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Peripheral sensory neurons widely innervate various tissues to continuously monitor and respond to environmental stimuli. Whether peripheral sensory neurons innervate the spleen and modulate splenic immune response remains poorly defined. Here, we demonstrate that nociceptive sensory nerve fibers extensively innervate the spleen along blood vessels and reach B cell zones. The spleen-innervating nociceptors predominantly originate from left T8-T13 dorsal root ganglia (DRGs), promoting the splenic germinal center (GC) response and humoral immunity. Nociceptors can be activated by antigen-induced accumulation of splenic prostaglandin E2 (PGE2) and then release calcitonin gene-related peptide (CGRP), which further promotes the splenic GC response at the early stage. Mechanistically, CGRP directly acts on B cells through its receptor CALCRL-RAMP1 via the cyclic AMP (cAMP) signaling pathway. Activating nociceptors by ingesting capsaicin enhances the splenic GC response and anti-influenza immunity. Collectively, our study establishes a specific DRG-spleen sensory neural connection that promotes humoral immunity, suggesting a promising approach for improving host defense by targeting the nociceptive nervous system.
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Peptídeo Relacionado com Gene de Calcitonina , Centro Germinativo , Imunidade Humoral , Baço , Animais , Masculino , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/farmacologia , AMP Cíclico/metabolismo , Dinoprostona/metabolismo , Gânglios Espinais/metabolismo , Centro Germinativo/imunologia , Camundongos Endogâmicos C57BL , Nociceptores/metabolismo , Proteína 1 Modificadora da Atividade de Receptores/metabolismo , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Transdução de Sinais , Baço/inervação , Baço/imunologia , FemininoRESUMO
Direct and precise monitoring of intracranial physiology holds immense importance in delineating injuries, prognostication and averting disease1. Wired clinical instruments that use percutaneous leads are accurate but are susceptible to infection, patient mobility constraints and potential surgical complications during removal2. Wireless implantable devices provide greater operational freedom but include issues such as limited detection range, poor degradation and difficulty in size reduction in the human body3. Here we present an injectable, bioresorbable and wireless metastructured hydrogel (metagel) sensor for ultrasonic monitoring of intracranial signals. The metagel sensors are cubes 2 × 2 × 2 mm3 in size that encompass both biodegradable and stimulus-responsive hydrogels and periodically aligned air columns with a specific acoustic reflection spectrum. Implanted into intracranial space with a puncture needle, the metagel deforms in response to physiological environmental changes, causing peak frequency shifts of reflected ultrasound waves that can be wirelessly measured by an external ultrasound probe. The metagel sensor can independently detect intracranial pressure, temperature, pH and flow rate, realize a detection depth of 10 cm and almost fully degrade within 18 weeks. Animal experiments on rats and pigs indicate promising multiparametric sensing performances on a par with conventional non-resorbable wired clinical benchmarks.
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Implantes Absorvíveis , Encéfalo , Hidrogéis , Monitorização Fisiológica , Ondas Ultrassônicas , Tecnologia sem Fio , Animais , Masculino , Ratos , Encéfalo/fisiologia , Hidrogéis/química , Concentração de Íons de Hidrogênio , Injeções/instrumentação , Pressão Intracraniana , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Ratos Sprague-Dawley , Porco Miniatura , Temperatura , Fatores de Tempo , Tecnologia sem Fio/instrumentaçãoRESUMO
Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.
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Eletromiografia , Eletrônica Médica , Nanoestruturas , Maleabilidade , Polímeros , Próteses e Implantes , Dispositivos Eletrônicos Vestíveis , Humanos , Nanoestruturas/química , Polímeros/química , Pele , Monitorização Fisiológica , Eletrônica Médica/instrumentação , Eletrônica Médica/métodos , Eletromiografia/instrumentaçãoRESUMO
Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.
