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1.
Arch Dermatol Res ; 316(6): 314, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822909

ABSTRACT

Herpes zoster (HZ) is rare in healthy children, but more prevalent in those with leukemia. Optimal timing of chemotherapy reinitiation after HZ treatment is challenging because chemotherapy suppresses immunity and increases risk of HZ relapse. We aimed to optimize the timing of chemotherapy reinitiation after HZ therapy in children with leukemia. The study included 31 children with acute leukemia and HZ infection. General information, clinical symptoms, laboratory test results, duration of HZ treatment, and prognosis were compared with those of children with leukemia alone. Correlation analysis was performed for 20 children who restarted chemotherapy after HZ treatment. Of 31 children with leukemia and HZ, 67.74% had lesions at multiple sites. The median time from chemotherapy initiation to HZ onset was 14.1 (1.5-29.5) months. Among 27 children included in the follow-up, there was one case of HZ relapse. After excluding children who did not continue chemotherapy after HZ treatment, the median interval between completion of HZ therapy and chemotherapy reinitiation in the remaining 20 children was 8.00 (- 3 to 27) days. Lymphocyte counts (LY#) on restarting chemotherapy correlated inversely with HZ lesion healing time (p < 0.05). LY# at the time of HZ onset were lower than those pre- and post-onset, and lower than those in the control group (p < 0.05). In conclusion, children with leukemia have a good HZ prognosis, but an increased risk of HZ recurrence. LY# at the time of chemotherapy reinitiation may be a useful indicator for selecting the optimal interval between antiviral therapy completion and chemotherapy reinitiation.


Subject(s)
Antiviral Agents , Herpes Zoster , Leukemia , Humans , Herpes Zoster/drug therapy , Child , Male , Female , Child, Preschool , Antiviral Agents/therapeutic use , Antiviral Agents/administration & dosage , Lymphocyte Count , Adolescent , Leukemia/drug therapy , Leukemia/complications , Prognosis , Time Factors , Retrospective Studies , Infant
2.
Oncol Lett ; 28(1): 337, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38846431

ABSTRACT

The present study aimed to investigate the anti-leukemic effects of dihydroartemisinin (DHA) on T-cell acute lymphoblastic leukemia (T-ALL) cell lines, Jurkat and Molt-4, and the underlying mechanisms. Cell Counting Kit-8 was performed to measure cell viability. Cell apoptosis and cell cycle distribution were assessed by flow cytometry. The expression levels of ATF4 and CHOP mRNA were assessed by reverse transcription-quantitative PCR, while the protein abundance of SLC7A11, GPX4, ATF4 and CHOP was determined by western blotting. Moreover, malondialdehyde, glutathione (GSH) and reactive oxygen species (ROS) assays were used to detect the levels of ferroptosis. The results showed that DHA suppressed T-ALL cell viability in vitro, and induced cell cycle arrest at S or G2/M phase. DHA also induced ROS burst, activated endoplasmic reticulum (ER) stress, disrupted the system Xc--GSH-GSH peroxidase 4 antioxidant system, and increased lipid peroxide accumulation, resulting in cell death. By contrast, the pharmacological inhibition of ferroptosis alleviated DHA-induced cell death, confirming that DHA induces T-ALL cell death via ferroptosis. Mechanistically, the effect of DHA on ferroptosis was partly mediated by downregulating SLC7A11 and upregulating the ATF4-CHOP signaling pathway, which is associated with ER stress. These results indicated that DHA may induce ferroptosis in T-ALL cell lines and could represent a promising therapeutic agent for treating T-ALL.

