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BACKGROUND: The primary screening technique for precancerous lesions and cervical cancer is human papillomavirus (HPV) testing, and HPV self-sampling has been shown to be consistent with clinician sampling in terms of the accuracy of the results and may improve cervical cancer screening rates. The aim of this study was to understand the level of awareness, experience, acceptability, and preference for vaginal HPV self-sampling among women in Jiangsu, Zhejiang, and Shanghai, China, and to analyze the possible influencing factors to determine the feasibility of implementing self-sampling. METHODS: Overall, 1793 women were included in the data analysis. A self-administered questionnaire was utilized. In addition to descriptive analysis, univariate and multivariate analyses were used to explore the associations between sociodemographic features, history of cervical cancer screening, and the level of awareness, experience, acceptability, and preference for HPV self-samples. RESULTS: The participants' level of awareness of and experience with HPV self-sampling were moderate. A total of 88.8% of participants rated the acceptability as "high", and self-sampling was preferred by 64.2% of them for cervical cancer screening. People aged 45 to 54 years showed a preference for both clinician sampling(OR = 1.762 (1.116-2.163)) and self-sampling (OR = 1.823 (1.233-2.697)). Those who had graduated from high school or above (OR = 2.305 (1.517-3.503), OR = 2.432 (1.570-3.768), OR = 3.258 (2.024-5.244)) preferred clinician-sampling, and those with a bachelor's degree or above (OR = 1.664 (1.042-2.657)) preferred self-sampling. Middle- and high-income individuals showed no preference for either sampling method (OR < 1). CONCLUSIONS: HPV self-sampling is widely accepted, but awareness, experience and preferences need to be improved. These results may help to adjust public health strategies for the early inclusion of HPV self-sampling as a screening method in national initiatives to prevent cervical cancer.
Subject(s)
Early Detection of Cancer , Health Knowledge, Attitudes, Practice , Papillomavirus Infections , Patient Acceptance of Health Care , Uterine Cervical Neoplasms , Adult , Aged , Female , Humans , Middle Aged , Young Adult , China/epidemiology , Cross-Sectional Studies , Early Detection of Cancer/methods , Early Detection of Cancer/psychology , Human Papillomavirus Viruses , Papillomavirus Infections/diagnosis , Patient Acceptance of Health Care/statistics & numerical data , Patient Acceptance of Health Care/psychology , Patient Preference/statistics & numerical data , Self Care/methods , Self Care/statistics & numerical data , Specimen Handling/methods , Surveys and Questionnaires , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virology , Vaginal Smears/methods , Vaginal Smears/statistics & numerical dataABSTRACT
Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have the capability to induce specific protein degradation. While playing a revolutionary role in effectively degrading the protein of interest (POI), PROTACs encounter certain limitations that impede their clinical translation. These limitations encompass off-target effects, inadequate cell membrane permeability, and the hook effect. The advent of nanotechnology presents a promising avenue to surmount the challenges associated with conventional PROTACs. The utilization of nano-proteolysis targeting chimeras (nano-PROTACs) holds the potential to enhance specific tissue accumulation, augment membrane permeability, and enable controlled release. Consequently, this approach has the capacity to significantly enhance the controllable degradation of target proteins. Additionally, they enable a synergistic effect by combining with other therapeutic strategies. This review comprehensively summarizes the structural basis, advantages, and limitations of PROTACs. Furthermore, it highlights the latest advancements in nanosystems engineered for delivering PROTACs, as well as the development of nano-sized PROTACs employing nanocarriers as linkers. Moreover, it delves into the underlying principles of nanotechnology tailored specifically for PROTACs, alongside the current prospects of clinical research. In conclusion, the integration of nanotechnology into PROTACs harbors vast potential in enhancing the anti-tumor treatment response and expediting clinical translation.
