Quaternary ammonium salt polymers, a kind of polyelectrolyte with a quaternary ammonium group, are widely used in traditional and emerging industries due to their good water-solubility, adjustable cationicity and molecular weight, high efficiency and nontoxicity. In this paper, firstly, the properties and several synthesis methods of typical quaternary ammonium salt monomers were introduced. Secondly, the research progress on the synthesis of polymers was summarized from the perspective of obtaining products with high molecular weight, narrow molecular weight distribution and high monomer conversion, and special functional polymers. Thirdly, the relationships between the structures and properties of the polymer were analyzed from the perspectives of molecular weight, charge density, structural stability, and microstructural regulation of the polymer chain unit. Fourthly, typical examples of quaternary ammonium salt polymers in the application fields of water treatment, daily chemicals, petroleum exploitation, papermaking, and textile printing and dyeing were listed. Finally, constructive suggestions were put forward on developing quaternary ammonium salt polymers with high molecular weights, strengthening the research on the relationships between the structures and their properties and pinpointing relevant application fields. Water-soluble polymers are a kind of strong hydrophilic macromolecule that can dissolve or swell in water to form aqueous solutions or dispensing systems. Because of the changeable features of their molecular weight, hydrophilic strength and quantity of feature function groups, water-soluble polymers are widely used in papermaking, water treatment, oil drilling, daily chemicals, and other traditional areas; they also play a key role in strategic emerging industries such as medicine, photovoltaics, artificial intelligence and new energy materials ,2,3,4,5.According to the ionic properties of hydrophilic groups, water-soluble polymers can be divided into cationic, anionic, amphoteric and non-ionic types. Cationic polymers herein can usually be formed by homopolymerization, copolymerization with other monomers or modification of other typical function groups based on their monomers ,7. BecauAmong all quaternary ammonium salt monomers, diallyl quaternary ammonium salt, acryloxyalkyl quaternary ammonium salt and acrylamide alkyl quaternary ammonium salt have been the most widely studied. Diallyl quaternary ammonium salt is represented by diallyl dimethyl ammonium chloride (DMDAAC); acryloxyalkyl quaternary ammonium salt is represented by acryloyl oxygen ethyl trimethyl ammonium chloride (DAC) and methyl acryloyl oxygen ethyl trimethyl ammonium chloride (DMC); and acrylamide alkyl quaternary ammonium salt is represented by acrylamide propyl trimethyl ammonium chloride (APTAC) and methyl acrylamide propyl trimethyl ammonium chloride (MAPTAC) in this paper. The classification of cationic monomers and structures of representative quaternary ammonium salt monomers can be seen in In this paper, firstly, the synthesis methods of the typical quaternary ammonium salt monomers and their polymers are introduced. Then, the relationships between the structures and properties of the polymers are analyzed. Finally, typical examples of the investigation on quaternary ammonium salt polymers in the application fields are listed.DMDAAC is an excellent water-soluble quaternary ammonium salt that contains two unsaturated double bonds; it is a white acicular crystal and has a melting point of 146~147 °C. It is soluble in acetone, methanol, methyl-2-pyrrolidone, tetramethyl urea and dimethyl formamide. At room temperature, its solution is very stable. Furthermore, it is non-hydrolytic, non-flammable, less irritating to the skin and has low toxicity. Since its polymerization reaction activity is low and a small amount of cross-linking reaction always exists, it is difficult to obtain a high molecular weight product . This caDimethylamine has been commonly used as a raw material to synthesize DMDAAC, which goes through two reaction steps of tertiary amination and quaternarization of dimethylamine with allyl chloride, as shown in The two-step method for intermediate tertiary amine purification after separation and distillation results in a high-purity monomer product. This leads to good polymerization performance. Therefore, the two-step method has become the main method of monomer preparation in the laboratory. In 1951, Butler G B  first reThe synthetic process of the monomer was typically conducted as follows. In 1967, Harada S  added anThe one-step method is simple, mature, and provides high yield characteristics. It has been widely used in industrial production. However, as an obvious disadvantage, the product obtained by this method contains a large number of by-products. Furthermore, the subsequent purification process is complex, resulting in difficulty obtaining a high purity monomer product, which seriously affects its further polymerization performance ,16,17.For example, Hunter  preparedIn 2019, Zhang Y J  purifiedDAC (or DMC) can dissolve in water, methanol, and ethanol, but not in acetone, ester, or hydrocarbons. Most of its industrial products are aqueous solutions with a weight concentration of about 80%. Because the monomer contains a highly active vinyl group far from a positive charged quaternary ammonium salt, i. e., an electron-withdrawing group, it can be used to synthesize high molecular weight polymers under certain conditions. The products obtained by its homopolymerization or copolymerization have good conductivity and a certain temperature and salt resistance, which allows them to be used as one kind of cationic polymer flocculant widely used in the fields of wastewater and sludge treatment, oil exploitation, papermaking and textile printing and dyeing ,19,20,21DAC (or DMC) is prepared by the quaternization of dimethyl amine ethyl acrylate DMAEA (or methyl dimethyl amine ethyl acrylate DMAEMA) and monochloromethane. DMAEA (or DMAEMA) as an intermediate can be obtained by the alkyl acid esterification method, the methyl acryloyl chloride esterification method, the high-temperature pyrolysis method and the transesterification method. Notably, the transesterification method is the most important method for the preparation of DMAEA (or DMAEMA) and is also the method used in current industrial production. In this method, acrylate or (methyl acrylate) and dimethyl amino ethanol react with each other to form the intermediate via a transesterification reaction under a catalyst, and therefore, the reaction core is the selection of the catalyst . The rep2CO3 as a catalyst, the ease of causing a double bond addition as a side-reaction when using an alkali metal catalyst, the sensitivity to water itself and need for the product to be purified by distillation when using a titanium alkoxide catalyst, the low conversion rate (83.5%) when using K3PO4 as a catalyst, and the long reaction time (8 h) with 95% conversion rate when using dibutyltin oxide as a catalyst.In 2004, Mainz et al.  summarizIn addition, other catalysts may be used, including alkali metal oxides and metal alkoxy compounds. When using zirconium acetylacetone as a catalyst, the purity of the tertiary amine ester product was 98.89%, and other impurities such as methyl methacrylate were 0.04%. Under the same conditions, the purity was 93.30% when using dibutyl stannic oxide as a catalyst. The purity was only 86.09% when using tetraisopropyl titanate as a catalyst.3Cl under atmospheric or pressurized conditions to prepare an 80% DAC (or DMC) aqueous solution. This method has effectively solved the mass and heat transfer in the reaction process, and the post-treatment of the crude product is relatively simple. The product quality was significantly better than the products obtained by direct reaction of DMAEA (or DMAEMA) with CH3Cl or reaction in organic solvents [The quaternization reaction usually uses 75% solution of DMAEA (or DMAEMA) and CHsolvents ,25,26. BThe structure of APTAC (or MAPTAC) is similar to that of DAC (or DMC), but there is a critical difference in that the amide bond in the former has replaced the acryl oxygen bond in the latter, which has overcome an easily hydrolysable disadvantage of DAC (or DMC) monomers by ester groups and led to an even broader application scope. Thus, APTAC (or MAPTAC) has become a cationic monomer with a broad prospect in production for cationic polymer products both of high molecular weight and with valuable performance in heat- and pressure resistance and acid- and alkali resistance.APTAC (or MAPTAC) is usually obtained through the quaternary ammoniumized reaction of dimethyl amine propyl acrylamide, DMPA , and halogenated hydrocarbons. This reaction condition is mild and can be industrially operated with a high monomer yield. For example, Humbert  in 1985 N,N-dimethyl propylene diamine and acrylic acid or its derivants  under catalytic action. DMPMA is prepared by the amidation of N,N-dimethyl propylene diamine and methyl methacrylate under the catalytic action of metal-organic compounds. However, the synthesis of intermediate DMPA (or DMPMA) is difficult due to its harsh reaction conditions and low yield, resulting in high costs for the synthesis process of APTAC (or MAPTAC) [Generally, DMPA is prepared by the amidation of  MAPTAC) ,29,30. TN,N-dimethyl propylene diamine and acrylic acid as raw materials, toluene as a solvent, and 4-aminophenol as an inhibitor to prepare DMPA at 180–185 °C for 2 h. DMPA was finally obtained after heating and reflux-dehydrating. The results showed that the industrial yield of this reaction was low, only 54.8%, and there were many side reactions. In 1994, Takao Yuuichi et al. [N,N-dimethyl propylene diamine as raw materials, methanol as a solvent, methyloxy hydroquinone as a polymerization inhibitor, calcium hydroxide as an amination catalyst and concentrated sulfuric acid as a pyrolysis catalyst to obtain DMPA. This method achieved a yield of 77%. It is worthwhile to pay attention to the investigation of synthesis techniques of DMPA, especially those focused on the improvement of yield, the reduction of byproducts and the environmental friendliness of processing.In 1984, Makita Muneharu  used N,Ni et al.  used metN,N-dimethyl propylene diamine quickly into a mixed boiling solution of methyl methacrylate and catalyst, and then added excessive N,N-dimethyl propylene diamine at the reflux head temperature of 70~90 °C for 90 min. They then gradually heated the solution to 150 °C. DMPMA was obtained with a 92% yield by removing unreacted methyl methacrylate in a vacuum at 130 °C.In contrast to preparing DMPA, the synthesis of DMPMA is relatively not so difficult. In 1979, Franz  added N,N,N-dimethyl propylene diamine to synthesize DMPMA in inert organic solvents such as toluene. Linear fat hydrocarbons were used