3.
Plant Dis ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831590

ABSTRACT

Pumpkin (Cucurbita moschata), which belongs to the gourd family (Cucurbitaceae), is widely planted throughout the world. In June 2023, many pumpkin plants (cv. Miben) displayed leaf blight and chlorosis in fields located in Suizhou (31.99°N, 113.02°E), Hubei Province, China. The disease incidence ranged from 30 to 40% in nine fields, 6.3 ha in total. The symptoms were irregularly shaped lesions that expanded along the mid-vein until the leaf turned brown and wilted. Fungal isolations were performed as described previously (Liu et al. 2023). Twenty pumpkin leaf samples with typical symptoms were collected and cut into 1 cm×1 cm pieces. The diseased tissue was surface-sterilized in 75% ethanol for 30 sec, plated on potato dextrose agar (PDA) medium and incubated at 25℃ for 3 days. Then, the emerging single fungal hyphal tip was transferred onto PDA plates to obtain purified isolates. A total of eighteen isolates on PDA plates were initially white and then developed to dark gray. The 5-day-old cultures growing on mung bean medium produced conidia that were black, single-celled, smooth, spherical or oblate, and ranged in size from 14.5 to 20.8 µm×13.3 to 20.5 µm (n=50). Therefore, the isolates were morphologically identified as Nigrospora sphaerica. Moreover, the genomic DNA of the isolates (HB-P1,HB-P2, and HB-P3) was extracted for amplification and sequencing of the regions of internal transcribed spacer (ITS) (White et al. 1990), nuclear large subunit rRNA (nLSU) (O'Donnell 1992; Rehner and Samuels 1994), and ß-tubulin (TUB2) (Glass and Donaldson 1995), with primers ITS1/ITS4, LROR/LR3, and Bt2a/Bt2b, respectively. Sequences were submitted to GenBank under accession numbers PP348112, PP348113, PP348114 (ITS), PP411414, PP411415, PP411416 (nLSU), and PP357438, PP357439, PP357440 (TUB2). BLASTn showed that the sequences ITS, nLSU, and TUB2 of HB-P1, HB-P2, and HB-P3 had >99% nucleotide identities ((ITS: 100%, 508/508 bp, MF996488.1; 99.8%, 506/507, ON326588.1; 100%, 500/500 ,MK748317.1), (nLSU: 99.83%, 573/574, KT462720.1; 99.83% , 574/575 bp, KT462720.1; 99.65%, 575/577, KT462720.1), and (TUB2: 100%, 388/388, MN719407.1; 99.74%, 387/388, MN719407.1; 100%, 387/387, MN719407.1)) with Nigrospora sphaerica, respectively. A multilocus (ITS, nLSU and TUB2) phylogenetic analysis indicated that the isolates were Nigrospora sphaerica. Pathogenicity of three isolates were tested on pumpkin plants (cv. Miben). Fifteen pumpkin plants were inoculated by spraying the leaves (1×106 spores/ml), respectively, and 10 pumpkin plants were treated with sterile water as a negative control. All plants were incubated in an artificial climate box (LongYue, ShangHai) at 25℃ for 12 days. The experiment was repeated three times. Twelve days later, the inoculated pumpkin plants developed symptoms of leaf blight, while the control plants remained healthy. Then, pathogens were re-isolated from the each leaf of inoculated pumpkin plants and not from the control plants. Nigrospora sphaerica has been previously reported to cause leaf spot on watermelon in Malaysia (Ismail and Abd Razak 2021). To our knowledge, this is the first report of N. sphaerica causing leaf blight on pumpkin in China. This new disease can cause leaf blight, which may affect pumpkin productivity.

4.
Front Pharmacol ; 15: 1396975, 2024.
Article in English | MEDLINE | ID: mdl-38725666

ABSTRACT

Osteosarcoma (OS) is the most common primary malignant bone tumor. In the clinic, usual strategies for OS treatment include surgery, chemotherapy, and radiation. However, all of these therapies have complications that cannot be ignored. Therefore, the search for better OS treatments is urgent. Black phosphorus (BP), a rising star of 2D inorganic nanoparticles, has shown excellent results in OS therapy due to its outstanding photothermal, photodynamic, biodegradable and biocompatible properties. This review aims to present current advances in the use of BP nanoparticles in OS therapy, including the synthesis of BP nanoparticles, properties of BP nanoparticles, types of BP nanoparticles, and modification strategies for BP nanoparticles. In addition, we have discussed comprehensively the application of BP in OS therapy, including single, dual, and multimodal synergistic OS therapies, as well as studies about bone regeneration and antibacterial properties. Finally, we have summarized the conclusions, limitations and perspectives of BP nanoparticles for OS therapy.

