Publications by authors named "Heng Wang"

860 Publications

Genetically Engineered Hematopoietic Stem Cells Deliver TGF-β Inhibitor to Enhance Bone Metastases Immunotherapy.

Adv Sci (Weinh) 2022 Aug 10:e2201451. Epub 2022 Aug 10.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, 199 Ren'ai Road, Suzhou, Jiangsu, 215123, China.

Owing to the immune microenvironment of bones and low selectivity of the drug, patients with bone metastases often respond poorly to immunotherapy. In this study, programmed cell death protein 1 (PD1)-expressing hematopoietic stem cells (HSCs) are genetically engineered for bone-targeted delivery of the transforming growth factor beta (TGF-β) small-molecule inhibitor SB-505124 ([email protected]). Intriguingly, compared to anti-PD-L1 monoclonal antibodies, as "living drugs", HSCs-PD-1 not only show great targeting ability to the bone marrow, but are also able to reduplicate themselves within the bone marrow niche and continuously express PD-1 molecules. The SB released from HSCs-PD-1 competitively bound to TGF-β receptors on CD4 T cells and facilitate CD4 T cell differentiation to helper T (T )1 and T 2 cells, thereby reprogramming the local immunosuppressive milieu of the bone marrow. Additionally, HSCs-PD-1 can block programmed death-ligand 1 on tumor and myeloid cells, resulting in reinvigorated anti-tumor immunity of T cells. In conclusion, in the present study, an alternative cell engineering strategy is delineated for immune checkpoint blockade therapy, to target bone metastasis using HSCs as a platform, which shows great promise in the treatment of bone metastases.
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http://dx.doi.org/10.1002/advs.202201451DOI Listing
August 2022

Graphene-Dominated Hybrid Coatings with Highly Compacted Structure on Stainless Steel Bipolar Plates.

ACS Appl Mater Interfaces 2022 Aug 8. Epub 2022 Aug 8.

School of Materials Science and Engineering, University of Shanghai for Science and Technology, No. 516 Jungong Road, Shanghai 200093, China.

Highly conductive corrosion protection coatings are necessary for metallic bipolar plates (BPs) of the proton-exchange membrane fuel cell. Graphene coatings have the potential of protecting metal substrates from corrosion without obscuring their excellent electrical conductivity. The electron transfer in the coatings facilitates the formation of galvanic cells, so the challenge is to block the mass transfer of the corrosion process. Here, we constructed highly compacted hybrid coatings with aligned water-dispersible graphene layers. The water-dispersible graphene (SG) held an electrical conductivity of >270 S cm while providing an unprecedented dispersibility, which can be redispersed from filter cake with a concentration of 120 mg mL or even dry state. The cohesion of the hybrid coatings was attributed to the interaction between highly aligned SG layers and the heterointerface between SG and polydopamine (PDA), as proven by the molecular dynamics simulations. The hybrid coatings presented a corrosion current density of 0.023 μA cm and an interfacial contact resistance of 9.94 mΩ cm, which meets the requirements of corrosion protection and electron transfer for the coatings on metallic BPs. The water-based fabrication method of the graphene-dominated hybrid coatings was a promising alternative of the vacuum-based deposition method for industrial production.
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http://dx.doi.org/10.1021/acsami.2c09999DOI Listing
August 2022

Identification of Crucial Gene Modules Related to the Efficiency of Anti-PD-1/PD-L1 Therapy and Comprehensive Analyses of a Novel Signature Based on These Modules.

Front Genet 2022 22;13:893380. Epub 2022 Jul 22.

Department of Plastic and Aesthetic Surgery, Huadong Hospital, Fudan University, Shanghai, China.

Biomarker development for clinical checkpoint inhibition is still in its early stages. It is critical to determine the cause of the lack of a long-term response in patients after immune checkpoint blockade (ICB) treatment and to develop composite biomarkers or signatures to improve personalized approaches. Three modules that were significantly correlated with the immunotherapeutic response were identified. Stimulatory pathways of cellular immunity, extracellular matrix formation-related pathways, and ATP metabolism-related pathways were enriched. Two distinct transcriptional subtypes were determined. Tumor microenvironment (TME) characteristics were highly correlated with "hot" and "cold" tumors. The ICB score was significantly correlated with clinical characteristics including age, Breslow depth, Clerk level, AJCC stage, and T stage. Meanwhile, a low ICB score is characterized by increased activation of immunity, a higher level of immune infiltration, and immune molecule expression. The ICB score showed a robust ability to predict melanoma prognosis in the discovery, internal validation, and external validation cohorts. In addition, a low ICB score was linked to a higher CR/PR rate in the immunotherapeutic cohort. The ICB score could reflect the pre-existing immune features and the expression pattern of "Cold" versus "Hot" tumors in melanoma patients. Thus, it has the potential to serve as a reliable predictor of melanoma prognosis and response to ICB therapy.
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http://dx.doi.org/10.3389/fgene.2022.893380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354784PMC
July 2022

A deep learning model based on dynamic contrast-enhanced magnetic resonance imaging enables accurate prediction of benign and malignant breast lessons.

Front Oncol 2022 22;12:943415. Epub 2022 Jul 22.

Department of Radiology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objectives: The study aims to investigate the value of a convolutional neural network (CNN) based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting malignancy of breast lesions.

Methods: We developed a CNN model based on DCE-MRI to characterize breast lesions. Between November 2018 and October 2019, 6,165 slices of 364 lesions (234 malignant, 130 benign) in 364 patients were pooled in the training/validation set. Lesions were semi-automatically segmented by two breast radiologists using ITK-SNAP software. The standard of reference was histologic consequences. Algorithm performance was evaluated in an independent testing set of 1,560 slices of 127 lesions in 127 patients using weighted sums of the area under the curve (AUC) scores.

