Compared with the traditional activated sludge process, a membrane bioreactor (MBR) has many advantages, such as good effluent quality, small floor space, low residual sludge yield and easy automatic control. It has a promising prospect in wastewater treatment and reuse. However, membrane fouling is the biggest obstacle to the wide application of MBR. This paper aims at summarizing the new research progress of membrane fouling mechanism, control, prediction and detection in the MBR systems. Classification, mechanism, influencing factors and control of membrane fouling, membrane life prediction and online monitoring of membrane fouling are discussed. The research trends of relevant research areas in MBR membrane fouling are prospected. Membrane bioreactors (MBRs) combine both biological treatment and physical separation (using membranes) of various pollutants to treat domestic and industrial liquid wastes. Due to the combination of the above-mentioned processes, MBRs produce treated effluents of higher quality compared to the conventional activated sludge process . MBRs arMembrane fouling can be classified into internal fouling, external fouling and concentration polarization fouling. The fouling caused by the deposition as well the adsorption of solutes and colloidal particles on the interior of the membrane pores is called internal fouling and sometimes referred to as pore blocking . The depMembrane fouling has traditionally been divided into reversible fouling and irreversible fouling according to the degree of removal of foulants . Reversi2NH4PO4 and CaCO3. Biofouling is caused by the interaction between biological substances and membranes. Gao et al. [According to the composition of pollutants, membrane fouling can be divided into organic fouling, inorganic fouling and biofouling. Organic fouling is caused by organic macromolecules. Wang et al.  found tho et al.  found tho et al. . The mico et al. .There are many factors that cause membrane fouling, including the material of the membrane module, the pressure difference across the membrane during filtration, the cross-flow velocity, the hydraulic retention time (HRT), the sludge retention time (SRT), microbial polymerization and dissolution processes, and mixing . These fIntrinsic properties of the membrane that affect membrane fouling include material, hydrophilicity/hydrophobicity, surface charge, roughness, pore size, porosity, and structure of the membrane module.Commonly used membranes are mainly classified into organic membranes, ceramic membranes, and metal membranes according to the type of materials used to synthesize membranes. Among them, the organic membranes have a low cost and mature manufacturing process, and are currently the most widely used . HoweverWith the continuous application of membrane bioreactors, membrane fouling has become a major bottleneck limiting its further development ,29. At tThe hydrophilicity/hydrophobicity of the membrane is usually characterized by the contact angle θ. The larger the value of θ, the stronger the hydrophobicity of the membrane surface. The value of θ angle has a certain relationship with the morphology of the membrane surface and the pore size of the membrane. The hydrophilicity/hydrophobicity of the membrane material has a great influence on the anti-fouling performance of the membrane . The hydThe natural organic matter present in wastewater is divided into strongly hydrophobic, weakly hydrophobic, polar hydrophilic and neutral hydrophilic organic matter, and is filtered separately. It is found that the most important organic matter causing the decrease of membrane flux is neutral hydrophilic organic matter. It is believed that the presence of more hydrophilic organic matter in the raw water causes more serious membrane fouling . HoweverWhen the membrane surface charge is the same as the charge of the pollutants present in the wastewater, it can improve the membrane surface contamination and increase the membrane flux. In general, the colloidal particles in the aqueous solution are negatively charged. So, if the material having a negative potential is used as the membrane material, it can prevent membrane fouling due to the repellent effect of similar charges.2CO3 and CuCl2 solutions and they found that SG membranes have negative surface charges. At the same time, the absolute values of electric density, zeta potential and charge density increased with the increase of cation or anion valence state. The higher the operating pressure difference and the concentration of the liquid solution, the lower the velocity of the cross flow and the influence of the valence state of the ions. The cation of the same valence state have a greater effect on the charge performance of the membrane than the anions [Lin et al.  investige anions . Figure As can be seen from the figure, the actual molecular weight distribution range of hydrophilic/hydrophobic organics is relatively small, mainly concentrated in the range of <10,000 Dalton. The proportion of organic molecules with HPO < 10,000 Dalton is close to 70%, and especially the proportion of organic molecules with HPI < 10,000 is up to 80%.In a treatment study of wastewater containing micropollutants , it was It is found from Membrane porosity and roughness also have a potential impact on membrane fouling behavior. Generally, the larger the porosity, the smaller the transmembrane pressure (TMP). However, as the porosity changes, the surface properties of the membrane, such as roughness, also change. This in turn changes the possibility of adsorbing contaminants on the membrane surface. The organic membrane porosity is usually higher than that of the inorganic membrane, but the flux is often lower than that of the inorganic membrane ,42. WhenThe membrane module is the core of membrane separation technology. For a membrane separation process, not only membranes with excellent separation characteristics but also membrane modules and devices with compact structure and stable performance must be applied in large-scale industrial processes . In the It can be seen that under the same operating conditions, the flow condition of the membrane bioreactor with the membrane component placed vertically is better, and the shear effect of gas–liquid two-phase flow generated by aeration scour is much stronger than that of the horizontal release device.Since FMX maintains high flux and recovery rate under the most challenging conditions, it has been used for wastewater treatment, separation and dewatering in manufacturing processes and recovery applications in various industries. Chen et al.  comparedOperating conditions affecting membrane fouling include membrane flux, TMP, aeration, cross-flow velocity (CFV), SRT, HRT, and temperature. Furthermore, mode of operation, including influent water quality and sludge loading, directly affects membrane fouling factors.In membrane filtration operations, membrane flux and TMP are two quantities associated with each other . If othe4+-N will increase, but the sludge floc size will decrease, the impact on sludge concentration and sludge load is weak. As the amount of aeration increases, the total amount and composition of SMP will change [Aeration is an important parameter in the operation of MBR. It not only provides the oxygen necessary for metabolism of activated sludge, but also washes the surface of the membrane, avoids the deposition of pollutants and slows the fouling of the membrane. Therefore, membrane bioreactors often use relatively larger aeration . The chal change . Among tl change . Moderatl change . Zhang el change  found thThe change in CFV changes the diffusion caused by shear to affect the migration of particles from the surface of the membrane, which in turn affects the thickness of the cake layer. The membrane flux increases approximately linearly with increasing CFV. However, the CFV is not as a large factor as the aeration, and the better the membrane filtration performance will be after CFV exceeds the critical value. However, when the CFV exceeds a certain threshold, the TMP will increase as the CFV increases . This isSRT can affect MLSS (mixed liquid suspended solids), sludge composition, EPS and other parameters which are important operating conditions affecting membrane fouling rate in an MBR. HRT has an indirect effect on membrane fouling. First, changes in HRT will directly lead to changes in membrane flux, which in turn will change the state of membrane filtration and affect the rate of membrane fouling .When investigating the effect of HRT on membrane fouling in a split-type anaerobic membrane bioreactor (AnMBR) treating beer wastewater, it was found that shorter HRT can produce higher OLR and F/M, which in turn affects the metabolic activities of anaerobic microorganisms and microbial metabolites (the content of EPS and SMP), and sludge particle size increases, resulting in serious membrane fouling . The chaThis indicates that shorter HRT will lead to rapid increase of TMP and aggravate membrane fouling, which is not conducive to long-term stable operation of AnMBR.Sludge properties have an important effect on membrane fouling . The ratTemperature changes affect the enzyme activity, mass transfer rate and microbial activity of anaerobic microorganisms. Changing the viscosity of the liquid can affect the treatment efficiency and stability of the reactor . A studyGenerally, the increase in temperature will decrease the viscosity of the mixed liquor in the MBR, (i) increase the solubility of suspended particles, (ii) increase the mass transfer diffusion coefficient , (iii) pWhen studying a forward osmosis membrane bioreactor, temperature has a significant effect on the forward osmosis process. The water flux increases with increasing temperature. The influence of the temperature of the draw solution is significantly higher than that of the feed solution, and only the temperature of the draw solution is increased, which can obtain higher water flux and lower membrane fouling under the premise of significantly reducing the heat consumption of the system, which is an efficient operation mode .Among the many factors affecting membrane flux, the mode of operation is the key to the successful application of membrane technology in wastewater treatment. The cross-flow velocity can control the size of the permeate flux and to some extent contain membrane fouling . The dynFor pressure-driven membrane filtration processes, operating pressure is