5.
Mol Biol Rep ; 51(1): 602, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698158

ABSTRACT

BACKGROUND: Low-temperature severely limits the growth and development of Camellia oleifera (C. oleifera). The mitogen-activated protein kinase (MAPK) cascade plays a key role in the response to cold stress. METHODS AND RESULTS: Our study aims to identify MAPK cascade genes in C. oleifera and reveal their roles in response to cold stress. In our study, we systematically identified and analyzed the MAPK cascade gene families of C. oleifera, including their physical and chemical properties, conserved motifs, and multiple sequence alignments. In addition, we characterized the interacting networks of MAPKK kinase (MAPKKK)-MAPK kinase (MAPKK)-MAPK in C. oleifera. The molecular mechanism of cold stress resistance of MAPK cascade genes in wild C. oleifera was analyzed by differential gene expression and real-time quantitative reverse transcription-PCR (qRT-PCR). CONCLUSION: In this study, 21 MAPKs, 4 MAPKKs and 55 MAPKKKs genes were identified in the leaf transcriptome of C. oleifera. According to the phylogenetic results, MAPKs were divided into 4 groups (A, B, C and D), MAPKKs were divided into 3 groups (A, B and D), and MAPKKKs were divided into 2 groups (MEKK and Raf). Motif analysis showed that the motifs in each subfamily were conserved, and most of the motifs in the same subfamily were basically the same. The protein interaction network based on Arabidopsis thaliana (A. thaliana) homologs revealed that MAPK, MAPKK, and MAPKKK genes were widely involved in C. oleifera growth and development and in responses to biotic and abiotic stresses. Gene expression analysis revealed that the CoMAPKKK5/CoMAPKKK43/CoMAPKKK49-CoMAPKK4-CoMAPK8 module may play a key role in the cold stress resistance of wild C. oleifera at a high-elevation site in Lu Mountain (LSG). This study can facilitate the mining and utilization of genetic resources of C. oleifera with low-temperature tolerance.


Subject(s)
Camellia , Cold-Shock Response , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Cold-Shock Response/genetics , Camellia/genetics , Gene Expression Regulation, Plant/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , MAP Kinase Signaling System/genetics , Cold Temperature , Transcriptome/genetics , Multigene Family , Mitogen-Activated Protein Kinase Kinases/genetics , Mitogen-Activated Protein Kinase Kinases/metabolism , Gene Expression Profiling/methods , Plant Leaves/genetics
6.
Orthop Surg ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806283

ABSTRACT

OBJECTIVE: How to minimize postoperative pain following knee replacement surgery has been a great challenge. This study was performed to evaluate the effect of applying a topical nonsteroidal anti-inflammatory drug (NSAID) lateral to the incision for postoperative pain following unicompartmental knee arthroplasty (UKA). METHODS: The randomized controlled trial enrolled 100 patients from August 2023 to January 2024. One hundred patients who underwent UKA were randomized into two groups. The intervention group received a topical NSAID lateral to the incision postoperatively, and the control group received a placebo lateral to the incision postoperatively. The primary outcome measures were the amount of opioid consumption and the visual analogue scale (VAS) score (12, 24, 36, 48, and 72 h after operation) for pain. The secondary outcome measures were the American Knee Society Score (AKSS, preoperation and 1-month follow-up after operation), the time of first analgesic demand, side effects of opioids, operation time, postoperative stay, surgery-related complications, and postoperative incision healing grade. Independent sample t test and paired sample t test were used to compare continuous data. Chi-square test and Fisher's precision probability tests were used to analyze the categorical data. RESULTS: Ninety-eight patients (intervention group, 48 patients; control group, 50 patients) were analyzed. Opioid consumption was significantly lower in the intervention group than in the control group during the first 12 h, 12 to 24 h, and 24 to 48 h postoperatively (p < 0.05). The VAS score for pain within 72 h postoperatively was significantly lower in the intervention group than in the control group (p < 0.05). There was no significant difference in the AKSS, operation time, postoperative stay, complications, or postoperative incision healing grade between the two groups. The time of first analgesic demand for patient-controlled analgesia was significantly later in the intervention group than in the control group (p < 0.05). There were fewer side effects of opioids in the intervention group (8.3%) than in the control group (18.0%). CONCLUSION: Postoperative application of topical NSAIDs lateral to the incision is an effective and safe method for pain management after UKA, helping to decrease the pain score and reduce opioid consumption postoperatively with no increase in side effects.

