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Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.
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Antineoplásicos , Sistemas CRISPR-Cas , Resistencia a Medicamentos Antineoplásicos , Irinotecano , Oxaliplatina , Proteínas Serina-Treonina Quinases , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Oxaliplatina/farmacologia , Irinotecano/farmacologia , Sistemas CRISPR-Cas/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Neoplasias Colorretais/genética , Neoplasias Colorretais/tratamento farmacológico , Animais , Neoplasias/genética , Neoplasias/tratamento farmacológico , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Background: Solitary fibrous tumor (SFT) is a rare soft tissue tumor originating from mesenchymal cells. Thus far, there have been no reported cases of SFT closely related to the iliac vessels. Case presentation: An elderly woman was found to have had a lower abdominal mass for more than 20 years. The enhanced computerized tomography (CT) showed a progressively enhanced hypervascular mass. The external iliac blood vessels were closely related to the mass, which was misdiagnosed as an ovarian tumor. During laparotomy, the external iliac vein was seen to penetrate the tumor, and the external iliac artery was seen to penetrate the tumor capsule. The retroperitoneal tumor was diagnosed during the operation. The surgical plan of complete tumor resection, severing of the external iliac arteries and veins, and blood vessel replacement was implemented. Pathological immunohistochemistry showed positive results for STAT6 and CD34, confirming the diagnosis of giant retroperitoneal SFT. The risk is classified as high and requires long-term follow-up. There has been no local recurrence or distant metastasis almost 1 year after surgery. Conclusion: The incidence of giant retroperitoneal SFT is rare, and the diagnosis can be confirmed through preoperative imaging examination and pathological examination. If the SFT capsule is intact, there is a chance of surgical resection. For SFTs that are penetrated by the iliac blood vessels, adequate preparation must be made before the surgery is performed. Removing the tumor and the iliac blood vessels at the corresponding site and then replacing it with artificial blood vessels is a feasible method with less risk of bleeding. In this case, imaging showed a progressively enhancing hypervascular mass in the lower abdomen, which was related to blood vessels. Preoperative biopsy and pathological testing can confirm the diagnosis. Neoadjuvant therapy or interventional therapy before surgery can shrink the tumor, making the surgical procedure relatively easy with less risk of bleeding.
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The individual HLA-related susceptibility to emerging viral diseases such as COVID-19 underscores the importance of understanding how HLA polymorphism influences peptide presentation and T cell recognition. Similar to HLA-A*0101, which is one of the earliest identified HLA alleles among the human population, HLA-A*2601 possesses a similar characteristic for the binding peptide and acts as a prevalent allomorph in HLA-I. In this study, we found that, compared with HLA-A*0101, HLA-A*2601 individuals exhibit distinctive features for the T cell responses to SARS-CoV-2 and influenza virus after infection and/or vaccination. The heterogeneous T cell responses can be attributed to the distinct preference of HLA-A*2601 and HLA-A*0101 to T cell epitope motifs with negative-charged residues at the P1 and P3 positions, respectively. Furthermore, we determined the crystal structures of the HLA-A*2601 complexed to four peptides derived from SARS-CoV-2 and human papillomavirus, with one structure of HLA-A*0101 for comparison. The shallow pocket C of HLA-A*2601 results in the promiscuous presentation of peptides with "switchable" bulged conformations because of the secondary anchor in the median portion. Notably, the hydrogen bond network formed between the negative-charged P1 anchors and the HLA-A*2601-specific residues lead to a "closed" conformation and solid placement for the P1 secondary anchor accommodation in pocket A. This insight sheds light on the intricate relationship between HLA I allelic allomorphs, peptide binding, and the immune response and provides valuable implications for understanding disease susceptibility and potential vaccine design.
