The assessment of semen quality is used to identify factors that influence sperm performance and diagnose male infertility. From the earliest works to the present day, a considerable number of analytical techniques have been developed. These tests study many aspects of the morphology and physiology of the spermatozoan; however, their ability to predict male fertility remains low. Some of these techniques have been automated, which can make the test results more objective, but others still require subjective evaluation. The introduction of computer-assisted sperm analysis (CASA) systems and flow cytometry has revolutionized sperm quality analysis in recent decades. However, the use of these advanced techniques remains experimental, with only a few of them having successfully led to practical applications in routine commercial semen evaluation. Future sperm biology research should focus on developing analytical techniques that have a greater capacity to predict male fertility and can be used in both the laboratory and the field. Field adaptation will require progress in automation and simplification, to produce precise, economical and efficient techniques. Nevertheless, as technology advances in these analytical tests and research continues, our greater understanding of male fertility will aid the development of new methods of sperm evaluation.This Special Issue of Biology entitled “Sperm quality: Past, present and the future knowledge we need” focuses on understanding the quality of spermatozoa in three sub-sections: (1) the function of the sperm cell, (2) its ability to withstand cryopreservation and (3) its performance both in vitro and in vivo. Combined, this Special Issue contains 11 published peer-reviewed papers.An important endeavor in the creation of this Special Issue was to delve into aspects related to the biology and physiology of spermatozoa. In this regard, sperm capacitation is essential for the acquisition of fertilizing capacity, and, although it has been extensively studied in many species, there are still aspects that remain unclear. Many studies have been conducted to establish a suitable capacitation medium for different species, because effective in vitro sperm capacitation is required for successful in vitro fertilization (IVF). Most of the media examined include bovine serum albumin (BSA) and bicarbonate, but these compounds may not be necessary to capacitate sperm from all species. Chaves et al.  demonstrThe development and maturation of spermatozoa, as well the acquisition of motility and capacitation, are strongly coordinated by sperm protein phosphorylation, among other protein post-translational modifications. Serrano et al.  reviewedThe use of sperm preservation has long been considered a vital reproductive technology in human medicine, livestock artificial breeding and wildlife conservation programs. Cryopreservation, in particular, not only facilitates biobanks and the storage of precious genetic material but also maximizes long-term fertility and genetic gain. Ever since glycerol was discovered to be an effective cryoprotectant in 1947, the species-specific protocols and media used have undergone extensive research to optimize sperm survival and quality post-thaw. The basic principles involved in the freeze–thaw process, including the cooling curve, freezing rate and thawing, will always remain; however, as technology advances and procedures are automated, there is always the opportunity to update and improve the quality of spermatozoa post-thaw. Within this Special Issue, knowledge on the impact of cryopreservation on the metabolome of turkey spermatozoa was reported, recommendations were made regarding the use of the sperm-rich fraction or entire ejaculate for improved boar sperm storage and fertility, and a novel enzyme was suggested to reduce the viscosity associated with wildlife ejaculates, improving the cryosurvival and availability of rhinoceros spermatozoa for wildlife conservation programs. These scientific papers represent some of the compelling research being conducted to advance our knowledge and understanding of sperm quality post-cryopreservation.Of all the animal industries, research on the impact of cryopreservation on avian sperm quality is likely to be the most limited in comparison to that of cattle, pigs or sheep. Paventi et al.  used nucBoar sperm storage protocols (both liquid and frozen) have undergone extensive development and optimization over time. A recent objective was to maximize the number of doses produced for artificial insemination from one ejaculate per male. Luongo et al.  investigEjaculates collected from wildlife species via electro-ejaculation are often highly viscous. It is suggested that this method of semen collection, artificially stimulates the accessory sex glands, altering the contribution of seminal plasma and physiological parameters of the ejaculate. Like that of the boar, the ejaculate of the rhinoceros is also fractionated, with a sperm-rich fraction predominantly being used for cryopreservation and artificial insemination. However, this renders the very expensive and labor-intensive procedure of collecting semen very inefficient, especially when considering the risk posed to valuable endangered animals. Any semen obtained from these viscous fractions are often of poor quality and do not survive the freezing process. Rickard et al.  investigThere is a direct relationship between sperm quality and fertility. Sperm quality refers to the health and characteristics of sperm cells, including their count, motility, morphology, and viability. These factors are crucial for successful the fertilization of an egg and the establishment of a viable pregnancy. Evaluating and addressing any issues with sperm quality through proper diagnosis and appropriate treatments can significantly improve the chance of inducing pregnancy. However, achieving satisfactory predictions based on the in vitro evaluation of sperm quality remains a challenge. Overall, the combination of scientific discoveries, technological innovations, advancements in optical physics, and computing techniques has significantly advanced our understanding of semen quality and its impact on fertility. These advancements could improve, significantly, the accuracy of semen analysis.In this sense, testicular ultrasound, a non-invasive diagnostic procedure, could be a useful tool. Recent ultrasound-video analysis and software developments have allowed the visualization of tissue at the microscopic level. Carvajal-Serna et al.  revealedOn the other hand, the analysis of sperm performance under in vitro conditions provides a good indication of fertilizing potential. Parameters such as motility, swimming kinetics, acrosome integrity, and ATP content are thus examined in efforts to characterize such potential. Hamster species are a good model for studying sperm parameters that are key determinants of fertilizing capacity because these species are at the higher end of the diversity of mammalian sperm morphology and performance. In vitro functional studies demand that sperm remain viable during a long period of time under conditions that resemble those in the female tract. Sperm from certain species require a supplementation of the incubation medium with factors that stimulate viability and motility, or that promote the acquisition of fertilizing capacity. Molecules important for sperm performance in hamsters have been identified, namely D-penicillamine, hypotaurine and epinephrine (PHE). Tourmente et al.  investigRegarding the relationship between the quality and fertility parameters, Yániz et al.  investigFinally, swine reproduction efficiency is determined by the fertility potential of the sow and sperm quality. The objective of Barquero et al.’s study  was to c


In recent years, cardiovascular disease in particular myocardial infarction (MI) has become the predominant cause of human disability and mortality in the clinical setting. The restricted capacity of adult cardiomyocytes to proliferate and restore the function of infarcted sites is a challenging issue after the occurrence of MI. The application of stem cells and byproducts such as exosomes (Exos) has paved the way for the alleviation of cardiac tissue injury along with conventional medications in clinics. However, the short lifespan and activation of alloreactive immune cells in response to Exos and stem cells are the main issues in patients with MI. Therefore, there is an urgent demand to develop therapeutic approaches with minimum invasion for the restoration of cardiac function.Here, we focused on recent data associated with the application of Exo-loaded hydrogels in ischemic cardiac tissue. Whether and how the advances in tissue engineering modalities have increased the efficiency of whole-based and byproducts (Exos) therapies under ischemic conditions. The integration of nanotechnology and nanobiology for designing novel smart biomaterials with therapeutic outcomes was highlighted.Hydrogels can provide suitable platforms for the transfer of Exos, small molecules, drugs, and other bioactive factors for direct injection into the damaged myocardium. Future studies should focus on the improvement of physicochemical properties of Exo-bearing hydrogel to translate for the standard treatment options. It has been well-established that a small fraction of injured cardiomyocytes is replaced following pathological conditions especially myocardial infarction (MI) due to the minimum regenerative potential of surrounding healthy cardiomyocytes . Thus, mAmong different stem cell types, mesenchymal stem cells (MSCs) are the main cell source used for the healing of injured myocardium . These cRegardless of cell type and the injection method, the regenerative outcome and restoration of cardiac tissue function are not satisfactory because of the low-rate engraftment capacity of transplant cells after administration into the target sites . Thus, tIn comparison with whole-cell-based therapies, the application of cell secretory vesicles like Exos is at the center of the debate. It was suggested that Exos are more stable for long periods after introduction into the target sites and exhibit appropriate biodistribution and immune tolerability . Based ode novo delivery approaches are mandatory to yield better regenerative outcomes.Despite putative advantages, the application of Exos in regenerative medicine encounters some fundamental limitations . At presIn recent decades, the application of hydrogels has been increased for in situ delivery of stem cells and nano-sized particles like Exos into the injured sites . It is pIn multicellular organisms, intercellular communication can be done in a paracrine manner via the unidirectional or bidirectional transfer of signaling molecules in addition to close physical cell–to–cell connection . To dateUpon the activation of the endosomal system, the membrane of early and late endosomes is invaginated into the lumen, leading to the formation of numerous intraluminal vesicles (ILVs). In the latter steps, late endosomes mature into multivesicular bodies (MVBs) . SimultaDespite the advantage of Exo application in regenerative medicine, several issues such as isolation modalities and purity rate limit the extensive application of Exos for the alleviation of different pathological conditions. For instance, it is highly recommended to isolate pure, homogeneous Exo pellets by using standard methods . SeveralIn recent years, we witnessed progress in cardiac tissue engineering to overcome limitations associated with whole-cell-based therapy approaches . CardiacRecently, Exos have gained the main focus in the diagnosis and treatment of cardiovascular diseases owing to their capability to reflect the physiological and pathological changes inside cardiac tissue . Since EThe advances in the technologies associated with the development of microgels, nanogels, and stimulus-responsive, adhesive, self-assembled injectable hydrogels have led to yielding better regenerative outcomes . Along wSeveral studies have used naked EVs, especially Exos, for the restoration of injured cardiac tissue. Despite the acceleration of the healing process within the cardiac tissue after Exo injection, they are cleared from the target sites due to prolonged instability, heterogeneous delivery rates, and reactive phagocytic cells –122. TheHydrogels are carrier platforms for controlled and sustained release of loaded Exos after introduction into the injured sites , 30. Usi2 bubbles increases the formation of interconnected porous networks within the hydrogels. These features help cell adhesion, migration, proliferation, and even ECM synthesis  and injected into the border zone of ischemic cardiac tissue in a rat model of MI ..9 particde novo modalities for improving therapeutic outcomes. It is thought that Exos employed in cell-free therapies are compromised by off-target effects and rapid elimination action. Thus, the application of hydrogels and 3D-engineered tissue matrices with Exos provides a suitable microenvironment to postpone Exo retention time in the damaged cardiac. However, there is still an avenue for researchers to optimize future approaches and expand studies to confirm the efficacy and safety of these promising approaches and ensure scientific and technology transfer to the appropriate clinical setting.Since Exos exhibit various regenerative properties in terms of cardiovascular diseases, especially in ischemic myocardial disease, attempts should be directed toward the advent and development of