7.
Biomed Pharmacother ; 175: 116748, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38776683

ABSTRACT

Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15 mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.


Subject(s)
Cardiotoxicity , Doxorubicin , Flavonoids , Gene Expression Profiling , Mice, Inbred C57BL , Oxidative Stress , Animals , Doxorubicin/toxicity , Flavonoids/pharmacology , Cardiotoxicity/prevention & control , Male , Mice , Oxidative Stress/drug effects , Gene Expression Profiling/methods , Cardiotonic Agents/pharmacology , Apoptosis/drug effects , Transcriptome/drug effects
8.
Nat Commun ; 15(1): 3743, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702316

ABSTRACT

Arteriovenous fistulas (AVFs) are the most common vascular access points for hemodialysis (HD), but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia (NIH). Our previous studies have revealed a highly conserved LncRNA-LncDACH1 as an important regulator of cardiomyocyte and fibroblast proliferation. Herein, we find that LncDACH1 regulates NIH in AVF in male mice with conditional knockout of smooth muscle cell-specific LncDACH1 and in male mice model of AVF with LncDACH1 overexpression by adeno-associated virus. Mechanistically, silence of LncDACH1 activates p-AKT through promoting the expression of heat shock protein 90 (HSP90) and serine/arginine-rich splicing factor protein kinase 1 (SRPK1). Moreover, LncDACH1 is transcriptionally activated by transcription factor KLF9 that binds directly to the promoter region of the LncDACH1 gene. In this work, during AVF NIH, LncDACH1 is downregulated by KLF9 and promotes NIH through the HSP90/ SRPK1/ AKT signaling axis.


Subject(s)
HSP90 Heat-Shock Proteins , Hyperplasia , Kruppel-Like Transcription Factors , Myocytes, Smooth Muscle , Neointima , Proto-Oncogene Proteins c-akt , RNA, Long Noncoding , Animals , Humans , Male , Mice , Arteriovenous Fistula/metabolism , Arteriovenous Fistula/genetics , Arteriovenous Fistula/pathology , Cell Proliferation , HSP90 Heat-Shock Proteins/metabolism , HSP90 Heat-Shock Proteins/genetics , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Mice, Inbred C57BL , Mice, Knockout , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Neointima/pathology , Neointima/metabolism , Phenotype , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Signal Transduction
9.
Article in English | MEDLINE | ID: mdl-38776197

ABSTRACT

Based on multi-omics data and drug information, predicting the response of cancer cell lines to drugs is a crucial area of research in modern oncology, as it can promote the development of personalized treatments. Despite the promising performance achieved by existing models, most of them overlook the variations among different omics and lack effective integration of multi-omics data. Moreover, the explicit modeling of cell line/drug attribute and cell line-drug association has not been thoroughly investigated in existing approaches. To address these issues, we propose RedCDR, a dual relation distillation model for cancer drug response (CDR) prediction. Specifically, a parallel dual-branch architecture is designed to enable both the independent learning and interactive fusion feasible for cell line/drug attribute and cell line-drug association information. To facilitate the adaptive interacting integration of multi-omics data, the proposed multi-omics encoder introduces the multiple similarity relations between cell lines and takes the importance of different omics data into account. To accomplish knowledge transfer from the two independent attribute and association branches to their fusion, a dual relation distillation mechanism consisting of representation distillation and prediction distillation is presented. Experiments conducted on the GDSC and CCLE datasets show that RedCDR outperforms previous state-of-the-art approaches in CDR prediction. The source code is available at https://github.com/mhxu1998/RedCDR.