Subject(s)
Neoplasms , Proteolysis , Humans , Neoplasms/drug therapy , Proteolysis/drug effects , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Nanoparticles/chemistry , Nanomedicine/methods , Nanotechnology/methods , Drug Delivery Systems/methods , Drug Carriers/chemistryABSTRACT
BACKGROUND: Plants have numerous defensive secondary metabolites to withstand insect attacks. Scoparone, which is extracted from the medicinal plant Artemisia capillaris, has potent acaricidal effects on Tetranychus cinnabarinus. Spirodiclofen, derived from a tetronic acid derivative, is a potent commercial acaricide that is extensively used globally. However, whether scoparone has synergistic effects when used in conjunction with spirodiclofen and the underlying synergistic mechanism remains unclear. RESULTS: Scoparone exhibited a potent synergistic effect when it was combined with spirodiclofen at a 1:9 ratio. Subsequently, cytochrome P450 monooxygenase (P450) activity, RNA-Seq and qPCR assays indicated that the enzyme activity of P450 and the expression of one P450 gene from T. cinnabarinus, TcCYP388A1, were significantly inhibited by scoparone and spirodiclofen + scoparone; conversely, P450 was activated in spirodiclofen-exposed mites. Importantly, RNAi-mediated silencing of the TcCYP388A1 gene markedly increased the susceptibility of spider mites to spirodiclofen, scoparone and spirodiclofen + scoparone, and in vitro, the recombinant TcCYP388A1 protein could metabolize spirodiclofen. Molecular docking and functional analyses further indicated that R117, which is highly conserved in Arachnoidea species, may be a vital specific binding site for scoparone in the mite TcCYP388A1 protein. This binding site was subsequently confirmed using mutagenesis data, which revealed that this binding site was the sole site selected by scoparone in spider mites over mammalian or fly CYP388A1. CONCLUSIONS: These results indicate that the synergistic effects of scoparone and spirodiclofen on mites occurs through the inhibition of P450 activity, thus reducing spirodiclofen metabolism. The synergistic effect of this potent natural product on the detoxification enzyme-targeted activity of commercial acaricides may offer a sustainable strategy for pest mite resistance management. © 2024 Society of Chemical Industry.
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To achieve a virological cure for hepatitis B virus (HBV), innovative strategies are required to target the covalently closed circular DNA (cccDNA) genome. Guanine-quadruplexes (G4s) are a secondary structure that can be adopted by DNA and play a significant role in regulating viral replication, transcription, and translation. Antibody-based probes and small molecules have been developed to study the role of G4s in the context of the human genome, but none have been specifically made to target G4s in viral infection. Herein, we describe the development of a humanized single-domain antibody (S10) that can target a G4 located in the PreCore (PreC) promoter of the HBV cccDNA genome. MicroScale Thermophoresis demonstrated that S10 has a strong nanomolar affinity to the PreC G4 in its quadruplex form and a structural electron density envelope of the complex was determined using Small-Angle X-ray Scattering. Lentiviral transduction of S10 into HepG2-NTCP cells shows nuclear localization, and chromatin immunoprecipitation coupled with next-generation sequencing demonstrated that S10 can bind to the HBV PreC G4 present on the cccDNA. This research validates the existence of a G4 in HBV cccDNA and demonstrates that this DNA secondary structure can be targeted with high structural and sequence specificity using S10.
Subject(s)
DNA, Circular , DNA, Viral , G-Quadruplexes , Hepatitis B virus , Single-Domain Antibodies , Humans , Hepatitis B virus/genetics , Hepatitis B virus/immunology , DNA, Circular/genetics , DNA, Viral/genetics , Hep G2 Cells , Single-Domain Antibodies/genetics , Single-Domain Antibodies/immunology , Single-Domain Antibodies/chemistry , Genome, Viral , Promoter Regions, Genetic , Virus Replication , Hepatitis B/virologyABSTRACT
Real-time monitoring of broken rails in heavy haul railways is crucial for ensuring the safe operation of railway lines. U78CrV steel is a common material used for heavy haul line rails in China. In this study, the semi-analytical finite element (SAFE) method is employed to calculate the dispersion curves and modal shapes of ultrasonic guided waves in U78CrV heavy steel rails. Guided wave modes that are suitable for detecting rail cracks across the entire cross-section are selected based on the total energy of each mode and the vibration energy in the rail head, web, and foot. The excitation method for the chosen mode is determined by analyzing the energy distribution of the mode shape on the rail surface. The ultrasonic guided wave (UGW) signal in the rail is analyzed using ANSYS three-dimensional finite element simulation. The group velocity of the primary mode in the guided wave signal is obtained through continuous wavelet transform to confirm the existence of the selected mode. It is validated that the selected mode can be excited by examining the similarity between the vibration shapes of a specific rail section and all modal vibration shapes obtained through SAFE. Through simulation and field verification, the guided wave mode selected and excited in this study demonstrates good sensitivity to cracks at the rail head, web, and foot, and it can propagate over distances exceeding 1 km in the rail. By detecting the reflected signal of the selected mode or the degree of attenuation of the transmitted wave, long-distance monitoring of broken rails in heavy-haul railway tracks can be achieved.