Results: The area under the receiver operating characteristic (ROC) curve was 0.955 for breast cancer prediction while the accuracy, sensitivity, and specificity were 90.3, 96.2, and 79.0%, respectively, in the slice-based method. In the case-based method, the efficiency of the model changed by adjusting the standard for the number of positive slices. When a lesion with three or more positive slices was determined as malignant, the sensitivity was above 90%, with a specificity of nearly 60% and an accuracy higher than 80%.

Conclusion: The CNN model based on DCE-MRI demonstrated high accuracy for predicting malignancy among the breast lesions. This method should be validated in a larger and independent cohort.
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http://dx.doi.org/10.3389/fonc.2022.943415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353744PMC
July 2022

Effects of sunshine duration on daily outpatient visits for depression in Suzhou, Anhui Province, China.

Environ Sci Pollut Res Int 2022 Aug 4. Epub 2022 Aug 4.

The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Previous epidemiological studies have reported seasonal variation patterns of depression symptoms, which may be influenced by bad weather conditions, such as a lack of sunlight. However, evidence on the acute effects of sunshine duration on outpatient visits for depression is limited, especially in developing countries, and the results are inconsistent. We collected daily outpatient visits for depression from the local mental health centre in Suzhou, Anhui Province, China, during 2017-2019. We defined the 5th and 95th sunshine percentiles as short and long sunshine durations, respectively. A quasi-Poisson generalized linear regression model combined with a distributed lag nonlinear model was used to quantitatively assess the effects of short and long sunshine durations on outpatient visits for depression. Stratified analyses were further performed by gender, age and number of visits to identify vulnerable populations. A total of 26,343 depression cases were collected during the study period. An approximate U-shaped exposure-response association was observed between sunshine duration and depression outpatient visits. The cumulative estimated relative risks (RRs) for short and long sunshine durations at lag 0-21 days were 1.53 [95% confidence intervals (CI): 1.14, 2.06] and 1.13 (95% CI: 0.88, 1.44), respectively. Moreover, a short sunshine duration was associated with a greater disease burden than a long sunshine duration, with attributable fractions (AFs) of 16.64% (95% CI: 7.8%, 23.89%) and 2.24% (95% CI: -2.65%, 5.74%), respectively. Subgroup analysis showed that males, people aged less than 45 years and first-visit cases may be more susceptible to a lack of sunlight. For a long sunshine duration, no statistically significant associations were found in any population groups. Our study found that a short sunshine duration was associated with an increased risk of depression. The government, medical institutions, family members and patients themselves should fully recognize the important role of sunlight and take active measures to prevent depression.
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http://dx.doi.org/10.1007/s11356-022-22390-5DOI Listing
August 2022

Fabrication of eco-friendly calcium crosslinked alginate electrospun nanofibres for rapid and efficient removal of Cu(II).

Int J Biol Macromol 2022 Aug 1;219:1-10. Epub 2022 Aug 1.

Ministry of Education Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science & Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address:

The preparation of low-cost adsorbents using naturally available biomaterials to realize the efficient removal of Cu(II) is urgently needed. Herein, low-cost and recyclable calcium crosslinked alginate electrospun nanofibres (SA-Ca) were prepared using low-cost materials via a low-energy-consumption process. The prepared SA-Ca possesses a porous network structure, and its average diameter, specific surface area, and tensile strength are approximately 129.6 nm, 3.409 m g, and 2.73MPa, respectively. The maximum adsorption capacity of SA-Ca for Cu(II) in aqueous solution is 285.5 mg g, and the adsorption can be completed in 0.5 h. The adsorption kinetics were well described by the general-order kinetic model, and the adsorption isotherm fitted to the Liu model. The study of the adsorption mechanism suggested that electrostatic attraction, ion exchange, and complexation cooperated to exert effects. More important, SA-Ca can be regenerated using CaCl/HCl solutions based on the ion-exchange mechanism without destroying the morphology of the nanofibres. Furthermore, a low concentration of Cu(II) (10 mg L) and other heavy metal ions [Pb(II) and Cd(II), each 10 mg L] were successfully removed from water, demonstrating that economical biocarbohydrate polymer-based nanofibres have great application prospects in the removal of heavy metal ions.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.221DOI Listing
August 2022

'Multiple and short-range' cross-linking of dialdehyde carboxymethyl cellulose contributes to regulating the physicochemical property of collagen fibril.

Int J Biol Macromol 2022 Jul 25;219:21-30. Epub 2022 Jul 25.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China; Shenzhen Institute of Nutrition and Health, Huazhong Agricultural University, Wuhan 430070, PR China; Agricultural Genomics Institute at Shenzhen, Chinese Academic of Agricultural Sciences, Shenzhen 518000, PR China. Electronic address:

Collagen fibril hydrogel (CH), with controllable micro-structure, sufficient modifying sites and excellent biocompatibility, has received widely attention in the regulation of biomacromolecules. Herein, dialdehyde carboxymethyl cellulose (DCMC) in different -CHO contents and molecular weights demonstrated two types of cross-linking behaviors to CH, 'limited and long-range' or 'multiple and short range' cross-linking, corresponding to -CHO content ranged from 0 to 53 % and 53 to 90 %, respectively. In regard of structure, non-destroying effect of DCMC on collagen was supported by FT-IR and XRD analysis. CH cross-linked by DCMC (CH-DC) showed declining porosity and aggregating fibrils as -CHO content of DCMC rising. In regard of physicochemical properties, DCMC with >53 % -CHO strengthened the hydrophilicity, thermal stability and degradation resistance of CH-DC. Also, there was 110 % growth on gel strength, 86 Pa enhancements on storage modulus, and 4.6 times decrease on the swelling ratio of CH-DC. Results indicated that DCMC with 79 % -CHO remarkably improved the physicochemical properties of CH via developing sufficient Schiff-base bonds with collagen fibril in a short distance. This study distinguished two patterns of DCMC cross-linking from physicochemical view. In other words, DCMC is potential to meet the requirement of protein-based materials with different expectations by adjusting its -CHO content and molecular weight.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.142DOI Listing
July 2022

A preliminary cumulative risk assessment of Diethylhexyl phthalate and Dibutyl phthalate based on the inhibition of embryonic development via the PPARγ pathway.