10.
Sci Data ; 11(1): 517, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38773139

ABSTRACT

This study investigates the adaptive strategies of the Alashan Ground Squirrel (Spermophilus alashanicus) in response to habitat changes, as rodents are sensitive indicators of ecosystem changes. Despite its ecological importance, the genome and microbiome of this species have not been thoroughly studied. This research fills this gap by presenting the first comprehensive metagenomic and transcriptomic datasets of the species. Transcriptomic data was collected from five tissue types, including heart, liver, cecum, muscle, and blood, resulting in the assembly of 72,156 unigenes. Metagenomic sequencing identified predominant bacterial groups such as Firmicutes, Bacteroidetes, Verrucomicrobia, Urovircota, and Proteobacteria. Our workflow involved RNA and DNA extraction, library preparation, assembly, and annotation, yielding valuable insights into gene discovery, microbial composition, and further genome and microbial function studies. In conclusion, our findings have significant implications for understanding the adaptive mechanisms of this species in response to environmental changes.


Subject(s)
Metagenomics , Sciuridae , Transcriptome , Animals , Bacteria/genetics , Bacteria/classification , Ecosystem , Metagenome , Microbiota , Sciuridae/genetics , Mongolia
11.
Article in English | MEDLINE | ID: mdl-38767994

ABSTRACT

Discovering the novel associations of biomedical entities is of great significance and can facilitate not only the identification of network biomarkers of disease but also the search for putative drug targets. Graph representation learning (GRL) has incredible potential to efficiently predict the interactions from biomedical networks by modeling the robust representation for each node. However, the current GRL-based methods learn the representation of nodes by aggregating the features of their neighbors with equal weights. Furthermore, they also fail to identify which features of higher-order neighbors are integrated into the representation of the central node. In this work, we propose a novel graph representation learning framework: a multi-order graph neural network based on reconstructed specific subgraphs (MGRS) for biomedical interaction prediction. In the MGRS, we apply the multi-order graph aggregation module (MOGA) to learn the wide-view representation by integrating the multi-hop neighbor features. Besides, we propose a subgraph selection module (SGSM) to reconstruct the specific subgraph with adaptive edge weights for each node. SGSM can clearly explore the dependency of the node representation on the neighbor features and learn the subgraph-based representation based on the reconstructed weighted subgraphs. Extensive experimental results on four public biomedical networks demonstrate that the MGRS performs better and is more robust than the latest baselines.

12.
Adv Mater ; : e2402517, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38808656

ABSTRACT

Miniature shape-morphing soft actuators driven by external stimuli and fluidic pressure hold great promise in morphing matter and small-scale soft robotics. However, it remains challenging to achieve both rich shape morphing and shape locking in a fast and controlled way due to the limitations of actuation reversibility and fabrication. Here, fully 3D-printed, sub-millimeter thin-plate-like miniature soft hydraulic actuators with shape memory effect (SME) for programable fast shape morphing and shape locking, are reported. It combines commercial high-resolution multi-material 3D printing of stiff shape memory polymers (SMPs) and soft elastomers and direct printing of microfluidic channels and 2D/3D channel networks embedded in elastomers in a single print run. Leveraging spatial patterning of hybrid compositions and expansion heterogeneity of microfluidic channel networks for versatile hydraulically actuated shape morphing, including circular, wavy, helical, saddle, and warping shapes with various curvatures, are demonstrated. The morphed shapes can be temporarily locked and recover to their original planar forms repeatedly by activating SME of the SMPs. Utilizing the fast shape morphing and locking in the miniature actuators, their potential applications in non-invasive manipulation of small-scale objects and fragile living organisms, multimodal entanglement grasping, and energy-saving manipulators, are demonstrated.