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Waveguide bends have become an interesting research direction because they allow highly curved light transmission in a limited space. Here, we propose waveguide bends supporting two TE modes by etching slots and adding germanium arcs in the inner side of a waveguide bend. Simulations show that the bending radius of our proposed base-mode T E 0 waveguide bend drops to 500 nm and its insertion loss (IL) is reduced to 0.13 dB with footprints as small as 0.75µm×0.75µm. For the higher-order T E 1 mode waveguide bend, we adjust the introduced structure in combination with the light field distribution. The IL of the waveguide bend is also reduced to 0.18 dB with footprints as small as 1.85µm×1.85µm. T E 0 mode has 410 nm bandwidth in the optical communication band while T E 1 mode has 330 nm bandwidth by keeping I L<0.5d B. Through the analysis of these structural characteristics, we believe that this method still has great potential in higher-order mode transmission.
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Here we explored the potential role of Gαi2 (G protein subunit alpha i2) in endothelial cell function and angiogenesis. Methods: Genetic methodologies such as shRNA, CRISPR/Cas9, dominant negative mutation, and overexpression were utilized to modify Gαi2 expression or regulate its function. Their effects on endothelial cell functions were assessed in vitro. In vivo, the endothelial-specific Gαi2 shRNA adeno-associated virus (AAV) was utilized to silence Gαi2 expression. The impact of this suppression on retinal angiogenesis in control mice and streptozotocin (STZ)-induced diabetic retinopathy (DR) mice was analyzed. Results: Analysis of single-cell RNA sequencing data revealed Gαi2 (GNAI2) was predominantly expressed in retinal endothelial cells and expression was increased in retinal endothelial cells following oxygen-induced retinopathy (OIR) in mice. Moreover, transcriptome analysis linking Gαi2 to angiogenesis-related processes/pathways, supported by increased Gαi2 expression in experimental OIR mouse retinas, highlighted its possible role in angiogenesis. In various endothelial cell types, shRNA-induced silencing and CRISPR/Cas9-mediated knockout (KO) of Gαi2 resulted in substantial reductions in cell proliferation, migration, invasion, and capillary tube formation. Conversely, Gαi2 over-expression in endothelial cells induced pro-angiogenic activities, enhancing cell proliferation, migration, invasion, and capillary tube formation. Furthermore, our investigation revealed a crucial role of Gαi2 in NFAT (nuclear factor of activated T cells) activation, as evidenced by the down-regulation of NFAT-luciferase reporter activity and pro-angiogenesis NFAT-targeted genes (Egr3, CXCR7, and RND1) in Gαi2-silenced or -KO HUVECs, which were up-regulated in Gαi2-overexpressing endothelial cells. Expression of a dominant negative Gαi2 mutation (S48C) also down-regulated NFAT-targeted genes, slowing proliferation, migration, invasion, and capillary tube formation in HUVECs. Importantly, in vivo experiments revealed that endothelial Gαi2 knockdown inhibited retinal angiogenesis in mice, with a concomitant down-regulation of NFAT-targeted genes in mouse retinal tissue. In contrast, Gαi2 over-expression in endothelial cells enhanced retinal angiogenesis in mice. Single-cell RNA sequencing data confirmed increased levels of Gαi2 specifically in retinal endothelial cells of mice with streptozotocin (STZ)-induced diabetic retinopathy (DR). Importantly, endothelial Gαi2 silencing ameliorated retinal pathological angiogenesis in DR mice. Conclusion: Our study highlights a critical role for Gαi2 in NFAT activation, endothelial cell activation and angiogenesis, offering valuable insights into potential therapeutic strategies for modulating these processes.
