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1.
Nanoscale Adv ; 6(18): 4522-4544, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39263397

ABSTRACT

As a type of innovative device, triboelectric nanogenerators (TENGs) are capable of converting mechanical energy into electrical energy through the triboelectric effect. Based on the working mechanism, the output performance of TENGs heavily relies on the triboelectric materials used. The modification of triboelectric materials is the most efficient way to improve the output performance of TENGs. Herein, this review focuses on the recent progress in triboelectric material design for high-performance TENGs. First, the basic theory of TENGs is introduced. Second, the relationship between the triboelectric materials and the output performance of TENGs is summarized in detail based on a theoretical model of the triboelectric charge dynamic equilibrium. Furthermore, the relevant strategies are analyzed in detail. Finally, challenges and shortcomings of the triboelectric materials for high-performance TENGs are discussed. This review provides a basis for the research status and future development of triboelectric materials.

2.
Plants (Basel) ; 13(18)2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39339520

ABSTRACT

To investigate the genetic basis of processing quality- and yield-related traits in bread wheat (Triticum aestivum L., AABBDD), a systematic analysis of wheat processing quality- and yield-related traits based on genome-wide association studies (GWASs) of 285 regional test lines of wheat from Hebei province, China, was conducted. A total of 87 quantitative trait loci (QTL), including twenty-one for water absorption (WA), four for wet gluten content, eight for grain protein content, seventeen for dough stability time (DST), thirteen for extension area (EA), twelve for maximum resistance (MR), five for thousand-grain weight (TGW), one for grain length, and six for grain width were identified. These QTL harbored 188 significant single-nucleotide polymorphisms (SNPs). Twenty-five SNPs were simultaneously associated with multiple traits. Notably, the SNP AX-111015470 on chromosome 1A was associated with DST, EA, and MR. SNPs AX-111917292 and AX-109124553 on chromosome 5D were associated with wheat WA and TGW. Most processing quality-related QTL and seven grain yield-related QTL identified in this study were newly discovered. Among the surveyed accessions, 18 rare superior alleles were identified. This study identified significant QTL associated with quality-related and yield-related traits in wheat, and some of them showed pleiotropic effects. This study will facilitate molecular designs that seek to achieve synergistic improvements of wheat quality and yield.

3.
Research (Wash D C) ; 7: 0437, 2024.
Article in English | MEDLINE | ID: mdl-39140092

ABSTRACT

Direct current triboelectric nanogenerators (DC-TENGs) are a groundbreaking technology to capture micromechanical energy from the natural environment, which is crucial for directly powering sensor networks. However, the research bottleneck in enhancing the triboelectric electrification capability and charge storage capability of dielectrics has hindered the overall performance breakthroughs of the DC-TENG. Here, a field emission model-based DC-TENG (FEM-TENG) is proposed, inspired by lightning rods. The enhanced local electric field between dielectric materials and electrodes induces strong electron tunneling, which improves charge neutralization on the surface of materials and their internal charge storage space, thereby utilizing the dielectric volume effect effectively and strengthening triboelectricity. Guided by the field emission model, the FEM-TENG with a historic crest factor of 1.00375 achieves a groundbreaking record of an average power density of 16.061 W m-2 Hz-1 (1,591 W m-3 Hz-1), which is 5.36-fold of the latest DC-TENG. In particular, the FEM-TENG with high durability (100%) truly realizes the collection of breeze energy and continuously drives 50 thermohygrometers. Four additional applications exemplify the FEM-TENG, enabling comprehensive sensing of land, water, and air. This work proposes a paradigm strategy for the in-depth utilization of dielectric films, aiming to enhance the output power of DC-TENGs.