Toxicol In Vitro 2022 Jul 25;84:105430. Epub 2022 Jul 25.

Key Laboratory of Health Risk Factors for Seafood of Zhejiang Province, Zhoushan Municipal Center for Disease Control and Prevention, Zhejiang 316021, China. Electronic address:

Background: Diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP) are the two most widely used plasticizers (PAEs) that may act as endocrine disruptors and cause developmental toxicity.

Methods: We measured intrauterine exposure to DEHP and DBP which are the two most widely used phthalates (PAEs) in the cord blood of 50 postpartum women using ultra-HPLC-tandem mass spectrometry and solid-phase extraction. The embryotoxicity of DEHP and DBP was evaluated using the human embryonic stem cell test (hEST). Based on the intrauterine exposure concentration of DEHP and DBP in pregnant women and the reference point of toxic effects in hEST, we used the reference point index (RPI) method to assess the cumulative risk of DBP and DEHP.

Results: The mean concentrations of DEHP and DBP were 99.9 μg/L and 24.7 μg/L, respectively. DEHP and DBP were weakly embryotoxic, and the benchmark dose lower confidence intervals were 29.99 and 0.99 μg/mL, respectively, as determined using hEST. Both DEHP and DBP inhibited embryonic development via PPAR/PTEN/Akt signal pathway.

Conclusion: The findings suggest that the cumulative risk in pregnant women with a high level of exposure should receive more attention in the future.
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http://dx.doi.org/10.1016/j.tiv.2022.105430DOI Listing
July 2022

Phosphopantetheinyl transferase ClbA contributes to the virulence of avian pathogenic Escherichia coli in meningitis infection of mice.

PLoS One 2022 28;17(7):e0269102. Epub 2022 Jul 28.

Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.

Avian pathogenic Escherichia coli (APEC), which has potential zoonotic risk, can cause severe systemic infections such as septicemia and meningitis in poultry. Colibactin is a hybrid non-ribosomal peptide/polyketide secondary metabolite produced by bacteria, which induces double-strand DNA breaks and chromosome instability in eukaryotic cells. ClbA is a 4'-phosphopantetheinyl transferase (PPTase) that is essential for colibactin and plays a role in siderophore synthesis. However, whether ClbA is associated with meningitis development in APEC is unclear. In this study, we abolished the clbA gene in the APEC XM strain, investigated the effect of clbA on colibactin synthesis and evaluated the pathogenic capacity of colibactin on meningitis development. Deletion of clbA reduced DNA damage to cells and hindered the normal synthesis of colibactin. Compared with the mice infected by wild-type APEC XM, the clbA deletion mutant infected mice had significant reduction in a series of characteristics associated with meningitis including clinical symptoms, bacterial loads of blood and brain, disruption of the blood brain barrier and the expression of inflammatory factors in the brain tissue. Complementation of ClbA recovered some APEC XM virulence. We conclude that ClbA is obligatory for the synthesis of colibactin and is responsible for the development of meningitis in mice infected by APEC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0269102PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333332PMC
August 2022

Dairy Cows Experimentally Infected With Bovine Leukemia Virus Showed an Increased Milk Production in Lactation Numbers 3-4: A 4-Year Longitudinal Study.

Front Microbiol 2022 11;13:946463. Epub 2022 Jul 11.

College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

Bovine leukemia virus (BLV) is widespread in global cattle populations, but the effects of its infection on milk quantity and quality have not been clearly elucidated in animal models. In this study, 30 healthy first-lactation cows were selected from ≈2,988 cows in a BLV-free farm with the same criteria of parity, age, lactation number, as well as milk yield, SCS, and composition (fat, protein, and lactose). Subsequently, these cows were randomly assigned to the intervention ( = 15) or control ( = 15) group, and reared in different cowsheds. Cows in the intervention group were inoculated with 1 × phosphate-buffered solution (PBS) resuspended in peripheral blood mononuclear cells (PBMC) from a BLV-positive cow, while the controls were inoculated with the inactivated PBMC from the same individual. From June 2016 to July 2021, milk weight (kg) was automatically recorded by milk sensors, and milk SCS and composition were originated from monthly performed dairy herd improvement (DHI) testing. Fluorescence resonance energy transfer (FRET)-qPCR and ELISA showed that cows in the intervention group were successfully infected with BLV, while cows in the control group were free of BLV for the entire period. At 45 days post-inoculation (DPI), the numbers of whole blood cells (WBCs) ( = 0.010), lymphocytes (LYMs) ( = 0.002), and monocytes (MNCs) ( = 0.001) and the expression levels of IFN-γ ( = 0.013), IL-10 ( = 0.031), and IL-12p70 ( = 0.008) increased significantly in the BLV infected cows compared to the non-infected. In lactation numbers 2-4, the intervention group had significantly higher overall milk yield ( < 0.001), fat ( = 0.031), and protein ( = 0.050) than the control group, while milk SCS ( = 0.038) and lactose ( = 0.036) decreased significantly. Further analysis indicated that BLV infection was associated with increased milk yield at each lactation stage in lactation numbers 3-4 ( = 0.021 or < 0.001), but not with SCS and milk composition. Together, this 4-year longitudinal study revealed that artificial inoculation of BLV increased the milk yield in cows in this BLV challenge model.
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http://dx.doi.org/10.3389/fmicb.2022.946463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309534PMC
July 2022

Response Characteristics of Electric Potential and Its Relationship with Dynamic Disaster during Mining Activities: A Case Study in Xuehu Coal Mine, China.

