Active packaging (AP) has been developed to improve the safety, quality and integrity of food, and minimise food waste, while its application in meat is scarce. This review aims to describe meat production and consumption culture in China and New Zealand to provide the context for packaging innovation requirements, focusing on the emerging opportunities for AP to be used for the improvement of the shelf-life of pre-rigor, aged, and frozen-thawed meat products. Sustainable polymers utilised in the manufacturing of AP, manufacturing techniques, the release mechanisms of actives, and legal and regulatory constraints are also discussed. Diverse market compositions and consumption cultures in China and New Zealand require different packaging solutions to extend the shelf-life of meat. AP containing antimicrobials, moisture regulating agents, and antioxidants may be used for pre-rigor, dry- and wet-aged products and in improving the quality and shelf-life of frozen-thawed meat. Further innovations using sustainably produced polymers for AP, along with incorporating active compounds of multiple functions for effectively improving meat quality and shelf-life are necessary. Challenges remain to resolve issues with scaling the technology to commercially relevant volumes as well as complying with the rigorous legal and regulatory constraints in various countries. Meat is a valuable food product, rich in essential proteins, lipids and micronutrients in forms that are readily digestible which often provide nutritional adequacy for a wide range of people. However, the nutritional composition and high-moisture content of meat also make it susceptible to deterioration in quality, arising from microbial spoilage and other enzymatic and oxidative deterioration ,2. LosseThe primary purpose of meat packaging is to provide a physical barrier that will protect the meat product from its surrounding environment, while also limiting microbial growth and oxidation, thereby extending the product’s shelf-life . HoweverActive packaging (AP) is a relatively new type of packaging which contains various active compounds, such as antioxidants, antimicrobials, moisture and various gas absorbers, and ultraviolet radiation absorbers, that interact with the packaged food or the surrounding environment to extend shelf-life by maintaining the quality, safety, and integrity of food. The active compounds from the package further increase the shelf-life of food products over and above conventional packaging by limiting the deleterious effects caused by oxidation, microbial growth, and moisture loss during storage .The application of AP in the food industry has been suggested as a strategy with the potential to contribute holistically to mitigate global warming, reduce fossil-energy demand and decrease acidification and eutrophication potential . HoweverRecently, there have been a number of reviews published that comprehensively summarise the types of AP and their applications for preserving or even enhancing the quality and safety of food products during storage ,12,13,14Meat is produced and marketed in a variety of formats and generally categorised as unprocessed or processed meat. Depending on the market, it is possible for a consumer to purchase meat pre-rigor (hot meat), post-rigor (aged meat) and after further processing . As such, packaging requirements differ depending on the type of meat products, route to market and target consumers, while maintaining the safety and quality of the product and minimising packaging costs.China is one of the most rapidly developing countries, with increasing demands for meat and meat products. As a result, China has become one of the largest countries in meat production and consumption worldwide. In 2021, China’s annual output of meat was 89.9 million tonnes (MT), of which pork was 53.0 MT, beef and veal was 7.0 MT, lamb and mutton was 5.1 MT and poultry was 23.8 MT . Most ofNew Zealand is one of the largest global producers and exporters of lamb and venison, and a minor global producer of beef and pork. In 2021, NZ produced 454 TT of lamb and mutton, 759 TT of beef and veal, 44.9 TT of pork and 10.7 TT of venison . The domFor thousands of years, the unique dietary habits of Chinese people have gradually coalesced to become an important part of traditional Chinese culture. Chinese foods are artistic and versatile, which means that the same food can be prepared differently depending on the region, season, and consumer, leading to variations in tastes. Traditionally, fresh meat is mostly prepared for stir-frying, stewing and braising. With the development of the economy in China over the last two decades, food consumption is not only for satiety, but also for sensorial and psychological satisfaction . The daiThe globalisation of markets and the introduction of western and other Asian foods and cuisine in China are altering consumer eating behaviours of meat and meat products . ConsumeNZ is a multicultural country with immigrants originating from all around the world. Food culture in NZ is represented by western food which considers food as the origin of nutrition and energy, therefore animal-derived proteins such as those from meat and dairy products, are the focal point of