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COVID-19 , Epitopos de Linfócito T , SARS-CoV-2 , Humanos , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , SARS-CoV-2/imunologia , SARS-CoV-2/genética , COVID-19/imunologia , COVID-19/virologia , Antígenos HLA-A/imunologia , Antígenos HLA-A/genética , Antígenos HLA-A/metabolismo , Antígenos HLA-A/química , Peptídeos/imunologia , Peptídeos/química , Alelos , Antígeno HLA-A1RESUMO
The orpiment (As2S3) is an important secondary mineral in the geochemical process of arsenic (As) in the environment. The dissolution of orpiment has a close relationship with the migration and transformation of As. The dissolved species of As2S3 is closely related to sulfide (S-II) in the anoxic and sulfidic environment. This paper focuses on the various As species formed when As2S3 dissolved in the presence and absence of excess S-II under anoxic conditions with simulation tests via X-ray absorption spectroscopy (XAS), liquid chromatography with (hydride generation) atomic fluorescence spectrophotometry, and Raman spectroscopy. The results showed that the As produced when As2S3 dissolved in the excess S-II contained a mixture of arsenite and thioarsenite (ThioAsIII). Based on the linear combination fitting, ThioAsIII is the dominant As species (88.2 %) with arsenite as the leftover component. However, the percentage of ThioAsIII decreased to 43.7 % if As2S3 dissolved in the absence of excess S-II, indicting ThioAsIII favored under sulfidic conditions. The findings may give further insights about the role and formation mechanism of ThioAsIII in the dissolution process of As2S3. ENVIRONMENTAL IMPLICATION: The dissolution of crystallization orpiment has a close relationship with the transport of As in the environment. Qualitatively and quantitatively identification of the dissolved species of As2S3 in the presence and absence of excess S-II may be helpful for a better understanding and predicting the fate of As. The formed trithioarsenite was the dominant dissolved species compared to arsenite in the sulfidic system. It has higher mobility than AsV and AsIII, and has been found in many As-related adsorption/desorption and redox reactions. Therefore, great cautions should be given when choosing technologies to remediate the As contaminated soils and waters.
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The refractive index (RI) measurment of the liquid often changes with the sensor's temperature. Accurate RI measurements require simultaneous measurements of the liquid temperature to calibrate the RI measurement. This study proposed what we believe to be a novel dual D-shaped plastic optical fiber sensor capable of simultaneously measuring both RI and temperature. A fluorescent material made of rhodamine B (RhB) is embedded in one of the D-shaped structures of the dual D-shaped fiber, which can be excited by a green laser to produce orange fluorescence. The fluorescence and the input laser of the fiber are superimposed at the output end of the fiber to form a specklegram containing information of two wavelengths. It was found through experiments that the effects of temperature and RI change on the red and green channels of the specklegrams are different, and the neural network can learn this feature to complete the measurement of both RI and temperature parameters. For RI sensing, the maximum error between the average predicted value and the true value of the test set is 0.0005. For temperature sensing, the maximum error between the average predicted value and the true value of the test set is 0.26°C. In addition, because the intensity change of the fluorescence varies linearly with RI and temperature, the sensor also has good stability.