Int J Environ Res Public Health 2022 Jul 23;19(15). Epub 2022 Jul 23.

Key Laboratory of Gas and Fire Control for Coal Mines, Ministry of Education, China University of Mining and Technology, Xuzhou 221116, China.

Across the world, coal resource is widely utilized in industrial production. During coal mining activities, dynamic disasters may be induced, such as coal and gas outbursts, or rock burst, resulting in serious accidents or disasters. Previous studies have shown that electric potential (EP) signals can be produced during the deformation and fracture process of coal and rock mass under load. The abnormal response characteristics of EP can reveal the damage evolution and failure feather of coal mass. In this paper, the response characteristics of EP signals are analyzed with high gas testing during mining activities within deep coal seams, and the relationship between the EP response and outburst disaster hazard is studied. The results show that: (1) Under the comprehensive action of mining stress and gas effect, the coal mass was damaged and fractured, which can produce abundant EP signals, while the temporal EP response characteristics can reflect the loading state and damage evolution process inside the coal seam. (2) When coal cannon and a sudden increase of gas concentration occurred in the coal mass, the EP signal was at a high level and fluctuated violently. This can be regarded as precursory information for an outburst risk, which was verified by monitoring the results of mining stress and electromagnetic radiation (EMR). (3) Based on the unilateral inversion imaging method, EP spatial distribution law was studied and abnormal zones with high-value were identified. The zone is close to, or coincident with, the high value interval of EMR intensity and count indexes, which revealed the distribution characteristics of coal damage localization. Hence, EP monitoring results can forecast precursor information of outburst hazards temporally, and identify local zones with outburst hazard spatially. This study provides a new idea and application basis for using the EP method to monitor and prevent coal and rock dynamic disaster hazards in the field.
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http://dx.doi.org/10.3390/ijerph19158949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330266PMC
July 2022

Precision Layered Stealth Dicing of SiC Wafers by Ultrafast Lasers.

Micromachines (Basel) 2022 Jun 27;13(7). Epub 2022 Jun 27.

The Institute of Technological Sciences, Wuhan University, Wuhan 430072, China.

With the intrinsic material advantages, silicon carbide (SiC) power devices can operate at high voltage, high switching frequency, and high temperature. However, for SiC wafers with high hardness (Mohs hardness of 9.5), the diamond blade dicing suffers from problems such as debris contaminants and unnecessary thermal damage. In this work, a precision layered stealth dicing (PLSD) method by ultrafast lasers is proposed to separate the semi-insulated 4H-SiC wafer with a thickness of 508 μm. The laser power attenuates linearly from 100% to 62% in a gradient of 2% layer by layer from the bottom to the top of the wafer. A cross section with a roughness of about 1 μm was successfully achieved. We have analyzed the effects of laser pulse energy, pulse width, and crystal orientation of the SiC wafer. The anisotropy of the SiC wafer results in various qualities of PLSD cross sections, with the roughness of the crystal plane {10-10} being 20% lower than that of the crystal plane {11-20}.
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http://dx.doi.org/10.3390/mi13071011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315561PMC
June 2022

Polarization Attack on Continuous-Variable Quantum Key Distribution with a Local Local Oscillator.

Entropy (Basel) 2022 Jul 18;24(7). Epub 2022 Jul 18.

Science and Technology on Communication Security Laboratory, Institute of Southwestern Communication, Chengdu 610041, China.

The estimation of phase noise of continuous-variable quantum key distribution protocol with a local local oscillator (LLO CVQKD), as a major process in quantifying the secret key rate, is closely relevant to the intensity of the phase reference. However, the transmission of the phase reference through the insecure quantum channel is prone to be exploited by the eavesdropper (Eve) to mount attacks. Here, we introduce a polarization attack scheme against the phase reference. Presently, in a practical LLO CVQKD system, only part of the phase reference pulses are measured to compensate for the polarization drift of the quantum signal pulses in a compensation cycle due to the limited polarization measurement rate, while the other part of the phase reference pulses are not measured. We show that Eve can control the phase noise by manipulating the polarization direction of the unmeasured phase reference to hide her attack on the quantum signal. Simulations show that Eve can obtain partial or total key rates information shared between Alice and Bob as the transmission distance increases. Improving the polarization measurement rate to 100% or monitoring the phase reference intensity in real-time is of great importance to protect the LLO CVQKD from polarization attack.
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http://dx.doi.org/10.3390/e24070992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320017PMC
July 2022

Expression Patterns of Necroptosis-Related Genes: Predicting Prognosis and Immunotherapeutic Effects in Cutaneous Melanoma.

J Oncol 2022 14;2022:5722599. Epub 2022 Jul 14.

Department of Plastic and Aesthetic Surgery, Huadong Hospital, Fudan University, Shanghai, China.

Background: Increasing evidence has shown a strong correlation between necroptosis and antitumor immunity. However, precise expression patterns of necroptosis-related genes in cutaneous melanoma (CM) have not been clearly elucidated nor have their effects on the immune cell infiltration in the tumor microenvironment.

Method: We investigated the expression patterns of necroptosis-related genes of individuals with cutaneous melanoma based on 67 necroptotic genes and methodically associated the expression patterns with the comprehensive characterization of tumor immune microenvironment. Using principal component analysis methods, the NRG score was developed to quantify the expression patterns of necroptotic genes in CM patients.