to remove the methanol by using the zeotropic nature of the organic solvent and methanol. With this method, the yield of DMPMA could reach more than 95%. However, due to the use of a large amount of poisonous organic solvent, there were obvious shortcomings in environmental protection and safety.In 2014, Liu Z Q  used metQuaternary ammonium salt polymers, according to their polymerization types, mainly include the homopolymer of the cationic monomer, the binary copolymer of the cationic monomer and other monomers like acrylamide (AM), the multiple copolymer of more than two monomers, and modified polymers. According to the polymer structure, they can be divided into linear polymers, micro-crosslinked polymers and crosslinked polymers. For linear polymers, which are one of the most widely synthesized and applied kinds, the molecular weight of the polymer products is used as an indicator in evaluation. Sometimes, the molecular weight distribution, monomer conversion and sequence structures are also used for specific purposes. Crosslinked polymers, however, are usually polymerized under the guidance of special functions for some application. This section summarizes the research progress on the synthesis of homopolymers and binary copolymers with high and serially intrinsic viscosity (characterization of molecular weight). Meanwhile, a brief overview of the research on polymers with narrow distributions of molecular weight, high monomer conversion rates in the product, and special function groups in the polymer chain is outlined. Here, the schematic diagram of cationic monomers, their polymerization processes and polymer products is shown in A quaternary ammonium salt polymer usually refers to a type of typical linear polymer. A linear polymer has different chain lengths characterized by different molecular weights or intrinsic viscosities which correspond to different properties and application performances. The improvement of or increase in the intrinsic viscosity means the possibility of synthesizing polymers with broader scopes and more grades in their serial intrinsic viscosity, which means that better polymer products with wider application performances can be achieved. Therefore, from the perspective of synthesis and processing research, how to obtain polymers with high intrinsic viscosity has been a very important purpose for the long term, and many researchers have been engaged continuously in this with long-term and in-depth work.For the ring closure polymerization of DMDAAC, its activity is impaired due to both the strongly electron-withdrawing effect of quaternary ammonium salt on the electronic cloud in double bonds with a short distance to the salt and the steric hindrance needed to be overcome in the ring closure process. Meanwhile, at an early time, limited by the level of synthesis technique, there were many by-products as impurities in the monomer product, leading to difficulty for researchers to obtain homopolymerization and copolymerization products with higher molecular weight ,35.Since 1956, studies on the synthesis of homopolymer PDMDAAC have been reported. The initial target polymer was a three-dimensional network product, but the obtained polymer was, in fact, a linear polymer of extremely low molecular weight with ring structure units as its chain. The typical representative of a homopolymer successfully synthesized in the early stage was made by Boothe J E.  In 1970,The typical and widely used copolymer of DMDAAC is the copolymer product of DMDAAC with AM, i.e., P(DMDAAC-AM), referred to as PDA. In 1960, its synthetic method was first reported . Then, fCompared with the molecular structure of monomer DMDAAC, the positive charge center in the structure of monomer DAC (or DMC) is far away from the double bond, which makes it easy to form polymers with high molecular weight via polymerization. Furthermore, by comparing the two monomers, it can be seen that DMC has one more methyl on the double bond than DAC, making it more stable. This also causes the reporting time of DMC to be earlier than DAC.2S2O8 as an initiator by Ringsdorf [In 1976, Nishikaji T  first syingsdorf  in 1977,ingsdorf . In 2015ingsdorf  in our gAt present, the typical copolymer of DMC is still the copolymer P(DMC-AM). There are numerous studies about the synthesis of P(DMC-AM), but in the first 20 years after its successful synthesis, the research focused on the low cationicity and the product intrinsic viscosity was generally limited. This led to the understanding that P(DMC-AM) cannot meet with requirements of high-sheared flocculation for some dewatering occasions. Therefore, gradually, another kind of cationic polymer P(DAC-AM) replaced its market dominance. Over more than 20 years, however, many researchers investigated how to obtain a high intrinsic viscosity polymer by adjusting the process parameters in the polymerization reaction system ,50,51. IWith the development of science and technology and the increased importance of environmental protection, the molecular weight of cationic polymers used as a flocculating and dehydrating agent has been gradually required to be higher. Interestingly, when comparing DAC with DMC, the double bond in DAC had one less methyl group than DMC, making the double bonds in the polymerization a much lower steric hindrance. Therefore, higher molecular weight polymers based on DAC could be synthesized. Its requirements in markets at the end of the 20th century exceeded the polymer of DMC and dominated a leading position in the world market ,52,53. OFor the copolymer of DAC and acrylamide AM, Cabestany et al.  first syIn the molecular structure of APTAC (or MAPTAC), the positive charge center is far from the double bond, so it also has high polymerization activity. At the same time, the amide group structure can overcome the shortcoming of the ester group in DAC (or DMC) easily to hydrolyze, which makes their polymers have a broader application field and prospect.5wM was synthesized for the first time [Monomer MAPTAC was first successfully prepared by Franz et al. in 1979 , but it rst time . Then, Prst time . The obtHowever, the copolymer of MAPTAC was studied earlier. In 1982, Phillips et al.  first usIn 1998, Mallon first synthesized APTAC, and then researchers conducted in-depth studies on its homopolymer and copolymer. In 2014, Li et al.  synthesiIn summary, for a cationic and linear polymer, the cationic unit structure is the primary element that dominates the essential properties of the polymer. Once the structures of monomers are determined, their proportions in the polymer (the cationicity) become the main factor that dominates the basic properties of the polymer. When the above two core elements were determined, the acquisition of polymers with a high molecular weight through the control and optimization of polymerization conditions became a common goal that researchers pursued for a long time. Synthetic processing of an obtained high molecular weight polymer could provide raw materials for exploring new properties and functions of the polymer and lay a foundation for obtaining products as raw materials with a wider serialization of molecular weight usable for the in-depth development of application fields. Therefore, over the years, researchers have pursued the improvement of the purity of the monomer to decrease side reactions and facilitate the optimization of the polymerization process, i.e., the appropriate conditions of monomer concentrations and initiator agent systems ,65,66. IIn addition to the ionicity and molecular weight, the importance of the molecular weight distribution and monomer conversion in the polymers cannot be ignored. Molecular weight distribution is a key factor influencing the performance of polymers. Polymers with different molecular weights have different properties, resulting in various performances in different applications. Generally, the polymer with a narrow distribution in a proper molecular weight can better improve utilization and performance to reduce the dose and achieve an efficient economy. Improving the monomer conversion can increase the utilization of a polymer and reduce the possible pollution of a toxic monomer residue while reducing the post-treatment process in applications. Therefore, in a synthetic process, it is of great significance to control or adjust the molecular weight distribution and to improve the monomer conversion of polymers.In the practical production and actual synthetic process for large-scale productions, the molecular weight distribution is generally not considered a main index in the evaluation but merely a parameter in the characterization of the target polymer, occasionally. However, for some polymers of low molecular weights to have fine functions in application, the determination of a molecular weight distribution coefficient is usually necessary. On the one hand, the reason for this is that polymers with a narrow molecular weight distribution obviously demonstrate some special functions when within a certain low molecular weight. On the other hand, it is difficult for an available instrument, like GPC, to test the molecular weight and distribution coefficient for polymers of a huge molecular weight.wM/nM and 0.4 million. In 2013, Xiong Q Y [Generally, in traditional polymerization methods, compared with aqueous polymerization, the molecular weight distribution obtained by emulsion polymerization is narrower. For example, in 2020, Yang et al.  synthesiiong Q Y  synthesinM and wM/M of 2.61 × 104 and 1.10, respectively. This was accomplished by adding the chain transfer agent and initiator dissolved in methanol into the MAPTAC solution for polymerization. Huang et al. [In addition, RAFT (reversible addition-fragmentation chain transfer) polymerization, which is characterized by a series of addition-fracture equilibria, was proposed to obtain polymers with a narrow distribution. The key factor in this process is the added chain transfer agents ,69,70. Dg et al.  synthesig et al. ,74,75 thIn practical synthetic processes, few studies used the monomer conversion as the main evaluation index; most studies used monomer conversion only as an auxiliary index. Generally, adjusting the reaction condition parameters during the synthesis process of polymers can not only reduce the molecular weight distribution coefficient, but also improve the monomer conversion. For example, in 2016, when synthesizing PDMDAAC, Zhang et al.  found thWith the rapid development of science and technology, the application field of cationic polymers such as the quaternary ammonium salts has been continuously expanded. When designing and synthesizing the target polymers, apart from the traditional indexes such as the molecular weight, the special functions of polymers have been increasingly usedas the guidance for polymerization.To obtain polymers with multiple properties and performances, many