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OBJECTIVE: To observe the effects of electroacupuncture (EA) on the autophagy of ovarian granulosa cells in rats with premature ovarian insufficiency (POI), and explore the mechanism of EA in improving POI. METHODS: Thirty-two female SD rats were randomly divided into a blank group (n=8) and a model making group (n=24). The rats in the model making group were injected intraperitoneally with cyclophosphamide for 15 days to establish the POI model (the dosage on the 1st day was 50 mg/kg, and 8 mg/kg from the 2nd day to 15th day). The successfully modeled rats were then randomly divided into a model group, an EA group, and an estradiol (E2) group, with 8 rats in each group. Rats in the EA group received EA at bilateral "Gongsun" (SP 4) with continuous wave, frequency of 2 Hz, and current intensity of 0.1 to 1 mA, 20 min per treatment, once daily for 14 days. Rats in the E2 group were administered with E2 (0.01 mg/mL) by gavage (10 mL/kg), once daily for 14 days. The changes in estrous cycle were observed by rapid Giemsa staining before and after modeling. After intervention, ovarian tissue morphology was observed by HE staining; serum levels of follicle-stimulating hormone (FSH), E2, anti-Mullerian hormone (AMH), and inhibin B (INHB) were detected by ELISA; immunofluorescence staining was used to observe the expression of p62 in ovarian granulosa cells; the ultrastructure of ovarian granulosa cells was observed by transmission electron microscopy, and the number of autophagosomes and autolysosomes was compared; Western blot and real-time fluorescence quantitative PCR were used to detect the protein and mRNA expression of p62, Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) in ovarian tissue. RESULTS: The results of vaginal smears in the blank group showed regular cyclical changes; the rats in the model group showed prolonged estrous cycle or cycle arrest, mostly in proestrus or metestrus, with overall ovarian atrophy, disordered structure, and decreased granulosa cells. Compared with the blank group, rats in the model group showed increased serum FSH level (P<0.01), decreased serum levels of E2, AMH, and INHB (P<0.01), decreased positive expression of p62 in ovarian granulosa cells (P<0.01), with obvious swelling of ovarian granulosa cells, mild to moderate swelling of mitochondria, slight expansion of rough endoplasmic reticulum, and hypertrophy of Golgi apparatus; the number of autophagosomes and autolysosomes in the ovaries was increased (P<0.01), the expression of p62 protein and mRNA was decreased (P<0.01), and the expression of Beclin-1 and LC3 protein and mRNA in ovarian tissue was increased (P<0.01). Compared with the model group, rats in the EA group and the E2 group showed decreased serum FSH levels (P<0.01), increased levels of E2, AMH, and INHB (P<0.01), increased positive expression of p62 in ovarian granulosa cells (P<0.01), alleviated degree of ovarian granulosa cell damage, with relatively intact organelle morphology, and decreased number of autophagosomes and autolysosomes in the ovaries (P<0.01); the rats also showed increased expression of p62 protein and mRNA (P<0.01), and decreased expression of Beclin-1 and LC3 protein and mRNA (P<0.01) in ovarian tissue. CONCLUSION: EA at "Gongsun" (SP 4) could improve ovarian reserve function in POI rats by reducing the number of autophagosomes and autolysosomes, up-regulating p62 expression, and down-regulating Beclin-1 and LC3 expression, thus inhibiting autophagy of ovarian granulosa cells, and regulating the serum levels of FSH, E2, AMH, and INHB.
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Autofagia , Eletroacupuntura , Células da Granulosa , Insuficiência Ovariana Primária , Ratos Sprague-Dawley , Animais , Feminino , Insuficiência Ovariana Primária/terapia , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/fisiopatologia , Ratos , Humanos , Células da Granulosa/metabolismo , Modelos Animais de DoençasRESUMO
Background: Malignant tumors of the ureteric bud are not common, and cervical involvement is even rarer. So far, there have been no such cases in the literature. Case summary: A 50-year-old woman developed intermittent light bleeding in the past 7 months and lower abdominal pain in the past 2 months. The human papillomavirus 16 (HPV) DNA, P16 chemical staining, thinPrep cytology test (TCT), and cervical and cervical canal tissue biopsy were all negative. Pelvic color Doppler ultrasound exhibited incomplete mediastinal uterus and heterogeneous echo from the cervical canal to the posterior wall of the cervix. Pelvic contrast-enhanced CT showed left cervical mass, left retroperitoneal mass, absence of the left kidney, and mediastinal uterus. An increase in human epididymal protein 4 (HE4) (133.6 pmol/L) was detected, while other tumor markers were at normal levels. Based on these examination results, a diagnosis of "cervical fibroids, left retroperitoneal mass, incomplete mediastinal uterus, left kidney deficiency"[SIC] was conducted, and expanded hysterectomy, right adnexectomy, and left retroperitoneal mass resection were performed. Through intraoperative rapid pathological diagnosis, postoperative pathological diagnosis combined with the re-evaluation of laboratory, and imaging and intraoperative examination results, the patient was diagnosed with ureteric bud intestinal-type adenocarcinoma involving the cervix. The patient has been tracked and followed up for approximately 11 months. She underwent six courses of chemotherapy. At present, the medication has been discontinued for 4 months, and there is no recurrence, metastasis, or deterioration of the tumor. Conclusion: For large masses of the cervix, it is feasible for the operation to be performed, improving the prognosis. There were a few limitations. A preoperative aspiration biopsy of masses was not performed to differentiate benign from malignant. Preoperative urography was not performed to clarify the function of the malformed urinary system structure. Partial cystectomy should be performed simultaneously with the resection of the ureteric bud for intestinal-type adenocarcinoma. In this case, a partial cystectomy was not performed, which can only be compensated with postoperative chemotherapy. Moreover, this patient did not undergo genetic screening, and it is currently unclear whether there are any genetic mutations associated with ureteric bud intestinal adenocarcinoma.