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Eletrofisiologia , Polímeros , Água , Animais , alfa-Ciclodextrinas/química , Eletrodos , Eletrofisiologia/instrumentação , Eletrofisiologia/métodos , Eletrofisiologia/tendências , Coração , Músculos , Polietilenoglicóis/química , Polímeros/química , Seda/química , Aranhas , Água/química , Hidrogéis/química , Eletrônica/instrumentação , Eletrônica/métodos , Eletrônica/tendênciasRESUMO
Commercial chemicals are used extensively across urban centres worldwide1, posing a potential exposure risk to 4.2 billion people2. Harmful chemicals are often assessed on the basis of their environmental persistence, accumulation in biological organisms and toxic properties, under international and national initiatives such as the Stockholm Convention3. However, existing regulatory frameworks rely largely upon knowledge of the properties of the parent chemicals, with minimal consideration given to the products of their transformation in the atmosphere. This is mainly due to a dearth of experimental data, as identifying transformation products in complex mixtures of airborne chemicals is an immense analytical challenge4. Here we develop a new framework-combining laboratory and field experiments, advanced techniques for screening suspect chemicals, and in silico modelling-to assess the risks of airborne chemicals, while accounting for atmospheric chemical reactions. By applying this framework to organophosphate flame retardants, as representative chemicals of emerging concern5, we find that their transformation products are globally distributed across 18 megacities, representing a previously unrecognized exposure risk for the world's urban populations. More importantly, individual transformation products can be more toxic and up to an order-of-magnitude more persistent than the parent chemicals, such that the overall risks associated with the mixture of transformation products are also higher than those of the parent flame retardants. Together our results highlight the need to consider atmospheric transformations when assessing the risks of commercial chemicals.
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Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Atmosfera/química , Monitoramento Ambiental , Retardadores de Chama/efeitos adversos , Substâncias Perigosas/análise , Internacionalidade , Organofosfatos/efeitos adversos , Ar/análise , Poluentes Atmosféricos/química , Poluentes Atmosféricos/intoxicação , Animais , Bioacumulação , Cidades/estatística & dados numéricos , Simulação por Computador , Ecossistema , Retardadores de Chama/análise , Retardadores de Chama/intoxicação , Substâncias Perigosas/efeitos adversos , Substâncias Perigosas/química , Substâncias Perigosas/intoxicação , Humanos , Intoxicação por Organofosfatos , Organofosfatos/análise , Organofosfatos/química , Medição de RiscoRESUMO
The cross-species characterization of evolutionary changes in the functional genome can facilitate the translation of genetic findings across species and the interpretation of the evolutionary basis underlying complex phenotypes. Yet, this has not been fully explored between cattle, sheep, goats, and other mammals. Here, we systematically characterized the evolutionary dynamics of DNA methylation and gene expression in 3 somatic tissues (i.e. brain, liver, and skeletal muscle) and sperm across 7 mammalian species, including 3 ruminant livestock species (cattle, sheep, and goats), humans, pigs, mice, and dogs, by generating and integrating 160 DNA methylation and transcriptomic data sets. We demonstrate dynamic changes of DNA hypomethylated regions and hypermethylated regions in tissue-type manner across cattle, sheep, and goats. Specifically, based on the phylo-epigenetic model of DNA methylome, we identified a total of 25,074 hypomethylated region extension events specific to cattle, which participated in rewiring tissue-specific regulatory network. Furthermore, by integrating genome-wide association studies of 50 cattle traits, we provided novel insights into the genetic and evolutionary basis of complex phenotypes in cattle. Overall, our study provides a valuable resource for exploring the evolutionary dynamics of the functional genome and highlights the importance of cross-species characterization of multiomics data sets for the evolutionary interpretation of complex phenotypes in cattle livestock.
