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1.
Front Plant Sci ; 15: 1365275, 2024.
Article in English | MEDLINE | ID: mdl-39315369

ABSTRACT

Bird invasion will reduce the yield of high-value crops, which threatens the healthy development of agricultural economy. Sonic bird repellent has the advantages of large range, no time and geographical restrictions, and low cost, which has attracted people's attention in the field of agriculture. At present, there are few studies on the application of sonic bird repellents in pear orchards to minimize economic losses and prolong the adaptive capacity of birds. In this paper, a sound wave bird repellent system based on computer vision is designed, which combines deep learning target recognition technology to accurately identify birds and drive them away. The neural network model that can recognize birds is first trained and deployed to the server. Live video is captured by an installed webcam, and the sonic bird repellent is powered by an ESP-8266 relay switch. In a pear orchard, two experimental areas were divided into two experimental areas to test the designed sonic bird repellent device, and the number of bad fruits pecked by birds was used as an indicator to evaluate the bird repelling effect. The results showed that the pear pecked fruit rate was 6.03% in the pear orchard area that used the acoustic bird repeller based on computer recognition, 7.29% in the pear orchard area of the control group that used the acoustic bird repeller with continuous operation, and 13.07% in the pear orchard area that did not use any bird repellent device. While acoustic bird repellers based on computer vision can be more effective at repelling birds, they can be used in combination with methods such as fruit bags to reduce the economic damage caused by birds.

2.
Plant J ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39312631

ABSTRACT

In plants, RNA silencing constitutes a strong defense against viral infection, which viruses counteract with RNA-silencing suppressors (RSSs). Understanding the interactions between viral RSSs and host factors is crucial for elucidating the molecular arms race between viruses and host plants. We report that the helicase motif (Hel) of the replicase encoded by apple stem grooving virus (ASGV)-the main virus affecting pear trees in China-is an RSS that can inhibit both local and systemic RNA silencing, possibly by binding double-stranded (ds) siRNA. The transcription factor related to ABSCISIC ACID INSENSITIVE3/VIVIPAROUS1 from pear (PbRAV1) enters the cytoplasm and binds Hel through its C terminus, thereby attenuating its RSS activity by reducing its binding affinity to 21- and 24-nt ds siRNA, and suppressing ASGV infection. PbRAV1 can also target p24, an RSS encoded by grapevine leafroll-associated virus 2 (GLRaV-2), with similar negative effects on p24's suppressive function and inhibition of GLRaV-2 infection. Moreover, like the positive role of the PbRAV1 homolog from grapevine (VvRAV1) in p24's previously reported RSS activity, ASGV Hel can also hijack VvRAV1 and employ the protein to sequester 21-nt ds siRNA, thereby enhancing its own RSS activity and promoting ASGV infection. Furthermore, PbRAV1 neither interacts with CP, an RSS encoded by grapevine inner necrosis virus, nor has any obvious effect on CP's RSS activity. Our results identify an RSS encoded by ASGV and demonstrate that PbRAV1, representing a novel type of RAV transcription factor, plays a defensive role against viral infection by targeting viral RSSs.

3.
Adv Mater ; : e2406559, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39295477

ABSTRACT

Solar-blind ultraviolet (UV) detection plays a critical role in imaging and communication due to its low-noise background, high signal-to-noise ratio, and strong anti-interference capabilities. Detecting the polarization state of UV light can enhance image information and expand the communication dimension. Although polarization detection is explored in visible and infrared light, and applied in fields such as astrophysics and submarine seismic wave detection, solar-blind UV polarization detection remains largely unreported. This is primarily due to the challenge of creating UV polarizers with high transmittance, high extinction ratio, and strong resistance to UV radiation. In this study, it is discovered that the space symmetry breaking of the ß-Ga2O3's b-c plane results in a significant optical absorption dichroic ratio. Leveraging ß-Ga2O3's high solar-blind UV response, a lensless solar-blind UV polarization-sensitive photodetector, circumventing the challenges associated with solar-blind UV polarizers is designed. This photodetector exhibits an exceptionally high intrinsic polarization ratio under 254 nm linearly polarized light, approximately two orders of magnitude higher than other reported nanomaterial-based polarization-sensitive photodetectors. Additionally, it demonstrates significant advantages in solar-blind UV imaging and light communication. This work introduces a novel strategy for solar-blind ultraviolet polarization detection and offers a promising approach for solar-blind light communication.