With an increasing burden of stroke and a lack of access to rehabilitation services in rural South African settings, stroke survivors rely on untrained family caregivers for support and care. Community health workers (CHWs) support these families but have no stroke-specific training.To describe the development of a contextually appropriate stroke training program for CHWs in the Cape Winelands District, South Africa.Twenty-six health professionals and CHWs from the local primary healthcare services participated in action research over a 15-month period from September 2014 to December 2015. The groups participated in two parallel cooperative inquiry (CI) groups. The inquiry followed the cyclical steps of planning, action, observation and reflection. In this article, the planning step and how the CI groups used the first three steps of the analyse, design, develop, implement, evaluate (ADDIE) instructional design model are described.The CHWs’ scope of practice, learning needs, competencies and characteristics, as well as the needs of the caregivers and stroke survivors, were identified in the analysis step. The program design consisted of 16 sessions to be delivered over 20 h. Program resources were developed with appropriate technology, language and instructional methodology.The program aims to equip CHWs to support family caregivers and stroke survivors in their homes as part of their generalist scope of practice. The implementation and initial evaluation will be described in a future article.The study developed a unique training program for CHWs to support caregivers and stroke survivors in a resource-constrained, rural, middle-income country setting. South Africa (SA) and other low- and middle-income countries (LMICs) have an increasing burden of stroke as a result of socio-economic development, urbanisation, increasing risk factors for noncommunicable diseases and a transition in the epidemiological profile of the population associated with ageing, increase in cardiovascular diseases and adoption of the Western lifestyle Donkor . While sThe local and international literature describes a myriad of caregiver training interventions in different levels of care, different settings and with different caregiver needs and stroke survivor stages of recovery  are delivered by nurse-led teams of community health workersNational initiatives to strengthen PHC rehabilitation services include strengthening the role of CHWs, as well as introducing midlevel rehabilitation workersThe Western Cape province in SA  has a hiThis article reports on the last stage of a multistage mixed-methods study . The firIn this last stage of this multistage mixed-methods study, a cooperative inquiry (CI) process was used Heron . CooperaThis article focuses only on the planning step of the CI, which corresponds with the analysis, design and development steps of the ADDIE model . A separThe study was conducted in the Breede Valley Subdistrict  of the CStroke clinical practice pathways, evidence-based practice guidelines, as well as referral guidelines, were absent on the HCBC platform, and stroke care was poorly coordinated   from theBoland Hospice, a nonprofit organisation, was funded by the Department of Health to deliver HCBC services in 10 municipal wards. Four home-based care coordinators, who were professional and enrolled nurses, were responsible for conducting assessments, designing treatment plans and supervising the 79 CHWs  deliveriThe Breede Valley Association for the Physically Disabled (APD), a nonprofit organisation, provided a range of services for persons with disabilities, including stroke survivors, such as access to education, employment and therapeutic counselling services.Undergraduate physiotherapy and speech therapy students from Stellenbosch University (SU)’s Rural Clinical School were placed in two of the municipal wards and often accompanied the CHWs. They were supervised by two physiotherapists and a speech therapist from the university.The researcher consulted with the respective service managers from all the groups described in the setting section to identify key role players. Because of practical and logistical considerations such as transport problems and work schedules, two cooperative inquiry groups (CIGs) were formed . All butThe CBS-CIG consisted of 18 service providers from the Cape Winelands District CBS management, Boland Hospice and APD. The MDP-CIG consisted of eight MDPs from the Breede Valley District and the university and included both clinical and educational expertise.Both CIGs engaged in a 15-month collaborative inquiry from September 2014 to December 2015. The inquiry focused on the interprofessional design and development of an appropriate training program for CHWs to train family caregivers of stroke survivors. Cooperative inquiry group members contributed from their own experience, knowledge and available evidence related to caregiver training needs and interventions. The researcher, who was ultimately responsible for driving the research agenda and processes, engaged in a consultative and collaborative manner , and permission was obtained from the Department of Health to conduct the study.This section reports on the results of the planning of the CIGs in the first three steps of the ADDIE model, namely analyse, design and develop.The following key factors that influenced the design of the training course were identified.The CHWs did not have any stroke- or rehabilitation-specific training. Their scope of practice already included health education, basic observations, training of family caregivers, assistance with daily living, monitoring patient and caregiver function and well-being, monitoring of treatment adherence, identification and referral of psychosocial problems and excluded patient assessment and care plan development  to support the theory and process of each session.Equipment for demonstration and practice purposes. A standard list of equipment would enable training in different settings, such as a nongovernment organisation, local health care facility or community centre. Although access to tables, chairs, therapy mats and examples of wheelchairs and assistive products would be readily available in most settings, it was unlikely that there would be enough beds or treatment plinths. Therapy mats could be used for practising bed mobility but not for bed or bath transfer training. The training manual had to guide trainers to use chairs and tables to allow simulated transfer practice. Examples of self-made assistive products were also needed.Learner’s manual for CHWs based on the content of the trainer’s manual, incorporating the formative assessments and model answers or checklists, as well as resources such as examples of referral forms.Detailed sequences of line drawings were needed to supplement the text of the learner’s manual. These same drawings would be used in the other resources as well.Booklet for caregivers and stroke survivors. A suitable caregiver and patient booklet was previously co-authored by the researcher and revised after a suitability study Botha  for use Formative assessments were integrated in each session through case studies and role play activities. Each of the case studies had model answers listed in both trainer’s and learner’s manuals and a checklist for performing activities. These assessments would assist both the trainers and the CHWs to provide or obtain constructive feedback on learning.Line drawings were commissioned from purpose-specific photographs taken by the researcher. The text for the trainer’s manual was developed first, and then the PowerPoints and learner’s manual were developed. The stroke survivor and caregiver information booklet were updated and translated. Training resources were developed in English using plain language. This challenged the MDPs. The learner’s manual and information booklet were picture based with limited text. The manuals and information booklet were developed as both hardcopy and online resources, together with the PowerPoint presentations.This study appears to be the first of its kind to design an appropriate stroke training program for CHWs to empower caregivers and stroke survivors in the home. Several stroke interventions, including caregiver training, have been developed through co-creation  (Bakas et al. The low educational levels of both the CHWs and the final target population impacted the selection of teaching methods and the development of training resources. The interactive nature of the adult education teaching model (Hanger & Wilkinson Poverty, technological barriers (Opoku, Stephani & Quentin With limited access to and availability of psychosocial services, this training program included a substantial focus on psychosocial support within the CHW’s scope of practice, including identification and referral of at-risk families. Although common in training programs in HICs, psychosocial support is less frequent in training programs in LMICs (Pitthayapong et al. Although the structure of the training program for CHWs followed a specific sequence and duration, the training of caregivers would be tailored to the stroke survivor’s specific level of functioning and care needs, similar to most training programs (Chaiyawat et al. As a participatory action research project, the involvement of the service providers was limited because of low numbers and high service demands. None had experience in designing a training program of this scale and nature. Fully collegial roles (Higginbottom & Liamputtong This study demonstrated how local healthcare services at the PHC level can design an appropriate, contextually relevant community-oriented intervention through a participatory approach. The CI planning step described in this article used the ADDIE model to analyse, design and develop an appropriate home-based stroke rehabilitation program to be delivered by CHWs in a low-resourced setting. This home-based stroke rehabilitation program and its accompanying training program for CHWs should be implemented and further evaluated in practice.