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Bovinos , Metilação de DNA , Cabras , Ovinos , Animais , Bovinos/genética , Cães , Humanos , Masculino , Camundongos , Estudo de Associação Genômica Ampla , Cabras/genética , Herança Multifatorial , Ovinos/genética , SuínosRESUMO
BACKGROUND: Characterization of regulatory variants (e.g., gene expression quantitative trait loci, eQTL; gene splicing QTL, sQTL) is crucial for biologically interpreting molecular mechanisms underlying loci associated with complex traits. However, regulatory variants in dairy cattle, particularly in specific biological contexts (e.g., distinct lactation stages), remain largely unknown. In this study, we explored regulatory variants in whole blood samples collected during early to mid-lactation (22-150 days after calving) of 101 Holstein cows and analyzed them to decipher the regulatory mechanisms underlying complex traits in dairy cattle. RESULTS: We identified 14,303 genes and 227,705 intron clusters expressed in the white blood cells of 101 cattle. The average heritability of gene expression and intron excision ratio explained by cis-SNPs is 0.28 ± 0.13 and 0.25 ± 0.13, respectively. We identified 23,485 SNP-gene expression pairs and 18,166 SNP-intron cluster pairs in dairy cattle during early to mid-lactation. Compared with the 2,380,457 cis-eQTLs reported to be present in blood in the Cattle Genotype-Tissue Expression atlas (CattleGTEx), only 6,114 cis-eQTLs (P < 0.05) were detected in the present study. By conducting colocalization analysis between cis-e/sQTL and the results of genome-wide association studies (GWAS) from four traits, we identified a cis-e/sQTL (rs109421300) of the DGAT1 gene that might be a key marker in early to mid-lactation for milk yield, fat yield, protein yield, and somatic cell score (PP4 > 0.6). Finally, transcriptome-wide association studies (TWAS) revealed certain genes (e.g., FAM83H and TBC1D17) whose expression in white blood cells was significantly (P < 0.05) associated with complex traits. CONCLUSIONS: This study investigated the genetic regulation of gene expression and alternative splicing in dairy cows during early to mid-lactation and provided new insights into the regulatory mechanisms underlying complex traits of economic importance.
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Lactação , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Animais , Bovinos/genética , Lactação/genética , Feminino , Splicing de RNA , Estudo de Associação Genômica Ampla , Perfilação da Expressão Gênica , Íntrons , TranscriptomaRESUMO
Understanding how life's essential homochiral biopolymers arose from racemic precursors is a challenging quest. Herein, we present a groundbreaking approach involving hierarchical chiral assembly-driven stereoselective ring-opening polymerization of ε-benzyloxycarbonyl-l/d-lysine N-carboxyanhydrides assisted by ultrasonication in an aqueous medium. This method enabled a narrow dispersity within a few minutes and the achievement of high molecular weight for polypeptides, employing a living polymerization mechanism. The polymerization of l and d enantiomers yielded predominantly right- and left-handed superhelical assemblies in a one-pot preparation, respectively. Notably, stereoselective polypeptide segments were efficiently prepared through hierarchical assembly-driven polymerization of racemic monomers in the absence of a catalyst. This research offers an innovative strategy for the convenient preparations of stereoenriched polypeptides and, more importantly, sheds light on the plausible emergence of homochiral peptides in the origin of life.
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Arsenic trioxide is an essential component of therapy for acute promyelocytic leukaemia (APL) and is currently dosed on actual body weight with no upper limit. Arsenic-induced neurotoxicity is a well-recognised complication; however, there is uncertainty about its relationship to arsenic dose and obesity. We conducted a large multicentre retrospective study of 487 patients with APL treated with arsenic-based therapy across 23 sites in Australia from 2008 to 2023. The primary outcome was incidence of neurotoxicity, and secondary outcomes included relationship of neurotoxicity to obesity and cumulative arsenic dose. Any-grade neurotoxicity occurred in 113 (23%) patients, predominantly peripheral neuropathy (91%). Most events were grade 1-2 severity (85%), with grade 3 events in 12% and grade 4-5 in 3%. The incidence of neurotoxicity increased with BMI (non-obese: 16%, obesity class I: 25%, obesity class II-III: 41%; p < 0.001). On univariable analysis, obesity class I (OR 1.81, p = 0.036), obesity class II-III (OR 3.93, p < 0.001), weight >100 kg (OR 2.72, p < 0.001), daily arsenic trioxide dose >15 mg (OR 5.05, p < 0.001) and cumulative induction dose >500 mg (OR 3.95, p < 0.001) were all significantly associated with neurotoxicity. Obesity class II-III and induction dose >500 mg remained significant on multivariable analysis. Our study highlights the strong association between BMI, arsenic trioxide dose and neurotoxicity. Pre-emptive dose reductions should be considered for obese patients receiving high doses of arsenic.