Subject(s)
Diabetic Retinopathy , Mice , Animals , Diabetic Retinopathy/drug therapy , GTP-Binding Protein alpha Subunit, Gi2/metabolism , GTP-Binding Protein alpha Subunit, Gi2/pharmacology , Endothelial Cells/metabolism , Angiogenesis , Streptozocin/adverse effects , Oxygen/metabolism , RNA, Small Interfering/metabolism , Cell ProliferationABSTRACT
In this Letter, we design and experimentally demonstrate compact mode converters with a lightning-like and arrow-like polygonal subwavelength grating (SWG) structure on a silicon-on-insulator (SOI) platform, which can convert the TE0 mode to the TE1 and TE2 modes, respectively. The footprints of the proposed TE0-1 and TE0-2 mode converters are only 4.44 × 1.3 and 5.89 × 1.8â µm2, respectively. The experimental results show the mode converters have a low insertion loss (<1â dB) and a broad bandwidth (>50â nm). The measured cross talks of the TE0-1 and TE0-2 mode converters are -7.2â dB and -10.3â dB, respectively. In addition, the proposed mode converters with the SWG structure have the advantage in fabrication, since only a one-step full-etching process is required.
ABSTRACT
The violent goods vibration during curve negotiation is a huge threat to the vehicle running safety. Qualified load restraint assemblies that can significantly suppress the cargo vibration are necessary. This study proposes a novel method for evaluating the essential restraint strength, focusing on the relative motion between cargo and wagon. In the beginning, as a comparison, current methods are used to calculate the necessary stiffness of lashings, which are adopted to restrain the cargo vibration on the wagon. Based on the data of the field test, the accuracy of the established wagon-cargo coupled dynamics model is validated. The loaded wagon model negotiates the curve under different running and loading conditions. The simulation results and analysis demonstrate effective strategies for suppressing the vibration of the cargo and reveal the necessary lashing stiffness. The comparison among the results of different evaluation methods shows that the stability of the cargo can be improved by optimizing the lashing stiffness with the method of dynamics simulations. We hope this study will make a positive contribution to the safety of railway freight transportation.
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Because chemical gas is sensitive to absorption in the 2 µm band, and 2 µm matches the absorption band of the remote sensing material, many remote sensors and optical sensors are designed to operate in the 2 µm wavelength region. In this paper, we designed an integrated 3 dB power splitter centered at 2 µm. The study of this device is built on a silicon-on-insulator (SOI) platform. We introduced a subwavelength grating (SWG) to improve the performance of the device. We used the three-dimensional finite-difference time-domain (3D FDTD) method to analyze the effect of the structure on the power splitter. The insertion loss (IL) of the fundamental TE mode is only 0.04 dB at 2 µm and its bandwidth of IL <0.45d B is 940 nm (1570-2510 nm). It is suitable for multidomain and all-band photonic integrated circuits at 2 µm.
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Background & Aims: Hepatitis D virus (HDV) is the causative agent of chronic hepatitis delta, the most severe form of viral hepatitis. HDV encodes one protein, hepatitis delta antigen (HDAg), in two isoforms: S- and L-HDAg. They are identical in sequence except that L-HDAg contains an additional 19-20 amino acids at its C-terminus, which confer regulatory roles that are distinct from those of S-HDAg. Notably, these residues are divergent between different genotypes. We aimed to elucidate the molecular determinants within the C-termini that are essential for the regulatory role of L-HDAg in HDV replication and assembly. Methods: Northern blot, reverse-transcription quantitative PCR, and a newly established HDV trans-complementary system were used in this study. Results: C-termini of L-HDAg, albeit with high sequence variation among different genotypes, are interchangeable with respect to the trans-inhibitory function of L-HDAg and HDV assembly. The C-terminus of L-HDAg features a conserved prenylation CXXQ motif and is enriched with proline and hydrophobic residues. Abolishment of the CXXQ motif attenuated the inhibitory effect of L-HDAg on HDV replication. In contrast, the enrichment of proline and hydrophobic residues per se does not modify the trans-inhibitory function of L-HDAg. Nevertheless, these residues are essential for HDV assembly. Mechanistically, prolines and hydrophobic residues contribute to HDV assembly via a mode of action independent of the prenylated CXXQ motif. Conclusions: Within the C-terminus of L-HDAg, the CXXQ motif and the enrichment of proline and hydrophobic residues are all essential determinants of L-HDAg's regulatory roles in HDV replication and assembly. This intrinsic viral regulatory mechanism we elucidated deepens our understanding of the unique life cycle of HDV. Impact and implications: Hepatitis D virus (HDV) encodes one protein, hepatitis delta antigen (HDAg), in two isoforms: S- and L-HDAg. They are identical in sequence except that L-HDAg contains an additional 19-20 amino acids at its C-terminus. This C-terminal extension in L-HDAg confers regulatory roles in the HDV life cycle that are distinct from those of S-HDAg. Herein, we found that C-termini of L-HDAg, although with high sequence variation, are interchangeable among different HDV genotypes. Within the C-terminus of L-HDAg, the prenylation motif, and the enrichment of proline and hydrophobic residues are all essential determinants of L-HDAg's regulatory roles in HDV replication and assembly.