4.
Infect Dis Poverty ; 13(1): 56, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090685

ABSTRACT

BACKGROUND: Non-pharmaceutical measures and travel restrictions have halted the spread of coronavirus disease 2019 (COVID-19) and influenza. Nonetheless, with COVID-19 restrictions lifted, an unanticipated outbreak of the influenza B/Victoria virus in late 2021 and another influenza H3N2 outbreak in mid-2022 occurred in Guangdong, southern China. The mechanism underlying this phenomenon remains unknown. To better prepare for potential influenza outbreaks during COVID-19 pandemic, we studied the molecular epidemiology and phylogenetics of influenza A(H3N2) and B/Victoria that circulated during the COVID-19 pandemic in this region. METHODS: From January 1, 2018 to December 31, 2022, we collected throat swabs from 173,401 patients in Guangdong who had acute respiratory tract infections. Influenza viruses in the samples were tested using reverse transcription-polymerase chain reaction, followed by subtype identification and sequencing of hemagglutinin (HA) and neuraminidase (NA) genes. Phylogenetic and genetic diversity analyses were performed on both genes from 403 samples. A rigorous molecular clock was aligned with the phylogenetic tree to measure the rate of viral evolution and the root-to-tip distance within strains in different years was assessed using regression curve models to determine the correlation. RESULTS: During the early period of COVID-19 control, various influenza viruses were nearly undetectable in respiratory specimens. When control measures were relaxed in January 2020, the influenza infection rate peaked at 4.94% (39/789) in December 2021, with the influenza B/Victoria accounting for 87.18% (34/39) of the total influenza cases. Six months later, the influenza infection rate again increased and peaked at 11.34% (255/2248) in June 2022; influenza A/H3N2 accounted for 94.51% (241/255) of the total influenza cases in autumn 2022. The diverse geographic distribution of HA genes of B/Victoria and A/H3N2 had drastically reduced, and most strains originated from China. The rate of B/Victoria HA evolution (3.11 × 10-3, P < 0.05) was 1.7 times faster than before the COVID-19 outbreak (1.80 × 10-3, P < 0.05). Likewise, the H3N2 HA gene's evolution rate was 7.96 × 10-3 (P < 0.05), which is 2.1 times faster than the strains' pre-COVID-19 evolution rate (3.81 × 10-3, P < 0.05). CONCLUSIONS: Despite the extraordinarily low detection rate of influenza infection, concealed influenza transmission may occur between individuals during strict COVID-19 control. This ultimately leads to the accumulation of viral mutations and accelerated evolution of H3N2 and B/Victoria viruses. Monitoring the evolution of influenza may provide insights and alerts regarding potential epidemics in the future.


Subject(s)
COVID-19 , Influenza A Virus, H3N2 Subtype , Influenza B virus , Influenza, Human , Molecular Epidemiology , Phylogeny , SARS-CoV-2 , Humans , COVID-19/epidemiology , COVID-19/virology , COVID-19/transmission , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H3N2 Subtype/isolation & purification , China/epidemiology , Influenza, Human/epidemiology , Influenza, Human/virology , Influenza B virus/genetics , Influenza B virus/isolation & purification , Influenza B virus/classification , SARS-CoV-2/genetics , Adult , Middle Aged , Male , Female , Pandemics , Young Adult , Aged , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Adolescent , Neuraminidase/genetics , Child , Child, Preschool
5.
ACS Appl Mater Interfaces ; 16(34): 44655-44664, 2024 Aug 28.
Article in English | MEDLINE | ID: mdl-39151073

ABSTRACT

The energy conversion efficiency of conventional binary dielectric triboelectric nanogenerators is not satisfactory due to the limitations of material selection and triboelectrification, which motivates the design of more efficient multicomponent structures to reveal the charge accumulation mechanism for improving the energy conversion efficiency. Herein, a rotating quaternary dielectric triboelectric nanogenerator (Q-TENG) is designed to construct a self-powered system integrating illumination, sensing, and electrochemical decolorization. Through the equivalent capacitance model, the mechanisms for charge generation, transfer, and accumulation in a Q-TENG are elucidated to achieve efficient matching of quaternary dielectric materials and high output performance. At a wind speed of 3.5 m s-1, the peak power density of the Q-TENG reaches 44.94 W m-2, setting a new record for a wind-driven TENG. A 5 ppm solution of methyl orange is completely degraded by the wind-driven Q-TENG in <6 h. This work not only guides the direction for constructing more efficient TENG systems but also promotes the practical development of self-powered electrochemical systems.