4.
Front Pediatr ; 12: 1430549, 2024.
Article in English | MEDLINE | ID: mdl-39268364

ABSTRACT

Monteggia fracture is a relatively uncommon injury in pediatric patients, accounting for less than 2% of forearm fractures, characterized by a combination of ulna fracture and radial head dislocation. Neglected Monteggia fractures define as those that have not received treatment within 3 weeks. In children, ulna fractures are easily diagnosed while radial head dislocation may be overlooked, necessitating open reduction after neglecting the Monteggia fracture and potentially causing additional trauma to the child. This study aims to review the pathological characteristics of neglected Monteggia fractures based on the length ratio of the ulna and radius, relative positions between the proximal ends of the ulna and radius, the integrality of annular ligament and the pathological change of proximal radioulnar joint. The findings will provide valuable insights and guidance for managing neglected Monteggia fractures.

5.
Nutrients ; 16(17)2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39275359

ABSTRACT

The journal retracts the article, "Antiproliferative Activity of Triterpene Glycoside Nutrient from Monk Fruit in Colorectal Cancer and Throat Cancer" [...].

6.
Food Res Int ; 195: 114942, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39277220

ABSTRACT

Frankincense is an important seasoning and spice known for its distinctive and intricate flavor profile. Considering the considerable variation in the aromatic quality of frankincense due to geographical origin, species diversity and cultivation conditions, frankincense from major global origins was characterized holistically for the first time. The electronic nose (E-nose) with headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and sensory evaluation were implemented to characterize the aroma components of 21 commercial varieties of frankincense from around the world. The results showed that a total of 149 volatile organic compounds (VOCs) of 10 categories were identified in frankincense, among which the numbers of alcohols, terpenes and esters compounds accounted for 22.15 %, 18.79 % and 15.44 % of the total VOCs of frankincense, respectively. The PLS-DA model effectively distinguished frankincense from Oman/Somalia and other origins. Furthermore, the study identified two differential VOCs with VIP > 1 in three Asian countries and five in six African countries. The total VOCs content and sensory characteristic score of "Lemon/Citrus" in Oman frankincense is significantly higher than other regions. The OAV results showed that 61 substances (e.g., Diacety, alpha-Pinene, Camphene, Myrcene) as key aroma compounds and OICS model indicated that p-Cymenol was found to contribute significantly to the citrus aroma in frankincense. This study identified the fundamental components of frankincense flavor and revealed different flavor descriptors of frankincense, which are crucial for reconstructing frankincense flavor and improving flavor quality.


Subject(s)
Electronic Nose , Gas Chromatography-Mass Spectrometry , Odorants , Solid Phase Microextraction , Volatile Organic Compounds , Gas Chromatography-Mass Spectrometry/methods , Volatile Organic Compounds/analysis , Odorants/analysis , Solid Phase Microextraction/methods , Humans , Female , Taste , Male , Adult , Smell
7.
Article in English | MEDLINE | ID: mdl-39219187

ABSTRACT

Ovarian cancer is one of the most prevalent malignancies among women. CircRNAs play key roles in the progression of ovarian cancer. This study aimed to investigate the mechanism of action of hsa_circ_0000129 and its effects on ovarian cancer. Expression of hsa_circ_0000129, tropomyosin 3 (TPM3), and miR-383-5p in ovarian cancer cell lines and tissue specimens was detected using qRT-PCR or western blotting. Cell counting kit-8 (CCK-8), colony formation, and transwell assays were performed to assess viability, proliferation, and migration of ovarian cancer cells. A xenograft model was used to study tumorigenicity of ovarian cancer cells in vivo. Luciferase and RNA immunoprecipitation assays were performed to determine binding between miR-383-5p and hsa_circ_0000129 or TPM3. Upregulation of hsa_circ_0000129 and TPM3 and downregulation of miR-383-5p were observed in ovarian cancer. Low hsa_circ_0000129 and TPM3 expression repressed viability, migration, and proliferation of ovarian cancer cells. Inhibition of miR-383-5p had a contrary effect. Furthermore, knockdown of hsa_circ_0000129 restricted the tumorigenicity of ovarian cancer cells. Mechanistically, hsa_circ_0000129 has a sponging effect on miR-383-5p, which targets TPM3. Hsa_circ_0000129 stimulated development of the malignant ovarian cancer phenotype by sponging miR-383-5p and releasing TPM3.