Result: Three different necroptotic subtypes were determined with marked survival differences, showing distinct characteristics of immune cell infiltration. The high NRG score group with comprehensive immunosuppression was characterized by the worse immunotherapeutic efficacy and the poor prognosis, while the low NRG score group indicated a robust activation of immune function and a better response to immunotherapy, which may be responsible for a better prognosis. Furthermore, the predictive ability of the NRG score on prognosis and immunotherapeutic benefits was further revalidated using the other independent datasets of cutaneous melanoma. The results indicated that patients with low NRG scores exhibited prolonged survival. Surprisingly, all patients with CM with clinical response, including complete response/partial response, belonged to the low NRG score group.

Conclusion: Our present work revealed the close association between expression patterns of necroptosis-associated genes and tumor immune microenvironment. NRG score can serve as a potential predictor to independently assess patients' prognosis with CM and effectively estimate the response to immunological therapy, thus facilitating the identification of appropriate candidates with CM for immunotherapy and the formulation of individualized therapeutic approaches.
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http://dx.doi.org/10.1155/2022/5722599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303167PMC
July 2022

Single-Cell Transcriptome Analysis Reveals Mesenchymal Stem Cells in Cavernous Hemangioma.

Front Cell Dev Biol 2022 5;10:916045. Epub 2022 Jul 5.

Department of Paediatric Surgery, Tianjin Medical University General Hospital, Tianjin, China.

A cavernous hemangioma, well-known as vascular malformation, is present at birth, grows proportionately with the child, and does not undergo regression. Although a cavernous hemangioma has well-defined histopathological characteristics, its origin remains controversial. In the present study, we characterized the cellular heterogeneity of a cavernous hemangioma using single-cell RNA sequencing (scRNA-seq). The main contribution of the present study is that we discovered a large number of embryonic mesenchymal stem cells (MSCs) in a cavernous hemangioma and proposed that cavernous hemangiomas may originate from embryonic MSCs. Further analysis of the embryonic MSCs revealed that: 1) proinflammatory cytokines and related genes , , , , and are significantly involved in the MSC-induced immune responses in cavernous hemangiomas; 2) is up-regulated in the embryonic MSC apoptosis induced by proinflammatory cytokines; 3) the UCHL1-induced apoptosis of MSCs may play an important role in the MSC-induced immune responses in cavernous hemangiomas; and 4) can be used as a marker gene to detect embryonic MSCs at different apoptosis stages. In addition to MSCs, ECs, macrophages, T lymphocytes and NKCs were intensively investigated, revealing the genes and pathways featured in cavernous hemangiomas. The present study revealed the origin of cavernous hemangiomas and reported the marker genes, cell types and molecular mechanisms, which are associated with the origin, formation, progression, diagnosis and therapy of cavernous hemangiomas. The better understanding of the MSC-induced immune responses in benign tumours helps to guide future investigation and treatment of embryonic MSC-caused tumours. Our findings initiated future research for the rediscovery of MSCs, cancers/tumours and the UCHL1-induced apoptosis.
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http://dx.doi.org/10.3389/fcell.2022.916045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294370PMC
July 2022

Phenylthiol-BODIPY-based supramolecular metallacycles for synergistic tumor chemo-photodynamic therapy.

Proc Natl Acad Sci U S A 2022 Jul 11;119(29):e2203994119. Epub 2022 Jul 11.

Department of Chemistry, University of Utah, Salt Lake City, UT 84112.

The development of more effective tumor therapy remains challenging and has received widespread attention. In the past decade, there has been growing interest in synergistic tumor therapy based on supramolecular coordination complexes. Herein, we describe two triangular metallacycles (1 and 2) constructed by the formation of pyridyl boron dipyrromethene (BODIPY)-platinum coordination. Metallacycle 2 had considerable tumor penetration, as evidenced by the phenylthiol-BODIPY ligand imparting red fluorescent emission at ∼660 nm, enabling bioimaging, and transport visualization within the tumor. Based on the therapeutic efficacy of the platinum(II) acceptor and high singlet oxygen (O) generation ability of BODIPY, 2 was successfully incorporated into nanoparticles and applied in chemo-photodynamic tumor therapy against malignant human glioma U87 cells, showing excellent synergistic therapeutic efficacy. A half-maximal inhibitory concentration of 0.35 μM was measured for 2 against U87 cancer cells in vitro. In vivo experiments indicated that 2 displayed precise tumor targeting ability and good biocompatibility, along with strong antitumor effects. This work provides a promising approach for treating solid tumors by synergistic chemo-photodynamic therapy of supramolecular coordination complexes.
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http://dx.doi.org/10.1073/pnas.2203994119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303851PMC
July 2022

Controllable Inverse Photoconductance in Semiconducting Nanowire Films.

Adv Mater 2022 Jul 19:e2204698. Epub 2022 Jul 19.

Department of Chemistry, Institute of Biomimetic Materials & Chemistry, Anhui Engineering Laboratory of Biomimetic Materials, Division of Nanomaterials & Chemistry, Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230026, China.

As a typical p-type semiconductor, tellurium (Te) has been widely studied for the construction of photodetectors. However, only the positive photoconductance of Te-based photodetectors based on the photoconductive effect has been observed in the reported literature. Herein, an unusual but interesting phenomenon, in that tellurium nanowires (NWs) behave with negative photoresponse to positive photoresponse under enlarged optical intensities from the UV to VIS-IR region is reported. According to the experiments and simulations, adsorbed oxygen on the surface of Te NWs plays a significant role in the abnormal photoresponse. The inverse photoconductance can be attributed to the competition between the photoconductive effect and the oxygen desorption effect. Moreover, the influence of the size and layers of Te NWs is also discussed. This inverse photoconductance phenomenon is further explored by introducing the Te-Au heterojunction system. Hot-electron injection at the Te-Au heterojunction interface induces a more obvious tendency to behave with a negative photoresponse. These findings will be beneficial for potential applications of Te-NW-based photodetectors.
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http://dx.doi.org/10.1002/adma.202204698DOI Listing
July 2022

Can e-commerce alleviate agricultural non-point source pollution? - A quasi-natural experiment based on a China's E-Commerce Demonstration City.

