Human T lymphotropic virus 1 (HTLV-1) is a public health issue for most countries and imposes important consequences on patients' health and socioeconomic status. Brazil is one of the global leaders of the public health response to these viruses. The country has challenges to overcome to implement meaningful policies aiming to eliminate HTLV-1/2. An analysis of strengths, weaknesses, opportunities, and threats (SWOT) for the implementation of public health policies on HTLV-1/2 was performed. The strengths identified were the Brazilian Unified Health System (SUS); Brazilian expertise in public health programs successfully implemented; currently available policies targeting HTLV; and strong collaboration with researchers and patient's representative. Lack of awareness about HTLV, insufficient epidemiological data, lack of reference centers for patient care, insufficient availability of confirmatory tests, lack of universal antenatal screening, and absence of cost-effectiveness studies were identified as weaknesses. Some interesting opportunities included the increased interest from international organizations on HTLV, possibility of integrating HTLV into other programs, external funding for research, available online platforms, opportunity to acquire data from HTLV-1/2 surveillance to gather epidemiological information, and HTLV policies that were implemented independently by states and municipalities. In addition to the COVID-19 pandemic, existing demands from different diseases, the country's demography and its marked sociocultural diversity and the volatility of the technical team working with HTLV-1/2 at the Brazilian Ministry of Health are threats to the implementation of public policies on HTLV-1/2. This SWOT analysis will facilitate strategic planning to allow continuous progress of the Brazilian response to HTLV-1/2 infection. Human T-lymphotropic virus (HTLV) is a public health issue for most countries. HTLV-1 was identified as the first human oncogenic retrovirus in 1980, and since then, few strategies have been implemented to control it. It is estimated that at least 5–10 million individuals are infected by HTLV-1 globally. However, there are major gaps in the epidemiology of infection, which create difficulties in assessing its public health burden and evaluating policies that favor the prevention and control of HTLV-1/2 (HTLV-1 is the etiologic agent of adult T cell leukemia lymphoma (ATLL), an aggressive neoplasm, and HTLV-1-associated myelopathy (HAM), a chronic severe myelopathy . This viSWOT analysis is a strategic planning technique that is commonly used in business planning to evaluate an organization's strategic position. The analysis comprises four core elements: strengths, weaknesses, opportunities, and threats. Here, a SWOT analysis is employed to achieve a situational evaluation of the implementation of public health policies for HTLV in Brazil to facilitate future strategic planning .Based on SWOT Analysis, governments can choose the appropriate strategy. The analysis' process for this study started by identifying the strategic management process and conducting an external and internal analysis. The external analysis identified the critical threats and opportunities for the implementation of HTLV related policies in the competitive Brazilian health scenario. While external analysis focused on the environmental threats and opportunities, internal analysis helped to identify structural strengths and weaknesses associated with HTLV policies and understanding which resources and capabilities are likely to be sources of reasonable advantage.The analysis was conducted by reviewing Brazilian official documents and papers related to HTLV approaches in Brazil and using researchers, government managers and non-governmental experiences and expertise regarding health policies in Brazil.Four strengths, i.e., what the Brazilian Ministry of Health (BMoH) excels at, were identified: the Brazilian Unified Health System, successful health programs already implemented in Brazil, specific policies on HTLV-1/2 that are already available in the country and the strong collaboration with HTLV experts and patient representatives.Sistema Único de Saúde, SUS). The SUS was proposed in the late 1980s and has been widely acknowledged as an example of successful health system reform in Latin America. It was structured on three principles: universality, comprehensiveness, and equity ; the “Mais Médicos Program,” recently renamed to “Doctors for Brazil,” which aims to meet a demand for the absence or scarcity of health professionals in regions with populations of higher vulnerability; the national system for organ and bone marrow donation and transplantation; the psychosocial care network; and the Popular Pharmacy Program that aims to supply essential medicines. In addition to the drugs offered by the popular pharmacy, there are drugs that are considered strategic and used for the treatment of diseases with an endemic profile that have a socioeconomic impact, such as for STI/AIDS , endemic diseases , thalidomide for systemic lupus erythematosus, multiple myeloma, hematological diseases and blood products, influenza and drugs and supplies for tobacco control .https://www.unasus.gov.br/). From this same perspective, the Virtual Learning Environment of the Unified Health System (AVASUS), which is also a virtual learning space developed for professionals and students in the health area and for civil society, has been implemented, and its main objective is to improve training, management and assistance in the SUS. AVASUS has ~2 million registrations, and a total of 315 active courses. One of them is the Course on Comprehensive Care for People with Sexually Transmitted Infections, which was a partnership with BMoH, PAHO and the Federal University of Rio Grande do Norte. The course is presented with subtitles in Spanish and English and includes a module about HTLV infection (https://avasus.ufrn.br/).The SUS has also presented some strategies for professional development and health education. Telessaúde  is a nationwide initiative that seeks to improve the quality of care and primary care in the SUS, integrating education and service through information technology tools, which offer conditions to promote tele-assistance and tele-education for health professionals. Additionally, the Open University System of the SUS (UNA-SUS) was implemented for professional training and continuing education needs. This system has a collaborative network that includes more than 35 higher education institutions that offer free online courses. UNA-SUS has more than 4.9 million enrollments, and more than 355 courses are offered nationwide  had laboratory services to support patient care, and only nine had a multidisciplinary team. There is also an unequal distribution of those centers, with the lowest numbers located in the North region . It is ihttp://htlv.eu/)  and the National HIV-1 and hepatitis B (HBV) networks. A hub-spoke system, such as that observed for patient care in services linked to universities that are similar to the Nacional Centre of Human Retrovirology (NCHR) in the UK (tlv.eu/) , could bConfirmatory testing for HTLV-1/2 infection is needed but is not offered for all individuals with a positive result on the screening test , 32. PCRPrevention of mother-to-child transmission is considered a priority; however, antenatal national screening has not been implemented nationally in Brazil. The BMoH recommends cabergoline for seropositive mothers and provision of formula for babies who are born to seropositive mothers . OptimalCost-effectiveness analyses are extremely limited in the HTLV-1/2 field and hampered by the lack of key information –37 but aDifferent opportunities were identified: increased prioritization by international organizations on HTLV, possibility of including HTLV in other programs, external funding for research, availability of online platforms, opportunity to acquire data from HTLV-1/2 surveillance to gather epidemiological information, and policies on HTLV that have already been implemented by some states and municipalities. Taking advantage of these timely opportunities will foster the implementation of policies on HTLV-1/2 in the country.https://www.youtube.com/channel/UCI6aLSTtk7chXMeybJ92Fhw).International organizations have been showing increased attention to HTLV. In 2019, the WHO held a global consultation on HTLV, which was followed by the publication of a fact sheet  and a teThis increased focus on HTLV-1/2 is catalytical for the implementation of policies by WHO Member States and facilitates the introduction of HTLV-1/2 into the governmental agenda. The HTLV community should take advantage of this opportunity to push for the advancement of public health policies toward this virus.The association of HTLV-1/2 with existing platforms, such as STIs, maternal health, and indigenous health, is an interesting alternative for optimizing resources. In fact, the inclusion of HTLV-1/2 in the Department of Chronic Diseases and STIs was beneficial and should be further put forward as universal knowledge in the country. The inclusion of HTLV-1/2 in awareness campaigns for other STIs is of utmost importance. This represents an opportunity, and policymakers need to take advantage of the network and human resources that are available for those programs to implement public health policies for HTLV. Apparently, there is no other country publishing specific guidelines to prevent sexual transmission of HTLV. In Brazil, HTLV has been included recently in the clinical protocol and therapeutic guidelines for sexually transmitted infections (STI) .The BMoH promotes scientific and technological development in the country by funding research projects in each of the Brazilian states in partnership with the research program for the SUS. In addition, there are possibilities with the Program for Institutional Development of SUS (PROADI-SUS); this is a program through which non-profit hospital institutions develop projects using their skills to qualify and develop processes to improve the assistance provided by SUS throughout Brazil. Presently, six hospitals of national excellence participate in this program. Additionally, there are national calls for partnerships with other federal ministerial areas and international agencies, including the Ministry of Science and Technology and PAHO. Recently, HTLV was included in two research opportunities that are currently underway. In 2019, the PROADI-SUS approved a project to assess the national prevalence of HTLV and other STIs and patterns of sexual behavior among