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Polarizers are used to eliminate the undesired polarization state and maintain the other one. The phase change material Ge2Sb2Se4Te1 (GSST) has been widely studied for providing reconfigurable function in optical systems. In this paper, based on a silicon waveguide embedded with a GSST, which is able to absorb light by taking advantage of the relatively large imaginary part of its refractive index in the crystalline state, a multifunctional polarizer with transverse electric (TE) and transverse magnetic (TM) passages has been designed. The interconversion between the two types of polarizers relies only on the state switching of GSST. The size of the device is 7.5µm∗4.3µm, and the simulation results showed that the extinction ratio of the TE-pass polarizer is 45.37 dB and the insertion loss is 1.10 dB at the wavelength of 1550 nm, while the extinction ratio (ER) of the TM-pass polarizer is 20.09 dB and the insertion loss (IL) is 1.35 dB. For the TE-pass polarizer, a bandwidth broader than 200 nm is achieved with ER>20dB and IL<2.0dB over the wavelength region from 1450 to 1650 nm and for the TM-pass polarizer, ER>15dB and IL<1.5dB in the wavelength region from 1525 to 1600 nm, with a bandwidth of approximately 75 nm.
ABSTRACT
Background and aims: The co-infection of hepatitis B (HBV) patients with the hepatitis D virus (HDV) causes the most severe form of viral hepatitis and thus drastically worsens the course of the disease. Therapy options for HBV/HDV patients are still limited. Here, we investigated the potential of natural killer (NK) cells that are crucial drivers of the innate immune response against viruses to target HDV-infected hepatocytes. Methods: We established in vitro co-culture models using HDV-infected hepatoma cell lines and human peripheral blood NK cells. We determined NK cell activation by flow cytometry, transcriptome analysis, bead-based cytokine immunoassays, and NK cell-mediated effects on T cells by flow cytometry. We validated the mechanisms using CRISPR/Cas9-mediated gene deletions. Moreover, we assessed the frequencies and phenotype of NK cells in peripheral blood of HBV and HDV superinfected patients. Results: Upon co-culture with HDV-infected hepatic cell lines, NK cells upregulated activation markers, interferon-stimulated genes (ISGs) including the death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), produced interferon (IFN)-γ and eliminated HDV-infected cells via the TRAIL-TRAIL-R2 axis. We identified IFN-ß released by HDV-infected cells as an important enhancer of NK cell activity. In line with our in vitro data, we observed activation of peripheral blood NK cells from HBV/HDV co-infected, but not HBV mono-infected patients. Conclusion: Our data demonstrate NK cell activation in HDV infection and their potential to eliminate HDV-infected hepatoma cells via the TRAIL/TRAIL-R2 axis which implies a high relevance of NK cells for the design of novel anti-viral therapies.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis D , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/metabolism , Ligands , Hepatitis D/metabolism , Interferons/metabolism , Hepatitis Delta Virus/genetics , Killer Cells, Natural , Tumor Necrosis Factors/metabolism , Apoptosis , Liver Neoplasms/metabolismABSTRACT
IMPORTANCE: Plasmid size is one of the factors affecting transfection efficacy in most of the molecular genetic research studies. One effective approach for reducing plasmid size is to replace relatively large, conventional antibiotic resistance genes with the short-size dfrB10 gene. The successful construct of a series of dfrB10-based tool plasmids and their functional validation, via comparison with original plasmids, suggest that dfrB10 is a potent drug resistance selection marker. The antibiotic trimethoprim offers convenient usage comparable to that of ampicillin or kanamycin. Additionally, fluorescence analysis has demonstrated the compatibility of TMP with protein expression in various host cells. Based on these findings, TMP-dfrB10 could be an alternative choice for future use in molecular genetic research studies that require miniature plasmids to achieve optimal results.