6.
Front Cell Infect Microbiol ; 14: 1399782, 2024.
Article in English | MEDLINE | ID: mdl-39027137

ABSTRACT

Background: Accurate detection of influenza virus in clinical samples requires correct execution of all aspects of the detection test. If the viral load in a sample is below the detection limit, a false negative result may be obtained. To overcome this issue, we developed a modified transport medium (MTM) for clinical sample transportation to increase viral detection sensitivity. Method: We first validated the MTM using laboratory-stocked influenza A viruses (IAVs: H1N1, H3N2, H7N3, H9N2) and influenza B viruses (IBVs: Yamagata, Victoria). We also tested clinical samples. A total of 110 patients were enrolled and a pair of samples were collected to determine the sensitivity of real-time polymerase chain reaction (RT-PCR) following MTM treatment. Result: After 24 h culturing in MTM, the viral loads were increased, represented by a 10-fold increase in detection sensitivity for H1N1, H9N2, and IBVs, a 100-fold increase for H3N2, and a 1,000-fold increase for H7N3. We further tested the effects of MTM on 19 IAV and 11 IBV stored clinical samples. The RT-PCR results showed that the positive detection rate of IAV samples increased from 63.16% (12/19) without MTM culturing to 78.95% (15/19) after 48 h culturing, and finally 89.47% (17/19) after 72 h culturing. MTM treatment of IBV clinical samples also increased the positive detection rate from 36.36% (4/11, 0 h) to 63.64% (7/11, 48 h) to 72.73% (8/11, 72 h). For clinical samples detected by RT-PCR, MTM outperformed other transport mediums in terms of viral detection rate (11.81% increase, P=0.007). Conclusion: Our results demonstrated that the use of MTM for clinical applications can increase detection sensitivity, thus facilitating the accurate diagnosis of influenza infection.


Subject(s)
Influenza A virus , Influenza B virus , Influenza, Human , Sensitivity and Specificity , Specimen Handling , Viral Load , Humans , Influenza, Human/diagnosis , Influenza, Human/virology , Influenza A virus/isolation & purification , Influenza A virus/genetics , Influenza B virus/isolation & purification , Influenza B virus/genetics , Specimen Handling/methods , Real-Time Polymerase Chain Reaction/methods , Culture Media/chemistry , Middle Aged , Female , Adult , Male
7.
Int J Mol Med ; 54(3)2024 Sep.
Article in English | MEDLINE | ID: mdl-38994767

ABSTRACT

Following the publication of the above article, the authors contacted the Editorial Office to explain that they had identified a pair of duplicate images in the control (Vehicle) group of mouse images in Fig. 1A on p. 1792. Specifically, the same image (corresponding correctly to the 'Day 5' experiment) was inadvertently chosen to represent the cutaneous manifestations of mice in the Vehicle group on 'Day 3' and 'Day 5' in Fig. 1A. This error arose as a consequence of repetitive application and duplication procedures within the image set, resulting in the inadvertent reuse of the same photo. Additionally, due to minimal alterations observed in the skin condition of mice from the control group following treatment, each mouse exhibited a similar appearance; this similarity further contributed to the delayed identification of this error during the paper revision stage. Consequently, this duplication of the same image was made as a result of insufficient scrutiny. The revised version of Fig. 1, showing the correct image for the 'Day 3' experiment in Fig. 1A, is shown on the next page. The authors can confirm that the error associated with the assembly of this figure did not have any significant impact on either the results or the conclusions reported in this study, and all the authors agree with the publication of this Corrigendum. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this; furthermore, they apologize to the readership of the Journal for any inconvenience caused. [International Journal of Molecular Medicine 43: 1789­1805, 2019; DOI: 10.3892/ijmm.2019.4098].

8.
J Am Chem Soc ; 146(28): 18967-18978, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38973592

ABSTRACT

Platensilin, platensimycin, and platencin are potent inhibitors of ß-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent-pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels-Alder reaction to prepare the common ent-pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom-transfer hydrogenation and subsequent Cu-catalyzed carbenoid C-H insertion afford platensilin. Furthermore, the intramolecular Diels-Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent-pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC80 = 0.0625 µg/mL) against S. aureus compared to platensimycin.


Subject(s)
Adamantane , Aminobenzoates , Aminophenols , Anilides , Polycyclic Compounds , Aminophenols/chemistry , Aminophenols/pharmacology , Aminophenols/chemical synthesis , Polycyclic Compounds/chemistry , Polycyclic Compounds/pharmacology , Polycyclic Compounds/chemical synthesis , Adamantane/chemistry , Adamantane/pharmacology , Adamantane/chemical synthesis , Adamantane/analogs & derivatives , Anilides/pharmacology , Anilides/chemistry , Anilides/chemical synthesis , Aminobenzoates/pharmacology , Aminobenzoates/chemistry , Aminobenzoates/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Staphylococcus aureus/drug effects , Molecular Structure , Cycloaddition Reaction , Microbial Sensitivity Tests , Stereoisomerism , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry
9.
China CDC Wkly ; 6(21): 469-477, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38854464