8.
J Clin Invest ; 134(18)2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39137044

ABSTRACT

BACKGROUNDTeplizumab, a non-FcR-binding anti-CD3 mAb, is approved to delay progression of type 1 diabetes (T1D) in at-risk patients. Previous investigations described the immediate effects of the 14-day treatment, but longer-term effects of the drug remain unknown.METHODSWith an extended analysis of study participants, we found that 36% were undiagnosed or remained free of clinical diabetes after 5 years, suggesting operational tolerance. Using single-cell RNA sequencing, we compared the phenotypes, transcriptome, and repertoire of peripheral blood CD8+ T cells including autoreactive T cells from study participants before and after teplizumab and features of responders and non-responders.RESULTSAt 3 months, there were transcriptional signatures of cell activation in CD4+ and CD8+ T cells including signaling that was reversed at 18 months. At that time, there was reduced expression of genes in T cell receptor and activation pathways in clinical responders. In CD8+ T cells, we found increased expression of genes associated with exhaustion and immune regulation with teplizumab treatment. These transcriptional features were further confirmed in an independent cohort. Pseudotime analysis showed differentiation of CD8+ exhausted and memory cells with teplizumab treatment. IL7R expression was reduced, and patients with lower expression of CD127 had longer diabetes-free intervals. In addition, the frequency of autoantigen-reactive CD8+ T cells, which expanded in the placebo group over 18 months, did not increase in the teplizumab group.CONCLUSIONThese findings indicate that teplizumab promotes operational tolerance in T1D, involving activation followed by exhaustion and regulation, and prevents expansion of autoreactive T cells.TRIAL REGISTRATIONClinicalTrials.gov NCT01030861.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases/NIH, Juvenile Diabetes Research Foundation.


Subject(s)
Antibodies, Monoclonal, Humanized , CD8-Positive T-Lymphocytes , Diabetes Mellitus, Type 1 , Humans , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/genetics , Male , CD8-Positive T-Lymphocytes/immunology , Female , Antibodies, Monoclonal, Humanized/therapeutic use , Adult , Adolescent
9.
J Thorac Dis ; 16(7): 4106-4119, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39144348

ABSTRACT

Background: Neoadjuvant therapy has become a mainstay of treatment for locally advanced resectable esophageal cancer. The objective of this research was to investigate the effectiveness and safety of neoadjuvant immunotherapy combined with chemotherapy in treating surgically removable esophageal squamous cell carcinoma (ESCC). Methods: From January 1, 2016 to April 1, 2023, we conducted a retrospective analysis of patients diagnosed with resectable esophageal cancer who underwent neoadjuvant immunotherapy combined with chemotherapy at The First Affiliated Hospital of Nanchang University. The primary endpoints of this study were pathologic complete response (pCR), major pathologic response (MPR) and disease-free survival (DFS). The secondary endpoints of this study were overall survival (OS), objective response rate (ORR) and safety. Results: A total of 122 patients with ESCC receiving neoadjuvant immune-chemotherapy (nICT) were included. Fifty-four patients achieved partial response (PR) and two patients achieved complete response (CR), with an ORR of 45.9%. Of the 106 patients who underwent surgery, a total of 28 patients achieved pCR (26.4%) and a total of 37 patients achieved MPR (34.9%). Grade 3 or higher adverse events occurred in 26 patients (21.3%). The most common postoperative complication was pneumonitis (25.5%). Conclusions: Neoadjuvant immunotherapy combined with chemotherapy demonstrates satisfactory efficacy in the treatment of locally advanced ESCC, with manageable treatment-related adverse events and postoperative complications.