the meal and vegetables are ancillary. Consumption of poultry, beef, and pork are the most popular, accounting for 96% of meat consumption in NZ. Fresh meat, which has been chilled and/or aged, is widely available in butcher stores and supermarkets and preferred by consumers over frozen meat; with grilling/braising, frying, roasting and stewing being the most common cooking methods. In addition, processed meat products, such as sausages, salami, ham, bacon and smoked meat are also high in demand, with 41.8% of New Zealanders eating processed meat one to two times per week, and 28.9% eating processed meat three or more times per week .The packaging requirements for meat and meat products have been driven by market composition and consumption habits across countries. For instance, packaging for Chinese markets need to consider issues around domestic distribution, retail display, wholesale, and household storage; whereas for NZ, it is essential to extend the quality of chilled and frozen meat fabricated as primal, sub-primal and retail-ready forms for global distribution and long-term storage. Therefore, a successful meat packaging format must meet not only consumer expectations on product safety and quality, but also satisfy the needs for mechanical properties and economic impacts, such as durability, ease of machining and cost-effectiveness.There are many packaging formats that are applied to chilled, frozen, and processed meat products to protect their safety, nutritional and sensory properties during distribution, storage, and display, as summarised in Different packaging technologies have their own advantages and disadvantages in maintaining the quality and consumer acceptance of fresh and processed meat products. The oxygen-permeable films used for aerobic packaging allow oxygen to diffuse from the environment into the meat surface to encourage the blooming of the meat. This process involves the formation of oxymyoglobin, which is associated with the fresh bright-red meat colour preferred by consumers. However, the exposure to an oxygen-rich environment also accelerates the deterioration of meat quality due to the growth of spoilage microorganisms and severe oxidative damage of lipids and proteins. As a result, vacuum packaging was developed to extend the shelf-life of meat products by creating an anaerobic environment, which is generated when a vacuum is applied within the package to remove ambient air around meat before sealing the pouches or rollstock . The vacThese different packaging formats are also commonly used together by the meat industry to create a variety of permutations, which optimise meat quality throughout its storage life. For wholesale and export markets, chilled meat is generally fabricated into primal or sub-primal cuts and packaged within flexible vacuum packaging or MAP, and then packaged within master packs at the meat processing facility. These master packs can also be vacuum or MAP for further protecting the safety and quality attributes during distribution. Similarly, frozen meat is packaged in shrink or vacuum packaging  or high-abuse bags. However, some wholesale meat packaging formats are also used in retail.At the retail level, the majority of chilled meat is prepared into retail-cuts and packaged in plastic trays with a transparent overwrap film or using MAP, with a small volume of aged meat products being available in vacuum packaged formats. Most large retailers (supermarkets) also have a frozen section for larger meat cuts and frozen and thawed section for retail cuts which are packaged using similar formats to their equivalent chilled products. In general, retail and portioned chilled meat prepared by an in-store butcher is packaged in oxygen-permeable packaging to ensure the bright-red fresh meat colour develops well during display for purchase by consumers. Whereas case-ready products prepared by the meat processor are packaged using vacuum, vacuum skin or MAP, which have a range of different gas-barrier properties  depending on the type of film used, and have been selected based on the desired appearance of the packaged meat .In recent years, the meat industry has faced challenges from the increasing consumer demand for non-animal protein alternatives in an effort to address the environmental and health concerns associated with meat production and red meat consumption . As suchPre-rigor meat, also called hot meat, is produced by fabricating a carcase immediately after slaughter, and the muscle has not entered rigor mortis when they are distributed to the market and purchased by consumers. Pre-rigor meat is well-known for its superior functionalities for producing processed meat, such as higher water holding capacity, binding and emulsifying properties and extractability of myofibrillar proteins . Good meExtensive studies have been performed focusing on packaging materials for post-rigor and aged meat products, however, research on pre-rigor meat is scarce. The packaging formats such as wrapping and vacuum packaging for hot-boned meat could be applied to package pre-rigor meat. There is a range of natural antimicrobials being used for the preservation of food products, which may have potential to be used in the future-developed