ABSTRACT

Introduction: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrates increased transmissibility compared to earlier strains, contributing to a significant number of fatalities in Hong Kong Special Administrative Region (HKSAR), China. Adequate medical resources and medications are essential in mitigating these deaths. This study evaluates the effects of supplementary resources from the Chinese mainland during the fifth wave of the pandemic in HKSAR. Methods: Vector autoregression (VAR) was employed to analyze data from the Oxford coronavirus disease 2019 (COVID-19) Government Response Tracker to assess the effectiveness of control measures during five waves of the pandemic in HKSAR. Additionally, a transmission dynamics model was created to investigate the influence of supplementary medical resources from the Chinese mainland and oral medications on mortality. Results: In the initial four waves, workplace closures, restrictions on public events, international travel bans, and shielding the elderly significantly influenced pandemic management. Contrarily, during the fifth wave, these measures showed no notable effects. When comparing a situation without extra medical resources or COVID-19 oral medication, there was a 17.7% decrease in COVID-19 fatalities with mainland medical resources and an additional 10.2% reduction with oral medications. Together, they contributed to a 26.6% decline in fatalities. Discussion: With the rapid spread of the virus, regional reallocation of medical resources may reduce mortality even when the local healthcare system is overstretched.

10.
Commun Biol ; 7(1): 630, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38789577

ABSTRACT

Therapeutic agents targeting cytokine-cytokine receptor (CK-CKR) interactions lead to the disruption in cellular signaling and are effective in treating many diseases including tumors. However, a lack of universal and quick access to annotated structural surface regions on CK/CKR has limited the progress of a structure-driven approach in developing targeted macromolecular drugs and precision medicine therapeutics. Herein we develop CytoSIP (Single nucleotide polymorphisms (SNPs), Interface, and Phenotype), a rich internet application based on a database of atomic interactions around hotspots in experimentally determined CK/CKR structural complexes. CytoSIP contains: (1) SNPs on CK/CKR; (2) interactions involving CK/CKR domains, including CK/CKR interfaces, oligomeric interfaces, epitopes, or other drug targeting surfaces; and (3) diseases and phenotypes associated with CK/CKR or SNPs. The database framework introduces a unique tri-level SIP data model to bridge genetic variants (atomic level) to disease phenotypes (organism level) using protein structure (complexes) as an underlying framework (molecule level). Customized screening tools are implemented to retrieve relevant CK/CKR subset, which reduces the time and resources needed to interrogate large datasets involving CK/CKR surface hotspots and associated pathologies. CytoSIP portal is publicly accessible at https://CytoSIP.biocloud.top , facilitating the panoramic investigation of the context-dependent crosstalk between CK/CKR and the development of targeted therapeutic agents.


Subject(s)
Cytokines , Polymorphism, Single Nucleotide , Receptors, Cytokine , Humans , Receptors, Cytokine/metabolism , Receptors, Cytokine/chemistry , Receptors, Cytokine/genetics , Cytokines/metabolism , Cytokines/genetics , Cytokines/chemistry , Databases, Protein , Phenotype
11.
Appl Microbiol Biotechnol ; 108(1): 298, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607493

ABSTRACT

Radopholus similis is a destructive, migratory, and endophytoparasitic nematode. It has two morphologically indistinguishable pathotypes (or physiological races): banana and citrus pathotypes. At present, the only reliable method to differentiate the two pathotypes is testing the infestation and parasitism of nematodes on Citrus spp. via inoculation. However, differences in inoculation methods and conditions adopted by different researchers complicate obtaining consistent results. In this study, the parasitism and pathogenicity of 10 R. similis populations on rough lemon (Citrus limon) seedlings and the tropism and invasion of rough lemon roots were tested. It revealed that populations SWK, GJ, FZ, GZ, DBSR, and YJ were citrus pathotypes, which showed parasitism and pathogenicity on rough lemon and could invade rough lemon roots, whereas populations XIN, ML, HN6, and HL were banana pathotypes, having no parasitism and pathogenicity on rough lemon and they did not invade the rough lemon roots. Four pectate lyase genes (Rs-pel-2, Rs-pel-3, Rs-pel-4, and Rs-pel-5) belonging to the Class III family from these populations were amplified and analysed. The gene Rs-pel-3 could be amplified from six citrus pathotype populations and was stably expressed in the four developmental stages of the nematode, whereas it could not be amplified from the four banana pathotypes. Rs-pel-3 expression may be related to the parasitism and pathogenicity of R. similis on rough lemon. Hence, it can be used as a molecular marker to distinguish between banana and citrus pathotypes and as a target gene for the molecular identification of these two pathotypes. KEY POINTS: • Four pectate lyase genes (Rs-pels) from Radopholus similis were cloned and analysed. • The expression of Rs-pels is different in two pathotypes of Radopholus similis. • A molecular identification method for two pathotypes of Radopholus similis using pectate lyase gene Rs-pel-3 as the target gene was established.