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Trióxido de Arsênio , Leucemia Promielocítica Aguda , Síndromes Neurotóxicas , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Trióxido de Arsênio/efeitos adversos , Trióxido de Arsênio/administração & dosagem , Trióxido de Arsênio/uso terapêutico , Idoso , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/epidemiologia , Obesidade/complicações , Austrália/epidemiologia , Arsênio/efeitos adversos , Arsênio/toxicidade , Adulto Jovem , Adolescente , Idoso de 80 Anos ou maisRESUMO
Interleukin-32 is a species-specific cytokine that plays an important role in inflammation, cancer, and other diseases; however, its role in reproductive and pregnancy-related diseases remains unknown. This study aimed to investigate the role of interleukin-32 in reproductive and pregnancy-related diseases. Placental tissues from patients with pregnancy-induced hypertension, healthy pregnant women, and trophoblast lines were analysed. Interleukin-32 expression was quantified via polymerase chain reaction and immunohistochemistry, and functional assays were performed after interleukin-32 modulation. Interleukin-32 was identified only in placental mammals, such as Carnivora, Cetartiodactyla, Chiroptera, Dermoptera, Lagomorpha, Perissodactyla, and Primates via bioinformatics. Immunohistochemistry and polymerase chain reaction revealed that interleukin-32 was highly expressed in human placental villi, poorly expressed in decidua and endometrial tissues, and was not detected in mouse tissues. Second, interleukin-32 upregulates miR-205 expression by increasing DROSHA expression, and miR-205 promotes interleukin-32 expression by targeting its promoter region. Interleukin-32 and miR-205 significantly enhanced the invasion ability of HTR8/SVneo cells (a trophoblast cell line) and the tube formation ability of human umbilical vein endothelial cells. Through quantitative reverse transcription polymerase chain reaction and western blotting, the interleukin-32/miR-205 loop increased MMP2 and MMP9 expression in HTR-8/SVneo cells via the nuclear factor kappa B signalling pathway. Finally, using quantitative reverse transcription polymerase chain reaction, interleukin-32 and miR-205 expression levels were significantly lower in the placentas of patients with pregnancy-induced hypertension than in women with normal pregnancies. In conclusion, interleukin-32 regulates trophoblast invasion through the miR-205-nuclear factor kappa B-MMP2/9 pathway, which is involved in pregnancy-induced hypertension.
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Plant cell deformations are driven by cell pressurization and mechanical constraints imposed by the nanoscale architecture of the cell wall, but how these factors are controlled at the genetic and molecular levels to achieve different types of cell deformation is unclear. Here, we used stomatal guard cells to investigate the influences of wall mechanics and turgor pressure on cell deformation and demonstrate that the expression of the pectin-modifying gene PECTATE LYASE LIKE12 (PLL12) is required for normal stomatal dynamics in Arabidopsis thaliana. Using nanoindentation and finite element modeling to simultaneously measure wall modulus and turgor pressure, we found that both values undergo dynamic changes during induced stomatal opening and closure. PLL12 is required for guard cells to maintain normal wall modulus and turgor pressure during stomatal responses to light and to tune the levels of calcium crosslinked pectin in guard cell walls. Guard cell-specific knockdown of PLL12 caused defects in stomatal responses and reduced leaf growth, which were associated with lower cell proliferation but normal cell expansion. Together, these results force us to revise our view of how wall-modifying genes modulate wall mechanics and cell pressurization to accomplish the dynamic cellular deformations that underlie stomatal function and tissue growth in plants.
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Proteínas de Arabidopsis/fisiologia , Arabidopsis/fisiologia , Estômatos de Plantas/fisiologia , Polissacarídeo-Liases/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Fenômenos Biomecânicos , Estômatos de Plantas/genética , Polissacarídeo-Liases/genéticaRESUMO
Morphine is a widely used opioid for the treatment of pain. Differences in drug transporter expression and activity may contribute to variability in morphine pharmacokinetics and response. Using appropriate mouse models, we investigated the impact of the efflux transporters ABCB1 and ABCG2 and the OATP uptake transporters on the pharmacokinetics of morphine, morphine-3-glucuronide (M3G), and M6G. Upon subcutaneous administration of morphine, its plasma exposure in Abcb1a/1b-/-;Abcg2-/--, Abcb1a/1b-/-;Abcg2-/-;Oatp1a/1b-/-;Oatp2b1-/- (Bab12), and Oatp1a/1b-/-;Oatp2b1-/- mice was similar to that found in wild-type mice. Forty minutes after dosing, morphine brain accumulation increased by 2-fold when mouse (m)Abcb1 and mAbcg2 were ablated. Relative recovery of morphine in small intestinal content was significantly reduced in all the knockout strains. In the absence of mOatp1a/1b and mOatp2b1, plasma levels of M3G were markedly increased, suggesting a lower elimination rate. Moreover, Oatp-deficient mice displayed reduced hepatic and intestinal M3G accumulation. Mouse Oatps similarly affected plasma and tissue disposition of subcutaneously administered M6G. Human OATP1B1/1B3 transporters modestly contribute to the liver accumulation of M6G. In summary, mAbcb1, in combination with mAbcg2, limits morphine brain penetration and its net intestinal absorption. Variation in ABCB1 activity due to genetic polymorphisms/mutations and/or environmental factors might, therefore, partially affect morphine tissue exposure in patients. The ablation of mOatp1a/1b increases plasma exposure and decreases the liver and small intestinal disposition of M3G and M6G. Since the contribution of human OATP1B1/1B3 to M6G liver uptake was quite modest, the risks of undesirable drug interactions or interindividual variation related to OATP activity are likely negligible.