researchers synthesized multipolymers by using a variety of monomers. For example, in 2018, Luo et al.  synthesiIn recent years, studies on the molecular brushes ,79 and mThe investigation of modification of, or grafting on, a polymer chain to explore its new uses or efficiency has been a research hotspot for many years ,83,84,85The properties of a compound are usually determined by its components and structure. In terms of linear quaternary ammonium salt polymers, if the structure of the positive charge unit and its proportion are certain, its characteristic properties and main functions are basically determined, such as its electric neutralization ability and structural stability. Furthermore, when controlling their molecular weights to be different, many properties and performances of the polymers also vary, such as their dispersion and flocculation functions. In addition to the charge density and molecular chain length, in some applications, changes in the molecular weight distribution and the microstructure of the cationic unit of the polymers may also result in significant functional differences.Linear cationic polymers have different chain structures and lengths which correspond to different structural properties and application functions. When the structure and proportion of the chain units are constant, i.e., the polymer type and charge density are the same, the properties and functions depend on the molecular weight.Homopolymers of quaternary ammonium salts generally have relatively lower molecular weight and are often used as dispersants, reinforcements, fungi- or bactericides in papermaking, textile printing and dyeing, and daily chemicals in other industrial fields, including raw water treatment ,88,89. I6 and 7.0 × 106 and used them to conduct flocculation experiments on kaolin wastewater. The results showed that the residual turbidity and the particle size d50 of the lower molecular weight polymer were 10.1 NTU and 468 μm, respectively, while the higher molecular weight polymer was 5.9 NTU and 566 μm, respectively.After a copolymerization of a cationic monomer and AM, the significant characteristic is that the molecular weight becomes greatly increased. This can often be used as a flocculant dehydrating agent for the treatment of wastewater and sludge dehydration and as a drilling fluid and fracturing fluid for petroleum exploitation ,19. For Therefore, it can be seen that the molecular weight required in different application fields is not the same. The synthesis of polymers with a serial molecular weight could not only give full play to its efficiency but also reduce the use of dosage to save raw materials, i.e., reduce waste discharge and protect the environment.Cationicity refers to the ratio of the number of cationic units to the total number of units in a polymer. It is also the measurement of molecular charge density. When the cationic unit is determined, the charge density of the homopolymer is done at the same time. Thus, when concerning the charge density, the material should be a copolymer. When the molecular weights of copolymers are closed, charge density must play a larger influence on its performance.On the one hand, the cationicity directly affects the morphology of a polymer in aqueous solution, because there is a certain repulsion between neighboring cationic charges on the molecular chain, which results in the extension of the molecular chain in aqueous solution . Chen etYang et al.  synthesiTherefore, it can be seen that different application fields require different copolymer cationicities. The synthesis of a serial cationicity polymer could meet different application requirements and give full play to the product efficiency.Quaternary ammonium salt polymers, as the most typical class of cationic polymers, are usually applied in the form of a solution, and their performance is always closely related to their properties in the solution state. The solution properties mainly manifest in the viscosity behavior, molecular morphology, and size of polymers, which depend on not only the salt solutions, but also the polymer’s molecular components and structures.2, AlCl3, Na2SO4 and Na3PO4). The results showed that the apparent viscosity in the inorganic salt solutions first decreased sharply to its lowest value with the increase in the salt concentration, remained stable when the added salt was monovalent, and increased with increased salt concentration when the added salts were multivalent. The aggregation model of the cationic polymer in salt solutions after the inflection point is shown in Fu et al. ,91 invesK and α values of the two coefficients in Mark-Houwink  are also different. There have been many studies conducted regarding the K and α values of PDMDAAC [K and α values of partially hydrolyzed polyacrylamide have also been studied [A given polymer’s molecular morphology is obviously affected by the ionic properties and temperature of its solvents. Under different solvents and temperatures, the extension state of the molecule is different, and the  PDMDAAC ,96, but  PDMDAAC . Otherwi studied . They arTypical quaternary ammonium salt polymers are usually used in aqueous solutions for water treatment, papermaking, textile dyeing and finishing, and other purposes ,88,89,95Studies on the stability of quaternary ammonium salt polymers found that the stability of the DMDAAC polymer and APTAC (or MAPTAC) polymer was significantly better than that of the DAC (or DMC) polymer. For example, Jia et al.  studied At present, no literature has systematically analyzed and compared the hydrolysis stability of these typical quaternary ammonium salt polymers, including the polymers with serial molecular weight or cationicities. The existing reports were only studies on a single polymer. Lin  studied In summary, it can be seen that the hydrolysis degree of quaternary ammonium salt polymers increases with increased solution pH and temperature as well as time. In addition, the DMDAAC polymer and APTAC (or MAPTAC) polymer had significantly better hydrolysis stability than the DAC (or DMC) polymer, and the homopolymer was usually better than the copolymer, which might be caused by the stability of characteristic groups on the units.The microstructure differences of a polymer, including differences in the unit structures, chain arrangement and molecular modification, influence the performance of the polymer.In 2013, Yu et al.  designedCMC values (surface tension at CMC) were 46.84, 41.46 and 31.92 mN/m, respectively; and HLB values  were 11.65, 10.70 and 9.75, respectively. These results indicated their ability to reduce surface tension and surfactivity, their efficiency to reduce surface tension, and their capacity for their solubility in oil to be increased.In 2019, Zhang et al.  modifiedFrom the perspective of microstructures, DMC and DAC monomers differ only by one methyl in the double bond on the cation unit, so there is little difference in almost all application fields of their corresponding polymers. However, in the experimental study, it was found that the treatment effects of P(DAC-AM) and P(DMC-AM) on wastewater (sludge) with different properties were significantly different. Chen et al. ,94 conduHowever, for the activated sludge from the cassava alcohol production process, it was found that although large flocs could be formed by using both polymers under the same conditions, the sludge cake after P(DAC-AM) treatment and then filtration was jelly-like and difficult to deeply dehydrate. However, after P(DMC-AM) treatment, flocs could be rapidly and deeply dehydrated to cakes, achieving a good dehydration effect. The simple explanation was that monomer DMC had one methyl more than DAC in its microstructure, which made the DMC polymer a little more lipophilic and provided a better dehydration effect on organic wastewater. The possible flocculation mechanism is displayed in Guo et al.  synthesiThe research on the modification of natural polymers has a long history. Modification can change both the featured and microstructures of a polymer. The modified polymer has the various advantages of biodegradability and a wide range of raw material sources, which can expand the application fields of the original polymer or improve its application efficiency. The modification of a natural polymer matrix by cationic monomers has been a hot research topic for many years.g and heated the solution formed at 80 °C for 30 min under nitrogen atmosphere. They then added MAPTAC and AM as modifying raw materials, added ammonium persulfate as an initiator in the solution after mixing evenly, and continued the reaction for 15 min. After finishing the reaction, the product was dehydrated with ethanol and dried at 50 °C for 24 h in a convection oven. The starch-grafted polymer was synthesized and found to be very effective in settling cement particles, which were successfully used to produce green fiber-cement composites. In 2020, Wang et al. [In 2013, Pourjavadi et al.  dissolveg et al.  synthesig et al. ,83,84,85In summary, it can be seen that the application efficiency of polymers can be improved and the application field can be expanded by modifying the microstructure, especially the cationic structure of polymers. Therefore, the precise regulation of polymeric microstructures has always been one direction of related research.As a kind of polyelectrolyte, the quaternary ammonium salt polymers can not only be used in traditional fields such as water treatment, daily chemicals, petroleum exploitation, papermaking, textile printing and dyeing, but also in strategic emerging industries such as pharmaceuticals, photovoltaics, artificial intelligence and new energy materials. Their unit structures, the proportion of cationic units and the molecular weights of polymers are their internal key factors that can be exploited to attain various advantages.Because of their adjustable charge density and molecular weight, quaternary ammonium salt polymers are mostly used as coagulants and flocculants in various raw water, wastewater and sludge treatments. When used, they can fulfill multiple functions, such as performing electric neutralization, acting as a compression double electric layer, and facilitating bridging and net capture. At this point, the characteristics of a quaternary ammonium salt monomer and its formed unit structure play a decisive role in its function utilization.Tiny-polluted raw water refers to surface water that is polluted by organic matter yet nevertheless exceeds the sanitary standard of some water quality indexes; it contains many kinds of organic matter of complex nature, but their concentrations are not high. With the development of society and the economy and the increase in population density, surface water, especially that used as a drinking water source, is becoming increasingly polluted, even as the people’s demand for drinking