Subject(s)
Tylenchoidea , Animals , Tylenchoidea/genetics , Plant Roots , Polysaccharide-Lyases/genetics , Seedlings
12.
MedComm (2020) ; 5(4): e518, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38525111

ABSTRACT

Perineural invasion (PNI) leads to the poor prognosis of head and neck squamous cancer (HNSCC) patients, but the mechanism of PNI remains unclear. Dickkopf-1 (DKK1), a secretory protein in the Wnt signaling pathway, was found indeed upregulated in HNSCC cells and tissues. Higher expression of DKK1 was statistically relevant to T stage, N stage, PNI, and poor prognosis of HNSCC. DKK1 overexpression enhanced the migration abilities of cancer cells. Moreover, DKK1-overexpressing cancer cells promoted cancer cells invasion of peripheral nerves in vitro and in vivo. Mechanistically, DKK1 could promote the PI3K-AKT signaling pathway. The migration abilities of neuroblastoma cells, which were enhanced by DKK1-overexpressing HNSCC cell lines, could be reversed by an inhibitor of Akt (MK2206). The association of DKK1 with PNI was also confirmed in HNSCC samples. Variables, including T stage, N stage, DKK1 expression, and PNI, were used to establish a nomogram to predict the survival probability and disease-free probability at 3 and 5 years. In summary, DKK1 can promote the PI3K-AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.

13.
Adv Mater ; 36(21): e2313953, 2024 May.
Article in English | MEDLINE | ID: mdl-38400833

ABSTRACT

Engineered bacteria are widely used in cancer treatment because live facultative/obligate anaerobes can selectively proliferate at tumor sites and reach hypoxic regions, thereby causing nutritional competition, enhancing immune responses, and producing anticancer microbial agents in situ to suppress tumor growth. Despite the unique advantages of bacteria-based cancer biotherapy, the insufficient treatment efficiency limits its application in the complete ablation of malignant tumors. The combination of nanomedicine and engineered bacteria has attracted increasing attention owing to their striking synergistic effects in cancer treatment. Engineered bacteria that function as natural vehicles can effectively deliver nanomedicines to tumor sites. Moreover, bacteria provide an opportunity to enhance nanomedicines by modulating the TME and producing substrates to support nanomedicine-mediated anticancer reactions. Nanomedicine exhibits excellent optical, magnetic, acoustic, and catalytic properties, and plays an important role in promoting bacteria-mediated biotherapies. The synergistic anticancer effects of engineered bacteria and nanomedicines in cancer therapy are comprehensively summarized in this review. Attention is paid not only to the fabrication of nanobiohybrid composites, but also to the interpromotion mechanism between engineered bacteria and nanomedicine in cancer therapy. Additionally, recent advances in engineered bacteria-synergized multimodal cancer therapies are highlighted.


Subject(s)
Nanomedicine , Neoplasms , Neoplasms/therapy , Neoplasms/drug therapy , Humans , Nanomedicine/methods , Animals , Bacteria , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
14.
BMC Bioinformatics ; 25(1): 29, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38233783

ABSTRACT

The impairment of sperm maturation is one of the major pathogenic factors in male subfertility, a serious medical and social problem affecting millions of global couples. Regrettably, the existing research on sperm maturation is slow, limited, and fragmented, largely attributable to the lack of a global molecular view. To fill the data gap, we newly established a database, namely the Sperm Maturation Database (SperMD, http://bio-add.org/SperMD ). SperMD integrates heterogeneous multi-omics data (170 transcriptomes, 91 proteomes, and five human metabolomes) to illustrate the transcriptional, translational, and metabolic manifestations during the entire lifespan of sperm maturation. These data involve almost all crucial scenarios related to sperm maturation, including the tissue components of the epididymal microenvironment, cell constituents of tissues, different pathological states, and so on. To the best of our knowledge, SperMD could be one of the limited repositories that provide focused and comprehensive information on sperm maturation. Easy-to-use web services are also implemented to enhance the experience of data retrieval and molecular comparison between humans and mice. Furthermore, the manuscript illustrates an example application demonstrated to systematically characterize novel gene functions in sperm maturation. Nevertheless, SperMD undertakes the endeavor to integrate the islanding omics data, offering a panoramic molecular view of how the spermatozoa gain full reproductive abilities. It will serve as a valuable resource for the systematic exploration of sperm maturation and for prioritizing the biomarkers and targets for precise diagnosis and therapy of male subfertility.


