical-proteomics approach to uncover actionable DDX targets, clearing a path towards characterization of novel molecular clamps and associated RNA helicase targets.

18.
Int J Biol Macromol ; 267(Pt 1): 131396, 2024 May.
Article in English | MEDLINE | ID: mdl-38582468

ABSTRACT

In this study, the novel polysaccharides named HSP-0 M and HSP-0.1 M were successfully purified from Huangshui (HS), and their structural properties and bioactivities were investigated. Structural analysis revealed that HSP-0 M had a molecular weight of 493.87 kDa and was composed of arabinose, galactose, glucose, xylose, and mannose in a molar ratio of 1.48:1.09:26.52:1.33:1.00. On the other hand, HSP-0.1 M was made up of fructose, arabinose, galactose, glucose, xylose, mannose, ribose, galacturonic acid and glucuronic acid in a ratio of 2.67:26.00:29.10:36.83:16.22:30.53:1.00:1.43:3.64 with a molecular weight of 157.6 kDa. Methylated and 2D NMR analyses indicated that T-Glcp-(1 â†’ 4)-Glcp-(1 â†’ 2)-Glcp-(1 â†’ 3)-Glcp was the primary chain of HSP-0 M, and the backbone of HSP-0.1 M was made up of →3)-Galp-(1 â†’ 6)-Manp-(1 â†’ 3)-Glcp-(1 â†’ 6)-Glcp-(1 â†’ 2)-Manp-(1 â†’ 6)-Glcp-(1 â†’ 3)-Galp. Morphological research showed that both polysaccharides were homogeneous as well as exhibit a web-like structure and an irregular lamellar structure. Furthermore, HSP-0 M demonstrated the capacity to safeguard Lactococcus lactis from damage caused by low temperatures and freeze-drying, while HSP-0.1 M exhibited noteworthy antioxidant activity. These results established a theoretical foundation for the applications of HSPs in food products, cosmetics, and medicines.


Subject(s)
Antioxidants , Molecular Weight , Polysaccharides , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Polysaccharides/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/isolation & purification , Monosaccharides/analysis , Monosaccharides/chemistry , Methylation
20.
Materials (Basel) ; 17(8)2024 Apr 21.
Article in English | MEDLINE | ID: mdl-38673273

ABSTRACT

The direct growth of III-V quantum dot (QD) lasers on silicon substrate has been rapidly developing over the past decade and has been recognized as a promising method for achieving on-chip light sources in photonic integrated circuits (PICs). Up to date, O- and C/L-bands InAs QD lasers on Si have been extensively investigated, but as an extended telecommunication wavelength, the E-band QD lasers directly grown on Si substrates are not available yet. Here, we demonstrate the first E-band (1365 nm) InAs QD micro-disk lasers epitaxially grown on Si (001) substrates by using a III-V/IV hybrid dual-chamber molecular beam epitaxy (MBE) system. The micro-disk laser device on Si was characterized with an optical threshold power of 0.424 mW and quality factor (Q) of 1727.2 at 200 K. The results presented here indicate a path to on-chip silicon photonic telecom-transmitters.

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