pregnant women.In 2021, the BMoH, in partnership with PAHO, co-founded a project conducted by public universities in the north, northeast and midwest regions on the implementation of HTLV laboratory diagnosis in Brazil. This project aims to expand the network for diagnosing HTLV-1/2 infection in six Brazilian capitals and to characterize the types and subtypes of HTLV-1/2 that are circulating in the Brazilian population. The project was initially funded by the National Council for Scientific and Technological Development in the Ministry of Science and Technology and the Brazilian Ministry of Health, initiated in 2019 in a partnership with the State Health Department of Para, Special Indigenous Sanitary District (DESAI) and Special Secretariat for Indigenous Health (SESAI) and 13 other research institutions. A large and comprehensive seroepidemiological study will provide specific and updated information in 11 states, from at least 6,000 persons from 50 population groups residing in urban, rural and indigenous areas. It is expected that at the end, this study will provide a more reliable figure of the prevalence of HTLV-1/2. Vulnerable populations, including quilombola , female sex workers (FSW), men who have sex with men (MSM), and indigenous communities, will be investigated, and full support will be provided, including training and information teaching programs for health professionals from the DSEI/SESAI and the preparation of an informational leaflet in indigenous languages. It is expected that such an opportunity will also help DESAI/SESAI to understand the current epidemiological situation of indigenous people.However, this should be expanded, and collaboration between these institutions and patient representatives and specialists should be supported. Some key areas for research were identified as (1) the development of a rapid, cost-effective point-of-care screening test, (2) the proposal of multicentric studies with validated methodologies for standardizing the diagnosis of HTLV-1/2 in the national territory; (3) the evaluation of HTLV mother-to-child transmission and policies to prevent vertical transmission; (4) cost-effectiveness studies; and (5) the development of new therapies and care for HTLV-1-associated diseases.https://www.youtube.com/channel/UCI6aLSTtk7chXMeybJ92Fhw)].Social media has played an important role in sharing health-related information. In recent years, the BMoH has been increasingly using their social media platforms to advertise about HTLV . There aHTLV-1/2 screening of blood and organ donors has been performed in the country for decades. However, these data have not been routinely used to inform policymakers about HTLV-1/2 prevalence and distribution. Although the burden of infection in this specific population may underestimate the real burden of HTLV-1/2 infection, it can be a starting point for those areas of the country where there are no data available about HTLV-1/2 distribution as has been done recently in China .Different states and municipalities have implemented policies for HTLV-1/2 independent of national financial support. Bahia, considered the epicenter of HTLV-1 infection in Brazil, has approved a program for the integral care of patients with HTLV infection . This shBrazil's demography and sociocultural diversity, demands of different health problems, including the COVID-19 pandemic, and the volatility of the technical team working on HTLV-1/2 at the BMoH are common causes hampering the implementation of policies toward HTLV-1/2 and therefore are considered threats.2, with more than 214 million individuals distributed in five different geographical regions. According to the International Monetary Fund the country is considered of medium income. The illiteracy rate of the population aged 15 and over in Brazil is 7.0% (2017). This rate varies across the country, being higher in the North and Northeast regions when compared to the South and Southeast. The country is marked by great sociocultural diversity and inequal income distribution. Its municipalities are highly diverse in terms of population size, structure of local and regional health systems, and the private sector's greater or lesser presence in some regions , neglected tropical infections, and recurrent epidemics. In 2016, NCDs were the leading cause of death, followed by interpersonal violence, but infectious diseases were still common causes . In thisThe pandemic caused by SARS-CoV-2 disrupted the health care system in every country worldwide . In BrazThe implementation of policies for preventing and controlling HTLV-1/2 infection are usually long-term actions that require long-term planning. Continuity needs to be guaranteed, despite changes in government parties. There is a need to assure that these policies, which will benefit the population in the short- and long-term period, should be dealt with as a country rather than as a government policy. The volatility of the technical team at the BMoH responsible for the HTLV response is detrimental to the continuous progress of policies on HTLV-1/2 in the country. It is also important to highlight that the volatility of state and municipal health teams in the public system may also impact the implementation of policies. The high turnover of health teams in public clinics, can impair patient's care, as it may be difficult to do a long-term follow-up of HTLV patients, individuals with life-long infection, and who usually present chronic diseases, impacting the quality of the service offered.HTLV-1/2 antenatal screening should be considered a priority. The expansion of confirmatory tests to all individuals with a positive screening test is needed. Mapping local policies to HTLV-1/2 in different Brazilian states will be beneficial for evaluating policies that can be easily expanded to a national level. The integration of HTLV-1/2 into existing programs and available networks may be achieved in a short-term period and at relatively low cost. A network comprising regional reference centers and local linked services needs to be organized. Training of healthcare professionals is essential to the success of every proposed policy.The government needs to continuously work in partnership with the scientific community and non-governmental organizations to increase the visibility of the HTLV infection. It should be interesting to support, whenever possible, initiatives proposed by partners, such as the propagation of National HTLV Day and World HTLV Day, and to expand the information network on HTLV-1/2. The conjunction of efforts between the government, health professionals and the scientific community, in addition to the active participation of organized civil society, provides conditions for adequately addressing HTLV-1/2 infection and its complications in the country.In conclusion, this analysis may help policymakers to develop a strategic planning with short and long-term goals to improve Brazil's response to HTLV-1/2 infection to facilitate the implementation of recommended policies targeting HTLV that were recently published . In addiThe original contributions presented in the study are included in the article/AM, CR, and RI conceptualized the manuscript. AM and CR drafted the initial manuscript. AM, CR, TA, GP, AV, and RI wrote and critically revised the final manuscript. All authors approved the final version of the manuscript.The authors acknowledge the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq (Research grants RI #312979/2018-5 and ACRV #301869/2017-0), the Brazilian Ministry of Health, the Pan American Health Organization and the Universidade Federal do Para (UFPA), PROPESP/2022, for their generous financial support.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This review discusses the SnRK1 signaling associated with different subcellular compartments and how this compartmentalization may contribute to the multitasking role of the SnRK1 complex. SNF1-related protein kinase 1 (SnRK1), the plant ortholog of mammalian AMP-activated protein kinase/fungal (yeast) Sucrose Non-Fermenting 1 (AMPK/SNF1), plays a central role in metabolic responses to reduced energy levels in response to nutritional and environmental stresses. SnRK1 functions as a heterotrimeric complex composed of a catalytic α- and regulatory β- and βγ-subunits. SnRK1 is a multitasking protein involved in regulating various cellular functions, including growth, autophagy, stress response, stomatal development, pollen maturation, hormone signaling, and gene expression. However, little is known about the mechanism whereby SnRK1 ensures differential execution of downstream functions. Compartmentalization has been recently proposed as a new key mechanism for regulating SnRK1 signaling in response to stimuli. In this review, we discuss the multitasking role of SnRK1 signaling associated with different subcellular compartments. Plants are sessile organisms continuously exposed to a wide range of environmental cues including light, wounding, or temperature, which have a major impact on their development and productivity. Consequently, they have developed sophisticated cellular mechanisms to survive in ever-changing environments. In this regard, the evolutionarily conserved protein SNF1-related kinase 1 (SnRK1) is considered as a master regulator that integrates external signals with plant growth (AKIN10/AKIN11/AKIN12 or KIN10/ KIN11/KIN12), of which α1 and α2 are partially redundant (snrk1α1/snrk1α2 (snrk1α1/1α2) double knockout appears to be lethal, supporting the non-functionality of SnRK1α3 (T175/176), whose phosphorylation has been reported to be critical for SnRK1 activity  motif, a carbohydrate-binding module (CBM), and a β-C-terminal domain (βCTD), whereas SnRK1β3 is formed exclusively by a βCTD . AlthougSnRK1 has been involved in the regulation of important cellular functions, including growth, autophagy, stress response, stomatal development, pollen maturation, hormone signaling, and gene expression  (T175A (T175A is expressed (T175D is translocated to the nucleus and promotes stabilization of the transcription factor SPEECHLESS (SPCH)  . HoweverSnRK1α has been recently localized in nuclear bodies (NBs), suggesting an exciting and unexplored role for the complex in the nucleus  Nietzsc. NBs areflz6 and flz10 single mutants, while the level of phosphorylated ribosomal protein S6 kinase (S6K), a well-established target of TOR, was found to be reduced. The authors propose a model where the interaction of SnRK1α with both FLZ6/10 proteins in the ER may mediate the antagonist signaling of the SnRK1/TOR module in plants under unfavorable conditions , namely TOR, regulatory-associated protein of TOR (RAPTOR), and lethal with SEC13 protein 8 (LST8) have been localized in the ER in distant lineages such as animals or algae . Jamsheesnrk1α1/1α2 double mutant compared with wild-type plants  and interacts with RAPTOR1B in the cytoplasm (RAPTOR (RAPTOR1A and RAPTOR1B) and LST8 (LST8-1 and LST8-2) genes, although LST8-2 shows undetectable transcript levels  assay showed that both aquaporin PIP1 and nitrate transporter 2.4 (NT2.4) interact with soybean SnRK1α  protein SLAC1 homolog 3 (SLAH3)   is a membrane-bound organelle that facilitates the digestion of macromolecules. However, lysosomes have been also proposed to have a key role in other cellular processes including cellular differentiation, metabolism, or signaling regulation . Thus, uin vivo on a conserved glycine residue at position 2 (Gly2)  and consists of the addition of the 14-carbon fatty acid, myristate, to the N-terminus via a covalent amide bond. This post-translational modification facilitates the association of proteins with cellular membranes. In the case of SnRK1, N-myristoylation of β-subunits has been reported to control both SnRK1 localization and activity  . N-myrisAs discussed above, the SnRK1α subunit is localized at the cytoplasm, nucleus, chloroplast, ER, or SGs, and this localization seems to be stimulus dependent in some cases. For example, under non-stress conditions, the α1 isoform exhibits a nuclear localization that is particularly prominent in Arabidopsis root meristem cells, and it delocalizes to the cytoplasm in response to ABA  revealed that both catalytic α-subunits and the regulatory SnRK1β1 are expressed throughout development and in different tissues (Several studies performed in mammals indicated that the gene expression pattern of AMPK subunits vary across tissues and cells, introducing a new level of heterotrimeric assembly complexity . Althoug tissues . Regardi tissues . This scSnRK1 signaling is an extremely complex pathway that remains poorly understood in plants. Extensive studies have provided resolution of SnRK1 signal transduction under a set of cellular and environmental cues. These studies include the identification of a plethora of phosphorylated and interacting targets. However, it remains largely unknown how SnRK1 can release a stimulus-type-specific response. This review provides a survey on how localized protein interaction can invoke targeted signaling programs. SnRK1 has been found to interact with targets in such different organelles as the cytoplasm, nucleus, chloroplast, ER, and SGs. Moreover, differential heterotrimeric assembly and the subunit expression pattern can add an extra level of specificity in the downstream SnRK1 response. Although several recent works have provided new insights into cellular compartmentalization of SnRK1, further studies are required to unravel the interplay between the spatiotemporal SnRK1 localization and its downstream signaling mechanisms.The following supplementary data are available at Table S1. SnRK1-interacting proteins shown in Table S2. Subcellular localization of SnRK1 subunits shown in erac315_suppl_Supplementary_MaterialClick here for additional data file.


The detection limit of the sensor was calculated to be 2 μM. Although the detection performance of this sensor is not competitive with high-performance electrochemical sensors, it has been able to meet the needs of POC detection. At the same time, the sensor has excellent anti-interference performance. It has also been used successfully to test urine and serum samples from healthy and gout patients.Point-of-care technology (POCT) is an important method in clinical testing in the future, which can achieve the purpose of rapid analysis. In this work, we assembled an electrochemical POC sensor for uric acid (UA) by surface modification of a screen-printed electrode. Copper nanowires were used as electrode modifiers to achieve high-performance electrochemical oxidation of UA. This electrochemical sensor can achieve linear detection of UA in the range of 10  The sensitivity, detection speed, and reliability of traditional molecular diagnostic methods have been continuously improved in recent years. However, due to its dependence on the isolation area of environmental control, large biochemical equipment, and the need for strict professional training of operators –4, it isPOCT devices are often equipped with biosensors. A biosensor refers to an analytical device for detecting analytes, usually through a small analytical system in which the biological components are fixed to a solid surface and interact with the analyte –18. ElecUric acid (UA) accounts for about half of the active antioxidant substances in the blood and can change the redox potential or prevent oxidative damage , 26. UA In this work, we constructed an in situ prepared copper nanowire (CuNW)-modified screen printing electrode (SPCE) for UA detection. Firstly, SPCE was used as the substrate electrode, and the copper film was reduced and deposited on the surface of SPCE by the electrochemical method. Then, copper hydroxide nanowires were grown in situ on the surface of SPCE by a mixed solution of ammonium persulfate and sodium hydroxide. CuOHNW was converted to CuNWs by high-temperature heating and electric reduction, and UA was detected by electrochemistry.Ammonium persulfate, sodium hydroxide, and sodium acetate were purchased from Sigma-Aldrich. Copper acetate, acetic acid, potassium bicarbonate, D-glucose, ascorbic acid, uric acid, and paracetamol were purchased from China Pharmaceutical Group Co. Ltd. All reagents were analytically pure.A CHI-660E Electrochemical Workstation (Shanghai Chenhua Instrument Co. Ltd.) has been used for electrochemical experiments. A three-electrode system was used in the experiment, with a screen-printed electrode as the working electrode, a platinum plate as the counter electrode, and Ag/AgCl (saturated KCl) as the reference electrode. The morphology of the samples was observed by a scanning electron microscope .2. The pH of the electrolyte was adjusted to 5.5 by HAc, and the copper film was deposited on the surface of SPCE for 8 min at the constant potential of −0.9 V. The electrodes were then removed from the electrolyte, rinsed with water, and blow-dried with nitrogen. The solution was stirred and kept at room temperature during the entire electrodeposition process. Then, Cu(OH)2NW was grown in situ on the surface of Cu/SPCE by soaking the prepared Cu/SPCE in a mixture of 0.133 M (NH4)2S2O8 and 2.667 M NaOH for 5 min. SPCE modified with Cu(OH)2NW was converted into copper oxide nanowire (CuONW) by heating it at 150°C for 12 h. Then, the SPCE modified with CuONW was used as the working electrode. The CuNW grown in situ on the SPCE was obtained by electric reduction at −0.7 V for 30 min in a 0.1 M KHCO3 solution (denoted as CuNW/SPCE).The preparation of CuNW was adopted from Xu et al.  with somIn this work, CuNWs were prepared in situ on SPCE. CuNW-modified SPCE was characterized by scanning electron microscopy and electrochemistry, and the electrocatalytic activity of the electrode on the UA was discussed. 2 can be converted to CuO as a precursor [2NW in situ on Cu/SPCE surface. Cu(OH)2NW was transformed into CuONW by heat treatment in an air atmosphere. Electrochemical reduction of CuONW was carried out in KHCO3 electrolyte containing saturated N2. As shown in In this work, we proposed a simple method for in situ preparation of CuNW on the surface of SPCE in the liquid phase and characterized the surface morphology by SEM. The rough surface structure of SPCE can be seen in recursor , 39. It −. This peak is usually used to study the electro-oxidation mechanism of UA. Compared with the CV curve without UA, some changes occur in the CV curve of the sensor in the presence of 2 mM UA. The peak of the curve disappears at 0.3 V, mainly due to the adsorption of UA onto the surface of CuNW. The peak centered at 0.6 V is the response of the sensor to the electrocatalytic oxidation of UA. A weaker oxidation peak was also observed at 0.6 V for Cu/SPCE than CuNW/SPCE. This phenomenon indicates that CuNW indeed causes the electrocatalytic oxidation signal of UA. In addition, this indicates that the sensor has a high electrocatalytic activity for electrochemical oxidation of UA [In order to evaluate the analytical applicability of the CuNW/SPCE, the electrochemical performance of the sensor for UA oxidation was investigated in buffer solution. The sensors were placed in buffer solutions with and without UA, and cyclic voltammetry (CV) scanning was performed in the potential range of −1.0 V to 0.8 V, as shown in on of UA –42.At the same time, the CV curves of the sensor for different concentrations of UA in the potential range of 0.0–0.8 V were also studied. As can be seen from μM to 2 mM can be obtained. The linear regression equation is ImA = 2.1 + 220C(mM), and the correlation coefficient r = 0.997. The detection limit can be calculated to be 2 μM. The current response of the sensor was obtained by adding UA at 0.6 V constant potential. As can be seen from N2 atmosphere for one month, indicating good stability of the sensor. The relative standard deviation of 6 measurements of UA with different sensors was used to evaluate the reproducibility of the measurements. The relative standard deviation of 2 mM UA is 4.3%. The results show that UA detection with sensors has high reproducibility.The loss of only 5% of the current response of the CuNW/SPCE to UA was observed in an Selectivity is one of the important characteristics of electrochemical UA sensors, especially for detecting UA in practical samples. Ascorbic acid, glucose, and acetaminophen commonly coexist with UA in serum samples as general interfering compounds . BecauseTo evaluate the practical application of the sensor, it was used to detect UA in serum and urine samples from gout patients and healthy persons, respectively. The sample was dropped into 0.1 M NaOH solution, the solution was stirred, and the current response at 0.6 V potential was recorded. As can be seen from μM to 2 mM, with a detection limit of 2 μM. In addition, this POC sensor has been successfully applied for the detection of UA in urine samples and serum samples.In conclusion, we proposed an electrochemical-based POC sensor for rapid UA detection. Commercial SPCE modified by CuNW has excellent electrocatalytic oxidation performance towards UA. This disposable sensor can be used for rapid detection of UA. The sensor provides linear detection of UA in the concentration range of 10