APs for pre-rigor meat. These antimicrobials include bio-preservative bacteria, naturally occurring organic acids, proteins and peptides, enzymes , and bacteriocins , and some metallic nanoparticles .Lactobacillus spp., Aerococcus spp., Carnobacterium spp., C. divergens and C. maltaromaticum, are considered as potential bio-preservative agents since they are naturally found in vacuum packaged meat and they are able to survive extreme changes in conditions, for instance, multiple freezing/thawing and high-pressure cycles [Bio-preservative bacteria have demonstrated promising roles in the improvement of product shelf-life by altering the ultimate microbial profile on the meat surface with generally recognised as safe (GRAS) bacterial species which have limited or no spoilage potential. Lactic acid bacteria (LAB), particularly e cycles . In addiEnterobacteriaceae (Serratia spp.) which can retard or inhibit the growth of other bacteria [Bacteriocins are antimicrobial peptides that can be produced by some naturally occurring bacteria from refrigerated meat, such as LAB and bacteria . They arbacteria . Nisin abacteria . As bactbacteria .L. sakei and S. liquefaciens, as well as Enterobacteriacae and LAB on bologna and pastrami when stored at refrigerated temperatures for up to 21 days [Naturally occurring organic acids such as formic, acetic, propionic, butyric, lauric, lactic, sorbic and benzoic acids  exhibit broad antimicrobial activity against yeasts, moulds and bacteria . Acetic  21 days . Antibac 21 days . Combini 21 days . Similar 21 days . HoweverPost-mortem ageing is a widely applied practice by the meat industry to achieve premium quality of meat. Consumers currently have an increased understanding that well-aged meat can provide eating quality resulting from satisfactory tenderness and a characteristic aged flavour. There are generally two types of ageing techniques: wet-ageing and dry-ageing. While meat ageing can add value to the product, ageing techniques do have challenges for meat processors, including high energy use, long processing times and potential losses. This section reviews some of the current challenges associated with wet- and dry-ageing to understand how recent advancements in AP could contribute to optimise the ageing process.Most primal meat cuts are vacuum packaged/wet-aged in commercial practice, especially during shipping and storage, before they are fabricated into retail cuts. Wet-ageing is considered as the most practical method of ageing in the meat industry owing to ease and flexibility for storage and transport, and for having very low losses during the ageing process . TherefoClostridium botulinum type B) [Using a higher ageing temperature favours the enzymatic activities to improve the ageing efficiency, and also reduces the time and energy needed for producing well-aged meat products. Wet-ageing at higher temperatures  has been used to accelerate the ageing process for developing desired tenderness and flavour of meat, however, the product life and quality of aged products is compromised as a result of quality deterioration from the growth of toxin-producing pathogens  , spoilag type B)  and incr type B) . As drip type B) . FurtherAdvancement in packaging research may identify opportunities to apply AP materials with greater moisture regulation abilities, which may reduce the direct contact of exudates with meat and minimise deterioration. Packaging formats which incorporate a moisture absorber could provide effective control of drip accumulation inside the packaging, thereby suppressing the growth of microorganisms . AbsorbeDry-aged meat products have been recognised as a premium food sought after by consumers for their characteristic dry-aged meat flavours such as nutty, roasted, sweet and umami . HoweverOne recent advancement in dry-ageing packaging demonstrated the feasibility of dry-ageing meat in a water-permeable ageing bag, known as ‘in-bag dry-ageing’, for producing a premium dry-aged product with more consistent quality and microbial safety ,54. The ® plastic bag is a thermoplastic elastomer made of flexible polymer and rigid polyamide with high permeability to water vapour, allowing rapid and even evaporation of water from meat, while also limiting the access of oxygen and microorganisms to the meat [Moisture evaporation during dry-ageing has been suggested to contribute to the development of the characteristic dry-aged flavour through its concentration effect on the flavour compounds . Therefothe meat . The resthe meat ,60, withthe meat . FurtherSo far, there is only one study by Gudjónsdóttir, et al.  which haDuring frozen storage, meat quality deterioration which results from enzymatic, physical, biochemical and microbiological activities is retarded due to the low temperature and the absence of free water in meat extending shelf-life. Freezing plays an essential role in the meat export industry by assuring the safety and superior quality of the meat products being supplied overseas, particularly for distant markets, for instance, the export from NZ to China, the US and European countries. However, the recent COVID-19 pandemic has caused severe disruptions within the meat supply chain resulting in the temperatory closure