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With the extensive industrialization and urbanization taking place in China during the recent decades, land use throughout the country has experienced profound changes influenced not only by the demand for population growth and living standard improvement but also by the constraints of series of land use policies. However, whether the conflict between the expansion of settlement land (SL) and the loss of cultivated land (CL) have been resolved at the national scale or transferred between the local regions remains unclear. Based on yearly ESA CCI land use and land cover products from 1992 to 2020, the long-term trends of quantity and spatial pattern of SL expansion and CL change in China from national and local views were investigated using trend statistic methods, and finally a comprehensive zoning framework was proposed to recognize the trade-off and synergies relationships between SL expansion and CL change. There are a continuous expansion of SL with global linear trends showing three breakpoints in 2000, 2005, and 2012, and a fluctuation decline of CL presented with four breakpoints in 1997, 2002, 2006, and 2013. Aggregation and dispersion tendencies with linear characteristics of SL expansion and CL change were found with breakpoints in 2001, 2008, 2012, and 2016 and breakpoints in 2001 and 2010, respectively. A spotty spatial pattern of SL was shown spatially coincident with urban agglomerations in China while the planar continuous characteristic was found for CL. Local counties were classified into five tradeoff and synergies zones (TSZs), where general synergies (G-S) and decoupling (D) of SL expansion and CL change were rare cases and the different change in quantity and trend of SL expansion and CL change in local counties was concealed by the national trend. A few scattered counties were belonging to G-S and D TSZs, while most of the counties in the central-east and western China were in General-Tradeoff (G-T) and Superior-Tradeoff (S-T) TSZs. Counties in south and north China with higher percentages of CL were more prevalent in Superior-Synergy (S-S) TSZ. Our findings explicated the complex relationships between SL expansion and CL change of China at the national scale and in local counties, which pointed out the differences of unified land use management activities across scales and could provide insights for future policy-making and management measures of land use to both ensure the national food security and promote regional sustainable development more synchronously.
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Conservação dos Recursos Naturais , Urbanização , China , Agricultura , HumanosRESUMO
The physiological role of Geobacter sulfurreducens extracellular cytochrome filaments is a matter of debate and the development of proposed electronic device applications of cytochrome filaments awaits methods for large-scale cytochrome nanowire production. Functional studies in G. sulfurreducens are stymied by the broad diversity of redox-active proteins on the outer cell surface and the redundancy and plasticity of extracellular electron transport routes. G. sulfurreducens is a poor chassis for producing cytochrome nanowires for electronics because of its slow, low-yield, anaerobic growth. Here we report that filaments of the G. sulfurreducens cytochrome OmcS can be heterologously expressed in Shewanella oneidensis. Multiple lines of evidence demonstrated that a strain of S. oneidensis, expressing the G. sulfurreducens OmcS gene on a plasmid, localized OmcS on the outer cell surface. Atomic force microscopy revealed filaments with the unique morphology of OmcS filaments emanating from cells. Electron transfer to OmcS appeared to require a functional outer-membrane porin-cytochrome conduit. The results suggest that S. oneidensis, which grows rapidly to high culture densities under aerobic conditions, may be suitable for the development of a chassis for producing cytochrome nanowires for electronics applications and may also be a good model microbe for elucidating cytochrome filament function in anaerobic extracellular electron transfer.