10.
Adv Mater ; : e2403696, 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39183501

ABSTRACT

Supercontinuum generation (SCG) from silica-based photonic crystal fibers (PCFs) is of highly technological significance from microscopy to metrology, but has been hindered by silica's relatively low intrinsic optical nonlinearity. The prevailing approaches of filling PCF with nonlinear gases or liquids can endow fibre with enhanced optical nonlinearity and boosted SCG efficiency, yet these hybrids are easily plagued by fusion complexity, environmental incompatibility or transmission mode instability. Here this work presents a strategy of embedding solid-state 2D MoS2 atomic layers into the air-holes of PCF to efficiently enhance SCG. This work demonstrates a 4.8 times enhancement of the nonlinear coefficient and a 70% reduction of the threshold power for SCG with one octave spanning in the MoS2-PCF hybrid. Furthermore, this work finds that the SCG enhancement is highly layer-dependent, which only manifests for a real 2D regime within the thickness of five atomic layers. Theoretical calculations reveal that the critical thickness arises from the trade-off among the layer-dependent enhancement of the nonlinear coefficient, leakage of fundamental mode and redshift of zero-dispersion wavelength. This work provides significant advances toward efficient SCG, and highlights the importance of matching an appropriate atomic layer number in the design of functional 2D material optical fibers.

11.
Ren Fail ; 46(2): 2390558, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39143823

ABSTRACT

BACKGROUND: There is a close clinical association between hypothyroidism and nephrotic syndrome (NS) was close, but whether there is genetic causality between the two is not known. OBJECTIVE: Using pooled data from a genome-wide association study (GWAS), the association between hypothyroidism and NS was explored via Mendelian randomization (MR) analysis. METHODS: Single-nucleotide polymorphisms (SNPs) associated with hypothyroidism (or NS) were screened as genetic instrumental variables (IVs) from pooled GWAS data, and inverse-variance weighting (IVW) was used for the main analysis to estimate causal effects, with MR-Egger, weighted median, and weighted mode used as complementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept, MR-PRESSO and leave-one-out, were also conducted to assess the robustness of the results. RESULTS: Genetically predicted hypothyroidism was positively associated with the risk of developing NS (IVW: OR = 1.18, 95% CI: 1.07-1.30, p = 0.00; MR-Egger: OR = 1.36, 95% CI: 1.10-1.68, p = 0.01), and the MR-Egger intercept (intercept = -0.02, p = 0.14), MR-PRESSO test (p = 0.14), Cochran's Q test (p = 0.15) and leave-one-out test results supported the robustness of the results. Genetically predicted NS status might not be associated with an increased risk of developing hypothyroidism (IVW: OR = 1.01, 95% CI: 1.00-1.03, p = 0.08; MR-Egger: OR = 1.01, 95% CI: 0.98-1.04, p = 0.43), and the MR-Egger intercept (intercept < 0.01, p = 0.69), MR-PRESSO test (p = 0.64), Cochran's Q test (p = 0.61) and leave-one-out test results supported the robustness of the results. CONCLUSION: Hypothyroidism status could increase the risk of developing NS.


Subject(s)
Genome-Wide Association Study , Hypothyroidism , Mendelian Randomization Analysis , Nephrotic Syndrome , Polymorphism, Single Nucleotide , Humans , Hypothyroidism/genetics , Hypothyroidism/complications , Nephrotic Syndrome/genetics , Nephrotic Syndrome/complications , Genetic Predisposition to Disease , Risk Factors
12.
Chem Rev ; 124(17): 9785-9865, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39132950

ABSTRACT

Over the past decade, research on atomically thin two-dimensional (2D) transition metal dichalcogenides (TMDs) has expanded rapidly due to their unique properties such as high carrier mobility, significant excitonic effects, and strong spin-orbit couplings. Considerable attention from both scientific and industrial communities has fully fueled the exploration of TMDs toward practical applications. Proposed scenarios, such as ultrascaled transistors, on-chip photonics, flexible optoelectronics, and efficient electrocatalysis, critically depend on the scalable production of large-area TMD films. Correspondingly, substantial efforts have been devoted to refining the synthesizing methodology of 2D TMDs, which brought the field to a stage that necessitates a comprehensive summary. In this Review, we give a systematic overview of the basic designs and significant advancements in large-area epitaxial growth of TMDs. We first sketch out their fundamental structures and diverse properties. Subsequent discussion encompasses the state-of-the-art wafer-scale production designs, single-crystal epitaxial strategies, and techniques for structure modification and postprocessing. Additionally, we highlight the future directions for application-driven material fabrication and persistent challenges, aiming to inspire ongoing exploration along a revolution in the modern semiconductor industry.