The research and application progress of resin-based composite materials in the field of electrical insulation has attracted considerable attention and emerged as a current research hotspot. This review comprehensively summarized the research and application progress of resin-based composite materials in the field of electrical insulation, providing detailed insights into their concept, properties, and preparation methods. In addition, a comprehensive evaluation of the electrical insulation performance, mechanical properties, and thermal properties of resin-based composite materials was presented, along with an in-depth analysis of their current application status. Despite the immense potential and development opportunities of resin-based composite materials, they also face several challenges. This review serves as a valuable reference and resource for researchers in related fields and aimed to promote further research and application development of resin-based composite materials in the field of electrical insulation. With the rapid development of science and technology, mankind’s demand and dependence on energy is growing. Against this background, it has become crucial to establish a reliable power system . Power eTo replace conventional insulating materials, composites have been extensively researched and developed because of their ability to combine the excellent properties of the internal component materials to improve the overall material performance. In insulating composites, polymers are considered to be the ideal matrix material because of their good electrical insulation properties, low cost, and excellent processability. Commonly used polymers include epoxy resins, phenolic resins (PF), polyether ether ketone (PEEK), polyphenylene sulfide (PPS), and polyetherimide (PEI), with resin materials being the most widely used ,3. HowevThis paper focused on the progress of research and application of resin matrix composites in the field of insulation. The whole paper can be divided into the following parts: resin matrix composite system and its molding process, research on resin matrix composites in the field of insulation, and application of resin matrix composites in the field of insulation. Finally, the corresponding conclusions and references are given.Resin matrix composites are a class of composites composed of resin matrix and reinforcement materials, which have the advantages of lightweight, high strength, excellent mechanical properties, and chemical resistance, etc. The resin matrix composites can be categorized into thermoset resin matrix composites and thermoplastic resin matrix composites. Depending on the resin matrix used, resin matrix composites can be divided into two categories: thermoset resin matrix composites and thermoplastic resin matrix composites. Among thermosetting resin matrix composites, the most widely used is epoxy resin matrix composites. In China, more than 10% of epoxy resins are used in composite manufacturing. In addition, phenolic resins are also widely used in resin materials for composites due to their excellent insulating properties, high thermal decomposition temperature, excellent flame-retardant properties, and low cost. In addition, specialty resins such as bismaleimide resins, phenolic resins, and cyanate ester resins are considered to be thermosetting resins with great potential for development due to their good electrical insulation, heat resistance, flame retardancy, transparency, and mechanical properties. Thermoplastic resin matrix composites often use general-purpose resins such as polypropylene (PP), polyethylene (PE), and polyvinyl chloride (PVC), as well as specialty resins such as polyphenylene sulfide (PPS) and polyether ether ketone (PEEK). Since thermoplastic resins are high molecular weight polymers, only a change in physical state occurs during processing, and unlike thermoset resins, they do not form a rigid, three-dimensional, cross-linked chemical structure, and, therefore, have the property of being repeatable ,7.Currently, there are several major molding processes for resin matrix composites, which are discussed below.The Resin Transfer Molding (RTM) molding process is one of the most practical processes available today. Compression molding uses a similar principle to the RTM molding process. By using a hot press as a pressurized warming device, the prepreg is placed in a pre-designed mold, then the mold is closed and cured to shape. Alternatively, vacuum bags and hot press tanks can be used to achieve the same effect. The process has the advantages of simple process flow, fast molding speed, and flexible adjustment of molding parameters. As shown in The Automated Fiber Placement (AFP) in situ curing process is an innovative process for processing resin matrix composites and is shown schematically in Using manual work, the fiber fabric and resin are spread on the mold, bonded, and then cured into shape . The proThe fibers are wound on the mold according to a certain pattern and then cured and demolded to form the product . The proVARI (Vacuum-Assisted Resin Injection) is a process that removes gas from fiber reinforcement in a vacuum state, impregnates fibers and their fabrics through resin flow and penetration, and solidifies at room temperature to form a certain fiber/resin ratio. This process method only requires vacuum pressure and no additional pressure. The entire operation process is carried out at room temperature without heating . The resin fully penetrates the skin and sandwich structure under vacuum, greatly improving the overall structural strength and reducing defects and complex processes introduced by secondary bonding.Electrical insulation properties are one of the most concerning properties in the research of insulating composites, which is also an important research hotspot in the development of electrical engineering. Insulating composites need to have the following electrical properties in electrical applications: (1) low conductivity; (2) high breakdown strength. The electrical insulating properties of composites are mainly determined by the electrical insulating properties of resin matrix. Epoxy resin composites are a class of insulating materials used in a large number of transmission cables, and their insulating properties are closely related to the safety of the transmission system. Organic compounds containing two or more epoxy groups in the molecule are called epoxy resins. This polymer material is generally presented as a liquid with a large viscosity at room temperature. In practical engineering applications, it is necessary to add different functional curing agents to the epoxy resin and then cure it at room temperature to form a solid polymer material with strong mechanical properties.Epoxy resin composites have the advantages of good processing performance, good dielectric properties, and good stability, and, thus, are widely used in low, medium, high, and ultra-high voltage distribution networks and high-energy electrical devices. However, epoxy resin composites have the disadvantages of poor toughness, poor heat resistance, and poor moisture resistance; thus, their dielectric properties are significantly affected in complex application environments.The electrical properties of epoxy resin composites are mainly evaluated by properties such as resistivity, dielectric constant, dielectric loss, and breakdown strength. Currently, the introduction of nanoparticles to prepare nanocomposite epoxy resin materials is the main way to enhance the electrical properties of epoxy resin composites. Aluminum trioxide nanoparticles are widely used as a common filler to optimize the electrical properties of epoxy resin composites. The research results ,16 show Silica fillers also play an important role in the modification of epoxy composites. The results of the study show that the addition of nano-silica fillers in micron filler composite epoxy resin can improve the resistance of the material to partial discharge  and, at Some of the studies focused on the differences between the effects of different fillers. The results  show thaIn addition to inorganic oxide nanoparticles, conductive carbon nanotubes and metal nanoparticles can also be added to insulating polymers. When nanoconductor particles are uniformly dispersed in insulating polymers in a certain amount, they not only improve the breakdown strength of the composite material, but also maintain a good dielectric stability, which is due to the unique ‘Coulomb blocking’ effect of nanoparticles.Epoxy resin composite materials will face various complex environments during service, and prolonged complex environments can lead to various electrochemical corrosion faults in the composite material, leading to electrical breakdown problems ,25,26,27In high-voltage cables and cable accessories, the main electrical aging phenomenon that leads to insulation failure is electrical tree damage, a condition that leads to pre-breakdown of the insulation. At present, adding organic additives to the resin is one of the main methods to improve the electrical insulation properties of the resin. Organic additives mainly include antioxidants and ultraviolet absorbers. Antioxidants prevent the oxidative degradation of materials by inhibiting the generation of free radicals in the oxidative degradation process; ultraviolet absorbers can convert ultraviolet light into thermal radiation and higher wavelengths of radiation that are harmless to polymer-insulating materials. The addition of organic additives can improve charge modulation properties and reduce the probability of electrical tree damage. In addition, some researchers have developed self-healing insulating materials to address the problem of electric tree damage. For example, In addition, space charge accumulation also has an important effect on the electrical insulation properties of materials. Even if the local electric field is not high, space charge accumulation will gradually degrade the dielectric properties and form defects, thus reducing the reliability and service life of the product . CurrentIn addition, the electrical insulation properties of resin matrix composites can also be studied by evaluating the breakdown strength and electrical strength to comprehensively understand and improve their properties, and the specific improvement means are the same as the above scheme. In summary, improving the electrical insulation properties of resin matrix composites mainly focuses on optimizing the formulation of the resin and using nanoparticles to improve its dielectric properties; however, it is difficult to satisfy other properties by only improving the electrical insulation properties of resin matrix composites, and there are major limitations in practical applications ,35,36.During the operation of power cables, the conductor temperature may reach 70 °C and 90 °C under both DC and AC conditions, while high voltage cables may even reach temperatures as high as 250 °C during an overload or short circuit. In practice, however, the heat generated by the center conductor of power cables accumulates on the inside of the insulation layer, and this heat is difficult to dissipate effectively due to the low thermal conductivity of the resin. As the transmission capacity and voltage level of the cable increase, the thickness of the insulating layer increases accordingly to cope with this problem, which further inhibits heat dissipation, leading to even more severe heat accumulation and seriously affecting the aging problem of the insulating equipment. Therefore, to improve the thermal conductivity of resins, researchers