13.
Article in English | MEDLINE | ID: mdl-38598403

ABSTRACT

Steady-state visual evoked potential (SSVEP), one of the most popular electroencephalography (EEG)-based brain-computer interface (BCI) paradigms, can achieve high performance using calibration-based recognition algorithms. As calibration-based recognition algorithms are time-consuming to collect calibration data, the least-squares transformation (LST) has been used to reduce the calibration effort for SSVEP-based BCI. However, the transformation matrices constructed by current LST methods are not precise enough, resulting in large differences between the transformed data and the real data of the target subject. This ultimately leads to the constructed spatial filters and reference templates not being effective enough. To address these issues, this paper proposes multi-stimulus LST with online adaptation scheme (ms-LST-OA). METHODS: The proposed ms-LST-OA consists of two parts. Firstly, to improve the precision of the transformation matrices, we propose the multi-stimulus LST (ms-LST) using cross-stimulus learning scheme as the cross-subject data transformation method. The ms-LST uses the data from neighboring stimuli to construct a higher precision transformation matrix for each stimulus to reduce the differences between transformed data and real data. Secondly, to further optimize the constructed spatial filters and reference templates, we use an online adaptation scheme to learn more features of the EEG signals of the target subject through an iterative process trial-by-trial. RESULTS: ms-LST-OA performance was measured for three datasets (Benchmark Dataset, BETA Dataset, and UCSD Dataset). Using few calibration data, the ITR of ms-LST-OA achieved 210.01±10.10 bits/min, 172.31±7.26 bits/min, and 139.04±14.90 bits/min for all three datasets, respectively. CONCLUSION: Using ms-LST-OA can reduce calibration effort for SSVEP-based BCIs.


Subject(s)
Brain-Computer Interfaces , Evoked Potentials, Visual , Humans , Calibration , Photic Stimulation/methods , Electroencephalography/methods , Algorithms
14.
J Cell Physiol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38646844

ABSTRACT

The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.

15.
Nat Nanotechnol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649746

ABSTRACT

Nanoresolved doping of polymeric semiconductors can overcome scaling limitations to create highly integrated flexible electronics, but remains a fundamental challenge due to isotropic diffusion of the dopants. Here we report a general methodology for achieving nanoscale ion-implantation-like electrochemical doping of polymeric semiconductors. This approach involves confining counterion electromigration within a glassy electrolyte composed of room-temperature ionic liquids and high-glass-transition-temperature insulating polymers. By precisely adjusting the electrolyte glass transition temperature (Tg) and the operating temperature (T), we create a highly localized electric field distribution and achieve anisotropic ion migration that is nearly vertical to the nanotip electrodes. The confined doping produces an excellent resolution of 56 nm with a lateral-extended doping length down to as little as 9.3 nm. We reveal a universal exponential dependence of the doping resolution on the temperature difference (Tg - T) that can be used to depict the doping resolution for almost infinite polymeric semiconductors. Moreover, we demonstrate its implications in a range of polymer electronic devices, including a 200% performance-enhanced organic transistor and a lateral p-n diode with seamless junction widths of <100 nm. Combined with a further demonstration in the scalability of the nanoscale doping, this concept may open up new opportunities for polymer-based nanoelectronics.

16.
Chembiochem ; : e202400105, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38639074

ABSTRACT

Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with in situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both in vitro and in vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.

17.
Urolithiasis ; 52(1): 63, 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613670

ABSTRACT

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.


Subject(s)
Calcium Oxalate , Kidney Calculi , Humans , Oxidative Stress , Inflammation/drug therapy , Epithelial Cells , Kidney Calculi/drug therapy , Kidney Calculi/prevention & control
18.
J Transl Med ; 22(1): 338, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594692