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Citocromos , Geobacter , Shewanella , Shewanella/genética , Shewanella/metabolismo , Shewanella/enzimologia , Geobacter/genética , Geobacter/metabolismo , Citocromos/metabolismo , Citocromos/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Transporte de Elétrons , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Microbiologically influenced corrosion (MIC) caused by corrosive microorganisms poses significant economic losses and safety hazards. Conventional corrosion prevention methods have limitations, so it is necessary to develop the eco-friendly and long-term effective strategies to mitigate MIC. This study investigated the inhibition of Vibrio sp. EF187016 biofilm on Geobacter sulfurreducens on carbon steel. Vibrio sp. EF187016 biofilm reduced the corrosion current density and impeded pitting corrosion. A thick and uniform Vibrio sp. EF187016 biofilm formed on the coupon surfaces, acting as a protective layer against corrosive ions and electron acquisition by G. sulfurreducens. The pre-grown mature Vibrio sp. EF187016 biofilms, provided enhanced protection against G. sulfurreducens corrosion. Additionally, the extracellular polymeric substances from Vibrio sp. EF187016 was confirmed to act as a green corrosion inhibitor to mitigate microbial corrosion. This study highlights the potential of active biofilms for eco-friendly corrosion protection, offering a novel perspective on material preservation against microbial corrosion.
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Cáusticos , Geobacter , Aço , Carbono , Corrosão , Cáusticos/farmacologia , BiofilmesRESUMO
High temperatures negatively impact the yield and quality of fruit crops. Exogenous melatonin (MT) application has been shown to enhance heat tolerance, but the response of endogenous MT to heat stress, particularly in perennial fruit trees, remains unclear. The present study investigated the effects of high temperatures on transgenic apple plants overexpressing the MT biosynthesis gene N-acetylserotonin methyltransferase 9 (MdASMT9). Endogenous MT protected transgenic plants from heat stress by increasing antioxidant enzyme activity and scavenging reactive oxygen species (ROS), and protecting the chloroplasts from damage. Application of MT and overexpression of MdASMT9 also reduced abscisic acid accumulation through promoting MdWRKY33-mediated transcriptional inhibition of MdNCED1 and MdNCED3, thus inducing stomatal opening for better heat dissipation. Furthermore, MT-enhanced autophagic activity through promoting MdWRKY33-mediated transcriptional enhancement of MdATG18a under heat stress. These findings provide new insights into the regulation of endogenous MT and its role in improving basal thermotolerance in perennial fruit trees.