tend to add highly thermally conductive reinforcements to resins to prepare resin matrix composites with excellent thermal conductivity ,38,39,40Epoxy resins, for example, have good thermal stability and low cost, but at the same time have low thermal conductivity (0.2 W/m-K) as well as a high coefficient of thermal expansion. To improve the thermal conductivity of epoxy resins, carbon, aluminum, magnetite, brass, copper, graphite, short carbon fibers, and copper nitride have been widely used as dopants to prepare epoxy resin-based composites. For example, Salunke et al.  investigCarbon nanomaterials have extremely high thermal conductivity and can be utilized to prepare epoxy composites with high thermal conductivity . The maiOxides have excellent mechanical properties and good insulating properties, which can also achieve the effect of enhancing the thermal conductivity of epoxy resin composites. Chen et al.  preparedResin matrix composites are usually subjected to severe static and dynamic loads when they are used as insulating materials, and the selection of lightweight and high-strength composites as insulating materials can effectively improve the safety of electrical equipment. At present, researchers have already made mature scientific achievements in the fields of wet thermodynamic properties of resin matrix composites, the influence of component material properties, and the influence of interfacial properties between components. According to the development of research methodology, in situ experiments at the micro- and nanoscale, macro-mechanical tests, and virtual tests based on multi-scale numerical simulations have been maturely applied to study the mechanical properties of resin matrix composites ,51,52,53According to the different microstructures of the reinforcement in resin matrix composites, they can be divided into particle-reinforced resin matrix composites, continuous fiber-reinforced resin matrix composites, short-fiber-reinforced resin matrix composites, and fiber-cloth-reinforced resin matrix composites, etc. ,57,58,59Short-fiber-reinforced composites as well as particle-reinforced composites within the resin matrix as the main load-bearing structure leads to composite performance and matrix mechanical properties are the same, while continuous fiber-reinforced composites can effectively play the excellent mechanical properties of fibers and greatly enhance the mechanical properties of composites. As shown in Resin matrix composites can be used in different forms as insulating materials in electrical equipment, microelectronics, LEDs, power generation, transportation, and aerospace, etc. ,68,69,70The above electrical equipment does not require high mechanical properties of insulating materials, but with the development of electrical equipment toward ultra-high voltage and other fields, breakthroughs in the mechanical properties of insulating materials have become an urgent problem to be solved at present. For example, the insulating tie rod as a circuit breaker transmission device plays the role of insulation and operation of the circuit breaker, which often needs to withstand a large switching overvoltage impact and compression, bending, stretching, and other mechanical loads. Therefore, it needs to have good resistance to bending, compression, and torsion, as well as good insulating properties. Currently, fiber-reinforced epoxy resin matrix composites have been widely used in the production of insulating tie rods, in which commonly used fibers include glass fibers, polyester fibers, and aramid fibers .Composite materials have also been used to a certain extent in the field of power transmission towers. Traditional cement poles or metal transmission towers generally have problems such as high weight and short service life ,77. The Distribution network cross-arms are another major application of composites in insulation. Composite cross-arms are light in quality and high in strength, which can effectively reduce the difficulty of installation and improve construction efficiency . The PenComposite insulators have also been used in a large number of applications in power systems. Compared with traditional insulators, composite insulators are highly resistant to contamination, which significantly improves the safety and stability of the power system . Europe As an important equipment for the construction of high-voltage power transmission projects, a high-voltage pipe sleeve plays the role of introducing or leading full voltage and current in the extra-high-voltage system and exerts its insulating and mechanical support effect. The composite high-voltage casing has been verified in the market for many years and has strong safety.This paper introduced the research and application of resin matrix composites in the field of insulation, focusing on the preparation process, insulating properties, thermal properties, and mechanical properties of resin matrix composites, to reveal the direction of the research and development of current researchers. Based on the current research, it can be seen that the resin matrix composites already have a mature preparation process, gradually to the direction of intelligence and automation, and reduce the cost of preparation; in the research of the performance of resin matrix composites, focusing on the electrical insulation properties, thermal conductivity, mechanical properties, and other aspects. At present, the research focus of resin matrix composites in the field of insulation mainly tends to seek for resin matrix composites with excellent mechanical properties and good thermal conductivity and insulation properties at the same time. According to the current status of the application of resin matrix composites in the field of insulation, it can be seen that the resin matrix composites with excellent insulating properties will gradually replace the traditional insulating materials and become the main application in the field of insulation.


Owing to the disparity between the computing power and hardware development in electronic neural networks, optical diffraction networks have emerged as crucial technologies for various applications, including target recognition, because of their high speed, low power consumption, and large bandwidth. However, traditional optical diffraction networks and electronic neural networks are limited by long training durations and hardware requirements for complex applications. To overcome these constraints, this paper proposes an innovative opto-electronic hybrid system that combines optical diffraction networks with electronic neural networks. Using scattering layers to replace the diffraction layers in traditional optical diffraction networks, this hybrid system circumvents the challenging training process associated with diffraction layers. Spectral outputs of the optical diffraction network were processed using a simple backpropagation neural network, forming an opto-electronic hybrid network exhibiting exceptional performance with minimal data. For three-class target recognition, this network attains a classification accuracy of 93.3% within a substantially short training time of 9.2 s using only 100 data samples (training: 70 and testing: 30). Furthermore, it demonstrates exceptional insensitivity to position errors in scattering elements, enhancing its robustness. Therefore, the proposed opto-electronic hybrid network presents substantial application prospects in the fields of machine vision, face recognition, and remote sensing. Advancements in technology, particularly in computing, during the 21st century have propelled humanity toward significant progress in intelligent fields, such as intelligent production, living, and manufacturing. Significant advancements have been achieved in the field of artificial intelligence (AI), which is based on computer technology. Neural networks, supporting target detection, play an indispensable role in machine vision, face recognition, remote sensing, and license plate detection ,4. IncreHowever, a disparity exists between the development of physical hardware and the practical application requirements, limiting the use of neural networks in computationally intensive applications, such as complex target recognition . To addrHowever, the implementation of neural networks using optical methods presents challenges in terms of complex hardware infrastructure, leading to increased hardware costs and complexity. To address these challenges, integrating neural networks with optical networks has been considered a new and promising approach.In traditional integration methods, electronic neural networks are used to train diffraction media, enabling them to acquire the necessary generalization capability for fully optical target classification. This process involves dividing the diffraction media into multiple sub-regions and optimizing the transmittance of each sub-region as a variable. However, this approach introduces a significant number of variables, which in turn slows the optimization process and imposes high hardware requirements. To address the challenges presented by the time-consuming training process of diffraction media in conventional optical diffraction networks, this paper proposes a novel method in which the diffraction layers in optical diffraction networks are replaced with fixed scattering media for target preprocessing. By adopting this approach, target discrimination is accomplished through a simple electronic neural network, which not only ensures a sufficient recognition speed but also mitigates the need for high hardware requirements associated with diffraction layers in optical diffraction networks. Artificial neural networks are connection models that emulate the human neural network in information processing and possess robust parallel data processing capabilities. The network comprises numerous nodes that resemble human neurons, responsible for transmitting and processing data. Specific models are constructed by adjusting the weights and biases of neurons in the network. The activation function in the network imparts strong generalization capabilities, rendering it highly suitable for applications such as target recognition.Different types of neural networks offer broad prospects in various applications, such as target recognition, classification, autonomous driving, translation, and clinical medicine ,10,11,12The integration of neural networks with optical technologies is a significant milestone in the field of optics, resulting in intelligent optics. This advancement has notably improved the bandwidth-related performance in wave-front detection and prediction ,14,15, iCurrently, various approaches, including increasing training data, regularization, and convex optimization , are empOptical computing methods have extensive applications in various fields, including data storage and image recognition, owing to their numerous advantages, such as low latency, large bandwidth, low power consumption, and robust parallel processing capabilities ,18,19. TDigital optical computing primarily relies on optical logic gates, whereas analog optical computing constructs networks through matrix multiplication and nonlinear functions . The reaThrough the training of multiple layers of diffraction media using neural networks, the method achieves non-linear mapping effects ,25, enabThe generalization ability of optical diffraction networks is closely related to the number of diffraction elements, necessitating a large number of such elements to achieve rapid target classification at the speed of light. However, this leads to a significant time requirement and