water quality is increasing. Therefore, many researchers began to explore new treatment techniques of tiny-polluted raw water in the late 20th century. PDMDAAC, with its high charge density, good stability, and low toxicity, was the first organic polymer approved by the FDA in the USA for use in drinking water production .As early as 1986, Tanaka  used a PHowever, many studies found that, when using PDMDAAC alone for coagulation treatment of raw water, it was difficult for its treatment effect to meet the required turbidity removal requirements, and its use cost was high. Therefore, in the conventional water supply process, it was not used alone but as a coagulant aid with inorganic flocculants. A typical representative work was what Li Xiao Xiao et al. ,109,110 In 2019, Shen et al.  studied Sludge treatment is one of the most important steps in a whole wastewater treatment process. Sludge first needs thorough dehydration treatment before entering the disposal step. At this step, the solid content of sludge is the most critical index. Thus far, the most feasible way to dehydrate sludge has been to use a cationic flocculant. This method facilitated a reduction in the sludge produced and the ease of mechanical dehydration, saving water, improving the effect of sewage treatment and reusing wastewater. It has been reported that P(DAC-AM) and P(DMC-AM) are currently the two most popularly used cationic flocculants in sludge treatment in the world.As early as 1980, Anon  proposedIn the practical application of sludge dewatering, it has been found that on the one hand, the larger the intrinsic viscosity was, the more obvious the flocculation bridging and dehydration effect were; on the other hand, a proper matching of the cationicity of the polymer to the ionicity of the sludge to be treated was critically necessary. Only a polymer with suitable cationicity could destroy the sludge colloid stability effectively, realizing the destabilization and flocculation of colloid particles ,113. ThaTypically, stable quaternary ammonium salt polymers are the homopolymers and copolymers containing a DMDAAC unit or APTAC (or MAPTAC) unit. Because they have certain sterilization and antistatic abilities due to their quaternary ammonium salt structure and also demonstrate salt and acid resistance due to their unit structure, when used for daily chemicals, these polymers have good stability and can be stably preserved for a long time to be able to fulfill their designated functions.Due to its stability, low toxicity, and bacteriostatic and antistatic properties, the homopolymer PDMDAAC has been widely used as a regulator, germicidal agent, antistatic agent, and softening agent in skin, hair, nail and tooth care products in daily cosmetics ,115,116.In addition to some homopolymer properties, such as stability and antibacterial and antistatic properties, the copolymer PDA had a much higher and adjustable molecular weight. When used with other components such as salts, surfactants, and care components in daily chemicals , it also had thickening properties and improved stability, among other functions. In 2014, Yamazaki  formulatPolymers containing an APTAC (or MAPTAC) unit, similar to the other quaternary ammonium salt polymers, have the advantages of possessing a positive charge and demonstrating a certain compatibility with anionic surfactants, resulting in good performance. Furthermore, because of the acid and alkali resistance and heat resistance of the amide linkage, it can still be stable after a long time under a wide pH range and high temperatures. Thus, it has been increasingly used in skin and hair care products ,121.As early as 2000, Wang et al.  synthesiA typical quaternary ammonium salt polymer is a multifunctional chemical agent in the oil field. Polymers containing DMDAAC or APTAC (or MAPTAC) are widely used in drilling, cementing, fracturing, acidification, water injection, water plugging and profile control and tertiary oil recovery due to its acid, alkali, salt, temperature and pressure resistance, especially as an auxiliary agent in the drilling, water injection and tertiary oil recovery fields.The structure of DMDAAC is stable, and its polymer had good temperature resistance, salt resistance, acid and alkali resistance. Therefore, it has been widely used as a fluid loss reducer, clay stabilizer for fracturing fluid, and dehydrating agent. DAC (or DMC) polymer was widely used in secondary oil recovery and oilfield wastewater treatment due to its high molecular weight, obvious thickening effect, and flocculation dehydration ability.In fact, the cationic copolymers used as fluid loss additives for drilling fluids were amphoteric ionic polymers that could be used in various types of water-based drilling fluid systems. Bai et al.  developeIn 2015, Lu et al.  successfAPTAC (or MAPTAC) polymer has become a new type of characteristic polymer used in the oil field because of its advantages of high molecular weight and good acid, alkali, salt, and high-temperature resistance. For example, the United States Exxon Mobil Research and Engineering Company used MAPTAC as a cationic monomer to study multi-function thickeners or gelling agents for acid, alkali, and salt solutions, which were mainly used for acidification and fracturing in oil and gas field development to increase oil and gas production .In 1986, Peiffer et al.  preparedThe use of chemical auxiliaries in papermaking is always an important means to perfect the papermaking process and improve product quality. A variety of polymers, including cationic polymers, play three main roles in the papermaking process: dispersion, enhancement, and flocculation. Therefore, they are used as fiber dispersants, paper dry strengthening agents, wastewater retention and filtration agents, and flocculants.PDMDAAC was originally used for special conductive paper in the paper industry. Since the 1970s, cationic polymers have been gradually applied in various fields of the paper industry . However2SO4, and N,N-dimethyl acrylamide to the polymer solution, which was used for flocculation of the papermaking wastewater treatment. The results showed that after adding the emulsion, the removal rate of chemical oxygen demand (COD) and suspended solids (SS) were 95% and 93%, respectively, with excellent flocculation performance. The above studies on the flocculation treatment of papermaking wastewater used high molecular weight, cationic polymers.In 2011, Zhao et al.  preparedCationic polymers have strong hygroscopicity, excellent absorbability and dispersibility, and affinity to fiber. Therefore, they can be used as a color fixing agent, antistatic agent, softener, and fabric finishing agent in the textile printing and dyeing industry. Particularly in recent years, with the wide application of reactive dyes, PDMDAAC as a representative color-fixing agent of reactive dyes without aldehyde was used. The product requires specific molecular weights, but also, in some places, there is more emphasis on molecular weight distribution because the advantages from a specific molecular weight range of the product in its application are more obvious. For example, as mentioned above, Yu et al.  measuredIn 2017, Zhou et al.  used a fIn recent years, researchers in many fields have been developing new application functions of polymers with cationic quaternary ammonium salt monomers and expanding their application fields. It has been preliminarily reported to be used as a drug carrier in medicine, as a sensor in electronic devices and as an electrode material in fuel cells.Quaternary ammonium salt monomers and their polymers have been used as medical fungicides for more than 100 years . In 2014In 2018, Loehmann et al.  synthesiIn 2014, Chen et al.  added moIn recent decades, with the deepening of research on quaternary ammonium salt monomers and their polymers, the molecular weight of the polymer products has been greatly improved, and the different effects of the structure features on their properties and performances in various application fields has gradually attracted attention. However, there are still many problems to be solved in the optimization of synthetic processes and the research on the relationship between the structure and their properties or performances in industrial applications.The improvement of the molecular weight of polymers is an unchanging topic. High molecular weight means that a wider range of serialized molecular weights of polymer products can be obtained, and products with more fine properties can meet the needs of different application fields, displaying a better application performance. At present, although the molecular weight of most quaternary ammonium salt polymers has been greatly improved, there is still significant room for them to be modified. As an example, acrylamide alkyl quaternary ammonium salts (APTAC and MAPTAC) obviously have space for their weight to be increased when compared with the other two kinds of quaternary ammonium salt polymers . Therefore, researchers can further attempt to improve the molecular weight of APTAC (or MAPTAC) based polymers from the aspects of raw material purity control, selection of polymerization methods and optimization processes to expand their application fields.The continuous improvement of high and serial molecular weight quaternary ammonium salt polymers provides a good foundation for research into the relationship between its structure and properties. Therefore, the abundant structural information of the polymer molecules, including unit structure, structure composition of chain segments (cationicity), molecular weight and its distribution, can provide many corresponding properties and performance parameters, especially regarding the different physical and chemical properties brought by the polymer’s characteristic functional groups and their molecular weights. In the face of this current situation and development trend, strengthening research on the thermal properties and solution properties of different quaternary ammonium polymers will lay a solid theoretical and experimental foundation for the development of their new functions and application fields.Quaternary ammonium salt polymers can be used in traditional fields, such as water treatment, daily chemicals, petroleum exploitation, papermaking, textile printing and dyeing, and in strategic emerging industries, such as pharmaceuticals, photovoltaics, artificial intelligence and new energy materials. The unit structure, proportion of cationic units and the molecular weight of polymers are the internal key factors responsible for their advantages, which can be exploited. It will be important to study the regulations of different polymers suitable for different application fields, analyze and master their working mechanisms, and select the most suitable polymer from the properties of applied objects for practical applications.