the most direct factor. There is a critical operating pressure during operation. Exceeding the critical pressure causes the membrane to foul extremely seriously . At highIn addition, the gas/water two-phase flow can increase the degree of turbulence in the pores, thereby enhancing the shear-carrying effect on the fouling layer on the membrane surface, and effectively suppressing membrane fouling, thereby increasing the permeate flux . IntermiThe activated sludge characteristics affecting membrane fouling include sludge components, MLSS, sludge viscosity, environmental conditions , EPS, SMP, inorganic matter and microbial communities present in the activated sludge . ExcessiThe sludge mixture consists of three components, namely suspended solids, colloids and dissolved matter. Membrane fouling is the result of a combination of all the above three components . The sluSome studies  summariz4 and CO2. The sludge formed is relatively loose, and the size of suspended particles in the mixed liquor is small [In the membrane fouling process of an integrated membrane bioreactor, a mud cake layer will be formed on the surface of the membrane, the resistance will increase, and the membrane flux will decrease. The formed mud-cake-layer resistance is related to the particle size. The smaller the particle size, the smaller the porosity of the mud cake layer, and the greater the resistance; the larger the particle size, the larger the porosity of the mud cake layer and the smaller the resistance of the mud cake layer . When wais small .In the application of a membrane bioreactor, MLSS is an important process parameter which directly affects the performance of the membrane . On the The sludge mass concentration gradually increases with the increase of sludge age. At the beginning of the operation of an MBR, the sludge mass concentration increases greatly, mainly because of the strong microbial metabolism and high sludge load during this period. After that, the sludge growth is slow but the sludge mass concentration increases rapidly until the middle stages of operation. In the later stage, the sludge mass concentration is limited by organic pollutants, and after the sludge mass concentration reaches a certain level, it no longer grows and gradually reaches a stable state . When thUnder the condition that the flow rate of the water is kept constant, as the mass concentration of the sludge increases, the viscosity of the mixed liquid also increases, causing serious membrane blockage, resulting in a decrease in membrane porosity, thereby increasing filtration resistance and increasing TMP . StudiesViscosity is essentially the ability of a molecule or solid particle in a liquid to resist external stress or shear forces. The greater the viscosity of a solution, the greater its ability to withstand external stresses or shear forces . The mixExcessive viscosity of the sludge mixture increases the likelihood of sludge adhering to the membrane surface, thereby accelerating membrane fouling. In addition, Hu  showed tThe effects of EPS and SMP on membrane fouling have received increasing attention in recent years. EPS includes insoluble organic matter secreted by cells, which is shed from the cell surface or caused by cell death. The main components are protein (EPSp) and carbohydrate (EPSc) . The EPSEPS is an important factor affecting sludge settling performance and membrane fouling rate in MBR. Excessive EPS will further deteriorate the mutual flocculation effect between microorganisms and weaken microbial flocs . The difSMP is a large class of soluble organic matter produced by microbial metabolism, including polysaccharides, proteins, humic acids and nucleic acids. The composition is extremely complex and poor in biodegradability . Due to The biological phase in the MBR will change the sludge morphology, particle size distribution (PSD), EPS, viscosity and other parameters affecting membrane fouling. Compared with the traditional activated sludge method, the evolution of microbial populations in the MBR system is characterized by few species, which are vast and with obvious dominant populations. With the extension of the running time, the dominant populations in the MBR system consist of swimming ciliates, worms and bell worms, beetles, and red spotted worms. Membrane fouling can be predicted by dominant populations that indicate the state of the sludge .The difference in biophase has a large effect on membrane filtration resistance. When the biophase is changed from a lower protozoan to a higher protozoa, it is reflected as a decrease in the starting point of the filtration resistance and slowing point in the growth rate of the microbial community. Wang et al.  showed tThe physical blending is to physically mix the membrane material matrix with the modifying additive in a certain ratio, and the modified additive does not react with the bulk of the membrane material . PhysicaThe advantage of blending modified hydrophilic polymer with PVDF polymer is that after adding relevant hydrophilic polymer to the film material, it can compensate for various performance defects of the film with raw material alone, and also can give the membrane material itself the new superiority . In the At present, in the improvement of the performance of the separation membrane, the polymers reported for blending with PVDF including polyvinylpyrrolidone (PVP), chloromethylated polysulfone (CMPS), polymethyl methacrylate (PMMA), poly vinyl acetate (PVAc), PEG, polyvinyl alcohol (PVA), sulfonated polystyrene (SPS), nylon 6, sulfonated polysulfone, polyacrylonitrile (PAN), polysulfone, and sulfonated polyaryl ether sulfone (SPES-C) .2O3, SiO2, TiO2, etc. The modified membrane prepared by using the blend casting solution perfectly combines the properties of the PVDF membrane with the hydrophilicity and heat resistance of the inorganic material to form a novel organic–inorganic composite membrane [Compared with hydrophilic polymer blending, blending small-molecular inorganic particles with PVDF to improve the hydrophilicity of the membrane is a rapid development in the recent years . Commonlmembrane .The chemical copolymerization modification can increase the hydrophilicity of the organic polymer film. This is carried out by adding a modified monomer to the original cast film material of the organic polymer film to cause a complicated copolymerization reaction and to form a new copolymer as a cast film material. Common methods for modifying membrane materials include copolymerization, block, chain extension, grafting, and so on. Sun et al.  induced Selina et al.  studied 2-NH2 nanoparticle suspension and 0.1 wt % of SA solution. The experimental results showed that this method can effectively improve the anti-fouling performance [The surface coating modification method refers to coating a hydrophilic substance on the surface of the hydrophobic film to be modified, thereby improving the anti-fouling performance of the film. A comb polymer was coated on a PSF ultrafiltration membrane and the modified membrane was characterized by infrared spectroscopy and X-ray photoelectron spectroscopy (XPS). The presence of the coating layer was confirmed by the above characterizations . Furtherformance .The plasma modification methods such as only plasma modify treatment (OPMT), plasma polymerization graft coating treatment (PPG-CT) and plasma trigger radical graft polymerization (PTRGP) on the surface of polymer materials can modify the membrane, but the modification mechanisms are slightly different. PTRGP method is the grafting of monomer on the surface of the membrane . The cop3H, -CO, and -NH2 [The low-temperature plasma treatment modification technology uses a gaseous substance such as an atom, a molecule or an ion in a state in which the positive and negative charges are in a plasma state to attack the polymer, and induces a chemical reaction such as hydrogen elimination on the surface of the membrane to introduce a large number of polar groups such as -OH, -COOH, -SOand -NH2 . This caand -NH2 .2/S2O82− The monomeric DMAEMA was successfully graft polymerized on the surface of the polysulfone microfiltration membrane to form a porous graft membrane PSF-g-PDMAEMA. Such a membrane can remove CrO42− ions in the water effectively by selective adsorption.Surface grafting refers to the modification of the thin layer on the surface of the membrane without changing the bulk properties of the membrane material so that a relatively stable chemical bond is formed between the membrane surface and the grafted polymer chain . The effIn recent years, research on membrane fouling control methods related to irradiation grafting has attracted more and more attention ,132,133.2·h), an increase of 29 L/(m2·h) compared to the original film. The hydrophilicity of the polypropylene hollow fiber membrane modified by ultraviolet irradiation improved significantly.Jin et al.  used polFactors that should be considered in the optimization of the membrane module are the shape of the membrane module, the placement of the module, hydraulic conditions, the diameter and the length as well as the tightness of the hollow fiber filaments . As can 3-N is also improved [Xiong et al.  used theimproved . Viet etimproved . Blandinimproved .There are some factors affecting membrane fouling that exist in the feed liquid. In general, the direct method of controlling the characteristics of the feed liquid is to add a flocculant or adsorbent to the feed liquid. Compared with the monomer salt, the polymeric salt can provide more positive charge and electrically neutralize the suspended particles in the liquid, which can improve the removal rate of the suspended particles and increase the diameter of the particles . The indAdding a commonly used adsorbent such as powdered activated carbon (PAC) to MBR can effectively control the development of membrane fouling, slow the rate of increase of TMP, and prolong the membrane operating cycle . PAC has3/SS) is 0.25 mg/g per day, which can reduce the EPS in the supernatant and enhance the suspended solids. In general, the control measures for membrane fouling are based on the factors that control membrane fouling. The common methods and principles of controlling membrane fouling are shown in The main operating conditions of MBR are membrane flux, operating pressure, aeration, pumping time and cleaning cycle. One measure commonly used in MBR is to control the membrane flux below membrane critical