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Malus , Melatonina , Termotolerância , Termotolerância/genética , Melatonina/farmacologia , Malus/genética , Antioxidantes/farmacologia , Resposta ao Choque Térmico/genética , Plantas Geneticamente Modificadas/genética , Espécies Reativas de OxigênioRESUMO
Zika virus (ZIKV) infection caused neurological complications and male infertility, leading to the accumulation of antigen-specific immune cells in immune-privileged organs (IPOs). Thus, it is important to understand the immunological responses to ZIKV in IPOs. We extensively investigated the ZIKV-specific T cell immunity in IPOs in Ifnar1-/- mice, based on an immunodominant epitope E294-302 tetramer. The distinct kinetics and functions of virus-specific CD8+ T cells infiltrated into different IPOs were characterized, with late elevation in the brain and spinal cord. Single epitope E294-302-specific T cells can account for 20-60% of the total CD8+ T cells in the brain, spinal cord, and testicle and persist for at least 90 days in the brain and spinal cord. The E294-302-specific TCRαßs within the IPOs are featured with the majority of clonotypes utilizing TRAV9N-3 paired with diverse TRBV chains, but with distinct αß paired clonotypes in 7 and 30 days post-infection. Specific chemokine receptors, Ccr2 and Ccr5, were selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of virus-specific CD8+ T cells after infection. Overall, this study adds to the understanding of virus-specific CD8+ T cell responses for controlling and clearing ZIKV infection in IPOs.IMPORTANCEThe immune-privileged organs (IPOs), such as the central nervous system and testicles, presented pathogenicity and inflammation after Zika virus (ZIKV) infection with infiltrated CD8+ T cells. Our data show that CD8+ T cells keep up with virus increases and decreases in immune-privileged organs. Furthermore, our study provides the first ex vivo comparative analyses of the composition and diversity related to TCRα/ß clonotypes across anatomical sites and ZIKV infection phases. We show that the vast majority of TCRα/ß clonotypes in tissues utilize TRAV9N-3 with conservation. Specific chemokine expression, including Ccr2 and Ccr5, was found to be selectively expressed in the E294-302-specific CD8+ T cells within the brain and testicle, indicating an IPO-oriented migration of the virus-specific CD8+ T cells after the infection. Our study adds insights into the anti-viral immunological characterization and chemotaxis mechanism of virus-specific CD8+ T cells after ZIKV infection in different IPOs.
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Linfócitos T CD8-Positivos , Privilégio Imunológico , Infecção por Zika virus , Animais , Masculino , Camundongos , Encéfalo/imunologia , Encéfalo/virologia , Linfócitos T CD8-Positivos/imunologia , Receptor de Interferon alfa e beta/genética , Zika virus , Infecção por Zika virus/imunologia , Camundongos Knockout , Testículo/imunologia , Testículo/virologiaRESUMO
In November 2022, the global human population reached 8 billion and is projected to reach 10 billion by 2060. Theories, models, and evidence indicate that global population growth (GPG) increases the likelihood of many adverse outcomes, such as biodiversity loss, climate change, mass migrations, wars, and resource shortages. A small body of research indicates that many individuals are concerned about the effects of GPG, and these concerns are strongly related to the willingness to engage in mitigative and preventative actions. However, scientific understanding of the factors that influence GPG risk perceptions remains limited. To help address this research gap, we conducted a study of the perceived risk of GPG among UK and US residents (N = 1029) shortly after the "8 billion milestone." Our results confirmed that GPG is perceived as a moderate-to-high risk and these perceptions have a strong positive relationship with the willingness to engage in and support risk management actions. Our participants believed that the worst effects of GPG were yet to come but would largely be geographically and socially remote. Despite their willingness to engage in risk management actions, our participants reported low self-efficacy and that governments (cf. individuals and communities) have the greatest capacity to influence GPG. Risk perceptions were strongly predicted by worldviews and were higher among our UK (cf. US) participants. We also found that the perceived benefits of GPG were low and found no evidence to suggest that risk perceptions were affected by exposure to media coverage of the 8 billion milestone.
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Crescimento Demográfico , Humanos , Estados Unidos , Reino Unido , Percepção , Medição de Risco , Feminino , Masculino , Risco , Adulto , Gestão de Riscos , Mudança ClimáticaRESUMO
Nitrogen (N) is an essential nutrient for crop growth and development, significantly influencing both yield and quality. Melatonin (MT), a known enhancer of abiotic stress tolerance, has been extensively studied. However, its relationship with nutrient stress, particularly N deficiency, and the underlying regulatory mechanisms of MT on N absorption remain unclear. In this study, exogenous MT treatment was found to improve the tolerance of apple plants to N deficiency. Apple plants overexpressing the MT biosynthetic gene N-acetylserotonin methyltransferase 9 (MdASMT9) were used to further investigate the effects of endogenous MT on low-N stress. Overexpression of MdASMT9 improved the light harvesting and heat transfer capability of apple plants, thereby mitigating the detrimental effects of N deficiency on the photosynthetic system. Proteomic and physiological data analyses indicated that MdASMT9 overexpression enhanced the trichloroacetic acid cycle and positively modulated amino acid metabolism to counteract N-deficiency stress. Additionally, both exogenous and endogenous MT promoted the transcription of MdHY5, which in turn bound to the MdNRT2.1 and MdNRT2.4 promoters and activated their expression. Notably, MT-mediated promotion of MdNRT2.1 and MdNRT2.4 expression through regulating MdHY5, ultimately enhancing N absorption. Taken together, these findings shed light on the association between MdASMT9-mediated MT biosynthesis and N absorption in apple plants under N-deficiency conditions.