China has great potential for engaging in global actions on antimicrobial resistance (AMR) control. This study aims to summarize the process of global AMR governance and provide relevant policy recommendations on how China could take more initiative in the global AMR governance. We searched for academic articles and official document published or issued before December 2020 in e-journal databases, official websites of major organizations, and the relevant national ministries. This review revealed that global action on AMR control has experienced three stages: (1) The beginning stage (1980s and 1990s) when actions were mainly sponsored by high-income countries and AMR surveillance was focused on hospitals; (2) The rapid development stage (2000–2010) when global AMR governance began to concentrate on joint actions in multi-sectors, and developing countries were gradually involved in global actions; (3) The comprehensive stage (2011 to present) when global actions on AMR have covered various fields in different countries. China’s AMR governance has fallen behind at the beginning but recently began to catch up with the global trend. The central government should take a far-fetched view, act decisively and positively towards the global efforts of addressing AMR to play a more active and greater role on the international stage. The decrease of mortality caused by infectious diseases has been considered to be partly due to the development of antibiotics. Thus, they are commonly used—and even overused—to prevent and treat bacterial infections in humans and animals. In recent years, the inappropriate use of antibiotics in hospitals has been reported in many low- and middle-income countries (LMICs) ,2,3. MorThe phenomenon of AMR comprises the resistance of bacteria to medicines used to prevent and treat bacterial infections. These drug-resistant strains may infect humans and animals, causing persistent infections that are more difficult to treat than infections by non-resistant bacteria, resulting in prolonged disease duration, increased mortality, and added treatment costs . For exaChina is one of the largest producers and consumers of antibiotics in the world. In 2013, a total of 162,000 tons of antibiotics were used in healthcare and agriculture in the country . As a coWe conducted this review at the macro-policy level with the aim of summarizing the major steps on combating AMR taken by the international community and China, comparing the progress of AMR governance between the two, providing relevant policy recommendations on how China could take more initiative in the global activities on AMR governance. We searched for academic articles, reports, official documents regarding AMR governance published or issued before December 2020 at the major periodical databases of PubMed, ISI Web of Science, Medline, and official websites of global organizations as well as relevant national ministries and commissions of China. Global and national activities and strategies on AMR governance were collected.Staphylococcus infections that first occurred in hospitals were increasingly prevalent in the early 1950s [Staphylococcus aureus has become the main cause of nosocomial infections since the 1980s [Since the discovery of penicillin in 1928, new antibiotics were continuously identified and developed. During the 1950s and 1960s, a variety of antibiotics were described, such as erythromycin, vancomycin, methicillin, and gentamicin ,16,17,18ly 1950s ,22, and he 1980s ,24,25. Ahe 1980s . ScientiBy reviewing of the global strategies and actions, we divided the progress of global AMR governance into three major stages.The first stage, also called “the initiating stage”, occurred between 1980s and 1990s. Led by the UN and WHO, the activities of combating AMR began to be implemented globally in the early 1980s. In November 1981, the global assembly on AMR governance held by the WHO Antimicrobial Resistance Working Group marked the beginning of global actions against AMR . In 1989During the same period, China was initiating reform and opening up to globalization. Various fields started to rapidly develop and the country began to correspond with international standards. In the 1980s, the first law on the administration of medicines for human use was formulated and announced by the national legislature . In the WHO Global Strategy for Containment of Antimicrobial Resistance in 2001, which provided an interventional framework to reduce AMR from eight important aspects [The rapid development stage took place from 2000 to 2010. In this stage, the consumption of antibiotics increased dramatically in LMICs . Drug re aspects . The WHO aspects .At this stage, China accelerated the pace of integration into the international economic society due to joining the World Trade Organization in 2001. Domestic measures against AMR in the medical and agricultural fields began during this period. The first official document on improving the rational use of antibiotics was issued by the national Medical Products Administration in 2003, which limited the activities of selling antimicrobials without prescription in retail pharmacies . During the Global Action Plan for Antimicrobial Resistance—based on the “One Health” approach [During this stage, which covers the period of 2011 to the writing of this review, the high-level meeting of the UN General Assembly and political forum summits raised the importance of AMR from simply a threat to human health to a severe challenge of economic and social development. To attract more global attention to AMR, NGOs and similar organizations began to undertake activities, such as holding sessions, publishing reports, and supporting programs ,50. In 2approach . The plaapproach .National Action Plan for the Prevention of Bacterial Resistance 2016–2020 [China has also begun to strengthen its governance against AMR since 2011. From 2011 to 2013, three-year special activities on reducing antibiotic use in secondary and tertiary hospitals were implemented across the country ,53,54. I016–2020 . China b016–2020 ,58. In t016–2020 . Colisti016–2020 . In 2018016–2020 ,62,63. HAfter nearly four decades of governance, the global has made some achievements in combating AMR. Compared to 2010, 12 and 8 countries of the 40 countries that provided data reported lower volume of human- and animal-use antibiotic consumption in 2020, with most of them were HICs . During China has also made some progress on controlling AMR in the last decade. The rate of prescribing antibiotics decreased from 19.4% in 2010 to 7.7% in 2017 for outpatients, and from 67.3% to 36.8% for inpatients in the surveillance hospitals; likewise, the identify rates of most of the concerning resistant pathogens, such as MRSA, carbapenem-resistant klebsiella pneumoniae, and third-generation cephalosporin-resistant Escherichia coli, etc. have declined . Howevermcr-1, a new and transmissible polymyxin-resistance gene [As one of the largest antibiotic producers and consumers, in addition to domestic AMR governance, China could also make more contributions to the global AMR governance. Compared with the global actions on AMR control, China’s actions are relatively lagging behind at each stage. However, China has taken more actions and begun to catch up with the international pace of AMR governance in recent years. The government has realized the importance of AMR governance. In some important international conferences such as the Hangzhou summit, Chinese health authorities expressed their willingness to contribute to global governance initiatives against AMR. China has a great capacity to contribute to global AMR governance. The Chinese healthcare system, led by the National Health Commission with a top-down management approach, has the advantage of rallying resources on effective governance actions, and has gained important successes. China is one of the countries has the highest burden of TB in the word. In 1990s, China implemented the DOTS strategy to control TB throughout the country. Then, along with international TB control projects, the central government provided technical, financial, and equipment resources to TB control institutions across the country ,72. Withnce gene . Based oNonetheless, China still faces a number of challenges in both domestic AMR governance and the level of contribution to global AMR governance. At present, the departmental cooperation led by the Medical and Health Hospital of the National Health and Wellness Committee still solely focuses on the clinical monitoring of AMR. This business division mechanism has made China unable to fully carry out its duties necessary to address the resistance issue, such as public education and awareness, as well as drug research. The current expert committee on AMR lacks expertise in the fields of agriculture, environment and policy making. In addition, there are regional differences in AMR governance. The surveillance of antibiotic use in urban areas, as well as secondary and tertiary level healthcare institutions is efficient; however, it is less adequate in rural areas and primary healthcare institutions . MoreoveThere are several implications for China to contribute to global AMR governance. First, a management department whose rank is higher than ministries should be established by the State Council. Its main responsibilities would be to coordinate cooperation among ministries, organize a comprehensive expert committee, prepare monitoring plans and indicator systems of antibiotic use and drug-resistance in various fields, and represent China in international communications. Second, researches on AMR should be facilitated and cross-border cooperation studies should be further expanded. Civil societies and various partnerships, such as “the Belt and Road” initiative, the Shanghai Cooperation Organization, or the 16 + 1 cooperation between Central and Eastern Europe could be utilized to support the global governance program of AMR. Third, more should be done to promote the disclosure of information; information transparency in the agricultural field should be enhanced. Work can be started by gradually sharing China’s population resistance data with the international community. Forth, high-level comprehensive talents should be cultivated, such as using advanced training or secondment opportunities to nurture diplomatic talents in the health field, transforming professional knowledge into diplomatic language. Some global AMR governance experts have played roles in existing international organizations, and these roles should be fully supported. Finally, pharmaceutical innovation should be encouraged. Pharmaceutical companies should be encouraged to invest more in the research and development of new and alternative drugs. The advantages of Chinese traditional medicine should also be fully exploited.This study has several limitations in terms of data collection. First, we only searched relevant journal articles in three international periodical databases due to the time constraint. Second, this study focused on studies or policies at the macro level without including studies at the molecular level because there are multiple studies regarding AMR at the molecular level and they provided limited information for this topic. Third, few literatures or documents on environmental aspects were collected and analyzed, thus more studies focusing on AMR in this field are recommended. Finally, it would be necessary to collect interpretations from official points of view.The global AMR governance has gradually progressed from focusing on clinical AMR surveillance to joint-actions against AMR across multiple sectors in the last forty years. China is catching up with the progress of international AMR governance, but the long-term strategies to tackle AMR in China are more concentrated on monitoring, especially in the agricultural and environmental fields. To contribute more to global AMR governance, the country should view it from the perspective of safeguarding public health, national health security, and the “One Health” principle, take a far-fetched view, and seize the opportunity to act decisively and positively toward the global efforts of addressing AMR, showing responsibility at an international level.