high hardware demands during the training of diffraction layers, particularly in multi-layer diffraction networks.Scattering, a common phenomenon in daily life, is often considered an error source owing to its distortion and attenuation effects on incident light in practical applications. In 2010, an article on super-resolution imaging triggered a surge in research on scattering media , leadingScattering media currently have extensive applications in various fields, such as super-resolution imaging, multispectral imaging, and non-line-of-sight imaging ,30, exhiBenefitting from the powerful generalization capability of scattering media for the white light input, this method enables efficient target preprocessing. The resulting spectral data are then processed using a simple electronic neural network, enabling rapid and accurate target discrimination. This opto-electronic hybrid strategy combines the strengths of scattering media and electronic neural networks, offering a promising method to address the challenges associated with traditional optical diffraction networks. In this opto-electronic hybrid network framework, fixed scattering layers were used to effectively replace the diffraction layers, eliminating the need for long training durations and high hardware requirements. Owing to the significant differences between spectral data of different target categories, accurate classification can be achieved using a simple neural network. This results in the realization of a near-light processing speed, similar to that of traditional optical diffraction networks, with modest hardware configurations.Furthermore, unlike traditional convolutional neural networks (CNNs) that require a lot of time for operations such as convolution and pooling during training, the optical network part of this structure can perform target preprocessing at the speed of light, thereby shortening the overall training time of the network. The adoption of simple electronic components further contributes to rapid target recognition, as illustrated in In the optical diffraction network configuration, two layers of scattering media and one layer of micro-lens array are utilized. The introduction of the micro-lens array, instead of the scattering layer, allows the incident light to be divided into different parts, enhancing the generalization capability of the optical diffraction network and leading to a high classification accuracy. The configuration is illustrated in The network is directly constructed using the existing scattering layer. Moreover, the scalar diffraction theory is employed to describe the transmission of complex amplitudes between different components in the optical diffraction model. This theory provides a rapid and accurate method for obtaining theoretical results while simplifying the transmission process of light in the system.In an optical neural network, the incident polychromatic light The complex amplitude transmittance function of the circular aperture stop can be represented as follows:The propagation of light between different elements follows the scalar diffraction theory. Therefore, the complex amplitude distribution in front of the target can be written as follows:When light propagates through a scattering medium, it scatters both forward and backward. In the case of a relatively thick scattering medium, multiple scatterings can occur, rendering it challenging to accurately represent light propagation with a single model. In speckle imaging and related fields, the memory effect of the scattering medium is a critical research focus. However, this memory effect is limited and inversely proportional to the thickness of the medium, which hinders the application of methods such as the cross-correlation method in speckle imaging. Numerous studies are currently exploring various methods to enhance the memory effect range of the scattering medium ,32,33; hIn addition to the memory effect, the transmission matrix of the scattering medium is a significant research focus ,35,36. TDuring the training process of this opto-electronic hybrid network, the optical diffraction network, utilizing the scattering layer, can generate spectral output data with significant variations, enabling rapid target classification without an extensive amount of data. Therefore, the use of scattering layers in the optical diffraction network can reduce the demand for electronic hardware of the network in complex applications.Unlike convolutional neural networks that can adjust parameters in real time during training, once the optical part of this opto-electronic hybrid network determines the scattering layer, the relevant parameters cannot be changed. However, employing scattering layers and micro-lens arrays facilitates maximizing the values of parameters that can be adjusted, similar to those achieved using a CNN. Even with a fixed structure, the optical diffraction network possesses adequate generalization capability for target recognition in complex scenarios, operating at the speed of light.In contrast, data processing stages, such as the electronic neural network, involve discrete data flow, which inevitably introduces the issue of discrete data sampling. The higher complexity or precision of desired functionality often requires a higher level of sampling or more parameters. However, this issue does not arise in practical optical paths, as operations within optical paths are continuous. Consequently, in contrast to the discrete transmittance during the training process of the traditional optical diffraction network, using the electronic neural network, the replacement of the diffraction layer with scattering media, allows target classification based on its inherent properties. Despite its powerful generalization capability, this approach may not yield definitive results, necessitating the electronic neural network to provide a definite classification outcome. Benefitting from the potent target feature extraction capability of the optical diffraction network, this study aims to use a simple three-layer backpropagation neural network (BPNN) to fulfill the role of the classifier b. The composition of the entire experimental setup includes: an incoherent light source, two collimating lenses, an aperture stop, an optical resolution plate, a micro-lens array, two scattering layers, a coupling lens, a splitting fiber, a CCD, and a spectrometer, as shown in To verify the specific application potential of the proposed structure, three experiments were designed. In the first experiment, two targets with the same area but different shapes were used as inputs to investigate whether the variations in received spectra were caused by different target intensities. The experiment also analyzed the influence of the relative positions of the scattering elements on the output results. In the second experiment, input targets consisting of squares, horizontal lines, and vertical lines from the same row of the calibration board were utilized. Variations in the input targets were achieved by altering relative distances or rotating the targets. For each target, 100 spectral data points were collected to construct a simple electronic neural network for basic target classification.In the third experiment, transparent thin plates were used to replace the targets, and a randomly perturbed tape was attached to simulate scenes with and without turbulence. The goal of this experiment was to verify the potential application of the proposed structure in classifying the turbulence intensity.In terms of acquiring training data, we used three patterns on the optical resolution plate: horizontal lines, vertical lines, and squares, as classification targets. During the collection of training data for each category of targets, the target is changed by changing the relative position of the optical resolution plate. Based on this approach, we collected 100 spectral data points for each category of targets, with 70 of them used for the training set, and the remaining 30 for the test set.In the optical diffraction network, using patterns from the optical calibration board as inputs may result in varying target areas in many cases. As a result, the generalization ability of the optical diffraction network might not solely originate from the nonlinear mapping of the input wavelength intensity by the network. The generalization capability of the network could also be affected by the different target areas, introducing ambiguity in the mapping object of the network itself. To address this issue, two input targets, one square and one triangle, were employed. These targets with different shapes have the same area. In addition, we also analyzed the output spectra of targets with different areas and the same shape.We used squares and triangles with the same area but different shapes to verify the influence of shape on the output spectrum of the optical diffraction network, and we also used two horizontal lines with the same shape but different areas to verify the influence of area on the output spectrum. The spectral data are displayed in In traditional optical diffraction networks, the relative position error of the diffraction layer can be introduced during training to compensate for the decrease in network classification accuracy caused by assembly errors in the actual hardware structure . This inIn the experiment, changes in the output spectra were examined by adjusting the position and rotation angle of the second scattering layer. The axial displacement ∆z was varied within ±10 mm, and the rotation angle When the axial distances between the scattering layers change continuously, no significant alterations are observed in the output spectra, as illustrated in A possible reason for this outcome is that the output of the optical diffraction network is a spectrum, and the impact of the axial displacement between the diffraction layers on the output spectrum is substantially smaller compared with the influence of the scattering layers themselves. In this context, the spectral changes caused by the axial displacement between the diffraction layers are obliterated by the effect of the scattering layers on the output spectrum. When the angle of the scattering layer changes, the impact on the output spectrum exhibits a linear relationship. Consequently, the shape of the output spectrum remains consistent even with changes in the angle of the scattering layer.In the optical diffraction network, different targets yield different output spectra, and the subsequent electronic neural network determines the target categories based on these distinct output spectra. When the relative positions of the optical network change, the output spectra change proportionally; however, the spectral shape remains unchanged. Therefore, the optical diffraction network is not sensitive to the position errors of the scattering layers and other components, which is advantageous for installation and adjustment.In traditional optical diffraction networks, 3D printing technology or other methods can be used to convert the diffraction layers trained by the electrical network into actual hardware, and then build the actual optical path. After obtaining result data, the target category can be determined by processing the results with differential algorithms. However, when the diffraction layer is replaced with a scattering layer, the generalization ability provided by the scattering layer becomes less deterministic. As a result, an electronic neural network is required to act as a classifier for target classification during data processing, forming the fundamental concept of using opto-electronic hybrid