flux or sustainable flux operation. Zhang et al.  studied Membrane cleaning can effectively remove and control membrane fouling, reduce TMP, and restore membrane flux . The clePhysical cleaning mainly removes reversible contaminants in the membrane surface or membrane pores and the methods mainly include aeration, backwashing (air or filtrate), ultrasonication, sponge scrubbing and water washing. Physical cleaning allows the MBR to operate at a relatively constant flux without causing secondary contamination, but requires frequent cleaning at increased operating costs . AeratioBackwashing can remove most of the reversible pollutants and improve the membrane filtration performance. The key parameters affecting the backwashing effect are the backwash intensity, frequency, time and frequency-time ratio. Jiang et al.  found thUltrasonic online cleaning methods can effectively control membrane fouling . UltrasoChemical cleaning is required when physical cleaning does not meet membrane fouling requirements. Commonly used chemical agents include alkali cleaning agents, acid cleaning agents, oxidizing cleaning agents, and surfactants  . Alkali Electric cleaning achieves the effect of removing contaminants by applying an applied electric field on the film at a certain time interval to cause the contaminating particles to move away from the film surface in the direction of the electric field. However, this method requires that the film has a conductive function, or that the electrode can be mounted on the film surface, so that it is used less .Ultrasonic irradiation can clean the fouled membrane through the production of important physical phenomena including microjet, microstream and shock waves . Indeed,MBR technology is a highly competitive technology and has been widely used in various fields of wastewater reclamation and wastewater recycling. However, membrane fouling is a hindrance to the widespread promotion of this technology. Therefore, research on the causes, mechanisms and control technologies of membrane fouling is of vital importance to this technology. Although some achievements have been made, there is room for more improvements. The author believes that future research should focus on the following aspects:(1) Due to the heterogeneous structure and complexity of WOM or the dissimilar fouling behaviors between different organic surrogates, it is highly recommended that use should be made of real wastewater in combination with advanced DOM analysis such as FT-ICR-MS (Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometry), SEC-OCD, and CLSM, as well as online monitoring methods such as quartz crystal microbalance, or any visualization apparatus for exploring real-time organic membrane fouling formation. Real-time monitoring capabilities are also of great benefit for the optimization of the periodical cleaning of membranes during long-term FO processes. New data on the complex interactions between organic foulants and membrane materials can help the development of effective fouling control strategies for real wastewater. For instance, appropriate pretreatment can be developed/designed to effectively eliminate high molecular weight biopolymers  to mitigate FO membrane fouling. Finally, considering the typical short-term formation of irreversible fouling in FO processes, the limited operational test period, and bench-scale nature of many previous studies, pilot-scale FO systems should be operated and studied with due provision for long-term monitoring if transition to successful full-scale wastewater FO processes is to be realized.(2) An alternative solution for improvement of direct membrane filtration performance is to develop new membranes with increased anti-fouling properties. Several reported studies focused on developing the novel anti-fouling membranes and the lab-scale testing findings displayed their good performances in membrane fouling alleviation. In view of the absence of large-scale direct membrane filtration processes in the market, further research needs to be emphasized on (i) membrane fouling control technologies of direct membrane filtration, especially towards low energy consumption, less chemical usage, and easier operation and maintenance; (ii) development of novel membranes, especially having a mechanically robust nature with low-cost environmentally friendly materials and self-cleaning properties; (iii) comprehensive economic analysis, life cycle assessment, and carbon footprint analysis of different direct membrane filtration processes in order to identify the most suitable system configuration for further scale-up.2, etc., can produce hydroxyl radicals in the presence of ultrasonic irradiation. Generated hydroxyl radicals can degrade the foulants adsorbed on the surface of the membrane or captured in pores of the membrane, which consequently results in controlling the membrane fouling. High energy consumption of the ultrasonic transducers limits the application of ultrasound-MBR systems on a full scale. Further research is needed on the hybrid methods with low energy consumption for improving the application of ultrasonic technology in full-scale MBR systems.(3) The effect of the presence of ultrasound-active inorganic nanoparticles in the matrix of the membrane used in MBR systems can be investigated in future research. Ultrasound-active nanoparticles, i.e., ZnO, TiO(4) Aeration optimization, such as intermittent or cyclic aeration, automatic aeration control based on DO- or nutrient removal feedback and mechanically-assisted aeration scouring, has attracted much attention to achieve efficient membrane fouling control with less energy consumption. The method of aeration could be further optimized according to the CFD modeling on the fluidization and the scouring behavior of the particles in MBRs. Moreover, the attachment tendency of biofilm colonizers on the medium and membranes should be assessed. Moreover, chemical cleaning efficiency is highly related to the interaction between chemicals and foulants. The chemical reagent has greater potential to decrease the aging of membranes and even lead to the inactivation of microorganisms in the bioreactors. These adverse effects caused by the chemical cleaning will be highlighted in the future.


Periplaneta americana, which is an experimental system that has elucidated many important biophysical and cellular bases of intrinsic physiological properties of these neurons.Highly interconnected neural networks perform olfactory signal processing in the central nervous system. In insects, the first synaptic processing of the olfactory input from the antennae occurs in the antennal lobe, the functional equivalent of the olfactory bulb in vertebrates. Key components of the olfactory network in the antennal lobe are two main types of neurons: the local interneurons and the projection (output) neurons. Both neuron types have different physiological tasks during olfactory processing, which accordingly require specialized functional phenotypes. This review gives an overview of important cell type-specific functional properties of the different types of projection neurons and local interneurons in the antennal lobe of the cockroach  Periplaneta americana, an experimental system that has elucidated many important biophysical and cellular bases of intrinsic physiological properties of these neurons.In the previous decades, enormous progress has been made in understanding general mechanisms and principles of olfactory information processing at all levels of analysis - from the molecular and cellular to the circuit, system, and behavioral level. To a large extent, this progress was possible by taking advantage of comparative studies with various vertebrate and invertebrate experimental systems   Pere et al. , the OSNe et al. .The comprehensive studies on OSNs of trichoid sensilla from Tichy and co-workers and numerous studies on response properties of OSNs from other sensilla types Sass  have sho2+ imaging  blueprint. In insects, the first synaptic processing station for olfactory information is the AL, which is the functional analog of the vertebrate olfactory bulb. The antennal OSNs, typically each expressing a single functional receptor gene, send their axons to the AL, where they collate by receptor type and converge into specific glomeruli. In the glomeruli, they form synapses with PNs and LNs. The PNs relay information to higher-order neuropils. The LNs mediate complex inhibitory and excitatory interactions between and within the glomeruli to form the olfactory representation in the AL, which ultimately shapes the tuning profile of PNs.In the central nervous system, complex neural circuits have evolved to process olfactory information efficiently. The primary olfactory input is intensively processed by a highly interconnected network of different types of PNs and LNs before the PNs transmit the processed information into higher-order processing regions of the protocerebrum. The basic structure of these circuits is very similar across phyla and usually follows a general scheme with variations in the numbers of its neuropilar subunits, the glomeruli, and cellular components , where the somata of the different neuron types are organized in well separated and identifiable clusters. The vast majority of the cell bodies in the ventral part of the VSG belong to a cluster of uniglomerular PNs (uPNs). Somata of different sizes, which are located in the dorsal part of the VSG, usually belong to LNs. Directly dorsal to the uPN somata is a relatively homogenous, densely packed soma group belonging to spiking type I LNs, whose neurites give rise to the Y-shaped tract and exhibit GABA-like immunoreactivity Distler . The somP. americana, the ultrastructural organization of the glomerular neuropil has been analyzed in detail by early electron-microscopic studies, in which combinations of various labeling techniques were used to identify synaptic connections between different neuron types. These studies, which focused on OSNs, GABA-lir LNs, and uPNs, demonstrated synaptic connections between almost any possible combinations of these neuron types , which project from the AL to the protocerebrum. In es Malun : OSNs foA receptors, whereas the GABAB receptors mediated the slow, sustained IPSPs.Paired recordings confirmed the functionality of chemical synapses between cholinergic uPNs and GABAergic LNs, and between different GABAergic LNs  of the protocerebrum. They are cholinergic