Subject(s)
Anti-Bacterial Agents , Trimethoprim , Plasmids/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, MicrobialABSTRACT
Introduction: The COVID-19 pandemic and subsequent quarantine measures have led to a significant impact on mental health worldwide. Medical staff, in particular, have been exposed to high levels of stress due to their frontline work during the crisis. However, there is still limited research on the psychological mechanism among medical staff after quarantine. Methods: In this cross-sectional observational study, 150 medical staff from Shanghai YangZhi Rehabilitation Hospital, Shanghai, China, were enrolled in October 2022. SPSS 26.0 and PROCESS 4.0 model 6 were used to analyze the chain mediating effect of perceived stress, anxiety, resilience and depression among medical staff after quarantine. Anxiety and depression were compared during and after the quarantine. All scales have high validity and reliability in a Chinese population. Results: Our findings revealed a positive correlation between perceived stress and anxiety (r = 0.60, p < 0.001) and depression (r = 0.60, p < 0.001) levels among medical staff. Conversely, resilience was found to have a negative correlation with perceived stress (r = -0.67, p < 0.001), anxiety (r = -0.57, p < 0.001) and depression (r = -0.61, p < 0.001). The score of depression during the quarantine was higher than the score after the quarantine, but the p-value is only marginally significant (p = 0.067). The score of anxiety during the quarantine was significantly higher than the score after the quarantine (p < 0.05). Moreover, the chain mediation model suggested that anxiety and resilience could mediate the association between perceived stress and depression among medical staff following quarantine. Specifically, perceived stress had no direct effect on depression (ß = 0.025, t = 0.548, p = 0.59) but positively predicted anxiety (ß = 0.381, t = 8.817, p < 0.001) and resilience (ß = -1.302, t = -6.781, p < 0.001), which influenced depression levels indirectly through multiple pathways. The three indirect paths: the mediating role of anxiety, the mediating role of resilience, and the chain mediating role of both anxiety and resilience. Discussion: This study emphasizes the importance of psychological interventions aimed at protecting medical staff's psychological resilience and promoting coping mechanisms to manage stress during and after crises such as the COVID-19 pandemic. Additionally, our findings suggest that both anxiety and resilience play critical roles in mitigating the detrimental effects of perceived stress on mental health and further highlight the need for continued research to better understand the complex interplay of these factors.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Quarantine/psychology , Depression/epidemiology , Depression/psychology , Pandemics , Cross-Sectional Studies , Mediation Analysis , Reproducibility of Results , SARS-CoV-2 , China/epidemiology , Anxiety/epidemiology , Anxiety/psychology , Medical Staff , Stress, Psychological/epidemiologyABSTRACT
On-chip polarization management components play a critical role in tackling polarization dependence in the lithium-niobate-on-insulator (LNOI) platform. In this work, we proposed a reconfigurable TE-pass polarizer based on optical phase change material (GST) and the LNOI wafer. The key region is formed by a hybrid GST-S i 3 N 4 layer symmetrically deposited atop the centerline of the LNOI waveguide along the propagation direction where the GST is sandwiched in the middle of the S i 3 N 4 layer. Whether the polarizer will take effect depends on the phase states of the GST layer and the graphene and aluminum oxide layers are coated atop the G S T-S i 3 N 4 layer as the microheater to control the conversion of phase states. The proposed device length is 7.5 µm with an insertion loss (IL)=0.22 dB and extinction ratio (ER)=32.8 dB at the wavelength of 1550 nm. Moreover, it also has a high ER (>25d B) and a low IL (<0.5d B) in the operating bandwidth of 200 nm. Such a high-performance TE-pass polarizer paves a new way for applications of photonics integrated circuits.
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Despite the ongoing clinical trials and the introduction of novel treatments over the past few decades, ovarian cancer remains one of the most fatal malignancies in women worldwide. Platinum- and paclitaxel-based chemotherapy is effective in treating the majority of patients with ovarian cancer. However, more than 70% of patients experience recurrence and eventually develop chemoresistance. To improve clinical outcomes in patients with ovarian cancer, novel technologies must be developed for identifying molecular alterations following drug-based treatment of ovarian cancer. Recently, extracellular vesicles (EVs) have gained prominence as the mediators of tumor progression. In this study, we used mass spectrometry to identify the changes in EV protein signatures due to different chemotherapeutic agents used for treating ovarian cancer. By examining these alterations, we identified the specific protein induction patterns of cisplatin alone, paclitaxel alone, and a combination of cisplatin and paclitaxel. Specifically, we found that drug sensitivity was correlated with the expression levels of ANXA5, CD81, and RAB5C in patients receiving cisplatin with paclitaxel. Our findings suggest that chemotherapy-induced changes in EV protein signatures are crucial for the progression of ovarian cancer.