networks for target recognition.In the optical diffraction network, a micro-lens array is incorporated to partition the incident light into different segments, enhancing the nonlinearity of the network. In the experiment, the output spectra with and without the micro-lens array were compared to determine whether introducing the micro-lens array in the optical diffraction network could increase the level of differentiation in the output spectra and improve the accuracy of target classification. The output spectra are presented in Although the output spectra with and without the micro-lens array exhibit similar shapes, the intensity of the output spectra obtained with the micro-lens array is higher than that acquired without it. Notably, clear turning points are observed in the spectra at approximately 650, 800, and 850 nm. The increased intensity of the spectra obtained with the micro-lens array is primarily attributed to the focusing effect of the micro-lens array, which effectively harnesses the input light energy. As a result, the opto-electronic network with a micro-lens array enhances differentiation in the output spectra while improving the utilization of light energy. This approach effectively enhances the accuracy of classification in target recognition and other relevant fields. After confirming that the introduction of the micro-lens array can improve the nonlinear mapping ability of the network, we built a complete optical diffraction network, and established the data set according to the data acquisition process described in Notably, the output spectra of squares differ significantly from those of the other targets, whereas the output spectra of horizontal lines and vertical lines are similar but exhibit certain variations in the peak intensity and corresponding wavelengths. A comparison of the output spectra of the three categories in the same graph clearly reveals the distinctions between the spectra of different targets.During spectral reception, a CCD camera was employed to monitor the reception status of the spectral end, as shown in For implementing the classifier, a three-layer BPNN was employed, as illustrated in Utilizing the opto-electronic hybrid network with scattering layers, an appreciable classification accuracy of 93.3% was achieved for the three target categories. Notably, when compared with traditional CNNs and optical diffraction networks, the proposed network exhibited a slightly lower training accuracy. This discrepancy could be attributed to the similarity between the horizontal and vertical lines used in the experiment. The limited number of samples for these two targets resulted in a decreased accuracy in distinguishing them effectively.The use of the proposed opto-electronic hybrid network structure eliminates the time-consuming convolution and pooling operations in traditional electronic CNNs via optical diffraction networks, resulting in a significantly reduced training time and less sophisticated hardware requirements during training. A comparison of the traditional electronic CNN, traditional optical diffraction network, and improved opto-electronic hybrid network  demonstrIn certain applications, the optical path exposed to air is often affected by atmospheric turbulence, which can adversely impact precision measurements, geodesy, and guidance operations. Hence, assessing the strength of turbulence in the measurement area is necessary to guide relevant practical operations. Traditional methods for measuring the turbulence intensity rely on meteorological parameters, beam propagation, laser radar, and others, but they either have high costs or involve complex data processing.To address these challenges, a new approach is essential for simple turbulence intensity measurement. The emergence of neural networks has revitalized various fields, including turbulence measurement, leveraging big data in their applications. To verify the potential application of the proposed opto-electronic hybrid network in measuring the turbulence intensity, relevant experiments were conducted to distinguish between scenes with and without turbulence.The transparent region of the optical calibration board represents a turbulence-free scene, whereas the area covered with blue tape indicates the turbulent region a. FigureTo overcome the drawbacks of traditional optical diffraction networks and electronic neural networks, which involve high hardware requirements and long training durations, this study proposes an innovative opto-electronic hybrid network. In this architecture, the pre-training requirement of the diffraction layer in traditional optical diffraction networks is circumvented by replacing it with a scattering layer. The electronic neural network acts as a classifier for target classification.In opto-electronic hybrid networks, it can be considered that time-consuming operations such as convolution and pooling in traditional convolutional neural networks are achieved at the speed of light. This integration enables the rapid extraction of target features, while the retained simpler components effectively serve as a classifier for target classification. This opto-electronic network architecture achieves network training with lower hardware configurations and requires fewer data than the traditional networks, while retaining the advantages of traditional optical diffraction networks, such as a high speed, low power consumption, and large bandwidth. Before constructing the network, output spectra from two targets with equal areas but different shapes were compared. The findings revealed that the generalization ability of the opto-electronic hybrid network is not solely dependent on different target areas but rather on the distinct mappings of various wavelengths from different parts of the target by the scattering layer.Subsequent experiments were conducted to confirm the performance of this opto-electronic hybrid network. In a three-class application with similar targets, the network achieved a significant training time of 9.2 s and an appreciable accuracy of 93.3% when utilizing a CPU I5-7300H and GPU RTX 1050Ti. These results were obtained with 100 data points (70 for training and 30 for testing) collected for each target. This approach effectively reduces the training time while easing hardware requirements. For the improved optical diffraction network, the influence of the relative positions of the scattering layers on the output spectra was extensively investigated. The results indicated that changes in the axial displacement did not significantly affect the output spectra, whereas changes in the angle of the scattering layers had a linear impact on the output spectra. This insensitivity to the relative positions of the scattering layers in the optical diffraction network is advantageous for optical alignment. However, it also suggests that enhancing the generalization ability of the network through adjustments in the positions of the scattering layers is not feasible. Instead, the generalization ability can be improved by increasing the number of scattering layers or utilizing highly complex scattering layers. Finally, the potential application of the proposed opto-electronic hybrid network in classifying the turbulence intensity was demonstrated through experiments. Although uncertainties exist in the experimental setup, such as those related to environmental conditions, the experiment provides a basis for verifying the performance of the proposed architecture in turbulence intensity classification using a phase screen.In this paper, we designed an opto-electronic hybrid network based on scattering layers and verified its performance using a three-target classification task. In the optical diffraction network section, we studied the effects of target shape and area on the output spectrum, and explored the effects of the relative position of the scattering layer on the output spectrum. The results show that the network can respond well to changes in target shape and is insensitive to errors in the relative position of components. During the training process of the entire network, we used a total of 300 sample data, and finally completed the training of the network in 9.2 s under low hardware conditions, achieving a classification accuracy of 93.3%. The results show that this opto-electronic hybrid network can quickly complete training under low hardware conditions and has high accuracy. This research has application value in the fields of target detection, machine vision and turbulence intensity measurement.


The organization of eukaryotic genome in the nucleus, a double-membraned organelle separated from the cytoplasm, is highly complex and dynamic. The functional architecture of the nucleus is confined by the layers of internal and cytoplasmic elements, including chromatin organization, nuclear envelope associated proteome and transport, nuclear–cytoskeletal contacts, and the mechano-regulatory signaling cascades. The size and morphology of the nucleus could impose a significant impact on nuclear mechanics, chromatin organization, gene expression, cell functionality and disease development. The maintenance of nuclear organization during genetic or physical perturbation is crucial for the viability and lifespan of the cell. Abnormal nuclear envelope morphologies, such as invagination and blebbing, have functional implications in several human disorders, including cancer, accelerated aging, thyroid disorders, and different types of neuro-muscular diseases. Despite the evident interplay between nuclear structure and nuclear function, our knowledge about the underlying molecular mechanisms for regulation of nuclear morphology and cell functionality during health and illness is rather poor. This review highlights the essential nuclear, cellular, and extracellular components that govern the organization of nuclei and functional consequences associated with nuclear morphometric aberrations. Finally, we discuss the recent developments with diagnostic and therapeutic implications targeting nuclear morphology in health and disease. The foundation of life is dependent on the functional stratification of specialized subcellular compartments. In a eukaryotic system, the nucleus forms a distinctive micro-terrain to conceal the genetic material from damaging cytoplasmic enzymes and metabolism and to provide a unique regulatory molecular framework for the genome. The spatial encapsulation of the nucleus by the lipid bilayer forms a physical and physiological intercept between cytoplasmic processes and the genome that regulates them. The construct of the nucleus is collectively furnished by a nuclear envelope along with the underlaying chromatin fiber, intermediate filaments of nucleoskeleton, nucleoplasmic subcompartments and nucleolus. These contractual components collectively impose their own effect on the rigidity, morphology and size of the nucleus ,2,3. TheAlthough the nuclear size and morphology varies widely among unicellular and multicellular eukaryotes, its extent is precisely maintained in the individual cell type . HoweverNuclear aberrations may be either the cause of a disease or the consequences of cellular events related to the disease. In both of these situations, identifying the factors involved in the modifications could be used to pinpoint the onset of pathogenesis at an earlier stage. Moreover, understanding the connection between the nuclear morphology and the altered cellular and extracellular components could pave the way for designing targeted and effective treatment strategies for many related life-threatening diseases .In this review, we examined the