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Camundongos Knockout , Derivados da Morfina , Morfina , Animais , Morfina/farmacocinética , Morfina/metabolismo , Derivados da Morfina/metabolismo , Derivados da Morfina/sangue , Camundongos , Distribuição Tecidual , Masculino , Encéfalo/metabolismo , Analgésicos Opioides/farmacocinética , Analgésicos Opioides/metabolismo , Analgésicos Opioides/sangue , Camundongos Endogâmicos C57BL , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Fígado/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genéticaRESUMO
We report the continuous-wave (cw) difference-frequency generation (DFG) in a ZnGeP2 (ZGP) crystal that produces tunable long-wavelength infrared (LWIR) lasing. Particularly, we experimentally demonstrate the feasibility to drive DFG in ZGP by all-fiber near-infrared fiber lasers consisting of a 1.3â µm tunable cw random Raman fiber laser (RRFL) and a 1.5â µm erbium-doped fiber amplifier seeded by a tunable distributed feedback (DFB) laser, making the whole system compact and robust. As a result, the demonstrated LWIR DFG presents a broadband spectral tuning range spanning from 9.5 to 11.5â µm, and the output powers in the spectral range of 9.5-11â µm are larger than 40â µW pumped by watt-level fiber lasers. Meanwhile, as a typical application, a proof-of-concept demonstration of gas sensing of SF6 is executed based on the generated cw LWIR source. Our work demonstrates that the combination of ZGP crystal and fiber lasers can provide an effective and robust approach for the generation of cw LWIR radiation with useful power and broadband wavelength tunability.
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KEY MESSAGE: The first single dominant resistance gene contributing major resistance to the oomycete pathogen Phytophthora sansomeana was identified and mapped from soybean 'Colfax'. Phytophthora root rot (PRR) is one of the most important diseases in soybean (Glycine max). PRR is well known to be caused by Phytophthora sojae, but recent studies showed that P. sansomeana also causes extensive root rot of soybean. Depending upon the isolate, it might produce aggressive symptoms, especially in seeds and seedlings. Unlike P. sojae which can be effectively managed by Rps genes, no known major resistance genes have yet been reported for P. sansomeana. Our previous study screened 470 soybean germplasm lines for resistance to P. sansomeana and found that soybean 'Colfax' (PI 573008) carries major resistance to the pathogen. In this study, we crossed 'Colfax' with a susceptible parent, 'Senaki', and developed three mapping populations with a total of 234 F2:3 families. Inheritance pattern analysis indicated a 1:2:1 ratio for resistant: segregating: susceptible lines among all the three populations, indicating a single dominant gene conferring the resistance in 'Colfax' (designated as Rpsan1). Linkage analysis using extreme phenotypes anchored Rpsan1 to a 30 Mb region on chromosome 3. By selecting nine polymorphic SNP markers within the region, Rpsan1 was genetically delimited into a 21.3 cM region between Gm03_4487138_A_C and Gm03_5451606_A_C, which corresponds to a 1.06 Mb genomic region containing nine NBS-LRR genes based on Gmax2.0 assembly. The mapping results were then validated using two breeding populations derived from 'E12076T-03' × 'Colfax' and 'E16099' × 'Colfax'. Marker-assisted resistance spectrum analyses with 9 additional isolates of P. sansomeana indicated that Rpsan1 may be effective towards a broader range of P. sansomeana isolates and has strong merit in protecting soybean to this pathogen in the future.