The durability of the laser-printed colors is confirmed by fastness examination, including salt spray, double-85, light bleaching, and adhesion tests. These features render our technique to be competitive for industrial applications.It is a formidable challenge to simultaneously achieve wide-gamut, high-resolution, high-speed while low-cost manufacturability, long-term stability, and viewing-angle independence in structural colors for practical applications. The conventional nanofabrication techniques fail to match the requirement in low-cost, large-scale and flexible manufacturing. Processing by pulsed lasers can achieve high throughput while suffering from a narrow gamut of ~15% sRGB or angle-dependent colors. Here, we demonstrate an all-in-one solution for ultrafast laser-produced structural colors on ultrathin hybrid films that comprise an absorbent dielectric TiAlN layer coating on a metallic TiN layer. Under laser irradiation, the absorption behaviours of the TiAlN-TiN hybrid films are tailored by photothermal-induced oxidation on the topmost TiAlN. The oxidized films exhibit double-resonance absorption, which is due to the non-trivial phase shifts both at the oxide-TiAlN interface, and at the TiAlN-TiN interface. By varying the accumulated laser fluence to modulate the oxidation depth, angle-robust structural colors with unprecedented large-gamut of ~90% sRGB are obtained. The highest printing speed reaches 10 cm Structural colours are of broad interest in recent years, yet the conventional nanofabrication techniques fail to match the requirement for large-scale manufacturing. Here, the authors demonstrate the use of pulsed lasers to write structural colours with widegamut, high-resolution, high-speed while low-cost manufacturability, long-term stability, and viewing-angle independence. Therefore, the development of structural colors-based ink-free printers is demanded on looming. In recent years, the structural colors2 arising from light scattering, absorption, diffraction or interference by micro/nanostructures including plasmonic10 and all-dielectric metasurfaces21, diffractive elements23, microfibrillation and photonic crystals25, Fabry–Perot (FP) cavities31, multilayered dielectric films34, lossy dielectrics on metallic coatings35, Fano-resonance optical coatings36, are promising to achieve pigments-free colorful printing. It is hence becoming an attractive technique in many applications, such as the labeling of serial number, barcode, quick response code, company logo, trade marker, anti-counterfeiting, to name a few. However, surface coloring in terms of the conventional nanofabrication techniques, such as electron beam lithography38, focused ion beam milling39 and nanoimprinting lithography40, is facing the nanoscale and macroscale processing barrier. Production of large-scale colored surfaces with these techniques is incompatible with the demands of low-cost mass manufacturing.Inkjet or laser printers rely on ink or toner cartridges, in which colorful pigments serve to selectively absorb visible light within a spectral range. However, the conventional pigments are toxic and environment unfriendly. Further, their long-term stability in ambient conditions is generally poor, because the organic pigments tend to degrade over time and thus losing their chroma as well as brightness2/s41, is appealing to overcome this barrier. In addition, lasers are capable of large-scale fabrication on highly rough surfaces, which are challenging for conventional techniques such as electron beam lithography and nanoimprinting42. Laser coloring generally contains three approaches that are based on different mechanisms: plasmonic colors from randomly self-organized metallic nanoparticles42, diffractive colors from laser-induced periodic surface structures 45, and interfering colors from thin films including transparent oxide layer46 and FP-cavities48.As an alternative, surface coloring by lasers, exhibiting high throughput of >10 mm42 and low stability41. Passivation coatings are generally required to protect the colors, however, the passivation layer will change the colors because the plasmonic resonances are highly sensitive to the surrounding dielectrics49. LIPSS exhibit iridescence that strongly limits its practical applications in patterning50.The laser-produced plasmonic colors on noble metals exhibit the advantages of viewing angle-independent but face the problems of narrow gamut (~15% sRGB)51. This approach exhibits the advantages of high stability and productivity. In this case, colors come from interference of reflection from top and bottom surfaces of the oxide layer. The optical path difference δ between the two reflected beams can be expressed by h, n1 and θi denote the thickness and refractive index of the oxide film, and the incidence angle, respectively. At normal incidence (θi = 0), when λ, the specific color originates from constructive interference-enhanced reflection, the same effect that is responsible for soap bubbles. With the increase of oxide layer thickness, the color coordinates only move in a clockwise direction following an elliptic curve52, but green colors are difficult to be achieved and thus its gamut is also narrow (~35% sRGB)41. This has been attributed to the film thickness, which requires large enough for the origin of these colors associated with long-wavelength52. Furthermore, the colors from laser-induced oxide layer are dependent on viewing angles, which is disadvantageous for practical applications54.Another widely adopted laser coloring technique is in terms of laser-induced oxide layer, generally occurring on metallic surfaces such as titanium alloy or stainless steel56. The FP-cavities consist of two metallic layers that are separated by a lossless dielectric spacer layer. The reflected colors are strongly dependent on the thickness of dielectric layer and weakly sensitive to the thickness of the topmost metallic film. However, it is challenging to directly modify the spacer layer by lasers because of the high reflection of the metallic film. As an alternative, laser-induced polymer-assisted photochemical metal deposition (PPD) has been employed to control the thickness of the topmost metallic layer27. Nevertheless, this technique is also facing the problem of a narrow gamut (~25% sRGB). Further, both plasmonic colors and FP-cavities rely on noble metals such as Au, Ag and Cu, exhibiting low wear resistance and thus poor abrasion stability47.The structural colors originating from FP-cavities can be insensitive to the viewing angles57—are simultaneously achieved via laser-induced oxidation on TiAlN–TiN hybrid films.Here, we demonstrate a laser-coloring scheme to solve the aforementioned problems. Structural colors with wide gamut, durable, large-scale and viewing angle-insensitive—key parameters that are decisive for the adoption in decoration technologies58, serves as “inorganic ink” for laser color printing. The refractive indices of TiAlN and TiN are given in Supplementary Fig. 62, represent thickness-dependent colors, as displayed by the photograph in Fig. x–y chromaticity diagram , as numerically simulated in Fig. Changing structural colors of the thin film absorber by a transparent dielectric coating can be understood from the Snell’s law64. Figure Ls = 20 μm between each successive line. The applied laser repetition rate is f = 5 kHz, and the laser spot diameter is σ = 120 μm. Various vibrant colors, spanning from red, orange, yellow, green, blue to purple, are observed. The colors are dependent on the scanning speeds (v ranging from 1 to 400 mm/s) and laser pulse energy . These parameters define the total accumulated laser fluence v (or Neff) with respect to that of E suggests that the oxidation process is more sensitive to the latter. This can be attributed to that the oxidation depth does not linearly increase with Neff, because the penetration of O2 through the formed oxide layer decreases exponentially, decelerating and eventually halting the growth process. Interestingly, the generated colors can be locally retouched by a repeated scanning, which changes Ft, as shown in Fig. In experiments, the lossless dielectric layer is formed through laser-induced oxidation on the surface of TiAlN. As shown in Fig. f = 175 kHz, the printing throughput , focused ion beam (FIB) milling, atomic force microscopy (AFM), X-ray diffraction (XRD), and x-ray photoelectron spectroscopy (XPS). Figure +-FIB to observe their cross-sectional views, as depicted in Fig. 65. At medium power while high scanning speed, the color becomes green . After exposing to these extreme environments for 120 h, the adhesion of the structural colors remains to be the highest level, and the caused color differences are fairly small  with pulse duration of 10 ps, tunable repetition rate as well as pulse energy was focused by a lens  onto the samples. The incident laser beam diameter was 3 mm, and the spot diameter was measured to be 120 μm by a beam profiler. The samples were exposed to ambient environment. The laser beam was meanderingly scanned by two galvo mirrors for patterning via surface oxidation. The laser polarization was rotated by a quarter-wave plate to be circular, which is in order to avoid the formation of periodic ripples. For high resolution fabrication, the laser beam was coupled into an optical microscope and focused onto samples by an objective lens with NA = 0.9. The samples were installed on a 3D translation stage.2 flow of 14 sccm and Ar of 56 sccm. The TiAlN films were deposited as the same parameters for TiN while the power of Al target is DC 300 W. The AlN films were coated as the same for TiAlN while the Ti target was off. The thickness of our films was measured with a profiler (Stylus). According to the measured thickness, the permittivities were retrieved with a variable angle spectroscopic ellipsometer (Woollam). The scanning electron images, and energy dispersive X-ray spectra were measured by a field-emission scanning electron microscope . The x-ray diffraction analysis of the TiAlN-on-TiN coating on silicon wafer was carried out by Bruker D8 Discover.The TiN films were deposited on silicon wafers by RF magnetron reactive sputtering at 300 °C, power of 600 W, and Nx–y plane. One monitor was set 2 μm above the source to acquire the reflection spectra. The permittivities of the materials involved were measured with the aforementioned ellipsometer. The measured reflectance spectra at near-normal incidence were recorded using a Shimadzu UV–VIS–IR spectrophotometer (UV3600Plus + UV2700). The angle-dependent reflectance and transmittance spectra were measured by an Agilent Cary spectrophotometer . The colors in x–y chromaticity diagram were calculated based on the simulated and measured reflectance spectra and the color-matching functions defined by the CIE 193167. The spectral power distribution can be expressed as: P(λ) = I(λ)R(λ), in which I(λ) is the radiance spectrum of light source and R(λ) is the reflectance spectrum. The values X, Y, and Z are given byThe numerical computations were performed by using commercial software finite-difference-time-domain (FDTD) method . The light source was a plane wave spanning from 400 nm to 2000 nm. The top and bottom boundaries were perfectly matched layers (PML), while periodic boundary conditions were applied in 2h). The double-85 test is carried out within the standard of GB/T 1740-2007 for 120 h. The temperature and humidity are 85 °C and 85%. The light bleaching test (GB/T 1865-2009) is irradiated by 340 nm UV light with an irradiance of 0.51 W/(m2nm) for 120 h. The temperature and humidity are 65 °C and 50% RH, respectively. The adhesion test is performed by using 3 M tapes according to the standard of GB/T 9286-2021. The color differences (The color fastness tests include salt fog test, double-85 test, light bleaching test and adhesion test, which are generally required for printing industry. The salt fog test is performed according to the standard of GB/T 10125-2021 for 120 h. The density of NaCl is 50 g/L with a sedimentation rate of 2 ml/(80 cmFurther information on research design is available in the supplementary informationPeer Review FileDescription of Additional Supplementary FilesSupplementary Movie 1Reporting SummaryLasing Reporting Summary


Using the childbearing survey data from Hubei Province in March 2022, this article empirically analyzed the status quo of fertility intention and its influencing factors among Chinese married youth during the COVID-19 pandemic. In our analysis, fertility intention was operationalized as the ideal number of children and short-term fertility plan. Statistical results showed that the average ideal number of children stood at 1.652, which was lower than the population replacement level, whilst only 16.4% of married youth had a short-term fertility plan. By utilizing a binary logit regression model and the sheaf coefficient technique, we found that COVID-19-induced factors  had a more stable effect on fertility intention, especially on short-term fertility planning. Parenting perception characteristics exerted a great impact on the ideal number of children but a relatively small impact on short-term fertility planning. Meanwhile, married youth with stable jobs and a high family income did not necessarily show stronger fertility intentions than those with fewer socioeconomic resources. In addition, the findings also reveal that the relative importance of fertility-influencing factors could vary at different fertile stages, which have valuable implications for population policy in Chinese contexts. Driven by the accelerating industrialization process and the national fertility policy, China has undergone profound changes in demographic structure and the characteristics of fertility since the 21st century . In ordeIn the existing literature, social scientists often co-opt the Theory of Planned Behavior (TPB) to analyze the possible constraints of fertility intentions. As per Ajzen’s theoretical framework, fertility behaviors should be considered the outcome of “life choices” associated with childbearing decision-making processes, which are consequentially restrained by certain “life chances”  ,11. For Fertility intention is a multi-dimensional concept involving individuals’ expectations of the number, gender, and timing of children . AlthougIndividual socioeconomic status is frequently mentioned in previous research that aims to predict fertility intentions and behaviors. Relevant studies generally harness proxy variables such as occupation, income, and education to measure the level of socioeconomic status. Indeed, under the context of sluggish economic development, international and domestic researchers have paid close attention to the effect of employment status on fertility intention, positing that economic precariousness  would give rise to the postponement of parenthood ,30,31,32Apart from objective socioeconomic status, a couple’s subjective perceptions of parenting also play a significant role in the process of fertility decision-making. Under the context of intensive social competition, a growing number of Chinese parents feel anxious about whether or not they could give their children enough material resources to achieve higher prestige. Such a negative psychological state may lead to a decrease in the likelihood of having a child. For example, Xu and Pak once treated child-raising and fertility decisions as a Tullock contest model. They found that competitive pressure to allocate parenting resources resulted in the overaccumulation of human capital and low fertility . SimilarIn addition, the worldwide outbreak of the COVID-19 crisis has already induced a vast array of unexpected consequences on everyday life, contributing to the non-negligible change in fertility traits . In lighIn short, there has been a large body of published literature that theoretically or empirically discussed the issue of fertility intention and its social determinants. Although these illuminating studies have recognized the effects of different factors on fertility, more in-depth knowledge about the relative importance of various factors  is still missing in the existing literature. Moreover, there is obvious heterogeneity in childbearing decisions at different fertile stages. For instance, based on a recent survey of 1026 couples from Shanghai, Zhu et al. pointed out that the proportions of those who planned to rear a second/third child were approximately 16% and 9%, respectively . Therefo(1) Do socioeconomic status, parenting perceptions, and COVID-19-induced factors have a significant influence on the fertility intentions of Chinese married youth? Which type of factors matters more?(2) Are the effects of various factors on fertility intentions consistent across different fertile stages?This study was based on the Childbearing Survey in Hubei Province, which was jointly organized by the Population and Health Research Center of Zhongnan University of Economics and Law and the Yichang Municipal Health Commission. This survey was designed to investigate residents’ fertility intentions and the influencing factors under the three-child policy starting from May 2021, as well as to provide theoretical and empirical support for the construction of a “fertility-friendly society” in China. The survey subjects of childbearing age (20–45) were randomly selected in Yichang, Hubei Province. The survey scope covered the entire Yichang area, including 5 districts , 3 county-level cities , 3 counties , 2 autonomous counties (Changyang Tujia Autonomous County and Wufeng Tujia Autonomous County), and 1 high-tech zone (Yichang High-Tech Zone). A total of 32,248 samples of fertile age were collected online in March 2022. For the present study, married youth (below 35 years old) in their first marriage were selected from the database. After eliminating the data missing for key variables, 13,794 valid samples were finally obtained.The dependent variable was the fertility intention of married youth, which included two dimensions, i.e., the ideal number of children and short-term fertility plan. As for the ideal number of children, there was a question entitled “how many children would you like to have in an ideal situation”, with possible answers being “0, 1, 2, 3, or more than 3”. In order to highlight the differences in fertility intention tendency, we recoded this item into such a binary variable as “want 2 kids or more = 1, want 1 kid or none = 0”. As for short-term fertility plans, the survey asked the following questions: (1) Do you plan to have a child this year? (answered by childless respondents); and (2) do you plan to have another child this year? (answered by those who had at least one child). In fact, such two questions provided childbearing decision information about fertility timing as well the quantum. Based on the above two questions, we set up three dummy variables: “first child plan of childless family”, “second child plan of one-child family”, and “third child plan of two-child family”, with the coding “have fertility plan = 1, no short-term fertility plan = 0”, respectively.Regarding the operationalization of socioeconomic status, in this study, objective socioeconomic status was related to the following three variables: (1) Education level (years of schooling), including a master’s degree or above = 19, 4-year university degree = 16, 3-year college degree = 15, senior high/technical school = 12, junior high school = 9, primary school = 6, uneducated = 0; (2) employment status, including stable job, unstable job, and no job; and (3) household economic status, involving the objective annual income  and subjective household economic status . We used the principal component analysis to combine these two ordinal variables into a common factor, and then recoded the common factor into a continuous variable (ranging from 0–100) by means of the min–max transformation method.Regarding the operationalization of subjective parenting perceptions, we took into account two variables designed to identify the effect of young couples’ parenting perceptions on fertility intention. The first is educational expectations for children. There was one relevant question in the questionnaire: Which level of education do you expect your children to achieve in the future? There were three options for answering this question, namely, a master’s degree or above, a 4-year university degree, a 3-year college degree, or below. The other variable was the perception of multi-child family advantages. We used the following question: What do you think about raising multiple children compared with raising only one child? The answer options were recoded as two dummy variables, i.e., “multi-child family is better for children’s development” and “multi-child family has no obvious advantage”.Regarding the operationalization of COVID-19-induced factors, and consistent with a previous literature review, we utilized two questions in the questionnaire to measure COVID-19-induced factors. The first question pertained to changes in the marital relationship during the COVID-19 pandemic, with the options being “more intimate”, “no change”, and “more distant”. The second relevant question was as follows: How long do you think it would be