13.
Front Immunol ; 15: 1406671, 2024.
Article in English | MEDLINE | ID: mdl-39021573

ABSTRACT

Objective: We aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Methods: MDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes. Results: Our findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC. Conclusion: MDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Liver Cirrhosis , Liver Neoplasms , Monocytes , Humans , Carcinoma, Hepatocellular/diagnosis , Liver Neoplasms/diagnosis , Liver Neoplasms/blood , Male , Female , Liver Cirrhosis/diagnosis , Liver Cirrhosis/blood , Middle Aged , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/complications , Adult , Monocytes/immunology , Diagnosis, Differential , Biomarkers , Aged , ROC Curve , Biomarkers, Tumor/blood
14.
Science ; 385(6704): 99-104, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38963849

ABSTRACT

Rhombohedral-stacked transition-metal dichalcogenides (3R-TMDs), which are distinct from their hexagonal counterparts, exhibit higher carrier mobility, sliding ferroelectricity, and coherently enhanced nonlinear optical responses. However, surface epitaxial growth of large multilayer 3R-TMD single crystals is difficult. We report an interfacial epitaxy methodology for their growth of several compositions, including molybdenum disulfide (MoS2), molybdenum diselenide, tungsten disulfide, tungsten diselenide, niobium disulfide, niobium diselenide, and molybdenum sulfoselenide. Feeding of metals and chalcogens continuously to the interface between a single-crystal Ni substrate and grown layers ensured consistent 3R stacking sequence and controlled thickness from a few to 15,000 layers. Comprehensive characterizations confirmed the large-scale uniformity, high crystallinity, and phase purity of these films. The as-grown 3R-MoS2 exhibited room-temperature mobilities up to 155 and 190 square centimeters per volt second for bi- and trilayers, respectively. Optical difference frequency generation with thick 3R-MoS2 showed markedly enhanced nonlinear response under a quasi-phase matching condition (five orders of magnitude greater than monolayers).

15.
PLoS One ; 19(7): e0298353, 2024.
Article in English | MEDLINE | ID: mdl-38995910

ABSTRACT

CONTEXT: Nephrotic syndrome(NS) has emerged as a worldwide public health problem. Renal fibrosis is the most common pathological change from NS to end-stage renal failure, seriously affecting the prognosis of renal disease. Although tremendous efforts have been made to treat NS, specific drug therapies to delay the progression of NS toward end-stage renal failure are limited. Epimedium is generally used to treat kidney disease in traditional Chinese medicine. Icariin is a principal active component of Epimedium. METHODS: We used Sprague Dawley rats to establish NS models by injecting doxorubicin through the tail vein. Then icariin and prednisone were intragastric administration. Renal function was examined by an automatic biochemical analyzer. Pathology of the kidney was detected by Hematoxylin-Eosin and Masson staining respectively. Furthermore, RT-PCR, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Western Blot and Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling staining were employed to detect the proteins related to pyroptosis and EMT. HK-2 cells exposed to doxorubicin were treated with icariin, and cell viability was assessed using the MTT. EMT was assessed using Enzyme-Linked Immunosorbent Assay and Western Blot. RESULTS: The study showed that icariin significantly improved renal function and renal fibrosis in rats. In addition, icariin effectively decreased NOD-like receptor thermal protein domain associated protein 3,Caspase-1, Gasdermin D, Ly6C, and interleukin (IL)-1ß. Notably, treatment with icariin also inhibited the levels of TGF-ß, α-SMA and E-cadherin. DISCUSSION AND CONCLUSIONS: It is confirmed that icariin can improve renal function and alleviate renal fibrosis by inhibiting pyroptosis and the mechanism may be related to epithelial-to-mesenchymal transition. Icariin treatment might be recommended as a new approach for NS.


Subject(s)
Doxorubicin , Epithelial-Mesenchymal Transition , Flavonoids , Nephrotic Syndrome , Pyroptosis , Rats, Sprague-Dawley , Animals , Flavonoids/pharmacology , Epithelial-Mesenchymal Transition/drug effects , Pyroptosis/drug effects , Rats , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/pathology , Nephrotic Syndrome/metabolism , Male , Doxorubicin/pharmacology , Humans , Fibrosis/drug therapy , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Cell Line , Disease Models, Animal
16.
Acta Pharmacol Sin ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043970