Spiral-vane electrospinning (SVE), a novel needleless electrospinning, was proven effective in obtaining high-throughput production of nanofibers. However, the properties of the electrospun nanofibers produced by SVE remain relatively underexplored, especially in comparison with those made by traditional single-needle electrospinning (SNE). Hence, for the comparative study of SNE and SVE in this study, the difference in the preparation mechanism was first analyzed using numerical simulation, followed by the experimental analysis of the effects of spinneret types on the quality and biocompatibility of electrospun poly(caprolactone)/gelatin (PCL/Gel) nanofibers. The values predicted by the electric field results were consistent with the experimental data, showing that the PCL/Gel nanofibers prepared by SVE have higher yields than SNE. Although the different spinnerets  had little effect on the surface chemistry, thermal stability, and composition of the PCL/Gel nanofibers, they had great effects on the fiber diameter distribution and mechanical properties in which SVE-electrospun nanofibers have the wider diameter distribution and higher softness. Furthermore, the SVE-electrospun nanofibers were also proven to exhibit good biocompatibility for cell growth of human adipose-derived stem cells (hADSCs) and cell–fiber interactions. Summarily, compared to the traditional SNE, SVE-electrospun nanofibers exhibited many merits including high-throughput yield, good air permeability, and compliance, which provide a facile and effective platform for the improvement of nanofiber applications in biomedical fields . Owing to the characteristics of high specific surface area for biomolecule binding and biomimetic extracellular matrix (ECM)-like fibrous structure for cell growth, nanofibers are developed and widely used in the various biomedical fields, such as skin-beauty, wound dressings, and tissue engineering . Among tIn this context, needleless electrospinning that initiates the charged jets from the open free-liquid surface is exploited and demonstrated to present some unique advantages compared to multi-needle electrospinning, especially in the achievement of nanofibers with high throughput . It has Hence, as a newly exploited strategy of needleless electrospinning, spiral-vane electrospinning (SVE) was regarded as a very efficient device for preparing nanofibers with high quality and yield , and theIn tissue engineering, polymer blending for electrospinning is one of the most effective methods to provide desirable biocomposite nanofibers for the guidance of tissue remodeling . For exaw 550,000, Jinan Daigang Biomaterials) and Gel  with the weight ratio of 70:30 was prepared at the total concentration of 10% w/v and stirred for 12 h at room temperature. After the dissolved solution was transferred into a syringe with a 19 G blunt-tip needle, SNE was performed to generate PCL/Gel nanofibers using the following parameters: applied voltage 13 kV, flow rate 1 ml/h, needle tip to collector gap distance 15 cm, and ambient conditions . According to the resulting fiber morphology relying heavily on the applied voltage and the shape of the needleless spinneret in needleless electrospinning  as the dissolving solvent, the mixed polymer solution of PCL  electric fields of the single-needle system  and spiral-vane system  were simulated by the COMSOL Multiphysics software . The physical geometries of these electrospinning setups  were established according to their practical dimensions and locations. Then, all the electric field strengths and distributions were visualized using the software.Fiber morphology: surface morphologies of electrospun PCL/Gel nanofibers were observed by using a scanning electron microscope  at an acceleration voltage of 0.02–30 kV. Before SEM imaging, all the fibrous mats were sputter-coated for 30 s with gold to increase conductivity. The distribution of fiber diameter (n > 100) was further analyzed directly from the obtained SEM images using the ImageJ software .Surface chemistry and crystallinity structure: Fourier transform infrared (FTIR) spectroscopy of the electrospun PCL/Gel nanofibers was qualitatively analyzed by using an FTIR spectrometer  over the wavenumber range of 4,000–600 cm−1 at a scanning resolution of 2 cm−1. The crystalline structure of the PCL/Gel nanofibers was determined by using an X-ray diffractometer  at the operating voltage of 40 kV and current of 200 mA, respectively. After background subtraction, the crystallinity was calculated from the fractional area of the crystalline peaks to the total area.Thermal stability: thermogravimetric analysis (TG) of the electrospun PCL/Gel nanofibers was carried out using thermal analyzer apparatus . The 3–7 mg samples were heated in a nitrogen atmosphere in the temperature range from 30 to 800°C at the heating rate of 20°C min−1. Derivative thermogravimetry (DTG) was calculated from the derivate of the TG curve, which represents the difference in the thermogravimetry ratio of weight loss measurement at heating.Tensile properties: tensile properties of the electrospun PCL/Gel nanofibers were determined using a tabletop tensile tester  equipped with a 50 N load cell at ambient conditions. All samples were cut into a rectangle with 3 cm length and 1 cm width and fixed on the fixture of the biomechanics analyzer. Then, the stress–strain curves of the samples (n > 8) were recorded under stretching at a cross-head speed of 10 mm/min until fracture. The fibers’ mechanical parameters such as Young’s modulus, tensile strength, strain at break, and maximum load were further obtained from the stress–strain curve.Isolation of the primary hADSCs and cell culture: human adipose-derived stem cells (hADSCs) were extracted from adipose tissue according to the Animal Care and Experiment Committee of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. In brief, adipose tissue was immersed in 0.25% chloramphenicol solution for 15 min; after thoroughly rinsing in PBS solution three times, the tissue was cut into pieces and then shaken for digestion in type IV collagenase at 37°C for 1 h. The obtained cell suspension was finally centrifuged at 1,500 rpm for 5 min and then resuspended and cultured with mesenchymal stem cell medium  containing 5% fetal calf serum, 1% growth supplement, and 1% penicillin/streptomycin solution.Cell morphology: hADSCs were seeded onto the fibrous membranes in 24-well plates at a density of 5×104 cells/well. After 3 days of culture, the cell morphology was stained with TRITC-labeled phalloidin , and the cell nuclei were stained with 0.8 mg/ml 4′,6-diamidino-2-phenylindole  for 10 min at room temperature in the dark. Morphology of the hADSCs was observed using a laser confocal scanning microscope . ImageJ further analyzed cell numbers based on the obtained microscope images.Cell proliferation: hADSCs were seeded onto the PCL/Gel nanofibers at a density of 1×104 cells/well in 24-well plates. According to the manufacturer’s instruction, after 1, 3, 5, and 7 days of culture after seeding, cell proliferation was monitored by using the Cell Counting Kit-8 . In brief, the cellularized fibrous mats were incubated with a 300 μL culture medium containing 15 μL of CCK-8 at 37°C for 3.5 h. Then, 100 μL of the solution was transferred to a 96-well plate for absorbance measurements at 450 nm using a microplate reader  to analyze cell numbers.Cell spreading: cells were seeded onto the PCL/Gel nanofibers at a density of 5×104 cells/well in 24-well plates. After culturing the cell–fiber constructs for 2 days, cell spreading was observed by scanning electron microscopy . In brief, the samples were washed with PBS three times and fixed overnight at 4°C in 2.5% glutaraldehyde and then dehydrated through a graded series of ethanol  at 4°C for 15 min at each step. Once dried, the samples were examined by SEM at an acceleration voltage of 0.02–30 kV.Live/dead staining: cells were seeded onto the PCL/Gel nanofibers at a density of 5×104 cells/well in 24-well plates. After culturing the cell–fiber constructs for 3 days, live/dead assays  were used to evaluate the viability of hADSCs. In brief, 0.2% (v/v) calcein-AM and 0.3% (v/v) propidium iodide were mixed into PBS to make a working solution. After 30 min of incubation with the working solution at 37°C, cell viability was observed under a fluorescence microscope .Cell–fiber interaction: hADSCs were seeded onto the PCL/Gel nanofibers in 24-well plates at a density of 5×104 cells/well. After 3 days of culture, immunofluorescence staining was performed to examine the expression of integrin in cells to analyze the cell–fiber interaction. In brief, the cellularized fibrous mats were fixed using 4% paraformaldehyde for 30 min, permeabilized using 0.2% Triton X-100 for 5 min, and blocked using 10% goat serum for 30 min. After that, the rabbit anti-human integrin-β1 antibody  was incubated overnight at 4°C, followed by the incubation of goat anti-rabbit IgG (H + L) secondary antibody  for 90 min in the dark at room temperature. The cell nuclei were counter-stained with DAPI for 10 min at room temperature. Finally, the samples were observed using a laser confocal scanning microscope.p values  were considered statistically significant. All of the experiments were repeated at least three times.Data are presented as means ± standard deviation. Statistical analysis was carried out using the Origin 8.0 software, and Tukey’s HSD post hoc tests were used to make pair-wise comparisons between groups. The obtained Spiral-vane electrostatic machine, using spiral vane as a free surface spinneret, is a current exploited strategy to achieve the high-throughput production of nanofibers among needleless electrospinning. Similar to the traditional SNE, SVE involves an electrohydrodynamic process. Each peak position of the tiny fluctuations was electrified to generate a jet under the action of a high enough electric field, followed by stretching and elongation into nanofibers  Xue et . HoweverEz  at the needle spinneret and the spiral vane spinneret is different, in which the weak electric field is formed at the central position, while the strong electric field is at the outside position. Under this circumstance, the central jets suffer from a lower electrostatic force than the jets formed on the sides . However, the fiber diameter of SVE-electrospun nanofibers was observed to be distributed more widely than that of SNE-electrospun ones , which was also observed in other needleless electrospinnings  and 2,863 cm−1 (symmetric CH2 stretching) and those for Gel-related stretching modes appeared at approximately 1,535 cm−1 (a coupling of bending of the N-H bond and stretching of C-N bonds in amide II)  . Figuresmide II) . In contmide II) .For the underlying mechanisms, it is well known that there are several forces  exerting an influence on the fluid jets . Usuallyin vitro : the potential of multidirectional differentiation and the excellent ability to proliferate in vitro . Hence, in vitro . The resin vitro . It is win vitro . Due to in vitro . Likewisin vitro . Therefoin vitro . Neverthin vitro . This inThe results, as mentioned above, revealed that the PCL/Gel nanofibers electrospun by SVE had weaker mechanical properties than those electrospun by SNE . UsuallyIn this study, biocomposite PCL/Gel nanofibers were used for the comparative study of SNE and SVE. The numerical simulation revealed the expanded electric field distribution for high-throughput production of nanofibers in SVE. The results reported in physical properties demonstrated that although the type of spinneret  has no significant impact on the surface chemistry, thermal stability, and composition of the obtained electrospun nanofibers, the PCL/Gel nanofibrous membranes produced by SVE exhibited higher air permeability (more wide distribution of fiber diameter) and better compliance . Furthermore, the SVE-electrospun PCL/Gel nanofibers exhibited good biocompatibility for cell growth and cell–fiber interactions. This study provides a better understanding of the comparative study of SNE and SVE, offering essential knowledge in assisting the applications of SVE devices for the production of nanofibers to gain a larger market share, including tissue engineering, cosmetic product, and textile. In addition, although the results presented in this article were focused on PCL/Gel nanofibers, the observed performance variations of nanofibers can be speculated on other SVE-electrospun fibers, and the performed experimental scheme can also be a reference to the further comparative studies of other electrospinning setups.