good to get pregnant after vaccination? This question reflected the delayed effect of pregnancy preparation caused by vaccination. There were four possible answers, i.e., “more than 12 months”, “6 months to 12 months”, “3 to 6 months”, and “less than three months”.In the statistical analysis, we also introduced the following control variables: Gender ; age group ; household registration ; ethnic group ; and life satisfaction . Additionally, there was evidence that the childbearing expectation was closely associated with existing fertility experience and peer group relational networks ,54, so wThe statistical analysis was conducted in three steps. Firstly, we used descriptive methods to demonstrate the distribution characteristics of the current fertility structure in married Chinese youth. Next, based on binary logit regression models, we intended to examine the social determinants of fertility intention . In order to measure the relative contribution of different types of factors, all independent variables were simultaneously added to the regression model. Specifically, the statistical model is as follows:0 is the intercept term of the model. In Equation (1), Pr represents the probability of fertility intention. βThen, based on the above-mentioned logistic regression model, we further used the sheaf coefficient technique proposed by Heise . SupposiThus, Equation (1) can be rewritten into the following alternative form:Equation (5) is the equivalent form of Equation (1) using the iterative method. Next, based on the two dimensions of fertility intention , we further explored the possible inducers of low fertility intention. As shown in As mentioned above, this study was primarily concerned with the effects of socioeconomic status, parenting perceptions, and COVID-19-induced factors on fertility intention. p < 0.001). Meanwhile, education level also exerted a significant impact on the fertility plans of childless families; their probability of giving birth to another in the short term would be 9.5% lower for each additional year of schooling . However, for families with one or two kids already, respondents’ education level did not affect their fertility plan. Moreover, household economic status was partly associated with fertility intention: Every additional unit of household economic score would increase the chance of wanting at least two kids by 3.5% ; for one-child families, every additional unit of household economic score would enhance the chance of having a second child by 9.4% ; for childless and two-child families, household economic status seemed to be non-influential upon short-term fertility plans. Moreover, the effects of occupation on fertility intention were relatively weak: Young respondents with stable jobs  did not show evidently higher fertility intentions than those with no job. Such results indicated that when other factors are controlled, socioeconomic status might not necessarily be a reliable and strong predictor of fertility intention. Thus, the low fertility intentions of married youth cannot simply be attributed to the lack of affordability of child-rearing.Firstly, we examined the association between socioeconomic status and fertility intention. With other variables controlled for, each additional year of schooling decreased the likelihood of wanting more kids by approximately 4.8% . Compared with the samples who only expected their children to earn a 3-year college degree or below, the odds of having stronger fertility desire among those who expected their children to earn a master’s degree/bachelor’s degree increased by 21.8% /22.2% . In terms of fertility plans, compared with the reference group, those who believed “having more children is more beneficial to children’s development” presented a 35.4% higher chance of having a second child , while those who expected their children to obtain a master’s degree demonstrated a 61.5%  higher chance of having a first child for childless families. In addition, the influence of parenting perception on fertility intentions of two-child families seemed to be very weak.The results of logistic regression models also showed differentiated effects of subjective parenting perception on fertility intention. Those who held the view that having more children is beneficial for children’s development presented a 199.5% higher chance to want at least two kids ; at the same time, the probability of having a short-term fertility plan for childless families and one-child families also decreased by 76.8%  and 33.4% , respectively. Regarding two-child families, a worse marital relationship during the pandemic did not have a statistically significant effect on short-term fertility plans. Additionally, vaccination is a necessary measure to prevent and control the epidemic. However, because young people have different levels of concern about the side effects of vaccines, vaccination per se may bring about a delay in pregnancy preparation. To be specific, there was an inverted U-shaped relationship between the length of pregnancy preparation after vaccination and the ideal number of children, with the probability of wanting at least two kids significantly higher in the group of “waiting 3 months to 1 year”. Moreover, the longer the preparation interval of pregnancy , the lower the likelihood of having a short-term fertility plan for all three types of families (p < 0.01). As a result, the potential consequences of vaccination on pregnancy were still controversial among young people, which indeed restricted their fertility intention to some extent.Lastly, we further analyzed the impact of COVID-19-induced factors on fertility intention. Since the outbreak of COVID-19 in early 2020, working-from-home has become a common lifestyle and increased the frequency of face-to-face indoor interactions. The data in Although the above analyses confirmed that socioeconomic status, parenting perception, and COVID-19-induced factors exerted heterogeneous effects on the fertility intention of married youth, it was still unclear which type of factors had a greater effect and deserves more attention from policy makers. In In addition, since the sheaf coefficients are values obtained after standardized processing, the effect sizes of latent variables can thus be compared within the same model by limiting the sum of the effects of each latent variable to 1. As shown in Based on a childbearing survey in Hubei Province, China, this study pointed out that one-child families still accounted for the largest part of the current family structure in Chinese married youth. In terms of their fertility intention, the average ideal number of children stood at 1.652, which was lower than the population replacement level, whilst only 16.4% of married youth had a short-term fertility plan. Thus, it can be seen that China’s long-lasting family-planning policy has exerted a strong squeezing effect on the fertility intentions of contemporary youth. In view of this, by empirically analyzing the status quo of fertility intention and its influencing factors, this article would help us better interpret the social determinants of fertility intention and promote our understanding of the low-fertility problem in China.In the current study, we utilized a binary logit regression model and sheaf coefficient method to investigate the effects of socioeconomic status, parenting perceptions, and COVID-19-induced factors on fertility intention, and drew the following main conclusions. Firstly, COVID-19-induced factors  had a more stable effect on fertility intentions, especially on short-term fertility plans. Secondly, parenting perception characteristics exerted a large impact on the ideal number of children but a relatively small impact on the short-term fertility plan, indicating that actual fertility decisions were less likely to be restricted by subjective factors. Thirdly, married youth with stable jobs and high family incomes did not necessarily show stronger fertility intentions than those with fewer socioeconomic resources. Fourthly, the effects of different factors on the ideal number of children and short-term fertility plan seemed to be heterogeneous, which underlined the fact that fertility intention is related to the complex fertility decision-making process. Thus, it is inappropriate to simply use a single indicator  as its proxy variable.In view of these empirical findings, we intend to put forward the following policy suggestions. First of all, relevant authorities should attach great importance to the improvement of marital relationships during the COVID-19 pandemic. Professional counseling channels can be provided for couples who experience an emotional crisis so as to guide married youth to actively cope with the negative emotions caused by the epidemic. Then, it is necessary to pay attention to young people’s concerns about the side effects of the COVID-19 vaccine. The mainstream media need to report authoritative guidance on the vaccine’s potential influence on pregnant women based on experimental results, aiming to reduce the negative impact of information uncertainty on young people’s fertility intentions. Furthermore, in light of the heterogeneous effects of various factors on fertility intention, it is necessary to shift the focus of the pro-birth policy from economic assistance to providing comprehensive child-rearing services, aiming to alleviate youth’s anxiety about childbirth and construct a childbearing-friendly society. Finally, different interventions should be implemented for families at different fertile stages so as to effectively promote the actual effects of fertility policies.There are still some limitations to this study. First, our statistical analyses were based on a cross-sectional dataset, so the causal relationships between various factors and fertility intention cannot be clearly inferred. Therefore, a longitudinal design is needed to reconfirm our findings’ robustness. Second, this childbearing survey did not strictly adhere to the random sampling approach, so the representativeness of our research findings is insufficient to some extent; Moreover, the number of samples needs to be increased in order to avoid sample selection bias. Third, due to the limitation of questionnaire data, the measurements of some variables  are not rigorous, which may affect the precision of the research results. Fourth, since fertility behavior is, in essence, “relational”, it is also required to relationally penetrate and explain how interdependent networks  within the social field of fertility constrain the patterns of fertility practice among married youth.