and thus provide excitatory input to their postsynaptic targets in the protocerebrum, and in the input glomerulus of the uPNs also to LNs  action potentials upon odor stimulation or depolarizing current injection. Despite that uPNs receive primary sensory input in one glomerulus by one OSN type only, they usually respond to odorants of many different chemical classes with elaborate patterns that can include periods of excitation and inhibition PNs via the n-dorsal root tracts (ALT IV and lALT). In contrast to the uPNs, the mPNs innervate many glomeruli, usually with only sparse, locally restricted arborizations in each glomerulus. Forming numerous axonal side branches, the mPNs project to the lateral protocerebrum and the LH, while the calyces are only sparsely innervated or not at all  nonspiking type II LNs, in which odor stimulation evoked depolarizations, but no Na+-driven action potentials  spi+-driven action potentials upon odor stimulation or depolarizing current injection. They are broadly tuned and respond to different odorants with relatively similar firing patterns. Type I LNs give rise to the y-shaped tract  between AL neurons  increase of intracellular Ca2+.The different electrophysiological properties of the different AL neuron types, in particular their different In line with their different morphological and physiological properties and the resulting differences in computational capacity and synaptic release mechanisms, LNs also exhibit different neurotransmitter and modulator profiles. Mass spectrometric and immunocytochemical studies assign a variety of neurotransmitters and peptides to identified LN types Fig. .Fig. 6OvA- and slow GABAB receptor-mediated inhibitory action of type I LNs onto uPNs and other type I LNs , suggesting that they release ACh as their primary transmitter  of uPNs, for example, has the lowest threshold, the fastest inactivation rate, and the highest current density of AL interneurons (Paeger et al. 2+-activated K+ currents (Bradler et al. In this regard, the main task of PNs, the coding, and transmission of the processed odor information over long distances from the AL to the protocerebrum are relatively well defined. This task requires the ability to generate fast action potentials in relatively high frequencies, which is not only reflected in the expression of transient NaThe specific functional roles of the different LN types are less clear, especially the role of nonspiking type II LNs. The possibility that in addition and in parallel to spiking LNs, nonspiking LNs perform different tasks during olfactory processing has not been investigated in detail, although nonspiking LNs have been described in other insects (Tabuchi et al. ICa component might boost and shape dynamic signals such as excitatory postsynaptic potentials. Such mechanisms might help to shape functional compartments, for example, for local integration, or they might help to activate nearby output synapses as suggested by Laurent et al. (The precise synaptic organization, which determines the synaptic input and output regions of the neuron, can only be shown by electron microscopic studies. In any case, some hypotheses about the synaptic input and output regions of the LNs can be formed from the distinct morphologies of these neurons. The spiking type I LNs, for example, expressed different branching patterns in different glomeruli, suggesting a polar organization with defined input and output regions (see also Distler and Boeckh, t et al. . For nonTaken together, the summarized data illustrate that the different AL neuron types show functionally important differences in physiology, structure, biochemistry, and computational capacity. Future studies have to find out how neurons with cell type–specific physiological characteristics, together with the expression of different transmitters and neuromodulators that can act on significantly different time scales, effectively mediate the processing of odor information in local AL circuits.


The coronavirus disease 2019 (COVID-19) pandemic has immensely disrupted health care services globally. The pandemic has been particularly disruptive for cancer services and more so in low-resource settings. In this narrative review, we highlight the reported impact of the COVID-19 pandemic on cancer prevention, screening, diagnosis, treatment and research across the African continent. We also explore ways in which identified structural and contextual constraints can be navigated for the re-escalation of oncological activities, while discussing how the pandemic has necessitated the reimagination of how oncology services can be delivered now and in the future. We conducted a literature search of MEDLINE (via PubMed) and Scopus for relevant articles and synthesised the findings thematically. In spite of the dearth of data, available evidence suggests a substantial impact of the pandemic on the various aspects of cancer management in African countries. Aggravating factors include pre-existing health system and cancer management gaps in many countries within the region, which are typically faced with inadequate availability of oncology resources, oncologists and other vital resources; in addition to the acute and lingering consequences of social distancing, movement restrictions and other public health measures implemented to contain the spread of the virus. As the pandemic evolves and movement restrictions are eased, there is a need for the timely and safe return to normal oncological care. This will require a risk-adjusted and multidisciplinary approach, with the aim of mitigating the further impact of the disruption on cancer patients, their families and healthcare providers. The coronavirus disease 2019 (COVID-19) pandemic has immensely disrupted health care services globally . COVID-1Furthermore, disruptions of cancer services have resulted from the considerations that cancer patients are a high-risk population for COVID-19 infection, severe disease and fatal outcomes, either due to the immunosuppression caused by the malignancy itself, or by anticancer treatments such as chemotherapy and radiotherapy , 12. ConAs of 5 October 2020, the African region had recorded 1,518,662 confirmed COVID-19 cases and 36,921 deaths . The impTo identify the relevant evidence on the the impact of the COVID-19 pandemic on the cancer control and management landscape in African contexts, we conducted a literature search of MEDLINE (via LitCOVID in PubMed) and Scopus. Reference lists of relevant articles were also scanned for potentially relevant articles. This review follows the evidence synthesis format of narrative reviews , 19. FinTo mitigate the impact of the pandemic on cancer management, oncology centres and institutions across the continent have adopted clinical practice guidelines and recommendations to guide the re-organisation of cancer services to maximise the use of the limited available resources for cancer management in COVID-19 outbreak settings , 4, 20. While still limited, the evidence of the actual impact of the pandemic on African cancer screening and diagnostic programmes is beginning to emerge. In response to the early surge of COVID-19 cases, cancer screening programmes (including mammograms and pap smears) were suspended in Morocco , 26. A sOn 26 March 2020, the World Health Organization (WHO) recommended the temporary suspension of mass vaccination campaigns and restriction of routine immunisation services in settings where community transmission of COVID-19 has been established . These hA heightened perception of risk of contracting COVID-19 in a health care settings has led to the suspension of early diagnosis programmes globally , 33. ThiTo ensure the safety of patients and oncologists, outpatient cancer consultations have been reorganised to reduce patients’ access to the hospital, with tele-medicine outpatient consultation approaches being increasingly considered , 37. ThiData on the impact of the pandemic on the various cancer therapeutic modalities within the African region remain sparse. However, there is significant evidence of how cancer treatment has been affected in some settings across the continent. Since the start of the current pandemic, oncologists have had to grapple with the dilemma between the clinical responsibility of maintaining optimal cancer treatment and care on the one hand; and the public health necessity of limiting the spread of the virus by reorganising oncological care to reduce or delay treatment visits, on the other hand . Common Movement restrictions, shortage of protective gear and insufficient onsite testing kits for patients and oncology staff have posed additional barrier to cancer treatment in African countries. This has been the case in Ghana, where oncology centres have had fewer number of patients and staff, while chemotherapy has been halted for some patients and the start of adjuvant therapies has been delayed for others . SimilarThe situation has not been any better for radiation therapy. While scheduled appointments for patients on radiotherapy are mostly maintained, many patients are unable to access treatment for various reasons . It has For cancer surgical procedures, it was reported that access to cancer surgical services has been cancelled or reduced in 28.1% of hospitals surveyed in South Africa . This foThe care of children with malignant solid tumours in sub-Saharan Africa is compromised by resource deficiencies that range from inadequate healthcare budgets and a paucity of appropriately trained personnel, to scarce laboratory facilities and inconsistent drug supplies. Patients face difficulties accessing healthcare, affording investigational and treatment protocols and attending follow-up , 47. ChiAnother multi-country study involving some African countries, which assessed the barriers to paediatric oncology management during the COVID-19 pandemic, found that almost all oncology centres applied guidelines to optimise resource utilisation and patient safety, including delaying treatment visits, reducing staff and implementing social distancing. Overall, 30% of the participating centres reported that cancer care of children was negatively affected. Essential treatment, including chemotherapy, surgery and radiation therapy, was delayed in 29%–44% of centres, while 24% of centres restricted acceptance of new patients. Furthermore, about 70% of centres reported shortages in blood products, while 47%–62% reported interruptions