Probing charge and energy transport in molecular junctions (MJs) has not only enabled a fundamental understanding of quantum transport at the atomic and molecular scale, but it also holds significant promise for the development of molecular-scale electronic devices. Recent years have witnessed a rapidly growing interest in understanding light-matter interactions in illuminated MJs. These studies have profoundly deepened our knowledge of the structure–property relations of various molecular materials and paved critical pathways towards utilizing single molecules in future optoelectronics applications. In this article, we survey recent progress in investigating light-driven charge transport in MJs, including junctions composed of a single molecule and self-assembled monolayers (SAMs) of molecules, and new opportunities in optical sensing at the single-molecule level. We focus our attention on describing the experimental design, key phenomena, and the underlying mechanisms. Specifically, topics presented include light-assisted charge transport, photoswitch, and photoemission in MJs. Emerging Raman sensing in MJs is also discussed. Finally, outstanding challenges are explored, and future perspectives in the field are provided. Following the original idea of adopting individual molecules as functional elements or interconnects in electrical circuits proposed by Aviram and Ratner , the pasThanks to the rapid development of experimental techniques in MJ fabrications and measurements, researchers are now able to expand their investigations beyond pure charge transport. Many interesting transport phenomena in MJs have been reported to date, including the transistor (or gating) effect ,16,17,18To go beyond simple electrical measurements, powerful new experimental methods have been developed to reveal the chemical information of the molecular core in MJs, such as bond rotation, vibration, and rupture, which are usually not accessible in conventional single-molecule conductance measurements. This has been achieved via integrating photo-detection techniques with MJ fabrication platforms, such as combining break junction measurements with tip-enhanced Raman spectroscopy (TERS) ,55,56,57To provide a detailed survey of these emerging optoelectronic phenomena in illuminated MJs, we present recent developments and progress of light-driven charge transport and optical sensing in MJs, including single MJs and self-assembled monolayer (SAM) junctions. The rest of the paper is structured as follows: first, we introduce advances in studying the optoelectronic effect in MJs, including the observation and understanding of photo-conductance enhancement, photoswitching, and photoemission; then we demonstrate recent progress in the emerging Raman sensing in MJs; lastly, we discuss outstanding challenges and new opportunities associated with these topics .Controlling charge transport through molecules by optical means has become a key approach in molecular electronics in the past decade. Molecular junctions excited by external light have been recently investigated in various experimental setups and simulated by different theoretical models. These studies aim to provide a fundamental understanding of charge transport phenomena associated with photon irradiation. In this section, we concentrate on discussing several key transport behaviors observed in illuminated MJs, including light-driven conductance enhancement, photoswitching, and photoemission.Photon-assisted charge transport in tunnel junctions composed of single molecules, namely a change in molecular junction conductance under illumination, has been observed in distinct molecular systems. In these measurements, the conductance of single MJs was performed using single-molecule break junction techniques, such as the scanning tunneling microscopy break junction (STM-BJ) and mechanically controllable break junction (MCBJ) techniques. The heart of these break junction techniques is that single molecules are repeatedly linked between two metal electrodes via chemical anchoring groups modified at the two terminals of the target molecule. Junction formation is mechanically facilitated by a piezo transducer controlled by computer programs with subnanometer precision. To account for the variability of molecular conformation and contact geometry in break junction measurements, researchers usually construct histograms composed of thousands of individual conductance vs. time traces to obtain the peak value of the conductance histogram which is also considered as the most probable conductance of a single molecule. More details about the break junction techniques can be found in previous reviews ,60.By comparing single-molecule conductance measured with and without light illumination in a break junction setup, conductance increase has been observed in various molecular species. Several distinct transport mechanisms were proposed to account for the observed conductance enhancement as detailed below:Photo-induced molecular structure change. Light illumination on photochromic molecules and their derivatives, like dihydroazulene and triphenylmethane leuco, is known to alter their structures . . 2-azobedistance d.In addition, visible (520 nm) or UV (365 nm) light can covert a spiropyran moiety between the “open” merocyanine (spiropyran-open) and “closed” spiropyran (spiropyran-closed) forms. Employing eutectic Ga-In (EGaIn) as the top contact e, Kumar 4 for the diarylethene/bisthienylbenzene bilayer system. As a comparison, the MJ with a 9 nm thick diarylethene single layer displayed a relatively low ON/OFF ratio of 200~400  oligomers, which were deposited by an electrochemical reduction of a diazonium salt on glassy carbon and gold electrodes . A metal 200~400 d. The ONTo conclude on the light-driven charge transport in MJs, recent developments in photo-induced transport phenomena and underlying mechanisms of commonly used molecular species in both single MJ and SAM junction forms are presented. We also introduced recent advances in electroluminescent in MJs. These insights prompt novel molecular electronics designs and call for more emphasis to be put on molecule/electrode interface engineering and junction architectures as key factors for the development of molecular-scale photodetectors, memory devices, and light-emitting components.In situ observation of geometrical and structural kinetics and dynamics of a single molecule has been a long-standing goal in chemistry and is also fundamentally critical for understanding the structure–property relations and transport mechanisms of molecules in electronic devices. To gain deeper insights into the influence of the molecular core and how it bonds to electrodes on electrical properties, researchers have adopted powerful optical detection techniques, such as Raman spectroscopy, to acquire bond vibrational fingerprints of MJs and further obtain electrical and spectroscopical information simultaneously. This new approach has offered unique opportunities to understand molecular-level mechanisms for a wide variety of molecular species. In this section, we discuss recent experimental advances in revealing the chemical information of MJ devices via integrating Raman spectroscopy into molecular junction platforms.Liu et al. introduced a new approach called “fishing-mode” tip-enhanced Raman spectroscopy (FM-TERS) in which molecule-to-surface bonding can be characterized during electron transport a 126]. . 126]. TIn addition to the TERS-STM-BJ and MCBJ-SERS platforms, Jeong et al. designed and fabricated a MEMS-based break junction (MEMS-BJ) device, the heart of which is a Si microelectromechanical-system (MEMS) chip . This ME−3.0 G0 (H-high conductance) and 10−3.8 G0 (L-low conductance)   surface. A 55 nm Au core and 2 nm thick SiO2 shell nanoparticles (SHINs) were prepared first, then 4,4′-BPY SAMs were drop-casted onto the Au (111) surface (−1 appeared in the hybrid solvents (water added to BMIPF6 with different volume ratios) above 10% −1 band was originating from the strong interaction between the pyridyl ring and the Au substrate and can be ascribed to the flat orientation. Thus, combining both SHINERS and STM-BJ was a good way to probe the interfacial effects on molecular adsorption at atomically flat surfaces. Zhang et al. adopted SHINERS to study the adsorption and photo-induced behavior of dye (N719) molecules on different TiO2 (hkl) surfaces [2(hkl) surfaces and plays a determining role in its stability. Additionally, it was indicated that N719 molecules exhibited long-term stability when adsorbed on TiO2 (111), which will be helpful for the rational design of dye-sensitized solar cells.However, a potential drawback of the techniques introduced above is that the total Raman scattering signal from the tip area is rather weak. To overcome this issue, the shell isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) technique was invented and used in MJ studies. Recently, Yu et al. combined the STM-BJ technique and SHINERS to probe a solvent-induced interfacial electronic effect  for tuning the electron transport and adsorption geometries of the 4,4′-bipyridine  single-molecule on the Au (111) surface . As showuctance) b. A simi(BMIPF6) c. Conduc surface d. In sucdodecane d. This ssurfaces . ThiocyaTo further enhance the sensitivity of Raman scattering, other factors that modulate the Raman response have been investigated. For example, Guo et al. recently employed a modified MCBJ technique and demonstrated a single-molecule based field-effect Raman scattering device in two-terminal MJs coupled with an additional third electrode as gate . The junIn this section, we have presented several emerging techniques that combined Raman spectroscopy with MJ techniques, including TERS, MCBJ-SERS, MEMSBJ-SERS, and SHINERS. These experimental tools have been proven to be capable of directly monitoring conformational change, chemical reaction, and molecule/electrode interface coupling in MJ systems, which were inaccessible in conventional electrical measurements. Beyond the common two-terminal layout, molecular orbital gating has also been shown to effectively enhance the Raman scattering intensity. It is anticipated that these techniques will be extensively used to capture a complete picture of the molecular behavior in future MJ measurements.As a remarkably fertile platform for studying physical phenomena at the molecular scale, MJs have enabled direct investigation of light-matter interactions at the single-molecule level. The past decade has seen a rapidly growing interest in understanding how charge transport in MJs is impacted by light illumination and a variety of emergent effects associated with it. In this review, we have systematically discussed recent progress in probing the electrical and optical properties of illuminated MJs composed of a wide spectrum of molecular species in both single-molecule and SAM configurations. Not only have these recent studies proven that transport properties of MJs can be effectively modulated by optical means, but they have also demonstrated that combining optical sensing techniques, like Raman spectroscopy, with electrical measurements could vastly deepen our knowledge of the structure–property correlation of individual molecules in the junction. More excitingly, optoelectronic behaviors similar to (and even beyond) those of conventional semiconductor materials, such as photoswitching and photoemission, have also been experimentally realized in molecular-scale devices. It is evident that this new knowledge and technical advancements have laid a solid foundation for the development of future molecular optoelectronic components.However, before molecular-scale optoelectronics become practical in our daily lives, several outstanding challenges need to be addressed. First, there still exist open questions in understanding light-driven transport in MJ devices, for example, how to isolate the effect of light-molecule interactions from other interactions involved in the junction. Second, there is a clear limitation in suitable molecular candidates. Future improvements in designing and synthesizing new molecular species with promising optoelectronic properties are required. The optoelectronic properties of more complex systems, such as supramolecules, molecular machines, and polymers, have rarely been examined. It is expected that new quantum transport phenomena, which are not possible in the bulk (or ensemble measurements), may occur in these systems. Third, discrepancies have been observed between single-molecule and SAM junctions composed of the same molecule. It is critical to uncover the origin of this inconsistency, as it is beneficial for designing large area devices via molecular assembly. Fourth, there is an urgent need to investigate emerging MJ device structures and architectures, such as incorporating plasmonic nanostructures into MJs. These new devices and measurement schemes may catalyze novel optoelectronic functionalities that were previously not envisioned. Specifically, as demonstrated in several recent studies, the integration of plasmonics with molecular junction electronics has become a promising future direction for molecular optoelectronics. Lastly, from the theoretical point of view, it has remained challenging to precisely simulate the transmission of MJs and the effect of light illumination. It is evident that the development of accurate computational tools is urgently required.Finally, we note that breakthroughs in this multidisciplinary research area will rely on intimate collaborations from materials synthesis, instrumentation, nano-characterization, and theoretical simulation to establish the fundamental mechanisms and to develop new design principles at both the molecular and device levels. Given the remarkable advances in recent years and continued efforts by researchers in this field worldwide, there is no doubt that optoelectronics research at the molecular scale will continue to progress and achieve the transition from the research laboratory to real applications.