Plant nutrition, growth, and response to environmental stresses are pH-dependent processes that are regulated at the apoplastic and subcellular levels. The root apoplastic pH is especially sensitive to external cues and can also be modified by intracellular inputs, such as hormonal signaling. Optimal crosstalk of the mechanisms involved in the extent and span of the apoplast pH fluctuations promotes plant resilience to detrimental biotic and abiotic factors. The fact that variations in local pHs are a standard mechanism in different signaling pathways indicates that the pH itself can be the pivotal element to provide a physiological context to plant cell regions, allowing a proportional reaction to different situations. This review brings a collective vision of the causes that initiate root apoplastic pHs variations, their interaction, and how they influence root response outcomes. The pH affects both the enzymatic and transporters activity and the protein-protein interactions since the structure and solubility of the proteins are dependent on their net charge and ionization of specific residues  plays a more crucial role in regulating essential processes like intercellular signaling, plant–microbe interactions, plant response to abiotic stresses, and water and nutrient transport  in pHapo has broadly been studied, other hormones are getting more attention as modulators of proton pump activity, such as cytokinin  forms carbonic acid (H2CO3), which together with the atmospheric pollutants acidify the soil .The acid growth theory is broadly assumed in the plant scientific community, which affirms that while acid pHin vivo pH-sensor based of fluorescent probes, H+-selective microelectrodes, or 31P nuclear magnetic resonance spectroscopy [reviewed in Geilfus  than the apoplast (low millimolar range per pH unit)   Geilfus  and Tsai Geilfus ]. Thankss Felle, . Ultimats Felle, . The cytapo  stays acid even when the pH of the media gets significantly more alkaline, highlighting the strong regulatory mechanisms involved in maintaining the pH stable   or FERONIA (fer-4), show an upregulation of defense-related genes, making them more tolerant to pathogen attack and supporting the potential direct connection between AHA activity and plant defense  that, in neutral and alkaline environments, will release H+ and acidify the apoplast and the rhizosphere  is coupled with the pH2+ ions to form the so-called egg-boxes alters the charge balance of the CW , whose carboxyl group is negatively charged. Pectin is secreted to the apoplast and heavily methylated at their GalAs. Its demethylation at the CW and the potential link with Ca2 with a strong influence on plant biology in alkaline soils  is considered a stress-response hormone whose signaling is triggered as a result of environmental stress including drought, high soil salinity, temperature, and metal soil contamination  are intimately related to auxin in regulating plant development. ET is also a major regulator of stress responses  hormonal actions usually antagonize those of auxin effects and can counterpart its signaling. CK has a key role in root growth, intervening in the balance between cell division and cell differentiation within the root tip  are plant steroidal hormones that, similar to auxin and CK, participate in the regulation of plant growth and differentiation by controlling cell division and expansion. BRs can activate the AHAs during hypocotyl elongation by inducing the phosphorylation in their penultimate amino acid (Thr)  small signaling peptides . RALFs papo suggests that pHapo is a way to escalate the cell response signal, acting as an element to regulate the activity and properties of many different proteins and molecules at once.Overall, having such a complex and evolving system that includes hormonal and small peptides regulation to modify pHapo have a direct impact on the CW integrity and the properties of the proteins embedded in it. The balance of protonation in pectin carboxyl groups determines their capacity to interact with cations, mostly Ca2+ to form the egg-box, and affects the pectin–cellulose and pectin–pectin interactions, which has a significant impact on the structure of the CW  represents the net charge between the cations and anions and it has a direct influence on the pH  use the H+ influx to pump Na+ extracellularly  are hypothesized to use the H+ gradient in a similar way to that described for NHXs, but it needs to be experimentally demonstrated . For example, the inactivation of the electrogenic proton pumps, and consequent alkalinization of the pHapo, have been implicated in the generation of SWPs  family act as sensors that convert the external signal into an increase in intracellular Ca2+ can activate the RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) PM-localized enzymes, that synthesize ROS, such as H2O2, in the apoplastic space during the plant electrical/ionic system signaling , which promote CW loosening  waves can propagate through different plant tissues similarly to electric and calcium waves during long-distance signaling , induce fast apoplastic acidification in the first stages of contact by increasing the AHA activity, which seems to be required for plant defense . JA triggers a cellular response that can travel quickly from the wound to distal cells and from the root to the shoot. In this process, the alteration of the pHapo is essential to create the intracellular signaling that includes the SWPs, glutamate, Ca2+, and ROS response. Concretely, during wound response, the activity of AHA1 is transiently inhibited at the beginning of the signaling, alkalinizing the pHapo. The apoplastic proton variance is required to generate the PM depolarization and to propagate the SWP. The AHA activity is also important during the PM repolarization phase, where its activity is recovered  to FMG-A and JCM. Open access funding provided by ETH Zurich.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


BRD1) encodes an epigenetic regulator that controls the expression of genetic networks linked to mental illness. BRD1 is essential for normal brain development and its role in psychopathology has been demonstrated in genetic and preclinical studies. However, the neurobiology that bridges its molecular and neuropathological effects remains poorly explored. Here, using publicly available datasets, we find that BRD1 targets nuclear genes encoding mitochondrial proteins in cell lines and that modulation of BRD1 expression, irrespective of whether it is downregulation or upregulation of one or the other existing BRD1 isoforms (BRD1-L and BRD1-S), leads to distinct shifts in the expression profile of these genes. We further show that the expression of nuclear genes encoding mitochondrial proteins is negatively correlated with the expression of BRD1 mRNA during human brain development. In accordance, we identify the key gate-keeper of mitochondrial metabolism, Peroxisome proliferator-activated receptor (PPAR) among BRD1’s co-transcription factors and provide evidence that BRD1 acts as a co-repressor of PPAR-mediated transcription. Lastly, when using quantitative PCR, mitochondria-targeted fluorescent probes, and the Seahorse XFe96 Analyzer, we demonstrate that modulation of BRD1 expression in cell lines alters mitochondrial physiology , metabolism (reducing power), and bioenergetics  in an expression level- and isoform-dependent manner. Collectively, our data suggest that BRD1 is a transcriptional regulator of nuclear-encoded mitochondrial proteins and that disruption of BRD1’s genomic actions alters mitochondrial functions. This may be the mechanism underlying the cellular and atrophic changes of neurons previously associated with BRD1 deficiency and suggests that mitochondrial dysfunction may be a possible link between genetic variation in BRD1 and psychopathology in humans.Bromodomain containing 1 ( Psychiatric disorders comprise a heterogeneous group of conditions collectively characterized by changes in patterns of thoughts, emotions, and behaviors. Their clinical profile is shaped by a range of environmental exposures  and moleBRD1, has been associated with mental illness in several genetic studies of common variants ) including the repeated experiments as random variable. Significant differences between genotypes were calculated using the ‘lmerTest’ package in R.17,000 cells were seeded in each well of a Cell-tak  coated 96-well XF96 cell culture microplate  and incubated in culture media for 16 h at 37 °C in a humidified atmosphere of 5% COBRD1 (BRD1-KD) [n = 976) and BRD1-L (n = 507), respectively 8.1% and 9.9% of those were nMT genes, representing a significant enrichment .In order to assess if BRD1 is a putative transcriptional regulator of nuclear-encoded mitochondrial (nMT) proteins –47, we eBRD1-KD) , 40. BRDBRD1-KD) ). When op = 2 × 10−9; BRD1-L: p = 7 × 10−17; and BRD1-S: p = 3 × 10−14, Fig. BRD1 is underexpressed in cells or one or the other BRD1 isoform is upregulated, similar overall shifts