in medication supplies, cancer surgery and radiation therapy .With the current border closures, many African countries which rely on imported medical supplies have been faced with the acute challenge of supply shortages. There have been concerns of the high possibility of drug stock being depleted in Ghana, as almost all the systemic therapy medications used in the country are imported . The sitThe disruption caused by the COVID-19 pandemic has not only affected the treatment and care of cancer patients, but has also undermined cancer research activities. This has been due the restrictions on non-essential services including closure of research sites and laboratories as well as the suspension of routine clinical research activities; the prioritisation of frontline COVID-19 care over research by clinicians and the re-allocation of health research resources to research on COVID-19 vaccine and therapeutics –55. For Reduced access to oncology services during the pandemic runs the very risk of increasing cancer morbidity and mortality, not only now but in the future . Hence, The prevailing low COVID-19 testing capacity and insufficient supply of PPE in most African countries present an immediate challenge to the resumption of full oncology services and research. Inadequate testing capacity can place patients and healthcare personnel at a higher risk of infection, while undermining efforts to re-introduce previously restricted or suspended cancer services . In spitCancer programmes should continue offering cervical cancer screening and diagnostic services, following strict COVID-19 preventive measures. Preventive measures may include managing daily appointments to avoid overcrowding and maintaining physical dancing in queues. To catch up on missed screening opportunities, people visiting health care facilities for other health reasons could be offered age- and gender-appropriate cancer screening and early diagnostic services. While implementing the phased return of cancer treatment services, lingering movement restrictions may hinder patient referral to facilities offering the highest level of care at this period. Hence, facilities that may not have radiotherapy services should consider lower-level treatment options such as the use of chemotherapy, pending the feasibility of access to higher-level oncology centres . It has Scaling up oncology services to pre-pandemic levels will require a multidisciplinary approach and increased communication between members of the oncology community for safely, efficiently and collaboratively returning to pre-pandemic standards of care . OncologAnother important consideration for the re-escalation of cancer services is the continent’s large population of persons who are infected with human immunodeficiency virus (HIV), many of whom have cancer as a co-morbidity , 63. ThoSome of the innovative approaches for adapting to the restrictive environment and mitigating the impact of the pandemic on cancer research include the adoption of remote practices to facilitate recruitment, patient contact, site visits, training and institutional review board communications. Other suggested approaches include the permission of protocol deviations, which may allow increased flexibility in the design and conduct of new trials . Cancer The present COVID-19 pandemic period has, in an unprecedented way, created new opportunities for telemedicine innovations to remotely assist in the monitoring of patients in health management. There has been widespread adoption of telehealth visits, virtual check-in services, e-visits, remote care management and remote patient monitoring to sustain patient care and management and mitigate the impact of the pandemic , 37. HowThe patient triage and treatment modification strategies necessitated by the COVID-19 pandemic have been unprecedented. These present opportunities for research to study the outcomes of patients who received modified and/or alternate cancer care schedules, to identify patient cohorts for whom treatment modifications may be beneficial in future pandemics.There are also lessons to learn from the way in which COVID-19 related cancer research is advancing at a breakneck speed, as well as how tele-multidisciplinary tumour boards have had to improvise with virtual meetings, broadening collaboration across the globe, for challenging cancer cases as well as for research. Overall, the pandemic has allowed the rethinking of ways of improving health systems efficiency, flexibility and resilience .Evidence of the extent of the impact of the pandemic on cancer care in African countries is beginning to emerge. While the African continent is arguably the least affected in terms of the absolute number of confirmed COVID-19 cases and deaths, the real impact of the pandemic on cancer management and broader health services may not be as mild. The implications of these disruptions are grim in resource-limited settings, particularly in the African region, where cancer programmes are typically under-resourced. As the pandemic evolves and movement restrictions are eased, there is a need for the timely and safe restoration of oncological care and research.None.None (the review was not funded).The review was conceived by JM. CAN wrote the first manuscript. JM provided conceptual and analytical insights to the subsequent versions of the manuscript. Both authors read and approved the final manuscript.


Secretory extracellular vesicles (EVs) are membrane-enclosed microparticles that mediate cell to cell communication in proximity to, or distant from, the cell of origin. Cells release a heterogeneous spectrum of EVs depending on their physiologic and metabolic state. Extracellular vesicles are generally classified as either exosomes or microvesicles depending on their size and biogenesis. Extracellular vesicles mediate temporal and spatial interaction during many events in sexual reproduction and supporting embryo-maternal dialogue. Although many omic technologies provide detailed understanding of the molecular cargo of EVs, the difficulty in obtaining populations of homogeneous EVs makes difficult to interpret the molecular profile of the molecules derived from a miscellaneous EV population. Notwithstanding, molecular characterization of EVs isolated in physiological and pathological conditions may increase our understanding of reproductive and obstetric diseases and assist the search for potential non-invasive biomarkers. Moreover, a more precise vision of the cocktail of biomolecules inside the EVs mediating communication between the embryo and mother could provide new insights to optimize the therapeutic action and safety of EV use. In mammals, the female reproductive trait, comprising ovaries, oviducts and uterus, plays a crucial role in the regulation of early and late reproductive events and provides the optimal environment for embryonic development. Secretory extracellular vesicles (EVs) are important for cell to cell communication, as they have a paracrine function being able to diffuse over a relatively short distance and produce a local action. It has been largely demonstrated that EV-associated activity is fundamental to reproductive success, mediating the fine-tuning of cellular cross-talk in the reproductive system, promoting embryo implantation and assisting successful pregnancy . EspeciaMembrane-enclosed microparticles were first isolated from biological materials such as animal platelet-free plasma , human sCells produce and release a heterogeneous spectrum of EVs differing in size and chemical and physical characteristics. Many methods based on centrifugation, filtration, precipitation and affinity interaction have been used to isolate EVs . The isoEach method present advantages and disadvantages and should be carefully chosen based on sample type, downstream application and scientific question. Some indications are reported in the guidelines presented by international EV body, ISEV ,35 and sAll procedures include methods for evaluation of vesicle morphology, size distribution and concentration so that the purified EVs can be correctly identified. A topographical EV view is obtained by direct imaging methods including scanning (SEM),transmission electronic microscopy (TEM) and cryo-electron microscopy (cryo-EM) that provide high resolution imaging and a more precise evaluation of vesicular size ,37. HoweExtracellular vesicles represent an important mode of intercellular communication by facilitating the horizontal cell to cell transfer of lipids, proteins, RNA species and DNA fragments. However, the functionality and characterization of EV molecular cargo is not always easy to interpret due to the presence of different isolate subtypes and the inability to further separate and to stratify these into distinct sub-populations ,44.Lipidomics and proteomics have identified about 2000 lipid and 3500 protein species isolated from EVs secreted by different cell sources ,46. ExtrThe emerging role of cell to cell communication is mediated by EV-associated small non-coding regulatory RNAs called microRNAs (miRNAs) and other non-coding RNAs by acting as “messengers” shuttled between different cell types. In fact, miRNAs can be specifically compartmentalized inside vesicles and released outside cells, as previously reported in mesenchymal stromal cells in human and equine studies ,52. HoweMany aspects of how miRNAs are selectively encapsulated in EVs and can mediate cell to cell communication are still not understood . MoleculOther nucleic acids, including mRNAs and DNAs, are important in regulation of gene expression but their role in the transfer of cell to cell information remains controversial. Transcripts have been observed to be delivered by EVs but rapidly degraded, whereas plasmid DNA can only be delivered by EVs for correct functioning in recipient cells . RecentlCell communication is fundamental for several molecular processes that allow populations of cells to exchange information with one another to aid specialization in tissue or coordinate multiple cross-organ interaction. Extracellular vesicles have been identified as one of the key players in regulating temporal sequences and spatial interaction, cell-to cell signaling in all events in sexual reproduction  and in embryo-maternal cross-talk . Extracellular vesicles in seminal fluids were observed to modulate sperm capacitation in man  and pigsThe successful of pregnancy requires a molecular dialogue between the embryo and the