ABSTRACT

Z-discs are core ultrastructural organizers of cardiomyocytes that modulate many facets of cardiac pathogenesis. Yet a comprehensive proteomic atlas of Z-disc-associated components remain incomplete. Here, we established an adeno-associated virus (AAV)-delivered, cardiomyocyte-specific, proximity-labeling approach to characterize the Z-disc proteome in vivo. We found palmdelphin (PALMD) as a novel Z-disc-associated protein in both adult murine cardiomyocytes and human pluripotent stem cell-derived cardiomyocytes. Germline and cardiomyocyte-specific Palmd knockout mice were grossly normal at baseline but exhibited compromised cardiac hypertrophy and aggravated cardiac injury upon long-term isoproterenol treatment. By contrast, cardiomyocyte-specific PALMD overexpression was sufficient to mitigate isoproterenol-induced cardiac injury. PALMD ablation perturbed the transverse tubule (T-tubule)-sarcoplasmic reticulum (SR) ultrastructures, which formed the Z-disc-associated junctional membrane complex (JMC) essential for calcium handling and cardiac function. These phenotypes were associated with the reduction of nexilin (NEXN), a crucial Z-disc-associated protein that is essential for both Z-disc and JMC structures and functions. PALMD interacted with NEXN and enhanced its protein stability while the Nexn mRNA level was not affected. AAV-based NEXN addback rescued the exacerbated cardiac injury in isoproterenol-treated PALMD-depleted mice. Together, this study discovered PALMD as a potential target for myocardial protection and highlighted in vivo proximity proteomics as a powerful approach to nominate novel players regulating cardiac pathogenesis.

17.
Nat Commun ; 15(1): 6222, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043633

ABSTRACT

Chimeric antigen receptor (CAR) T-cells targeting Fibroblast Growth Factor Receptor 4 (FGFR4), a highly expressed surface tyrosine receptor in rhabdomyosarcoma (RMS), are already in the clinical phase of development, but tumour heterogeneity and suboptimal activation might hamper their potency. Here we report an optimization strategy of the co-stimulatory and targeting properties of a FGFR4 CAR. We replace the CD8 hinge and transmembrane domain and the 4-1BB co-stimulatory domain with those of CD28. The resulting CARs display enhanced anti-tumor activity in several RMS xenograft models except for an aggressive tumour cell line, RMS559. By searching for a direct target of the RMS core-regulatory transcription factor MYOD1, we identify another surface protein, CD276, as a potential target. Bicistronic CARs (BiCisCAR) targeting both FGFR4 and CD276, containing two distinct co-stimulatory domains, have superior prolonged persistent and invigorated anti-tumor activities compared to the optimized FGFR4-specific CAR and the other BiCisCAR with the same 4-1BB co-stimulatory domain. Our study thus lays down the proof-of-principle for a CAR T-cell therapy targeting both FGFR4 and CD276 in RMS.


Subject(s)
B7 Antigens , Immunotherapy, Adoptive , Receptor, Fibroblast Growth Factor, Type 4 , Receptors, Chimeric Antigen , Rhabdomyosarcoma , Xenograft Model Antitumor Assays , Receptor, Fibroblast Growth Factor, Type 4/metabolism , Receptor, Fibroblast Growth Factor, Type 4/genetics , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/immunology , Rhabdomyosarcoma/genetics , Humans , Animals , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Cell Line, Tumor , Mice , Immunotherapy, Adoptive/methods , B7 Antigens/metabolism , B7 Antigens/immunology , B7 Antigens/genetics , MyoD Protein/metabolism , MyoD Protein/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Child , Female , Mice, SCID , Mice, Inbred NOD
18.
Chem Biol Interact ; 400: 111161, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39053793