ABSTRACT

BACKGROUND: SIRPB1 expression is upregulated in various tumor types, including gliomas, and is known to contribute to tumor progression; nevertheless, its function in the immune milieu of gliomas is still mainly unknown. METHODS: This study, we analyzed 1152 normal samples from the GTEx database and 670 glioma samples from the TCGA database to investigate the relationship between the expression of SIRPB1 and clinicopathological features. Moreover, SIRPB1 gene knockout THP-1 cell lines were constructed using CRISPR/Cas9 and were induced into a co-culture of macrophages and glioma cells in vitro to learn more about the role of SIRPB1 in the glioma immune milieu. Lastly, we established a prognostic model to predict the effect of SIRPB1 on prognosis. RESULTS: Significantly higher levels of SIRPB1 expression were found in gliomas, which had an adverse effect on the immune milieu and correlated poorly with patient survival. SIRPB1 activation with certain antibodies results in SYK phosphorylation and the subsequent activation of calcium, MAPK, and NF-κB signaling pathways. This phenomenon is primarily observed in myeloid-derived cells as opposed to glioma cells. In vitro co-culture demonstrated that macrophages with SIRPB1 knockout showed decreased IL1RA, CCL2, and IL-8, which were recovered upon ectopic expression of SIRPB1 but reduced again following treatment with SYK inhibitor GS9973. Critically, a lower overall survival rate was linked to increased SIRPB1 expression. Making use of SIRPB1 expression along with additional clinicopathological variables, we established a nomogram that showed a high degree of prediction accuracy. CONCLUSIONS: Our study demonstrates that glioma cells can be activated by macrophages via SIRPB1, subsequently reprogramming the TME, suggesting that SIRPB1 could serve as a promising therapeutic target for gliomas.


Subject(s)
Antibodies , Glioma , Humans , Calcium , Coculture Techniques , Computational Biology , Glioma/genetics , Syk Kinase/genetics , Tumor Microenvironment
19.
Nat Struct Mol Biol ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38548954

ABSTRACT

Oligopeptide permease, OppABCD, belongs to the type I ABC transporter family. Its role is to import oligopeptides into bacteria for nutrient uptake and to modulate the host immune response. OppABCD consists of a cluster C substrate-binding protein (SBP), OppA, membrane-spanning OppB and OppC subunits, and an ATPase, OppD, that contains two nucleotide-binding domains (NBDs). Here, using cryo-electron microscopy, we determined the high-resolution structures of Mycobacterium tuberculosis OppABCD in the resting state, oligopeptide-bound pre-translocation state, AMPPNP-bound pre-catalytic intermediate state and ATP-bound catalytic intermediate state. The structures show an assembly of a cluster C SBP with its ABC translocator and a functionally required [4Fe-4S] cluster-binding domain in OppD. Moreover, the ATP-bound OppABCD structure has an outward-occluded conformation, although no substrate was observed in the transmembrane cavity. Here, we reveal an oligopeptide recognition and translocation mechanism of OppABCD, which provides a perspective on how this and other type I ABC importers facilitate bulk substrate transfer across the lipid bilayer.

20.
IEEE Trans Image Process ; 33: 2530-2543, 2024.
Article in English | MEDLINE | ID: mdl-38530730

ABSTRACT

Existing human parsing frameworks commonly employ joint learning of semantic edge detection and human parsing to facilitate the localization around boundary regions. Nevertheless, the parsing prediction within the interior of the part contour may still exhibit inconsistencies due to the inherent ambiguity of fine-grained semantics. In contrast, binary edge detection does not suffer from such fine-grained semantic ambiguity, leading to a typical failure case where misclassification occurs inner the part contour while the semantic edge is accurately detected. To address these challenges, we develop a novel diffusion scheme that incorporates guidance from the detected semantic edge to mitigate this problem by propagating corrected classified semantics into the misclassified regions. Building upon this diffusion scheme, we present an Edge Guided Diffusion Network (EGDNet) for human parsing, which can progressively refine the parsing predictions to enhance the accuracy and coherence of human parsing results. Moreover, we design a horizontal-vertical aggregation to exploit inherent correlations among body parts along both the horizontal and vertical axes, which aims at enhancing the initial parsing results. Extensive experimental evaluations on various challenging datasets demonstrate the effectiveness of the proposed EGDNet. Remarkably, our EGDNet shows impressive performances on six benchmark datasets, including four human body parsing datasets (LIP, CIHP, ATR, and PASCAL-Person-Part), and two human face parsing datasets (CelebAMask-HQ and LaPa).


Subject(s)
Benchmarking , Learning , Humans , Semantics
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