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Glycine max , Phytophthora , Humanos , Glycine max/genética , Melhoramento Vegetal , Genes Dominantes , GenômicaRESUMO
KEY MESSAGE: A total of 416 InDels and 112 SNPs were significantly associated with soybean photosynthesis-related traits. GmIWS1 and GmCDC48 might be related to chlorophyll fluorescence and gas-exchange parameters, respectively. Photosynthesis is one of the main factors determining crop yield. A better understanding of the genetic architecture for photosynthesis is of great significance for soybean yield improvement. Our previous studies identified 5,410,112 single nucleotide polymorphisms (SNPs) from the resequencing data of 219 natural soybean accessions. Here, we identified 634,106 insertions and deletions (InDels) from these 219 accessions and used these InDel variations to perform principal component and linkage disequilibrium analysis of this population. The genome-wide association study (GWAS) were conducted on six chlorophyll fluorescence parameters (chlorophyll content, light energy absorbed per reaction center, quantum yield for electron transport, probability that a trapped exciton moves an electron into the electron transport chain beyond primary quinone acceptor, maximum quantum yield of photosystem II primary photochemistry in the dark-adapted state, performance index on absorption basis) and four gas-exchange parameters (intercellular carbon dioxide concentration, stomatal conductance, net photosynthesis rate, transpiration rate) and revealed 416 significant InDels and 112 significant SNPs. Based on GWAS results, GmIWS1 (encoding a transcription elongation factor) and GmCDC48 (encoding a cell division cycle protein) with the highest expression in the mapping region were determined as the candidate genes responsible for chlorophyll fluorescence and gas-exchange parameters, respectively. Further identification of favorable haplotypes with higher photosynthesis, seed weight and seed yield were carried out for GmIWS1 and GmCDC48. Overall, this study revealed the natural variations and candidate genes underlying the photosynthesis-related traits based on abundant phenotypic and genetic data, providing valuable insights into the genetic mechanisms controlling photosynthesis and yield in soybean.
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Estudo de Associação Genômica Ampla , Glycine max , Glycine max/genética , Estudo de Associação Genômica Ampla/métodos , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Fotossíntese/genética , Clorofila/metabolismoRESUMO
Canavalia gladiata leaf extract (CGLE) is extracted from crop waste employing a water decoction method. By employing electrochemical techniques, morphology analysis, quantum chemical calculations, and other methods, we extensively investigated the anticorrosion efficacy of CGLE on copper within a H2SO4 solution. The outcomes reveal that at 298 K, a CGLE concentration of 800 mg/L attains a remarkable inhibition efficiency (IE) of 96.8%. Additionally, we examined the impact of CGLE on the corrosion resistance of copper at varying temperatures. Even with rising temperatures, CGLE manages to sustain an IE of over 95%. This indicates that CGLE is mainly chemisorption based on the copper, leading to a strong adsorption. The surface test results show a noteworthy decrease in the extent of copper surface corrosion upon the introduction of CGLE. The study of the adsorption model demonstrates the alignment of CGLE adsorption onto the copper with the Langmuir adsorption.
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BACKGROUND: Tumor microenvironment (TME) heterogeneity is an important factor affecting the treatment response of immune checkpoint inhibitors (ICI). However, the TME heterogeneity of melanoma is still widely characterized. METHODS: We downloaded the single-cell sequencing data sets of two melanoma patients from the GEO database, and used the "Scissor" algorithm and the "BayesPrism" algorithm to comprehensively analyze the characteristics of microenvironment cells based on single-cell and bulk RNA-seq data. The prediction model of immunotherapy response was constructed by machine learning and verified in three cohorts of GEO database. RESULTS: We identified seven cell types. In the Scissor+ subtype cell population, the top three were T cells, B cells and melanoma cells. In the Scissor- subtype, there are more macrophages. By quantifying the characteristics of TME, significant differences in B cells between responders and non-responders were observed. The higher the proportion of B cells, the better the prognosis. At the same time, macrophages in the non-responsive group increased significantly. Finally, nine gene features for predicting ICI response were constructed, and their predictive performance was superior in three external validation groups. CONCLUSION: Our study revealed the heterogeneity of melanoma TME and found a new predictive biomarker, which provided theoretical support and new insights for precise immunotherapy of melanoma patients.