female reproductive tract that starts at the oviduct and continues until the formation of placenta. The first known molecules in this paracrine communication were the cytokines and growth factors, such as interleukin-1ß (IL-1ß), heparin-binding epidermal growth factor (HB-EGF), integrins and leukemia inhibitory factor (LIF) that act synergistically in the embryo-maternal crosstalk. The IL-1 increases the expression of molecules of adhesion of epithelial cells regulating the endometrial receptivity  and stimIndeed, the EVs mediate two-way trafficking of molecules for embryo-maternal communication. During embryo migration from the oviduct to the uterus, the embryo undergoes distinct metabolic stages . Labelled in vivo EV preparations from bovine oviduct flushing were internalized by in vitro produced embryos . Both inThe biological function of EVs in regulating early embryo-maternal interaction results from the transfer of critical molecular cargos to distant or neighboring recipient cells or tissues. Although the latest high-throughput analytical platforms can perform detailed analysis of the lipid, glycolic, proteic and nucleic acid content in EVs , it is sSeveral proteins in EVs regulate different reproductive functions promoting fertilization and embryo implantation and growth. Extracellular vesicles released into the murine uterine luminal fluid deliver sperm adhesion molecule 1 (SPAM1) to sperm membranes, enhancing sperm fertility . ExtraceMicroRNAs encapsulated in secreted EVs play a significant role in intercellular communication reaching target cells and regulating mRNA and protein expression. Extracellular vesicles transferred from the embryo to the mother, or vice versa, transport miRNAs that target specific pathways for fertilization, embryo implantation and fetal development. Following hormone stimulation, in silico bioinformatic analysis showed that miRNA content, which potentially regulates critically important pathways for follicular oocyte maturation, changed in follicular fluid EVs . ExtraceThe EVs are important vectors of information and are involved both in physiological and pathological conditions. Indeed, during diseases, cell metabolism, physiology and behavior are modified causing alteration in cellular gene expression, protein content and EV cargo. This makes EVs important in the scientific field for their functional role in cell communication and in the medical field as biomarker or as therapeutic tools.The physiological level of circulating EVs in tissues, serum or other biological fluids is different considering the animal model, the time (hours or days) after disease, the kind of disease and the EV quantification method. However, this information, studied and identified in the different conditions, could help to identify the possible therapeutic dose.In the reproductive tract, EV-mediated communication between cells and embryo–maternal crosstalk is an essential process that occurs both in physiologic and in pathologic conditions. Therefore, molecular cargo of EVs and its release change in the pathologic condition by affecting maintenance, and progression of reproductive- and obstetric-related pathologies .Extracellular vesicles can regulate a variety of physiologic processes. The molecular cargo of EVs is strictly dependent on the status of the cell or tissue donor and can change in pathologic conditions such as cardiac disease, neurologic diseases and cancer . AlthougExtracellular vesicles eliminate these limitations. They are present in all biological fluids , and their involvement in different diseases make them inviting candidates as biomarkers. Collection of body fluids for screening of some diseases could avoid the necessity for invasive examinations . Inside Physiologic alterations occurring in the reproductive tract in pathologic conditions influence cell metabolism, changing gene expression and protein content and thus altering EV concentration, cargo and function. These alterations influence maintenance and progression of reproductive- and obstetric-related pathologies.In human medicine, decrease in fertility is an important issue. This may be correlated to environmental stressors. Phthalates and phenols are classes of potential endocrine disrupting chemicals present mainly in the environment and in food . PhthalaSeveral of the significant EV-miRNAs biomarkers found to be associated with phthalates and phenols play key roles in the ovarian follicle, consistent with the fact that the follicular fluid, contains a number of molecules including EV-miRNAs that create an appropriate microenvironment for the growth of oocytes ,141. ForThese data show that exposure to toxic compounds causes miRNAs alteration in human EVs isolated from follicular fluid, potentially affecting ovarian function. In the veterinary field, it is likely that exposure to toxic compounds such as Fusarium mycotoxins, frequently present in feed, might influence animal fertility and alter the miRNA expression in follicular fluid EVs. In man, but probably also in animals, fertility status is influenced by other factors such as advanced maternal age (AMA) or endometriosis that can impact the embryo-endometrial talk before implantation. In vitro studies revealed variation of EV-bound secreted miRNAs isolated from co-cultured endometrial cells and embryos from AMA and fertile controls, with 16 miRNAs increase in AMA and strong evidence of a negative regulation toward 206 target genes involved in cell adhesion. Co-cultured endometrial cells isolated from patients with endometriosis and embryos from fertile controls revealed EV alterations in 10 miRNAs, targeting 1014 genes crucial for development and implantation .Currently, in vitro embryo production is an important component of improved pregnancy rates in assisted reproduction in both human and veterinary medicine. Blastocyst quality is assessed morphologically by assessment of the expansion of the blastocoel cavity, as well as the appearance of the ICM and TE cells ,149,150.The miRNAs found outside the blastocyst in the spent medium are probably involved in implantation and in embryo-maternal cross-talking ,156,157.Pregnancy is a particular physiological condition for studying EVs. At first, unlike other conditions, the onset and end of pregnancy is known allowing you to follow changes in EVs throughout the period. In addition, the placenta produces specific markers that allow you to distinguish EVs from those produced by others cell types and, finally, the placenta is available at the end of pregnancy for study . PlacentDuring gestation, placenta-derived EVs can be bio-markers of feto–maternal health and evolution, indeed, EVs are involved in cell-to-cell communication between the placenta and peripheral blood immune cells. During the first trimester of pregnancy, extravillous trophoblast and/or syncytiotrophoblast cells release placental EVs into the maternal blood. These EVs suppress maternal T-cell signaling components promoting immunosuppression and maternal immune tolerance to the fetus. In man, the plasma concentration of EVs increases during pregnancy and with gestational age, indeed, the concentration of EVs in maternal peripheral blood is 20-fold greater compared to that found in nonpregnant women . The incIn addition, the secretion of EVs from the placenta can be influenced by the microenvironment. Indeed, variation in oxygen tension and glucose can increase bioactivity and release of exosome by trophoblast ,164. ExtSometime, the effects of high glucose concentration on the bioactivity of EVs are additive to those of oxygen tension when there is an association with maternal insulin resistance (resulting in hyperglycemia) and pre-eclampsia  . The ideSabapatha et al. (2006) evaluating the content of miRNAs in pregnant and control women report that the plasma concentration of EVs increases during pregnancy and with advancing gestational age . Pohler Since endometrial exosomes are implicated in the pathophysiology of implantation failure in infertility , currentThe EVs can be used for treatment of cancer and can be loaded with anti-cancer agents (in cells or in EVs) including doxorubicin, paclitaxel, curcumin, cisplatin, and methotrexate . ExtraceExtracellular vesicles can be administered via intravenous, subcutaneous, intraperitoneal, oral, and intranasal routes to reach the desired in vivo target sites, depending on the intended therapeutic action and tissues to be targeted . In the There are many considerations for optimization of the therapeutic action of EVs and to ensure treatments are safe. These include: 1) the cell type (such as the tissue source of MSCs); 2) the cell collection process and the expansion methods including culture conditions ; 3) the EV isolation and storage methods; 4) the modality of drug-loading and the quantification approaches; 5) the mechanism used to trigger EV release; 6) the design of cost-effective and scalable isolation processes and 7) the methods to ensure quality, safety, and consistency that are mandatory for clinical applications . VariatiThis review summarizes the role of EVs in cell to cell communication in animal reproduction. Remarkable progress has already been made, but many hurdles remain. Although, there is clearly evidence that EVs play crucial roles in many aspects of oocyte maturation, fertilization, implantation and embryo-maternal crosstalk, challenges remain in a partial understanding of which signaling biomolecules carried by EVs act to mediate cell to cell communication. In fact, cells release a heterogeneous population of EVs differing in size and molecular content that are often co-purified using conventional isolation methods. Molecular profiling gives an overall characterization of EV cargo that only partially represents the function of specific EV subpopulations in physiologic and pathologic conditions. The development of more reliable isolation methods and more sensitive technologies for physical and molecular characterization of EVs is needed to obtain more robust results that will improve our insight into the molecular basis of EV targeting of, and action on, recipient cells. Moreover, a more precise vision of the cocktail of molecules inside EVs that are transferred in the two-way trafficking between embryos and mothers will improve the identification of potential non-invasive biomarkers for specific pathologic conditions and will advance the use of EVs in innovative therapies in reproductive biomedicine.