Patent ductus arteriosus (PDA) is common among preterm neonates. Haemodynamically significant ductus arteriosus (hsPDA) can cause ductal steal and contribute to poor outcomes. Our aim was to evaluate ductus arteriosus patency and significance using two-site near-infrared spectroscopy (NIRS) measurements in preterm infants older than 72 h as a supplemental tool to echocardiography.In this prospective observational study, 123 preterm infants  < 32 weeks, birth weight < 1500 g) were enrolled. Sixty-four newborns had closed ductus arteriosus (noPDA), and 41 and 18 patients were assigned to the PDA and hsPDA groups, respectively, per predefined echocardiographic criteria. Cerebral and renal oxygenation were assessed during NIRS monitoring.2) (76.7 (±7.64)) was detected in the noPDA group than in the PDA (71.7 (±9.02)) and hsPDA (67.4 (±13.48)) groups (p < 0.001). Renal fractional tissue oxygen extraction (FTOE) (0.18 (±0.079)) was lower in the noPDA group than in the PDA (0.23 (±0.092)) and hsPDA (0.24 (±0.117))0.117 groups (p = 0.002). Cerebral oxygenation was significantly lower in the hsPDA group (77.0 (±5.16)) than in the noPDA (79.3 (±2.45)) and PDA (79.7 (±2.27)) groups (p = 0.004). There was no significant difference in cerebral fractional tissue oxygen extraction (FTOE) between any of the groups.A higher renal mean (±SD) regional tissue oxygen saturation (rSpOOur results suggest that renal oxygenation is affected by ductus patency in preterm infants older than 72 h. Significant differences in cerebral oxygenation were observed between the hsPDA group and the PDA and noPDA groups.ClinicalTrials.gov Identifier: NCT04295395. Registration date: 4 March 2020. This study was retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04295395. The prevalence rates of patent ductus arteriosus (PDA) among preterm infants at four days of age are approximately 10% among infants born at 30 through 37 weeks of gestation, 80% among those born at 25 through 28 weeks of gestation, and 90% among those born at 24 weeks of gestation [The presence of PDA can result in the ductal steal phenomenon, also known as haemodynamically significant PDA (hsPDA), leading to pulmonary hyperperfusion and systemic hypoperfusion. The ductal steal phenomenon reduces cerebral and renal regional blood flow and increases the risk of pulmonary and intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC), acute kidney injury, bronchopulmonary dysplasia (BPD), and death –6.Echocardiography, a noninvasive and relatively simple method for the diagnosis of ductus arteriosus (DA) patency at the bedside, is widely used in the neonatal population. It can address anatomical DA features ) and haemodynamic effects (shunt direction and size) by blood flow Doppler. However, echocardiography requires experience and specific training, and often, it cannot be performed in a timely manner by paediatric cardiologists.The haemodynamic significance of PDA, a very important factor, should be interpreted by considering gestational and chronological age and other possible contributors; however, debates about the most appropriate method of identification and even definition of hsPDA are still ongoing . More im2) and indirectly information on regional organ perfusion. It is based on the relative transparency of biological tissues  and the ability to differentiate oxygenated haemoglobin from deoxygenated haemoglobin, as they have distinct absorption spectra. The ratio of oxygenated and total haemoglobin represents the rSpO2 [Near-infrared spectroscopy (NIRS) is a noninvasive clinical tool that can provide continuous and real-time information regarding regional tissue oxygen saturation . Informed parental consent was obtained before enrolment. Very low birth weight (VLBW) (< 1500 g) infants with gestational ages (GAs) less than 32 weeks and older than 72 h who underwent echocardiographic screening for PDA were included in the study. The exclusion criteria were major congenital anomalies, the need for cardiovascular support with vasopressor medication and culture-proven sepsis.A prospective observational centre-based study was carried out in a tertiary-level NICU. The study was approved by the regional ethics committee and registered at Data collection: Perinatal and demographic data were collected, and cranial baseline ultrasound data were obtained after enrolment. NIRS  was used for two-site regional tissue oxygenation measurements. Neonatal/paediatric sensors (SenSmart 8004CB-NA non-adhesive with EQUANOXTM technology) were applied to the forehead lateral to the midline, superior to the eyebrow and inferior to the hairline on either the left or right posterior flank above the iliac crest and below the costal margin to measure cerebral and renal rSpO2, respectively, using a wrap to secure the sensor. The NIRS apparatus was left in place for 12 h for continuous data acquisition. Recordings were briefly interrupted every 3 h to reposition the sensor medially or laterally to prevent skin bruising or breakdown. During data recording, minimal-handling nursing care guidelines were followed [2 was measured to calculate the fractional tissue oxygen extraction (FTOE), which reflects the balance between tissue oxygen delivery and tissue oxygen consumption, indirectly reflecting tissue perfusion [2 and with lower and upper alarm limits of 88 and 96%, respectively. Cerebral-to-renal oxygenation ratio (CROR) was calculated from regional renal and cerebral tissue oxygenation levels. For each studied infant, data were collected on GA, birth weight, sex, type of delivery, antenatal steroids, Apgar scores at 1 and 5 min, surfactant administration, blood pH, lactate, platelet count, haemoglobin, haematocrit, FiO2 requirement at enrolment, need for respiratory support ) or invasive ), and urine output. Statistical analysis: The frequency and mean (standard deviation) are used to describe quantitative and qualitative data, respectively. The chi-squared test was used to compare quantitative parameters between subject groups. One-way ANOVA was used to evaluate the mean differences among subject groups. Post hoc analysis with Bonferroni adjustment for multiple comparisons was used for pairwise comparisons. A two-tailed p-value less than 0.05 was considered to be significant. Statistical analysis was performed using Statistical Analysis System (SAS) package version 9.2.Study participants were classified into 3 groups: infants with no PDA (1), infants with haemodynamically insignificant PDA (2) and infants with hsPDA (3). According to the clinical protocol used in our NICU, haemodynamic significance was determined by echocardiographic ductal left-to-right shunt, volume overload according to a LA/Ao ratio ≥ 1.4 and DA size > 2 mm. Echocardiography was performed after the 3rd day of life to avoid possible bidirectional shunting during the transitional period. Patients with open DA without the aforementioned haemodynamic significance criteria were assigned to the PDA group. All echocardiographic studies were performed by a paediatric cardiologist. DA was evaluated from a high parasternal view using colour Doppler assessment. The DA diameter was measured at the narrowest point. The LA/Ao ratio was measured in the parasternal long axis view using the M-Mode. Ductal closure was documented by no ductal blood flow on colour Doppler scanning. If echocardiography showed closed DA or ductus patency, the measurements were considered valid for 24 h. The resistive index (RI) was evaluated in the anterior cerebral artery (ACA) using pulsed-wave Doppler on the day of NIRS monitoring. followed . All 12 erfusion . All gron = 10), congenital malformations (n = 5) and sepsis/haemodynamic instability (n = 9)  older than 72 h of life cerebral oxygen saturation is significantly lower in infants with echocardiographic signs of highly significant PDA compared to patients with no PDA and closed DA. We also demonstrated that renal regional oxygenation is higher in patients with no PDA or closed DA than in infants with PDA and hsPDA. In contrast, cerebral oxygenation in infants with hemodynamically insignificant PDA and was not found to be different from that of neonates with closed DA. Regional oxygenation reflects the amount of oxygen used by the tissue. Our study found significantly lower cerebral rSpOe groups , 16, 17.erfusion , 19. In erfusion . Additioerfusion . In our patients . Howeverpatients  found hin et al.  and Poonn et al.  found si2 and FTOE than cerebral measurements in infants with hsPDA [2, but a study by Arman et al. found that Doppler and NIRS measurements correlated significantly [Our study also showed that neonates with PDA and hsPDA have significantly lower renal saturation levels and higher FTOE than infants with no PDA. These findings are contrary to those of Chock VY et al., where renal saturation below 66% was associated with hsPDA . We specth hsPDA . Despiteficantly .There are several possible reasons for these inconsistent findings. Some of the studies evaluated only ductal size and did not evaluate flow pattern and/or possible volume overload , 17. MorOther findings associated with hsPDA or PDA were not different from previous findings. The lactate level did not differ among the groups, as previous studies demonstrated it to be a poor indicator of PDA . PlateleWe acknowledge the limitations of our study. First, we did not obtain fluid therapy data before inclusion, which could have influenced the grouping of the sample. We also chose to evaluate PDA after a transitional 3-day period to avoid the confounding bias caused by neonatologists, rather than paediatric cardiologists, assessing the haemodynamic significance and possible closure of PDA. Furthermore, the neonates in the studied groups differed significantly, and the hsPDA group consisted of infants with the lowest GAs and birth weights. However, this inverse correlation with GA and birth weight is well known and to be expected given the relatively large sample size , 33. Sec2 and FTOE are affected earlier by ductus presence and are more sensitive to ductal steal than cerebral rSpO2. The authors conclude that NIRS can be used as a supplementary tool to provide additional information in VLBW, < 32-week GA, preterm infants older than 72 h regarding treatment initiation.In our cohort, we found a statistically significant difference in cerebral oxygenation between the hsPDA group and the PDA and noPDA groups. Furthermore, we suggest that renal rSpO