diverse cellular activities associated with regulating nuclear size and morphology. We investigated how the altering or malfunctioning of certain factors affects the shape, size and organization of the nucleus. We have also underlined the concepts involved in specific theranostic approaches for early and targeted diagnosis and treatment of nuclear deformation that accompanies pathogenesis.The structural components of a nucleus, such as chromosomes, nucleoplasmic compartments, nuclear envelope proteins and lipid bilayer, are the core elements involved in the regulation of nuclear morphology. Each component has a distinct functionality and approach by which they help to maintain the characteristic shape and size of the nucleus. Here, we will evaluate the mechanisms of individual nuclear constituents that collectively gather to fabricate the controlled morphology of the nucleus in normal and diseased condition.Nuclear envelopes are the structural and physiological interface between the central genomic material and cytoplasm of the cell. The double lipid membrane of the nuclear envelope originates from ER and remains in continuous contact with its network afterward. In contrast to the origin, both the outer nuclear membrane (ONM) and inner nuclear membrane (INM) of the nuclear envelope are enriched with a very distinguished set of proteomes  15]. Th. Th15]. Another macromolecular assembly of NE that spans both INM and ONM is known as the linker of nucleoskeleton and cytoskeleton (LINC) complex. It physically connects the cytoskeletal framework to the nucleoplasmic filaments by forming a dynamic intermediate bridge between them. The elemental structure of LINC complex involves two transmembrane domains, ONM embedded KASH  motif and INM anchored SUN (Sad1 and UNC-84 protein) domain protein. KASH motif interacts bidirectionally with SUN domain as well as with the actin filaments, microtubule and intermediate filaments network using different intermediate proteins, i.e., nesprin-1, nesprin-2, nesprin-3, dynein, kinesin and plectin, etc. In different species, at the nucleoplasmic front, various isoforms of SUN domain proteins  also bind to the NPC, lamina and chromatin using several intermediate proteins . The KASIn higher eukaryotes, lamin A/C, lamin B and other associated proteins assemble around the inner nuclear membrane and play a remarkable role in the regulation of nuclear forms and functions. The subtype of lamin B (lamin B1) in particular forms an outer loose meshwork surrounding the tighter, nucleoplasm facing, lamin A/C meshwork, and both isoforms assemble into a distinct but interlinked filamentous network. Cells devoid of lamin isoforms develop an irregular nuclear shape and become susceptible to large scale DNA damage due to a ruptured nuclear membrane . The rigIt is well-established that lamins and associated proteins not only form a structural element of the nucleus that maintains the nucleus’s stiffness and morphology, but they also play a crucial role in functional components by regulating gene’s radial position and expression ,64. The Nuclear envelopes are one of the most functional organelles of the cell and have many simultaneous operations, including signaling, transport, genome compartmentalization, gene regulation, lipid metabolism, DNA repair and cell division, etc. These functional assortments entirely rely on the composition and physicochemical properties of the lipid membrane. The regulation of fatty acid composition of phospholipids (PL) provides specific biophysical properties, such as fluidity, rigidity or curvature to the membrane, which are required for the maintenance of the integrity and morphology of the nucleus. Interestingly, INM itself could regulate lipid composition with the help of some membrane associated proteins. It was previously noted that INM might host the lipid metabolism to expand the membrane through localized stimulation of phospholipid biosynthesis . Later, monopolar spindle 3 (Mps3), which is lipid remodeling mechanism that uses the activity of SUN protein . A. A160]. Nuclear morphometry plays a significant role in the histopathological and cytological diagnosis of many diseases. For instance, a 35-month follow-up study on osteosarcoma patients revealed that nuclear morphological parameters, such as area and shape, could be applied to identify which patients had a good prognosis . It was Irregularities in nuclear size, shape and chromatin texture are often correlated with altered gene organization and expression in tumor cells . The remLmnb1, Tmpo, Nup205, Nup107, Nup85 and Nup35. The p53 protein indirectly represses these target genes using a cell cycle regulating protein complex [The nuclear–structural abnormalities-based prognostic or diagnostic approach has been further extended for the development of targeted and personalized treatment strategies . Moreove complex . This st complex , Cisplat complex , Actinom complex , are eme complex ,183.Such highly effective drugs restore the nuclear structure and could be also used to reveal the structural and functional connection of the nucleus. Advances in understanding the mechanism of nuclear structure-based pathophysiology will serve as powerful tool for increasing survival rate and reducing the treatment costs for many fatal diseases.The molecular mechanisms orchestrating nuclear morphology and their connection to disease development still need to be elucidated clearly. In this review, we have summarized various factors that are contributing to maintaining nuclear morphology and architecture in eukaryotic cells. In fact, the factors described above have profound effects on the structure and function of chromatin, showing correlations with the resulting gene expression and chromosome stability. Moreover, these factors act as a bridge between the cytoskeleton and nucleoskeleton, thus emerging as a promising signal transduction between the nucleus and cytoplasm. It was established that the abnormalities in nuclear morphology could be due to mutations, abnormal gene expression, altered signal transduction pathways and chromatin architecture as well as aneuploidy. In recent years, questions regarding the molecular mechanisms that regulate nuclear size and shape differently in normal and disease states remain largely unanswered. However, there is clear evidence that highlights the influence of abnormal nuclear morphology on different cellular functions, cell cycle, genomic stability, apoptosis and signal transduction pathways. The current literature supports the use of nuclear morphological abnormalities for the early diagnosis of diseases and is beginning to shed light on the use of theranostic approaches for the treatment of diseases. The identification of these nuclear morphological abnormalities-related targets for therapeutic intervention could be promising for personalized cancer treatment and eradication of life-threatening diseases.


Due to the limited scientific knowledge on the impact of commercial oenological additives on flavour perception, the aim of this work was to evaluate the effect of different types of oenological additives on the long-lasting flavour perception (flavour persistence) during wine tasting, also considering the effect of the individual PROP (6-n-propylthiouracil) taster status (PTS). To do so, white and red wines with two oenotannins  and a commercial yeast mannoprotein were prepared. A control wine of each type was also made without additives. All the wines were spiked with a mixture of aromatic compounds responsible for the “fruity” and “woody” notes. Retronasal aroma and astringency were evaluated at the same time using time–intensity (TI) methodology and a trained panel (n = 40), including PROP non-tasters (NTs) and tasters (Ts). The results showed a significant effect of PTS on the long-lasting perception of astringency, being Ts who showed higher values than NTs for most TI parameters. However, PTS did not affect aroma persistence. In addition, the three oenological additives had an effect on astringency and retronasal aroma perception. They significantly increased the long-lasting perception of astringency compared to the control, while gallotannin also increased the persistence of the woody aroma. The use of natural additives to improve the winemaking process is becoming a current practice in the oenological industry, leading to a large variety of commercial additives with different claims related to many technological and sensory properties in wines. Nonetheless, the number of scientific studies supporting the potential benefits of these compounds and their optimal usage during winemaking is still quite scarce. In general, most of these additives come from different sources, being oenotannins and yeast derivatives among the most commonly used. Oenotannins can come from grapes or other different botanical sources. The International Organization of Vine and Wine (OIV) defines their use for the stabilisation and fining of musts and wines, as well as to increase the antioxidant and antioxidasic capacity of grape juice and to promote colour stability (resolutions OIV-OENO-612–2019 and OIV-OENO-613–2019). Nonetheless, besides these effects, they can also affect some wine sensory properties such as aroma, astringency, and bitterness ,5,6. ThiBesides oenological tannins, yeast derivative products constitute a second type of oenological additives widely used during winemaking. They include different products such as inactivated yeast, inactivated yeast with glutathione, autolysate, yeast protein extract, and yeast wall mannoproteins ,12. TradInterestingly, tannins and mannoproteins are also polymers with the ability to bind the oral surfaces (mucoadhesion properties). For instance, Ginsburg and collaborators  showed tIn the case of mannoproteins, recent works using salivary proteins, protein-rich proline proteins (PRPs), and a cell-based model of the oral epithelium system also show that mannoproteins can interact with some salivary proteins and tannins, with an impact on astringency modulation ,27,28. BGiven the ability of tannins and mannoproteins to be retained on the oral surface together with the capacity of both types of polymers for binding aroma molecules, the hypothesis arises that they can have a preponderant role in flavour persistence, which is the long-lasting perception of flavour stimuli produced immediately after wine swallowing . This phIn this sense, it is also important to notice that wine flavour perception, including flavour persistence, might be greatly variable depending on many types of genetic, biological, physiological, and psychological factors . Among tConsidering the lack of specific studies focused on the effect of oenological additives on wine flavour persistence, the objective of this work was to test if three common commercial oenological additives, namely, hydrolysable tannins  and yeast mannoproteins, might affect the long-lasting flavour perception  of wines (red and white). For this purpose, a dynamic sensory technique (time–intensity) was used, which is based on scoring the evolution of the intensity of the flavour stimulus (fruity and woody aroma and astringency) from the moment it appears (immediately after the wine is tasted) until it is no longer perceived. Additionally, the effect of PTS (ability to perceive the bitter compound 6-n-propylthiouracil) was also tested by using a trained panel formed of tasters (n = 20) and non-tasters (n = 20).A red wine and a white wine from Tempranillo and Malvar grape varieties were industrially produced at the IMIDRA experimental winery . These wines were considered the control wines . Their