With the variety of toothbrushes on the market, the question arises, which toothbrush is best suited to maintain oral health? This thematic review focuses first on plaque formation mechanisms and then on the plaque removal effectiveness of ultrasonic toothbrushes and their potential in preventing oral diseases like periodontitis, gingivitis, and caries. We overviewed the physical effects that occurred during brushing and tried to address the question of whether ultrasonic toothbrushes effectively reduced the microbial burden by increasing the hydrodynamic forces. The results of published studies show that electric toothbrushes, which combine ultrasonic and sonic (or acoustic and mechanic) actions, may have the most promising effect on good oral health. Existing ultrasonic/sonic toothbrush models do not significantly differ regarding the removal of dental biofilm and the reduction of gingival inflammation compared with other electrically powered toothbrushes, whereas the manual toothbrushes show a lower effectiveness. Dental plaque  includes highly organized diverse microbial communities attached to the surface of hard tooth tissues. Oral biofilm’s role in the development of various diseases of the oral cavity and throat, including caries, periodontal diseases, endodontic infections, tonsillitis, alveolitis, among others, determines the clinical and biological relevance of studying this system . MoreoveBiofilm consortia are characterized by unique architecture and specific features of adhered cells, which are physiologically, metabolically, and morphologically different from their planktonic counterparts . MicrobiThe biofilm formation is a gradual process consisting of several successive stages: (a) acquired pellicle formation before adhesion of planktonic microflora; (b) primary (early) colonization with subsequent proliferation of adhered microorganisms; (c) secondary colonization/co-aggregation; and (d) biofilm maturation .The initial bacterial attachment to the acquired pellicle involves physicochemical and biochemical interactions  between molecules present at the tooth surface and those present on the cell surface .The combination of the primary adhesion, co-adhesion, and co-aggregation of bacteria accompanied by their rapid proliferation leads to effective colonization of host tissues and the quick formation of the dental microbial biofilm ,8. BiofiMature biofilms are represented by a multilayer structure with a heterogeneous population of cells surrounded by an extracellular polymeric substance (EPSs). Channels are penetrating the biofilm matrix, in which nutrients can circulate and metabolic waste products can be excreted. The EPSs consist of exopolysaccharides and proteins, as well as other macromolecules, such as nucleic acids, and lipids. The exopolysaccharide matrix provides versatile protection against toxins, pH and osmotic changes, ultraviolet radiation, and insiccation. Once embedded within a biofilm, bacteria gain resistance to the host immune system .Staphylococcus intermedius, Streptococcus oralis, S. mitis, S. mutans, S. anginosus, Selenomonas noxia, Veillonella parvula, Capnocytophaga gingivalis, Eikenella corrodens, Neisseria mucosa, Fusobacterium nucleatum, Treponema sokranskii, Prevotella melaninogenica, Propionibacterium acnes, and Leptotrichia buccalis; while the subgingival biofilm is composed predominantly of F. nucleatum, Campylobacter rectus, V. dispar, Porphyromonas gingivalis, P. intermedia, Tannerella forsythia, T. denticola, Actinomyces oris, S. anginosus, and S. oralis [The supragingival environment is colonized with species such as . oralis . These mOn the one hand, the biofilm can be considered as a commensal part of the natural immune system; while on the other hand, uncontrolled activities of pathogenic bacteria can cause health problems like gingival inflammation, characterized by redness of the gingiva, swelling, and bleeding . The infIn general, the efficiency of toothbrushing is dependent on the type of toothbrush, wearing of toothbrush , method In the early 1960s, powered toothbrushes were first introduced for commercial use and have represented an alternative to manual toothbrushing . Since tThe bristle motion of the toothbrush at different frequencies, apart from the direct scratching effect, generates a turbulent fluid flow that directly leads to hydrodynamic effects such as wall shear forces that act parallel to the tooth surface . ElectriNow we will try to address the issue regarding the effectiveness of ultrasonic toothbrushes in terms of their technical characteristics and in terms of the various hydrodynamic forces acting on the biofilm. Further, the performance of manual, sonic, and ultrasonic toothbrushes will be compared briefly regarding the reduction of plaque, gingival inflammation, and the number of bacteria forming the biofilm.In the late 18th century, the direct piezoelectric effect was discovered by Pierre and Paul-Jacques Curie, and it describes the accumulation of electrical charge in certain solids in response to applied mechanical stress. Conversely, materials as crystal quartz respond to an applied electrical field proportionally with mechanical deformation. This phenomenon, known as the “inverse piezoelectric effect,” was discovered by the physicist Gabriel Lippmann in 1881. However, the first practical application of piezoelectric crystals in ultrasonic transducers was implemented by Langevin in 1915 and it was only in the 1950s that crystal quartz was substituted with piezoceramics opening the gate for the development of commercial ultrasonic applications .Ultrasonic processes are characterized by the generation of sound waves at frequencies above the audible range for human beings. The use of ultrasound waves is diverse and ranges from the industrial technology, such as precision processing or semiconductor production, over or underwater communication, to the field of medicine where it is used, e.g., for diagnostic and sterilization procedures. The most common application represents the ultrasonic cleaner which generates and transfers ultrasound waves, usually ranging from 20–40 kHz to a fluid. The agitation of the fluid leads to the formation of quickly collapsing gas bubbles within the fluid that ablate adherent contamination . The exiOne of the main physical processes involved in ultrasonic cleaning is the cavitation effect, which includes initiation, growth, oscillation, and collapse of gas bubbles, resulting in significant mechanical forces responsible for permanent chemical and physical changes on the surfaces. The principle of cavitation can be categorized into stable and inertial cavitation. Stable cavitation means the use of low-intensity ultrasound energy to induce stable, resonant oscillations of the already existing microbubbles, so that shear forces act within the fluid flow. By increasing the ultrasound intensity, the microbubbles start to grow and finally collapse, giving a lot of heat to the inrushing fluid—the process referred to as inertial cavitation.The core technology of ultrasonic toothbrushes did not fundamentally alter since its first publication in 1992 by the inventor Robert T. Bock . The maiBock described three possible approaches for the removal of dental plaque from the teeth surface. The first approach involves placing an ultrasonic transducer directly in the mouth and allowing the waves to propagate through the fluid. It is comparable to the principle of the ultrasonic cleaner, where the transducer is supposed to be covered with the fluid completely. The movement of the transducer is not controllable and can potentially cause oral damage. The second approach, which is used widely in the current ultrasonic toothbrush technology, involves the use of ultrasonic energy to excite vibrations in the head of the toothbrush. The last approach describes a high energy device that is only used by professional dentists where the vibrations will be transmitted to a metallic tip .The first ultrasonic toothbrushes were constructed by placing an ultrasonic transducer into the head of a commercial toothbrush so that the mechanical deformation energy of the piezo-crystal could be transmitted to the bristles. The resulting mild cavitation in the dentifrice was supposed to agitate dental plaque on the surface of teeth and gingiva.The propagation speed of ultrasound is dependent on the medium, i.e., in a gaseous medium, the ability to propagate is low. Liquids allow higher propagation speeds and solids display the highest ones. Dental fluid during tooth brushing is usually a mixture of liquids  with entrapped air bubbles. The ultrasound wave is propagating through several liquid-air interfaces, consequently leading to a significant reduction of the intensity compared to the conditions in an ultrasonic cleaner.Although earlier attempts primarily were aimed at distributing the ultrasonic waves energy through the head of the toothbrush, the bristles, or the bubbly fluid between the bristles, this approach sometimes resulted in a reduction of energy propagation rather than facilitating bubble formation. Brewer  publisheComprehension of the mechanisms underlying the dental biofilm removal by ultrasonic waves presupposes a better understanding of the biological and physical interactions involved . The maiS. mutans) and gingival inflammation [Manual toothbrushes can be effective in teeth cleaning. This oldest toothbrushing method depends on the type of toothbrush, personal