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BACKGROUND: Research has indicated some women were in a state of uncertainty about pharmacological pain management decisions, which may lead to maternal anxiety and decisional regret. However, little is known about decisional conflict in the choice of epidural labour analgesia amongst Chinese women. AIM: This study aimed to investigate the level of and reasons underlying decisional conflict in Chinese women during their late pregnancy when making a decision on the use of epidural analgesia in labour. METHODS: A convergent parallel mixed methods study was undertaken, that included a quantitative survey (n = 323) and qualitative interviews (n = 17) with women recruited from a tertiary general hospital in Hangzhou, China. The quantitative survey assessed the level of and its influencing factors of women's decisional conflict, while the qualitative interview further explored experiences of and reasons underlying the conflict. FINDINGS: Participants reported a high level of decisional conflict (mean±SD, 39.59±15.92), which related to decision delay and/or negative perceptions about the decision. Multiple stepwise linear regression analysis identified that highest level of education and knowledge of epidural were negatively associated with decisional conflict (p<0.05). Four decision-making styles (rational, dependant, intuitive and avoidant decision-making) associated with different levels of decisional conflict, and four underlying reasons (personal characteristics, informational provision, emotional support and participation in decision-making) of the conflict were thematized. CONCLUSION: Decisional conflict related to epidural labour analgesia is a noteworthy issue amongst women during their late pregnancy. This study suggests a need for provision of family-centred shared decision-making practice about the use of epidural analgesia in labour.
Subject(s)
Analgesia, Epidural , Labor, Obstetric , Pregnancy , Female , Humans , Analgesia, Epidural/methods , Tertiary Care Centers , Emotions , China , Decision MakingABSTRACT
Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is a rare subtype of follicular dendritic cell sarcoma (FDCS) that primarily occurs in the liver and spleen. The etiology of IPT-like FDCS is unknown, and it has nonspecific clinical manifestations, imaging performance and laboratory test results. Recently, a patient with IPT-like FDCS was admitted to our hospital because of abdominal distension and anemia. Over the past 3 years, the patient has been followed up after a liver mass was found in a physical examination. The lesion gradually enlarged and caused compression symptoms. In November 2022, a tumor with a diameter of approximately 20 cm was found in the right posterior lobe of the liver after abdominal enhanced Magnetic resonance imaging (MRI) in our hospital. Liver tumor biopsy before the operation revealed a large number of hyperplastic plasma cells and a small number of spindle cells, and the spindle cells were atypical. After a complete examination, the patient underwent liver resection. Pathology after surgery confirmed liver IPT-like FDCS.
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Background: Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Worldwide, liver cancer is the fourth most common cause of cancer-related death. Recent studies have found that PIWI-interacting RNAs (piRNAs) participate in the occurrence and development of various tumors and are closely related to the growth, invasion, metastasis and prognosis of malignant tumors. Studies on the role and functional mechanism of piRNAs in HCC development and progression are limited. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of piR-017724 in both HCC tissues and cells. Based on the clinical data of HCC patients, the clinical and prognostic value of piR-017724 was further analyzed. Then, targeted silencing and overexpressing of piR-017724 in HCC cells was further used to examine the biological functions of piR-017724. In addition, the downstream target protein of piR-017724 was predicted and validated through high-throughput sequencing and public databases. Results: The piR-017724 was significantly downregulated in HCC tissues and cells, and the downregulation of piR-017724 was associated with tumor stage and poor prognosis in HCC. The piR-017724 inhibitor promoted the proliferation, migration and invasion of HCC cells, while the piR-017724 mimic had the opposite effect. However, the piR-017724 did not affect apoptosis of HCC cells. High-throughput sequencing and qRT-PCR confirmed a reciprocal relationship between piR-017724 and PLIN3. Therefore, we speculate that piR-017724 may inhibit the development and progression of HCC by affecting the downstream protein PLIN3. Conclusions: Our study shows that piR-017724, which is lowly expressed in HCC, inhibits the proliferation, migration and invasion of HCC cells and may affect the development of hepatocellular liver cancer through PLIN3, which provides new insights into the clinical application of piR-017724 in the treatment of hepatocellular carcinoma.