chemical composition is shown in To reinforce the aroma profile of the wines in two aroma descriptors of interest (fruity and woody), before the sensory test, all the wines were independently aromatised with two aroma mixtures, responsible for these aroma nuances using food-grade odorant compounds  from MerTherefore, a total of sixteen wines were produced: (a) eight red wines: control wine without and with the three additives aromatised with fruity and woody aroma mixtures, and (b) eight white wines produced under the same conditions . Forty individuals from two different PROP taste phenotypes (PROP tasters and non-tasters) see  were recIndividual taste PROP phenotype was tested using commercial strips impregnated with 6-n-propylthiouracil (3 µg/strip) from Sensonic International . Triangular tests were conducted with two blank samples (no impregnated strips)  and one impregnated sample to test whether consumers were able to recognise the PROP sample. If the volunteers did not perform the triangular test correctly, they were considered to be in the non-taster group. Individuals who positively recognised the PROP sample were retested and they evaluated the perceived intensity, which was assessed using the Generalised Labelled Magnitude Scale (gLMS) scale  . For eacThe absence of anosmia was previously confirmed by means of a triangular test with flavoured hydroalcoholic solutions. Individuals received specific training for the recognition of fruity and woody aromas as well as astringency using red and white wines. In the following sessions, training sessions for the recognition of the intensity of the different sensory stimuli perceived with the different types of wine were also carried out. Additionally, during these sessions, individuals were instructed in the use of the intensity scale , and in the TI methodology using tablets for sensory data collection. Samples (15 mL) were served in standard tasting glasses (20 mL) covered with plastic Petri dishes to avoid loss of volatiles. For this purpose, wine glasses were labelled with random 3-digit codes and presented simultaneously in a randomised order using a Balanced Complete Block design . Mineral® Cloud software  via tablets, where each consumer had a user profile and could access each of the tests.Sensory evaluation sessions were conducted using CompusenseFor the evaluation of the sensory stimuli , panellists gently rinsed their mouths with the wine (15 mL) for 30 s, then spat it out. During rinsing, special care was taken to keep the lips closed, not to swallow and not to open the velum–tongue border prior to expectoration. Then, they were instructed to swallow the remaining saliva in their mouth and to start the TI evaluation. For this, panellists moved the cursor along the unstructured scale (15 cm) to evaluate the astringency and aroma intensity perceived (of one single aroma attribute) that lasted for two minutes. The evaluation of the intensity of both stimuli in the same trial avoided the halo-dumping effect ,42. DataFor each sensory stimulus, TI curves were obtained by averaging the data at each point of time across the two groups of subjects (Ts and NTs). The raw data were obtained by Compusense software. Moreover, four typical time–intensity parameters were extracted from the TI curves using the XLSTAT Sensory software: time to reach the maximum intensity (Tmax), maximum intensity (Imax), duration time of the perceived stimuli (Tend), and area under the curve (AUC).p < 0.05 was always used. Statistical analyses were carried out using XLSTAT (Version 2019.01).Analysis of variance ANOVA (one-way or two-way) and mean comparison tests (Tukey) were applied to check the effect of PROP taste phenotype and the effects of the oenological additives on the different parameters  extracted from the astringency and aroma TI curves. A significance level of PROP taster status (PTS) has been associated with a higher individual ability to perceive sensory stimuli from wines . HoweverAs can be seen in In the case of white wines, there were also significant differences in the perception of astringency depending on PROP taster status, but only in white wines aromatised with fruity aroma notes. As occurred in red wines, in white wines, Ts showed higher T max values (40% more) than NTs. On the contrary, Ts showed 16.8% lower values of Imax compared to NTs. There were no differences between PROP phenotypes in the other TI parameters, showing a lower impact of the perception on the astringency in the case of white wines.As shown in In a further step of the work, the effect of the oenological additives in the perception of the astringency and retronasal aroma (fruity and woody) over time was also checked. Results corresponding to the differences in TI parameters considering the control wine and the wines supplemented with oenological additives are shown in p < 0.05) in the case of red and white fruity wines, but not in the case of wines aromatised with a woody aroma. In the case of red fruity wines, for both PROP taste phenotypes (T and NT), wines with oenological additives exhibited lower Tmax values compared to the control. The lower Tmax was more pronounced for Ts (60% lower compared to the control) than for NTs (34.6% lower compared to the control). A lower Tmax value means that the maximum intensity of perceived astringency will be quicker in wines with additives, and even faster for individuals of the T phenotype.As can be seen in p < 0.05) for Ts. Interestingly, they also exhibited higher Imax values of astringency for the three wines with additives compared to the control wine. Of the three additives, mannoproteins provoked the largest effect, increasing Imax by 27.4% compared to the control wine. On the contrary, the impact of the additives was not significant for the other TI parameters, nor in the case of wines (red or white) with a woody aroma.In the case of fruity white wines, the effect of oenological additives was only significant  or yeast mannoproteins, on the long-lasting flavour  perception  of red and white wines. Besides this main objective, the study also focused on testing if individual PROP taste phenotype  might have an effect on flavour persistence. The results of this study show that PTS has a significant impact on astringency perception, mainly in red wines. In this sense, the analysis of the parameters extracted from the TI curves  confirmeInterestingly, previous works with wines have related the individual ability to detect the bitterness of PROP with a higher ability to detect other basic tastes  and trigeminal sensations such as astringency . NonetheAdditionally, some previous works also suggested that the higher sensory ability of PROP taster individuals could also include a higher retro-olfactive performance . ResultsA second objective of the work was to check if the use of typical oenological additives in wines such as oenotannins and mannoproteins might have an impact on the long-lasting flavour perception. Although these types of additives have long been used and represent a common technological practice currently available for winemakers, the scientific studies devoted to understanding their sensory impact are relatively scarce, and to the best of our knowledge, there is no previous study devoted to knowing their impact on flavour persistence. The results from the present work show an impact of these additives on wine astringency in red and white wines, but only in those wines aromatised with a fruity aroma mixture and not in the case of the wines aromatised with a woody aroma . This cop < 0.05) lower Tmax values compared to the control  but also depending on the aroma considered (fruity or woody). In this sense, the addition of additives in red fruity wines decreased Tmax (above 30%) compared to the control wine . This meIn the case of white fruity wines, the effect of the additive or retronasal aroma was similar to that found for the fruity red wine, that is, a reduction in Tmax compared to the control . NonetheOn the other hand, besides the effect of the additives on the fruity aroma perception of white wines, they also had an effect on the woody aroma persistence. For instance, the addition of gallotannin in white woody wines significantly increased AUC compared to the control , while tBesides an effect at the cognitive level, other explanations, involving physicochemical interactions between the additives and the aroma compounds included in the aroma mixture, could also contribute to explaining the opposite effect of gallotannin and mannoproteins on the woody persistence in white wine. In this sense, it has been previously shown that the addition of some kinds of polyphenolic extracts, especially flavan-3-ols, increased oral aroma persistence, therefore prolonging the release of certain volatile compounds by the tertiary interactions among oral mucosa, polyphenols, and aroma compounds . These aThe fact that the addition of ellagitannin did not induce a higher aroma persistence like gallotannin did shows the necessity of more studies comparing chemically different types of oenotannins in order to unravel the molecular action mechanisms which might help in the development of additives with better technological properties for improving aroma persistence.Additionally, the existence of physicochemical interactions between mannoproteins and aroma compounds can also explain the reduction in aroma persistence that these yeast polysaccharides produced in white woody wines. In fact, previous studies showed hydrophobic interactions between mannoproteins and aroma compounds, mainly of hydrophobic nature, able to reduce aroma release ,16. ConsResults from this study using time–intensity methodology confirm the significant effect of individual PROP taste phenotype on the long-lasting astringency perception after wine consumption. PROP taster individuals  showed higher values for most TI parameters  compared to non-taster individuals. The effect of taste phenotype was more evident in red wines than in white wines. Nonetheless, PROP phenotype did not affect the long-lasting aroma perception of the tested aromas (fruity and woody) in either red or white wines. Additionally, the results showed that common oenological additives of different natures, such as hydrolysable tannins  and yeast polysaccharides (mannoproteins) added at recommended concentrations to red and white wines have an impact on flavour persistence, affecting astringency and retronasal aroma perception. This effect depends on the wine type (red or white) and the type of aroma considered. For instance, they affect the astringency perception of red and white wines, but only in those wines with a fruity flavour. In red wines, they reduce the time to reach the maximum astringency intensity (Tmax), while in white wines, they induce a higher maximum intensity. In the case of aroma persistence, in red and white fruity wines, the addition of these additives allows for reaching the maximum intensity of fruitiness sooner. This was especially relevant in the case of mannoproteins in white fruity wines. On the contrary, none of the additives have a significant effect on the woody aroma in red wines, while in white wines, the addition of gallotannin significantly increased the global woody aroma perception (AUC) compared to the control. Overall, the wide diversity of chemical structures and properties of oenotannins and mannoproteins offers a great opportunity to use them as oenological tools to improve and/or modulate the aromatic persistence of wine. However, further in vivo analytical and sensory studies will be necessary to select the ones that provide the best results.