in expression profiles are observed.We then compared the overall changes in the expression profile of nMT transcripts to the profiles of all transcripts in BRD1-L, BRD1-S, and BRD1-KD cells and found a significant shift in the profile towards a negative fold change (downregulation) for nMT transcripts  Fig. , we obseBRD1 and mitochondrial function in brain tissue [BRD1 is correlated with the expression of nMT transcripts in the developing human brain. Particularly, we compared expression correlation across 13 developmental stages and 26 different brain regions of BRD1 and all protein-coding transcripts as well as BRD1 and nMT transcripts in the Brainspan dataset . We found that the correlation values of all protein-coding transcripts center on zero (mode = −0.07), indicating no general correlation in expression of protein-coding genes with BRD1 expression. However, when we compared the distribution of correlation values for nMT transcripts (n = 961), we observed a significant shift towards negative correlation   Fig. .Fig. 2Spr < −0.5), we found a significant enrichment of nMT transcripts in 28 out of 33 spatiotemporal intervals (fraction of nMT transcripts between 6.3 and 22%) and a significant underrepresentation in 2 out of 33 intervals (fraction of nMT transcripts between 3.4 and 3.8%). Furthermore, nMT transcripts were significantly underrepresented among positively correlated transcripts (r > 0.5) in 28 out of 33 spatiotemporal intervals (fraction of nMT transcripts between 1.1 and 3.9%), and significantly overrepresented in 2 out of 33 spatiotemporal intervals (fraction of nMT transcripts 7.3 and 7.6%). Supporting a role for BRD1 as a transcriptional regulator of nMT genes, GOTERM enrichment analysis of all genes with r < −0.5  as input gene set (n = 1757) found a significant enrichment of genes annotated to mitochondrial processes  of all brain regions (r1–r4) Fig.  and we cses Fig. , includinMT-all = −0.65, p = 1 × 10−20) and DNMT1 , while this shift was much smaller with KAT7  or not significant with KAT5  . These 18 genes were significantly enriched for binding sites of the Peroxisome proliferator-activated receptor proteins PPARγ (p = 0.02) and PPARδ (p = 0.03) as well as two subunits of the nuclear transcription factor Y (NF-Y)   HEK293T cells (clone 1–4)  and Androgen receptor  was significantly increased in BRD1CRISPRex6/+ cells, whereas transcription mediated by Glucocorticoid receptor  and Vitamin D receptor  was significantly decreased   Fig. , suggest clone 1– (SupplemBRD1 or overexpression of either of the two BRD1 isoforms (BRD1-L or BRD1-S), would influence mitochondrial biology. Hence, we investigated mitochondrial amounts and function in naïve HEK293T (control), BRD1-L, BRD1-S and BRD1CRISPRex6/+    Fig. . BRD1-L ent Fig. . Further05) Fig. .Fig. 4InBRD1 levels or increased levels of either of the two BRD1 isoforms on mitochondria-related processes in the same cell lines. First, we estimated mitochondrial oxidative stress levels by measuring levels of mitochondrial superoxide and second, we estimated cellular oxidative stress levels by measuring thiol redox status (TRS). Whereas we did not observe any statistically significant differences in mitochondrial superoxide levels between cell lines      Fig. , we did 05) Fig. . In cont04) Fig. . Increas66) Fig. , indicatRapid calcium influx through plasma membrane receptors and voltage-dependent ion channels in neurons plays a key role in neurosignaling . BecauseBRD1 expression in the brain, we measured the effect of BRD1 levels on oxygen consumption rates (OCR) reflecting mitochondrial electron transport and oxidative phosphorylation function, using the XFe96 extracellular flux analyzer. Based on these data, we calculated the effect size (β) of hampered and increased BRD1 levels relative to the control cell line (naïve HEK293T cells) (β = 0) on the following parameters: Basal respiration; ATP-linked respiration; Coupling efficiency; Maximal respiration; Non-mitochondrial oxygen consumption; Proton leakage; and Spare respiratory capacity (%) , maximal respiration , and proton leakage  were reduced in BRD1-L cells compared to controls. On the other hand after adjustment, ATP-linked respiration was no longer significantly increased compared to controls , while coupling remained unchanged. Taken together, these data suggest that BRD1-L cells might compensate for reduced basal respiration by promoting more/larger mitochondria or vice versa. Eukaryotic cells produce energy by oxidative phosphorylation and glycolysis, and most cells possess the ability to switch between these two pathways depending on changing environment. To evaluate whether cells experiencing dysfunctions in oxidative phosphorylation would produce energy by glycolysis instead, we measured changes in the extracellular acidification rates (ECAR) that result from the conversion of pyruvate generated by glycolysis to lactate. BRD1CRISPRex6/+ cells had reduced ECAR values compared to control, indicating more quiescent cells. BRD1-L cells had slightly increased ECAR levels, indicating that the cells are more energetic, whereas the ECAR levels of BRD1-S cells remained unchanged compared to the controls  [Brd1+/− mice that do survive into adulthood have reduced dendritic arborization and spine density and aberrant spine morphology, phenotypes that have previously been linked to mitochondrial dysfunction and that could lead to cortical under-connectivity and cognitive impairments [In this line, dysfunctional mitochondrial bioenergetics could explain some of the previously observed phenotypes in the brains of ups (P0) . Neuronsairments , 90–92. BRD1 gene is the only fully contained protein-coding gene in a genomic region (Chr22:49238268–50248907/hg19), that seems critical in the formation of a 22q13.3 large-deletion and Phelan-McDermid syndrome specific genome-wide DNA methylation epi-signature [CRISPRex6/+ cell line) are mitochondrially compromised and hypometobolic, lymphoblastoid cell lines from individuals with this Phelan-McDermid syndrome DNA methylation epi-signature  show significantly different and specific metabolic profiles characterized by reduced energy production in the presence of high-efficiency energy sources, decreased ability of metabolic adjustment to environmental changes, as well as abnormal responses to hormones and cytokines regulating energy storage, proliferation, growth, and inflammation [BRD1 might be responsible for a phenotypically distinct clinical subtype of Phelan McDermid syndrome. Specific evidence of respiratory chain dysfunction in Phelan-McDermid syndrome, especially involving the complex I and IV, has previously been demonstrated in patient-derived buccal swaps [BRD1 deletions also had respiratory chain complex abnormalities. We further observe in the study by Schenkel et al. [BRD1 gene itself is differentially methylated (10-14% increased methylation as determined by three probes close to the transcription start site) in the absence of one copy of BRD1 but also the PPARG gene at chromosome 3 encoding PPARγ shows 13% decreased methylation (as determined by one probe in the PPARG 5′ UTR). Unfortunately, the study of the Phelan-McDermid syndrome cells did not include genome-wide gene expression measurements, neither did our own study of the BRD1CRISPRex6/+ cell line. However, indeed the BRD1-KD cells [PPARG and the BRD1CRISPRex6/+ cell line show a more than the expected 50% decrease in BRD1 expression. We thus speculate, based in our joint findings, that heterozygosity for a BRD1 gene deletion/inactivation not only leads to further epigenetic downregulation of the remaining copy of BRD1 but also to metabolic/mitochondrial dysfunction due to, at least partly, downstream epigenetic effects of BRD1 deficiency on the expression of PPARG.Of particular importance in the understanding of the molecular, cellular, and clinical manifestations of BRD1 deficiency in humans, it has recently been shown that the ignature . Candidaammation . Thus, Bal swaps . Of notel et al.  that notBRD1 and changes in BRD1 levels lead to aberrant mitochondrial bioenergetics in an isoform-specific manner. Mitochondrial dysfunction provides a possible mechanistic explanation for the phenotypes observed in Brd1+/− mice and a conceivable link between genetic variation in BRD1 and psychopathologies in humans. Since mitochondrial modulators are emerging as an effective alternative treatment paradigm in psychiatric disorders [BRD1-based cell and mouse models should address both short- and long-term effects of such drugs as well as their underlying mechanisms of action.In conclusion, we show that BRD1 regulates the expression of genes important for mitochondrial function, likely through its interaction with selected transcription factors and epigenetic modifiers, or through indirect modulation of mitochondrial biology. We furthher show that proper function of mitochondria seems to be dependent on a balanced expression of isorders , future Supplementary informationTable S1