motivation, brushing motions, and manual agility. Saruttichart et al. compared performances of a manual toothbrush and an ultrasonic toothbrush (without bristle motion) in patients with fixed orthodontic appliances in terms of reducing plaque and microbial load (in particular ammation . Over 30n = 21) were divided into three groups according to the toothbrushing. The ultrasonic and sonic brush removed noticeably more S. mutans than the manual one. A similar conclusion was made by Zimmer et al. [n = 64).On the other hand, many other available studies report on significantly better removal of plaque by oscillating and/or rotating ultrasound toothbrushes compared to manual ones. In the short-term study by Costa , the actr et al.  based onIt can be concluded that correctly performed manual toothbrushing is effective but can be outperformed by ultrasonic cleaning, provided the acoustic action is combined with mechanical movements.Powered toothbrushes are beneficial for patients lacking manual dexterity or for simplifying self-performed oral hygiene . RegardiIndependent on the action mode, cavitational effects seem to always be present upon brushing to a greater or lesser extent. The cavitational removal of bacteria from a dental surface occurs in a three-phase system of air bubbles, fluid, and solid surface. The desired ultrasonic cavitation occurs at higher intensity levels and lower frequencies , and it The biofilm strength (both cohesive and adhesive) depends on the physical properties of the tooth surface, where irregularities provide more space for bacteria to colonize and to be more protected from hydrodynamic forces. Hydrodynamic forces acting in the oral cavity  are caused by (a) fluid flow and (b) cavitation effects of entrapped air bubbles in the dental fluid. The turbulent fluid flow of oral fluid usually results from the bristle motion at high frequencies. The application of acoustic energy alone (without bristles) may generate shear forces due to the formation of water streams and shock waves. However, the degree of contribution of ultrasound waves to oral biofilm reduction needs to be studied carefully . The quaBussher et al.  reportedThe systematic review of Schmidt  showed tTakenouchi et al. showed that ultrasonic toothbrushes were more effective in decreasing dental microbial load and increasing the flow rate of the dental fluid over a study time range of four weeks . The ult®  with Oral-B sonic toothbrushes and showed no significant difference in the reduction of gingival symptoms. Both test groups showed a significant reduction but no complete elimination after 30 days. The long-term study by Lv et al. [The short-term study of Forgas–Brockmann et al.  evaluatev et al.  comparedp = 0.098) result in comparison to oscillatory-rotary toothbrushes. However, all compared modes of actions: manual, oscillatory-rotary, and ultrasound showed an enhancement in dental biofilm decomposition that may correspond to the instructions that the participants received, and accordingly, their oral hygiene may have been conducted better. Costa [S. mutans. However, the ultrasound treatment showed a better result in the removal of plaque.In the single-brushing study of Anas et al. , studentr. Costa  who compIn another study, Biesbrock et al.  evaluateIn favor of the ultrasound treatment and consistent with the statements of Anas  are the S. mutans from different surfaces with a self-made toothbrush that could apply ultrasonic and sonic frequencies. They showed that the simultaneous application of multiple frequencies displayed the best efficiency [Several further studies  is explicitly based on hydrodynamic forces since it applies streams of water sprayed in steady pulses. The water jet, acting like traditional teeth floss, removes plaque and trapped food resting between the teeth . The maiWater flossers are helpful for people with dexterity issues, such as arthritis, who find string flossing difficult. Among the disadvantages could be the high price and large space required for storage. Jolkovsky and Lyle in their recent review extensively addressed the water flosser safety issues and disproved suggestions of possible detrimental effects of this technique .Our aims were (a) to briefly summarize the existing knowledge on dental biofilm formation and its removal, and to (b) overview the existing experimental and clinical studies on the efficacy of ultrasonic toothbrushes with the estimation of their potential. Included studies were considered based on the technical and microbiological aspects of ultrasound applications in the oral cavity, as well as in terms of quantitative biofilm removal, hydrodynamic phenomena, and the improvement of oral health-related to the reduction of plaque and gingival inflammation.It is challenging to assess the efficiency of different toothbrushes, as there are so many factors contributing to the removal of plaque and the maintenance of oral hygiene. Nevertheless, published data indicate that ultrasonic, as well as electric toothbrushes, maintain better oral hygiene than manual counterparts. By direct comparison of different toothbrushing systems, most clinical trials show that the sonic/ultrasonic toothbrushes perform better than purely non-acoustic powered brushes. Sonic/ultrasonic toothbrushes may have the potential to reduce more dental biofilm by stimulating more hydrodynamic effects and also by forcing more efficient brushing motions.The core technology of ultrasonic toothbrushes remains the ultrasound-induced vibration of the bristles. The analysis of the reports and reviews published in recent years allows us to conclude that the mechanical energy transferred from the piezoelectric element leads to the vibration of the bristles. This primarily but not solely causes the cleaning action in the oral cavity. In addition to evoking high-frequency bristle motions, ultrasonic waves induce high velocity flows of oral fluids and additional acoustic microstreaming which indicates a better removal of dental biofilm than the sole application of mechanical scratching or sonic frequencies.The differences in the reduction of dental plaque by ultrasonic vs. sonic toothbrushes were not statistically significant. Both types of toothbrushes showed successful removal of plaque and reduction in gingival infection but no elimination of already existing periodontal diseases, as well as no difference in the infiltration of supra- and sub-gingival regions. The combination of both types, sonic and ultrasonic, showed the most promising result in maintaining good oral health.Although the ultrasonic cleaners also use the acoustic energy in a liquid medium, they are not directly comparable to ultrasonic toothbrushes since acoustic waves in the mouth are propagating through a multiphase system. Further investigations are needed to clarify the correlation between the manner of application of acoustic waves on the teeth surface  and the resulting hydrodynamic forces.® Sonic-Fusion-Technology is based on the synergy between sonic toothbrushes and the water flosser. The toothbrush head contains a built-in water flosser tip. To determine the plaque reducing effectiveness of the Sonic-Fusion device, Qaqish et al. carried out an experimental study and found that the Sonic–Fusion® group was more than twice as effective as the standard brushing and flossing group, for all measurements [An interesting and promising trend in oral hygiene technologies could be hybrid solutions, combining different physical mechanisms for more efficient plaque removal. Waterpikurements .Future approaches may also include analysis of the ultrasound signals for estimation of cleaning efficacy. Such a technology has been already described by Zhang et al.  and deteAnother interesting, current trend is piezoelectric ultrasound tooth-whitening devices that utilize the same hydrodynamic effects but additionally change the chemical properties of the biofilm to whiten the teeth. In comparison to the conventional whitening method which uses LED light, an ultrasound whitening apparatus works in combination with hydrogen peroxide and carbamide peroxide. The ultrasound-driven decomposition of these chemicals as they get exposed to a resonant frequency (1.6–1.8 MHz) in the oral cavity leads to an in-situ release of reactive oxygen species that enter the enamel and dentin and bleach  the teeth surface. The accompanying pressure and temperature gradients lead to the damage of the bacterial biomass. The ultrasonic whitening procedure distinguishes itself by a significantly shorter operation time and fewer toxic effects . FurtherAlthough this paper represents a thematic rather than a systematic literature review, the authors express their commitment to Cochrane’s fundamental principles and try to keep this study close to the PRISMA protocol guidelines developed for better transparency of systematic reviews. A comprehensive literature search was carried out in Web of Science, PubMed, and Google Scholar databases up to 01-02-2020 (the date when the searches were last performed). The performed queries can be divided into three separate search groups, addressing the three main thematic domains of this review: (1) “oral microbiota,” “dental plaque,” “dental biofilm”; (2) “toothbrushing,” “powered toothbrushes” “dental plaque removal” and more specifically (3) “sonic toothbrushing” and “ultrasonic toothbrushing.” Only articles published in English and related to the study topic were included in this review.