Subject(s)
Infertility, Male , Sperm Maturation , Male , Humans , Animals , Mice , Sperm Maturation/genetics , Semen , Spermatozoa/metabolism , Epididymis/metabolism , Infertility, Male/metabolism
15.
Protein Expr Purif ; 216: 106431, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38184161

ABSTRACT

Human pepsinogens (mainly pepsinogen I and pepsinogen II) are the major inactive precursor forms of the digestive enzyme pepsin which play a crucial role in protein digestion. The levels and ratios of human pepsinogens have demonstrated potential as diagnostic biomarkers for gastrointestinal diseases, particularly gastric cancer. Nanobodies are promising tools for the treatment and diagnosis of diseases, owing to their unique recognition properties. In this study, recombinant human pepsinogens proteins were expressed and purified as immunized antigens. We constructed a VHH phage library and identified several nanobodies via phage display bio-panning. We determined the binding potency and cross-reactivity of these nanobodies. Our study provides technical support for developing immunodiagnostic reagents targeting human pepsinogens.


Subject(s)
Pepsinogens , Single-Domain Antibodies , Humans , Pepsinogens/metabolism , Single-Domain Antibodies/genetics , Gastric Mucosa/metabolism , Pepsin A
16.
Hum Reprod ; 39(2): 310-325, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38011909