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Malus , Melatonina , Melatonina/metabolismo , Malus/genética , Malus/metabolismo , Nitrogênio/metabolismo , Proteômica , Plantas Geneticamente Modificadas/genéticaRESUMO
Investigating immune memory to vaccinia virus and pre-existing immunity to mpox virus (MPXV) among the population is crucial for the global response to this ongoing mpox epidemic. Blood was sampled from vaccinees inoculated with vaccinia virus Tiantan (VTT) strain born before 1981 and unvaccinated control subjects born since 1982. After at least 40 years of the inoculation, 60% or 5% VTT vaccinees possess neutralizing antibodies (NAbs) to VTT or MPXV, with at least 50% having T cell memory to VTT protein antigens. Notably, 46.7% vaccinees show pre-existing T cell responses to MPXV. Broad pre-existing CD8+ T cell reactivities to MPXV are detected not only against conserved epitopes but also against variant epitopes between VTT and MPXV. Persistent NAbs and T cell memory to VTT among vaccinees, along with pre-existing T cells to MPXV among both vaccinees and the unvaccinated population, indicate a particular immune barrier to mpox.
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Mpox , Vaccinia virus , Humanos , Monkeypox virus , Imunidade Celular , Anticorpos Neutralizantes , China , Epitopos , Imunidade HumoralRESUMO
Multiple-input multiple-output (MIMO) detectors have been a key technology in communication systems. In this paper, a new MIMO detector is designed by combining the adaptive learning rate (ALR) with the convolutional neural network (CNN) and successfully implementing it in a mode division multiplexing (MDM) optical transmission system. The results show that the training and test accuracy of the signal in the system we proposed reaches 100%. What is more, we used the ALR-CNN to compare the performance with conventional detection algorithms. The results confirm that our DLNN exceeds the conventional MIMO detectors in performance and is able to achieve the ideal QPSK BER level. The minimum difference in the SNR is about 9.5 dB at a BER of the 10-3 order.
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Background: Disseminated tuberculosis is an uncommon but devastating form of tuberculosis, possibly developing with the immune response of patients. COVID-19 infection may produce an immunosuppressive effect with possible implications for tuberculosis dissemination. Case presentation: A 17-year-old female patient with a history of tuberculous pleurisy presented to the hospital with a high fever and life-threatening dyspnea after contracting a COVID-19 infection. Her condition deteriorated rapidly with grand mal epilepsy and acute gastrointestinal bleeding with a grossly depressed CD4 T-cell count, which was indicative of her profoundly immunosuppressed state. After identifying Mycobacterium tuberculosis in her cerebrospinal fluid and a subcutaneous abscess in her left lower back, she was diagnosed with disseminated tuberculosis involving both lungs, the central nervous system, the terminal ileum, the liver, bilateral adnexal tissue, and subcutaneous soft tissue in accordance with the chest and abdominal CT. Empirical treatment was initiated with dexamethasone (5 mg/day) and an anti-tuberculosis regimen of isoniazid, rifampicin, pyrazinamide, amikacin, and meropenem, which was replaced with faropenem after she left the hospital. The therapeutic effect was considered satisfied in the second month of follow-up. Conclusion: To the best of our knowledge, we report the first case report of disseminated tuberculosis after COVID-19 infection. Tuberculosis may disseminate and progress during the COVID-19 pandemic, requiring more significant studies to provide better diagnosis and treatment options for the co-infection.