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Imunoterapia , Melanoma , Análise de Sequência de RNA , Análise de Célula Única , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Melanoma/genética , Melanoma/terapia , Melanoma/imunologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Aprendizado de Máquina , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Prognóstico , Linfócitos B/imunologiaRESUMO
The high environmental concentrations, persistence, and toxicity of synthetic musk compounds (SMCs) necessitate a better grasp of their fate in wastewater treatment plants (WWTPs). To investigate the importance of WWTPs as pathways of SMCs to the environment, air and wastewater samples were collected at four WWTPs in Ontario, Canada. Polycyclic musks (PCMs) were present at higher concentrations than nitro musks (NMs) and macrocyclic musks (MCMs). Three PCMs [galaxolide (HHCB), tonalide (AHTN), and iso-E super (OTNE)] were the most abundant compounds (0.30-680 ng/m3 in air, 0.40-15 µg/L in influent, and 0.007-6.0 µg/L in effluent). Analyses of multiyear data suggest that risk management measures put in place have been effective in reducing the release of many SMCs into the environment. The highest removal efficiency, up to almost 100% of some SMCs, was observed for the plant with the longest solid retention time. A fugacity-based model was established to simulate the transport and fate of SMCs in the WWTP, and good agreement was obtained between the measured and modeled values. These findings indicate that the levels of certain SMCs discharged into the atmospheric and aquatic environments were substantial, potentially resulting in exposure to both humans and wildlife.
Assuntos
Ácidos Graxos Monoinsaturados , Poluentes Químicos da Água , Purificação da Água , Humanos , Poluentes Químicos da Água/análise , Águas Residuárias , Ontário , Benzopiranos/análiseRESUMO
Metasurfaces have garnered significant attention in recent years due to their substantial electromagnetic (EM) wave manipulation capabilities. However, most previously documented metasurfaces have been limited to controlling just a single EM wave mode, encompassing transmission, reflection, or absorption. Such limitations have impeded the broader applications of metasurfaces. To address this issue, this study introduces a multi-functional metasurface (MFM) in the utilization of Ge2Sb2Te5 (GST), vanadium dioxide (VO2), and graphene. This novel design enables real-time control over the transmission, absorption, and reflection of EM waves as necessitated through thermal control, allowing for seamless transitions from complete transmission to complete reflection. Furthermore, this configuration achieves extensive broadband perfect absorption, spanning up to 1.83 THz. The optical response mechanism of this MFM across distinct operational modes is meticulously analyzed through electric field distribution. Remarkably, this proposed MFM exhibits polarization insensitivity and maintains good optical performance even under conditions of wide-angle incidence. With the ability to switch to different operating modes according to the needs of different environments, the proposed MFM has the potential to be used in a wide range of scenarios, including radar stealth, wireless communications, and military search.
RESUMO
Reduced empathy and elevated alexithymia are observed in autism spectrum disorder (ASD), which has been linked to altered asymmetry in brain morphology. Here, we investigated whether trait autism, empathy, and alexithymia in the general population is associated with brain morphological asymmetry. We determined left-right asymmetry indexes for cortical thickness and cortical surface area (CSA) and applied these features to a support-vector regression model that predicted trait autism, empathy, and alexithymia. Results showed that less leftward asymmetry of CSA in the gyrus rectus (a subregion of the orbitofrontal cortex) predicted more difficulties in social functioning, as well as reduced cognitive empathy and elevated trait alexithymia. Meta-analytic decoding of the left gyrus rectus annotated functional items related to social cognition. Furthermore, the link between gyrus rectus asymmetry and social difficulties was accounted by trait alexithymia and cognitive empathy. These results suggest that gyrus rectus asymmetry could be a shared neural correlate among trait alexithymia, cognitive empathy, and social functioning in neurotypical adults. Left-right asymmetry of gyrus rectus influenced social functioning by affecting the cognitive processes of emotions in the self and others. Interventions that increase leftward asymmetry of the gyrus rectus might improve social functioning for individuals with ASD.