ABSTRACT

STUDY QUESTION: What is the mechanism behind cryoinjury in human sperm, particularly concerning the interplay between reactive oxygen species (ROS) and autophagy, and how does it subsequently affect sperm fate? SUMMARY ANSWER: The freeze-thaw operation induces oxidative stress by generating abundant ROS, which impairs sperm motility and activates autophagy, ultimately guiding the sperm toward programmed cell death such as apoptosis and necrosis, as well as triggering premature capacitation. WHAT IS KNOWN ALREADY: Both ROS-induced oxidative stress and autophagy are thought to exert an influence on the quality of frozen-thawed sperm. STUDY DESIGN, SIZE, DURATION: Overall, 84 semen specimens were collected from young healthy fertile males, with careful quality evaluation. The specimens were split into three groups to investigate the ROS-induced cryoinjury: normal control without any treatment, sperm treated with 0.5 mM hydrogen peroxide (H2O2) for 1 h, and sperm thawed following cryopreservation. Samples from 48 individuals underwent computer-assisted human sperm analysis (CASA) to evaluate sperm quality in response to the treatments. Semen samples from three donors were analyzed for changes in the sperm proteome after H2O2 treatment, and another set of samples from three donors were analyzed for changes following the freeze-thaw process. The other 30 samples were used for fluorescence-staining and western blotting. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm motility parameters, including progressive motility (PR %) and total motility (PR + NP %), were evaluated using the CASA system on a minimum of 200 spermatozoa. The proteomic profiles were determined with label-free mass spectrometry (MS/MS) and protein identification was performed via ion search against the NCBI human database. Subsequently, comprehensive bioinformatics was applied to detect significant proteomic changes and functional enrichment. Fluorescence-staining and western blot analyses were also conducted to confirm the proteomic changes on selected key proteins. The ROS level was measured using 2',7'-dichlorodihydrofluorescein diacetate labeling and the abundance of bioactive mitochondria was determined by evaluating the inner mitochondrial membrane potential (MMP) level. Molecular behaviors of sequestosome-1 (p62 or SQSTM1) and microtubule-associated proteins 1A/1B light chain 3 (LC3) were monitored to evaluate the state of apoptosis in human sperm. Fluorescent probes oxazole yellow (YO-PRO-1) and propidium iodide (PI) were utilized to monitor programmed cell death, namely apoptosis and necrosis. Additionally, gradient concentrations of antioxidant coenzyme Q10 (CoQ10) were introduced to suppress ROS impacts on sperm. MAIN RESULTS AND THE ROLE OF CHANCE: The CASA analysis revealed a significant decrease in sperm motility for both the H2O2-treatment and freeze-thaw groups. Fluorescence staining showed that high ROS levels were produced in the treated sperm and the MMPs were largely reduced. The introduction of CoQ10 at concentrations of 20 and 30 µM resulted in a significant rescue of progressive motility (P < 0.05). The result suggested that excessive ROS could be the major cause of sperm motility impairment, likely by damaging mitochondrial energy generation. Autophagy was significantly activated in sperm when they were under oxidative stress, as evidenced by the upregulation of p62 and the increased conversion of LC3 as well as the upregulation of several autophagy-related proteins, such as charged multivesicular body protein 2a, mitochondrial import receptor subunit TOM22 homolog, and WD repeat domain phosphoinositide-interacting protein 2. Additionally, fluorescent staining indicated the occurrence of apoptosis and necrosis in both H2O2-treated sperm and post-thaw sperm. The cell death process can be suppressed when CoQ10 is introduced, which consolidates the view that ROS could be the major contributor to sperm cryoinjury. The freeze-thaw process could also initiate sperm premature capacitation, demonstrated by the prominent increase in tyrosine phosphorylated proteins, verified with anti-phosphotyrosine antibody and immunofluorescence assays. The upregulation of capacitation-related proteins, such as hyaluronidase 3 and Folate receptor alpha, supported this finding. LARGE SCALE DATA: The data underlying this article are available in the article and its online supplementary material. LIMITATIONS, REASONS FOR CAUTION: The semen samples were obtained exclusively from young, healthy, and fertile males with progressive motility exceeding 60%, which might overemphasize the positive effects while possibly neglecting the negative impacts of cryoinjury. Additionally, the H2O2 treatment conditions in this study may not precisely mimic the oxidative stress experienced by sperm after thawing from cryopreservation, potentially resulting in the omission of certain molecular alterations. WIDER IMPLICATIONS OF THE FINDINGS: This study provides substantial proteomic data for a comprehensive and deeper understanding of the impact of cryopreservation on sperm quality. It will facilitate the design of optimal protocols for utilizing cryopreserved sperm to improve applications, such as ART, and help resolve various adverse situations caused by chemotherapy, radiotherapy, and surgery. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Major Innovation Project of Research Institute of National Health Commission (#2022GJZD01-3) and the National Key R&D Program of China (#2018YFC1003600). All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Semen Preservation , Semen , Male , Humans , Reactive Oxygen Species/metabolism , Semen/metabolism , Sperm Motility , Hydrogen Peroxide , Proteomics , Tandem Mass Spectrometry , Spermatozoa/metabolism , Oxidative Stress , Cryopreservation/methods , Semen Preservation/adverse effects , Semen Preservation/methods , Necrosis/metabolism
17.
Adv Healthc Mater ; 13(11): e2303643, 2024 04.
Article in English | MEDLINE | ID: mdl-38115727

ABSTRACT

Photodynamic therapy (PDT) with aggregation-induced emission (AIE) photosensitizers (PSs) is a promising therapeutic strategy to achieve better anticancer results. However, eradicating solid tumors completely by PDT alone can be difficult owing to the inherent drawbacks of this treatment, and the combination of PDT with other therapeutic modalities provides opportunities to achieve cooperative enhancement interactions among various treatments. Herein, this work presents the construction of a biocompatible nanocomposite, namely CaO2@DOX@ZIF@ASQ, featuring light-responsive reactive oxygen species (ROS) generation and tumor-targeting oxygen and hydrogen peroxide discharge, as well as controlled doxorubicin (DOX) and copper ion release, thus allowing the combined PDT/CT/CDT effect by AIE PS-enhanced PDT, DOX-based chemotherapy (CT), and copper-involved Fenton-like reaction-driven chemodynamic therapy (CDT). In vitro and in vivo studies verify that the generation of both ROS and O2 by this nanomedicine, stimulated by light, exhibits superior anticancer efficacy, alleviating tumor hypoxia and achieving synergistic PDT/CT/CDT therapeutic effect. This multifunctional nanomedicine remarkably suppresses the tumor growth with minimized systemic toxicity, providing a new strategy for constructing multimodal PDT/CT/CDT therapeutic systems to overcome hypoxia limitations, and potentially increase the antitumor efficacy at lower doses of PSs and chemotherapeutic drugs, thus minimizing potential toxicity to non-malignant tissues.