Sci Total Environ 2022 Jul 16;846:157423. Epub 2022 Jul 16.

Northwest Institute of Historical Environment and Socio-Economic Development, Shaanxi Normal University, Xi'an, Shaanxi 710119, China. Electronic address:

Agricultural non-point source pollution is an important driving factor that causes systemic pollution of the ecological environment and directly threatens the sustainable development of agriculture, human health, and safety. As a new engine to reshape the agricultural development model, e-commerce is of great significance to the mitigation of agricultural non-point source pollution. This study regards China's National E-commerce Demonstration Cities (NEDCs) as a quasi-natural experiment and uses the Multi-period difference in difference (DID) method to investigate the impact of urban e-commerce development on agricultural non-point source pollution and its mechanism. The results show that compared with the control group, the NEDC policy reduced the total fertilizer consumption in the pilot cities by 7.5 percentage points, and at the same time had a reduction effect on the consumption of nitrogen fertilizers, pesticides, and agricultural films. According to the analysis of the underlying mechanism, this abatement effect is achieved by increasing the economic performance of the NEDC pilot cities represented by GDP and GDP per capita, and promoting technological innovation represented by green patents and green utility patents. The analysis of heterogeneity finds that the reduction effect of e-commerce on agricultural non-point source pollution is stronger in areas such as main grain production areas and high-value agrochemical input areas. Accordingly, this study proposes that the government should pay attention to regional heterogeneity and formulate support policies for agricultural e-commerce based on local conditions. Moreover, we should actively advance the development of the new business model of "e-commerce + agriculture" and promote the organic integration of agricultural development and ecological civilization.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157423DOI Listing
July 2022

Expression Regulation Mechanisms of Sea Urchin () Under the High Temperature: New Evidence for the miRNA-mRNA Interaction Involvement.

Front Genet 2022 29;13:876308. Epub 2022 Jun 29.

Key Laboratory of Mariculture & Stock Enhancement in North China's Sea, Ministry of Agriculture and Rural Affairs, Dalian Ocean University, Dalian, China.

In the context of global warming and continuous high temperatures in the northern part of China during summer, the mortality rate of our main breeding species, reached 80% in 2020. How sea urchins respond to high temperatures is of great concern to academia and industry. In this study, we examined the antioxidant enzyme activities of different color tube-footed sea urchins under heat stress and compared their transcriptome and microRNA (miRNA) profiles using RNA-Seq. The results showed that the antioxidant enzyme activities of sea urchins were altered by thermal stress, and the changes in peroxidase activities of red tube-footed sea urchins were particularly significant. Investigations revealed that 1,079 differentially expressed genes (DEGs), 11 DE miRNAs, and 104 "DE miRNA-DEG" pairs in total were detected in sea urchins under high temperature stress. Several mRNA and miRNAs were significantly changed (e.g. , , miR-184-p5, miR-92a, miR-92c, and miR-124-p5), suggesting these genes and miRNAs exerted important functions in response to high temperature. At the transcriptional level, red tube-footed sea urchins were found to be more sensitive to high temperature and could respond to high temperature rapidly. DE miRNA-mRNA network showed that miR-92b-3p and PC-5p-7420 were the most corresponding miRNAs. Five mRNAs () may be potential markers of sea urchin response to high temperature. Possible interaction between miRNA-mRNA could be linked to protein folding in the endoplasmic reticulum, Phagosomes, and calcium transport. This study provides a theoretical basis for the molecular mechanism of sea urchin heat tolerance and information that will aid in the selection and breeding of sea urchins with high temperature tolerance.
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http://dx.doi.org/10.3389/fgene.2022.876308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277089PMC
June 2022

A Triplex PCR Method for Distinguishing the Wild-Type African Swine Fever Virus From the Deletion Strains by Detecting the Gene Insertion.

Front Vet Sci 2022 28;9:921907. Epub 2022 Jun 28.

Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

To date, there is no effective vaccine or antiviral therapy available to prevent or treat African swine fever virus (ASFV) infections. ASFV gene deletion strains have been proposed as promising anti-ASFV vaccine candidates. In recent years, most ASFV gene deletion strains worldwide have been recombinant strains expressing or as markers. Therefore, in this study, a new triplex real-time PCR (RT-PCR) method was established for the broad and accurate differentiation of ASFV wild-type . gene deletion strains. We designed three pairs of primers and probes to target , and , and RT-PCR was used to detect these three genes simultaneously. The detection method prevented non-specific amplification of porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus, circovirus type 2, pseudorabies virus, and classical swine fever virus genes. The minimum copy number of standard plasmid DNA detected using triplex RT-PCR was 9.49, 15.60, and 9.60 copies for , and , respectively. Importantly, of the 1646 samples analyzed in this study, 67 were positive for ASFV, all corresponding to the wild-type virus. Overall, our data show that the triplex RT-PCR method established in this study can specifically identify both ASFV wild-type and gene deletion strains.
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http://dx.doi.org/10.3389/fvets.2022.921907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274085PMC
June 2022

Selenomethionine protected BMECs from inflammatory injury and oxidative damage induced by Klebsiella pneumoniae by inhibiting the NF-κB and activating the Nrf2 signaling pathway.

Int Immunopharmacol 2022 Jul 9;110:109027. Epub 2022 Jul 9.