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COVID-19 , Mycobacterium tuberculosis , Tuberculose Pleural , Humanos , Criança , Feminino , Adolescente , Pandemias , Isoniazida/uso terapêuticoRESUMO
In this paper, the graphdiyne (GDY)-polymethyl methacrylate (PMMA) films are prepared by a spin-coating method. The PMMA films have the function of isolating GDY from air and protecting the GDY from mechanical damage. The nonlinear optical properties of GDY-PMMA films are probed experimentally. The nonlinear optical responses of GDY-PMMA films with a modulation depth of â¼4.94% and saturated magnetization of â¼0.3M W/c m 2 are proved. When the GDY-PMMA films are applied to an erbium-doped hybrid passively mode-locked fiber laser (saturable absorber), the bound-state solitons, which are also called soliton molecules, can be obtained. The soliton molecule has a time separation of 13.31 ps, and the spectral modulation period of 0.58 nm. Along with the pump power increase, the separation of bound-state pulses becomes larger. When the pump power is fixed, stable bound solitons can be observed without any degeneration for more than 4.5 h. It is demonstrated that GDY-PMMA films have excellent nonlinear optical performance in a near-infrared regime, which we believe can be a novel type of photonics instrument and has a number of properties that are potentially promising in the ultrafast properties of laser.
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Understanding the nature of arsenic (As) adsorbed on FeIII oxyhydroxides, and the subsequent behavior of As during the crystallization process, is critical to predicting its fate in a range of natural and engineered settings. In this work, As adsorbed on FeIII oxyhydroxides formed in the different reaction media at different pH values were characterized with X-ray diffraction (XRD), Raman spectra, transmission electron microscopy (TEM), and extended X-ray absorption fine structure spectroscopy (EXAFS) to determine how As is redistributed during the crystallization process. Results showed that at pH 12, a quarter of the added As was still left in the liquid phase with the formation of goethite and hematite as the major and minor product. The concentration of As was found to be the lowest at pH 4 which is independent of the reaction media, indicating the importance of pH value in the crystallization process of the As adsorbed FeIII oxyhydroxides. Under acidic conditions, sulfate and chloride media favored the formation of goethite and hematite, respectively. Arsenic can indeed be incorporated into the structure of the formed goethite at pH 4. The morphology of the formed products changed to rhombus-like particles if both goethite and hematite appeared as the later as the dominant product.
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Excessive fructose intake is associated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD). The gut microbiome (GM) and bile acids (BAs) are involved in the pathogenesis of NAFLD, but the impact of fructose on their cross-talk is unclear. In this study, adult male C57BL/6J mice were fed a normal diet with tap water (ND) or with 4% fructose in the drinking water (Fru), 60% high-fat diet with tap water (HF) or with 4% fructose solution (HFF) for 12 weeks. Targeted BA analysis was performed in five anatomical sites including the liver, ileum contents, portal serum, cecum contents, and feces. Metagenomic sequencing was performed to explore gut dysbiosis. Within 12 weeks, the 4% fructose diet could initially stimulate gut dysbiosis and BA upregulation in the ileum, portal serum, and cecum when the intestinal and hepatic transport system remained stable without hepatic lipid accumulation. However, the chronic consumption of fructose promoted HF-induced NAFLD, with significantly increased body weight, impaired glucose tolerance, and advanced liver steatosis. BA transporters were inhibited in HFF, causing the block of internal BA circulation and increased BA secretion via cecum contents and feces. Notably, lithocholic acid (LCA) and its taurine conjugates were elevated within the enterohepatic circulation. Meanwhile, the Clostridium species were significantly altered in both Fru and HFF groups and were closely associated with fructose and BA metabolism. In summary, excessive fructose caused gut dysbiosis and BA alterations, promoting HF-induced NAFLD. The crosstalk between Clostridium sp. and LCA species were potential targets in fructose-mediated NAFLD.