Subject(s)
Doxorubicin , Nanomedicine , Photochemotherapy , Photosensitizing Agents , Reactive Oxygen Species , Photochemotherapy/methods , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Animals , Doxorubicin/pharmacology , Doxorubicin/chemistry , Humans , Reactive Oxygen Species/metabolism , Nanomedicine/methods , Mice , Cell Line, Tumor , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Mice, Inbred BALB C , Female , Copper/chemistry , Copper/pharmacology , Mice, Nude
18.
BMC Med Educ ; 23(1): 852, 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37946176

ABSTRACT

Medical AI has transformed modern medicine and created a new environment for future doctors. However, medical education has failed to keep pace with these advances, and it is essential to provide systematic education on medical AI to current medical undergraduate and postgraduate students. To address this issue, our study utilized the Unified Theory of Acceptance and Use of Technology model to identify key factors that influence the acceptance and intention to use medical AI. We collected data from 1,243 undergraduate and postgraduate students from 13 universities and 33 hospitals, and 54.3% reported prior experience using medical AI. Our findings indicated that medical postgraduate students have a higher level of awareness in using medical AI than undergraduate students. The intention to use medical AI is positively associated with factors such as performance expectancy, habit, hedonic motivation, and trust. Therefore, future medical education should prioritize promoting students' performance in training, and courses should be designed to be both easy to learn and engaging, ensuring that students are equipped with the necessary skills to succeed in their future medical careers.


Subject(s)
Education, Medical, Undergraduate , Education, Medical , Students, Medical , Humans , Curriculum , Perception
19.
Pak J Med Sci ; 39(4): 1003-1007, 2023.
Article in English | MEDLINE | ID: mdl-37492300

ABSTRACT

Objective: To analyze the value of combined detection of tumor markers, neutrophil to lymphocyte ratio (NLR), D-dimer and T lymphocyte in the diagnosis of colon cancer. Methods: This is a retrospective study. A total of 80 patients with colon cancer and 80 patients with benign colon mass admitted to Baoding NO.1 Central Hospital from June 10, 2021 to December 10, 2022 were divided into the study group and the control group. Further comparison was performed on the tumor markers, NLR, D-dimer and T-lymphocyte levels between the two groups, associated with the comparison of corresponding levels of colon cancer at different stages. In addition, correlation analysis was carried out focusing on the above indicators with colon cancer. Results: Carcinoembryonic antigen (CEA), CA199, NLR, D-dimer and CD8+ cell count levels in the study group were significantly higher than those in the control group, while CD4+ cell count and CD4+/CD8+ ratio were obviously lower (P<0.05). Among I-IV colon cancer, the highest levels of CEA, CA199, NLR, D-dimer, CD4+ and CD4+/CD8+ ratio were found in patients with Stage-IV colon cancer, while the level of CD8+ was the lowest (P<0.05). Correlation analysis indicated that CEA, CA199, NLR, D-dimer and CD8+ were positively correlated with whether the patient had colon cancer (r=0.841, 747,991,889,565, all P<0.05), but negative correlations with CD4+ and CD4+/CD8+ ratio (r=-0.999, -0.994, all P<0.05). Conclusion: The detection of tumor markers combined with NLR, D-dimer and T-lymphocytes has reference value in the diagnosis of colon cancer.

20.
Adv Mater ; 35(40): e2302954, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37354126

ABSTRACT

Improving the output energy and durability of triboelectric nanogenerators (TENGs) remains a considerable challenge for their practical applications. Owing to the interface effect of triboelectrification and electrostatic induction, thinner films with higher dielectric constants yield a higher output; however, they are not durable for practical applications. Herein, the dielectric surface effect is changed into a volume effect by adopting a millimeter-thick dielectric film with an inner porous network structure so that charges can hop in the surface state of the network. Charge migration inside the dielectric film is the key factor affecting the output of the triboelectric nanogenerator (TENG) with a thick film, based on which each working stage follows the energy-maximization principle in the voltage-charge plot. The maximum peak and average power densities of the TENG with polyurethane foam film in 1 mm thickness reach 40.9 and 20.7 W m-2  Hz-1 , respectively, under environmental conditions, and the output charge density is 5.14 times that of TENGs with a poly(tetrafluoroethylene) film of the same thickness. Superdurability is achieved in the rotary-mode TENG after 200 000 operation cycles. This study identifies the physical mechanism of the thick dielectric film used in TENGs and provides a new approach to promote the output and durability of TENGs.

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