College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu 225009, China; Co-innovation Center for Prevention and Control of Important Animal Infection Disease and Zoonoses, Yangzhou, Jiangsu 225009, China; Joint International Research Laboratory of Agriculture and Agri-product Safety of the Ministry of Education, Yangzhou, Jiangsu 225009, China. Electronic address:

Klebsiella pneumoniae (K. pneumoniae) is one of the main environmental pathogens causing bovine mastitis. The incidence of bovine mastitis caused by K. pneumoniae is increasing worldwide. Selenium is an essential trace element that has multiple physiological functions, such as antioxidant and anti-inflammatory activities. Therefore, this study aimed to verify whether selenomethionine (SeMet) could contribute to alleviating the inflammatory injury and oxidative damage induced by K. pneumoniae. Bovine mammary epithelial cells were cultured in vitro and pretreated with 4 μM SeMet before being infected with K. pneumoniae. Western blot analysis was used to detect the expression of the related proteins in the NF-κB and Nrf2 signaling pathways. The gene expression levels of IL-1β, IL-6, IL-8, TNF-α, Nrf2, Keap1, NQO-1 and HO-1 were detected using RT-qPCR. The levels of MDA, GSH-PX, SOD, CAT and T-AOC were detected by commercial assay kits. Flow cytometry was used to determine the level of intracellular ROS, and immunofluorescence was used to detect the nuclear localization of Nrf2 protein. Briefly, SeMet downregulated the phosphorylation levels of IκBα and p65 proteins and the gene expression levels of IL-1β, IL-6, IL-8 and TNF-α were also decreased. Moreover, the protein and gene expression levels of Nrf2, NQO-1 and HO-1 were upregulated, and the nuclear expression of Nrf2 protein was also promoted, which enhanced the activity of antioxidant enzymes. In conclusion, SeMet protected BMECs from inflammatory injury and oxidative stress induced by K. pneumoniae by inhibiting the NF-κB and activating the Nrf2 signaling pathway.
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http://dx.doi.org/10.1016/j.intimp.2022.109027DOI Listing
July 2022

Case Report: The First Report on Isolation From Corneal Ulcer in a Bulldog.

Front Vet Sci 2022 24;9:934081. Epub 2022 Jun 24.

College of Veterinary Medicine, Yangzhou University, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China.

A 5-year-old castrated male bulldog was diagnosed with a corneal ulcer accompanied by edema and conjunctival hyperemia. Ophthalmic examination and microbiological analysis were performed, and the bacteria were found to be gram-negative and globular. The isolated clone was identified as (MZ579539) MALDI-TOF MS and 16S rDNA sequencing. Antimicrobial susceptibility testing showed that the bacteria were sensitive to tetracycline and chloramphenicol, but resistant to levofloxacin and ciprofloxacin. After a conjunctival flap was placed, tobramycin ophthalmic solution and 5% sodium hyaluronate were administered. Following surgery, the ulcer was effectively controlled, and after 3 weeks, the cornea healed. This is the first case report of a canine corneal ulcer associated with , which should be considered when corneal ulceration or keratitis were suspected.
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http://dx.doi.org/10.3389/fvets.2022.934081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9265251PMC
June 2022

Sequence similarity suggests molecular mimicry-induced cardiovascular symptoms in multisystem inflammatory syndrome in children (MIS-C).

Immunol Lett 2022 Jul 6. Epub 2022 Jul 6.

Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital. Electronic address:

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http://dx.doi.org/10.1016/j.imlet.2022.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259193PMC
July 2022

Correction: Hu et al. Direct Bragg Grating Inscription in Single Mode Step-Index TOPAS/ZEONEX Polymer Optical Fiber Using 520 nm Femtosecond Pulses. 2022, , 1350.

Polymers (Basel) 2022 Jun 29;14(13). Epub 2022 Jun 29.

Department of Electromagnetism and Telecommunication, University of Mons, Boulevard Dolez 31, 7000 Mons, Belgium.

The authors wish to make a change to the published paper [...].
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http://dx.doi.org/10.3390/polym14132640DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268787PMC
June 2022

Neuroinflammation Involved in Diabetes-Related Pain and Itch.

Front Pharmacol 2022 20;13:921612. Epub 2022 Jun 20.

Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China.

Diabetes mellitus (DM) is a global epidemic with increasing incidence, which results in diverse complications, seriously affects the patient quality of life, and brings huge economic burdens to society. Diabetic neuropathy is the most common chronic complication of DM, resulting in neuropathic pain and chronic itch. The precise mechanisms of diabetic neuropathy have not been fully clarified, hindering the exploration of novel therapies for diabetic neuropathy and its terrible symptoms such as diabetic pain and itch. Accumulating evidence suggests that neuroinflammation plays a critical role in the pathophysiologic process of neuropathic pain and chronic itch. Indeed, researchers have currently made significant progress in knowing the role of glial cells and the pro-inflammatory mediators produced from glial cells in the modulation of chronic pain and itch signal processing. Here, we provide an overview of the current understanding of neuroinflammation in contributing to the sensitization of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, we also summarize the inflammation mechanisms that contribute to the pathogenesis of diabetic itch, including activation of glial cells, oxidative stress, and pro-inflammatory factors. Targeting excessive neuroinflammation may provide potential and effective therapies for the treatment of chronic neuropathic pain and itch in DM.
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http://dx.doi.org/10.3389/fphar.2022.921612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251344PMC
June 2022

Self-Assembled Metallacage with Second Near-Infrared Aggregation-Induced Emission for Enhanced Multimodal Theranostics.

J Am Chem Soc 2022 Jul 5;144(28):12825-12833. Epub 2022 Jul 5.

Center for AIE Research, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060, China.