ABSTRACT

Hepatocellular carcinoma (HCC) is characterized with high recurrence and mortality, and the clinical treatments for HCC are very limited. Hepatocellular carcinoma stem cells are the root of HCC progress, recurrence, and multidrug resistance. Ovatodiolide (OVA) is a bioactive diterpenoid served as an inflammatory and immunotherapeutic responses modulator. In this research, we found OVA inhibited HCC stemness through inhibiting MTDH gene transcription. Moreover, we firstly discovered transcription factor SP1 bound to the promoter region of MTDH to transcriptionally regulate MTDH level. Mechanically, we demonstrated OVA decreased SP1 protein stability to transcriptionally inhibit MTDH gene, and inhibited the nuclear translocation of p65, and then diminished IL-6 level to suppress JAK/STAT3 signaling pathway, eventually decreases CD133 level and the stemness of HCC. Furthermore, we demonstrated ACT004, OVA derivative with high metabolic stability towards cytochrome P450 enzymes, showed no genotoxicity and no accumulative or delayed toxicities after long-term administration in rats. And the in vivo efficacy experiments indicated ACT004 inhibited tumor growth of hepatocellular carcinoma. In conclusion, we revealed the mechanism of OVA in regulating HCC stemness, detected the toxicity of OVA derivative and evaluated the in vivo efficacy which lays a foundation for further discovery of anti-HCC stem cell agents and provide a new strategy for the application of OVA in clinical treatment.


Subject(s)
Carcinoma, Hepatocellular , Diterpenes , Liver Neoplasms , STAT3 Transcription Factor , Signal Transduction , Animals , Humans , Male , Rats , Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Diterpenes/pharmacology , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Membrane Proteins/metabolism , Membrane Proteins/genetics , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Rats, Sprague-Dawley , Signal Transduction/drug effects , STAT3 Transcription Factor/metabolism
19.
Sci Rep ; 14(1): 15956, 2024 07 10.
Article in English | MEDLINE | ID: mdl-38987349

ABSTRACT

With global warming, heat stress has become an important factor that seriously affects crop yield and quality. Therefore, understanding plant responses to heat stress is important for agricultural practice, but the molecular mechanism of high-temperature tolerance in garlic remains unclear. In this study, 'Xusuan No. 6' was used as the experimental material. After heat stress for 0 (CK), 2 and 24 h, transcriptome sequencing was used to screen metabolic pathways and differentially expressed genes (DEGs) closely related to heat stress and was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 86,110 unigenes obtained from the raw transcriptome sequencing data were spliced. After 2 h of heat treatment, the expression levels of 8898 genes increased, and 3829 genes were decreased in leaves. After 24 h, the expression levels of 7167 genes were upregulated, and 3176 genes were downregulated. Gene Ontology enrichment analysis showed that DEGs were mainly enriched in seven categories: cellular processes, metabolic processes, binging, catalytic activity, cellular anatomical entity and protein-containing complex response to stimulus. Kyoto Encyclopedia of Genes and Genomes pathway enrichment showed that DEGs are involved in protein processing in the endoplasmic reticulum, plant hormone signal transduction, phenylpropanoid biosynthesis, and photosynthetic antenna proteins. Six genes were selected and further verified by qRT-PCR. In this study, the full-length transcriptome of garlic was constructed, and the regulatory genes related to the heat resistance of garlic were studied. Taken together, these findings can provide a theoretical basis for the cloning of heat resistance genes in garlic and for the analysis of heat resistance mechanisms.


Subject(s)
Garlic , Gene Expression Profiling , Gene Expression Regulation, Plant , Heat-Shock Response , Transcriptome , Garlic/genetics , Garlic/metabolism , Heat-Shock Response/genetics , Gene Ontology , Plant Proteins/genetics , Plant Proteins/metabolism
20.
Nat Nanotechnol ; 19(7): 907-918, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38987649

ABSTRACT

The exceptional physical properties of two-dimensional (2D) van der Waals (vdW) materials have been extensively researched, driving advances in material synthesis. Epitaxial growth, a prominent synthesis strategy, enables the production of large-area, high-quality 2D films compatible with advanced integrated circuits. Typical 2D single crystals, such as graphene, transition metal dichalcogenides and hexagonal boron nitride, have been epitaxially grown at a wafer scale. A systematic summary is required to offer strategic guidance for the epitaxy of emerging 2D materials. Here we focus on the epitaxy methodologies for 2D vdW materials in two directions: the growth of in-plane single-crystal monolayers and the fabrication of out-of-plane homostructures. We first discuss nucleation control of a single domain and orientation control over multiple domains to achieve large-scale single-crystal monolayers. We analyse the defect levels and measures of crystalline quality of typical 2D vdW materials with various epitaxial growth techniques. We then outline technical routes for the growth of homogeneous multilayers and twisted homostructures. We further summarize the current strategies to guide future efforts in optimizing on-demand fabrication of 2D vdW materials, as well as subsequent device manufacturing for their industrial applications.

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