The construction of supramolecular coordination complexes (SCCs) featuring prominent cancer theranostic functions is an appealing yet significantly challenging task. In this study, we rationally designed and facilely constructed a prism-like metallacage C-DTTP with efficient fluorescence emission in the second near-infrared (NIR-II) region through the assembly of an aggregation-induced emission-active four-arm ligand with 90° Pt acceptors Pt(PEt)(OTf). C-DTTP held the longest maximum emission wavelength (1005 nm) compared with those previously reported SCCs up to now and exhibited both a high photothermal conversion efficiency (39.3%) and significantly superior reactive oxygen species generation behavior to the precursor ligand. In vitro and in vivo assessments demonstrated that the metallacage-loaded nanoparticles with excellent biocompatibility and stability were capable of simultaneously affording precise tumor diagnosis and complete tumor elimination by means of NIR-II fluorescence/photothermal dual imaging-guided photodynamic/photothermal synergistic therapy.
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http://dx.doi.org/10.1021/jacs.2c03895DOI Listing
July 2022

Selenomethionine alleviates NF-κB-mediated inflammation in bovine mammary epithelial cells induced by Escherichia coli by enhancing autophagy.

Int Immunopharmacol 2022 Jul 1;110:108989. Epub 2022 Jul 1.

College of Veterinary Medicine, Yangzhou University; Jiangsu Co-innovation Center for the Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009 Jiangsu, China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou, 225009 Jiangsu, China. Electronic address:

Autophagy is crucial for the maintenance of homeostasis under stimuli related to infection. Selenium (Se) plays variable roles in defence against infection and Selenomethionine (Se-Met) is a common Se supplementation. This study aimed to understand whether Se-Met could regulate the nuclear factor-kappa B (NF-κB) signaling pathway through autophagy. Mammary alveolar cell-T (MAC-T) was challenged with Escherichia coli (E. coli). Western blotting and real-time quantitative PCR (RT-qPCR) were used to detect the protein expression and mRNA expression of cytokines. Immunofluorescence assays were performed to observe the expression of intracellular LC3. The results showed that E. coli inhibited autophagy by decreasing the LC3-Ⅱ protein levels, and the Atg5 and Beclin1 protein levels were increased after 4 h. Infection also decreased the number of LC3 puncta. E. coli increased the phosphorylation of p65 and IκBα protein. Concomitantly, the levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α mRNA increased at 3 and 4 h post-infection. We further explored the regulatory role of autophagy on NF-κB-mediated inflammation with autophagy modulators and shAtg5. The results indicated that the autophagy activator reduced the phosphorylation of p65 and IκBα and the mRNA expression of IL-1β, IL-6, IL-8 and TNF-α. Additionally, activating autophagy weakened the adhesion to MAC-T of E. coli. Autophagy inhibitors exacerbated NF-κB-mediated inflammation and strengthened the adhesion of E. coli to cells. We then examined the effects of Se-Met on NF-κB-mediated inflammation through autophagy. The data suggested that Se-Met enhanced LC3-II expression, inhibited the E. coli-induced phosphorylation of p65 and IκBα, and suppressed the adhesion ability of E. coli to MAC-T and that the effects of Se-Met in attenuating NF-κB-mediated inflammation were partially blocked by an autophagy inhibitor. In summary, Se-Met alleviated NF-κB-mediated inflammation induced by E. coli by enhancing autophagy in bovine mammary epithelial cells.
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http://dx.doi.org/10.1016/j.intimp.2022.108989DOI Listing
July 2022

Experimental demonstration of high-rate discrete-modulated continuous-variable quantum key distribution system.

Opt Lett 2022 Jul;47(13):3307-3310

A high-rate continuous-variable quantum key distribution (CV-QKD) system based on high-order discrete modulation is experimentally investigated. With the help of the novel system scheme, effective digital signal processing (DSP) algorithms and advanced analytical security proof methods, the transmission results of 5.059 km, 10.314 km, 24.490 km, and 50.592 km are achieved for 1 GBaud optimized quantum signals. Correspondingly, the asymptotic secret key rates (SKRs) are 292.185 Mbps, 156.246 Mbps, 50.491 Mbps, and 7.495 Mbps for discrete Gaussian (DG) 64QAM, and 328.297 Mbps, 176.089 Mbps, 51.304 Mbps, and 9.193 Mbps for DG 256QAM, respectively. Under the same parameters, the achieved SKRs of DG 256QAM is almost same as ideal Gaussian modulation. In this case, the demonstrated high-rate discrete-modulated CV-QKD system has the application potential for high-speed security communication under tens of kilometers.
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http://dx.doi.org/10.1364/OL.456978DOI Listing
July 2022

Genome-Wide Identification and Characterization of Genes in Reveals Their Potential Role in Trichome Development.

Front Genet 2022 8;13:921096. Epub 2022 Jun 8.

State Key Laboratory of Cotton Biology /Institute of Cotton Research, Chinese Academy of Agricultural Science, Anyang, China.

Trichomes protect plants against insects, microbes, herbivores, and abiotic damages and assist seed dispersal. The function of genes have been found to be involved in the trichome development but the research on the underlying genetic and molecular mechanisms are extremely limited. Herein, genome wide identification and characterization of genes was performed. In total, 26 family members were identified in Gossypium species. Phylogenetic analysis, structural characteristics, and synteny analysis of s showed the conserved evolution relationships of . The promoter analysis of genes revealed hormone, stress, and development-related cis-elements. Gene ontology (GO) enrichment analysis showed that the genes were largely related to biological regulation, developmental process, multicellular organismal process. Protein-protein interaction analysis predicted several trichome development related proteins (SIM, LGO, and GRL) directly interacting with genes. Further, nine putative -miRNAs were also identified, targeting genes. RNA-Seq data of (with trichomes) and (with no trichomes) was used to perform the co-expression network analysis. was identified as a hub gene in a co-expression network analysis. RT-qPCR of gene in different tissues suggests that this gene has higher expressions in the petiole and might be a key candidate involved in the trichome development. Virus induced gene silencing of confirms its role in trichome development and elongation. Current results provide proofs of the possible role of genes and provide preliminary information for further studies of functions in trichome development.
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http://dx.doi.org/10.3389/fgene.2022.921096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213653PMC
June 2022
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