of processing plants and disruption to trade routes . In manyLipid and protein oxidations are the main causes of quality deterioration during frozen storage and the subsequent thawing process, which lead to discolouration, texture changes and the formation of off-flavour and toxic compounds . Some st® and FreshilizerTM). Likewise, the incorporation of ascorbic acid into high barrier bio-polymer films or containers has also been explored to protect meat products from oxidation [Another strategy which has been commonly used in meat industry is to reduce the oxygen content in the packaging through vacuum packaging or MAP , essential oils from spices and grain residues  and plant extracts  ,70. The tty food , pomegratty food  and graptty food . Naturaltty food . Researctty food  and thymtty food , and seatty food , which cPolymers used in packaging can generally be considered as non-edible or edible and are derived from renewable or non-renewable feedstocks. In addition, packaging polymers are generally also considered in view of their end-of-life disposal, whereby the polymers are either degradable or non-degradable. Naturally occurring polymers such as polysaccharides, proteins and lipids, as well as those derived from biosynthetic pathways (such as polylactic acid) are bio-degradable in general .The most common packaging materials  applied Growing demand for sustainable packaging materials has triggered a shift towards the development of renewable polymers with improved functional features ,11. Rene®) are also considered edible. They biodegrade more readily than polycaprolactone and PLA, being degraded within 3 months during soil burial or composting [Recent research into AP for meat products has extended into the potential for active components to be incorporated into edible films and coatings to address both environmental concerns, by utilising food co-products as a source of active compounds or polymers, and consumer demands for natural foods . In genemposting . Furthermposting . Food-grmposting . There imposting  with taiPlastic packaging for meat products is generally considered in terms of its physical properties including rigid, semi-rigid and flexible. Rigid trays are pre-made by packaging manufacturers prior to their use in the meat processing plant, butchery, or supermarket by compression moulding, which involves shaping a rigid sheet or film to the shape of a mould using heat and pressure to form trays. The process is more cost-effective than using injection moulding due to the lower cost to produce the mould (only one side of a mould is required) and its higher throughput. Rigid trays can be produced using either a mono-layer  film, or a multi-layer film if specific barrier properties are required. These rigid packages are primarily used for individual packaging of portioned meat products in supermarkets, then covered with overwrap or sealed with film for retail display.Flexible and semi-rigid packaging such as chub, pouches or thermoformed webs are produced in the meat processing plant, butchery, or supermarket from rollstock or film manufactured by packaging companies. Flexible packaging films used as overwrap, chub or pouches can be produced from mono-materials such as LDPE or PVDC. In these cases, film or rollstock is produced by extruding the mono-material and then shaping it into a film using either a flat filming technique  to produce a sheet, or a film blowing technique  to produce a tube, or cut to produce two sheets. However, some packaging formats  utilise multi-layer films to improve overall packaging performance. In addition, most of the semi-rigid packaging materials  also utilise multi-layer structures, produced analogously to flexible multi-layer films.For most applications, mono-material films are unable to meet all the packaging requirements for the distribution and sale of meat products thereby multi-layers packaging films with different types of polymers are commonly used . Multi-lThe technologies available to introduce active compounds to packaging can be used in-line with the processes used to manufacture sheets and films for rigid, semi-rigid and flexible packaging. Active agents can be incorporated into packaging through a variety of methods, but in general are included in a mobile state  or in an immobilised state (preventing the active agent from migrating to the surface of the food) . For incIndirect headspace diffusion method results in a high degree of migration of the actives onto the meat through sorption from the headspace onto the meat surface but limits its efficacy to the vicinity of its exposure. By contrast, direct contact methods tend to have greater immediate efficacy, as the active acts on the entire product surface that the packaging is in contact with, which in the case of fresh and processed meat is sufficient as the interior may often be considered sterile, and most of the deterioration occurs at the surface where microorganisms are growing . HoweverFood safety is a global priority and is one of the major objectives of the current food legislation in order to promote sustainable development of meat industry. Packaging-related laws and regulations are being promulgated and implemented globally, which play an important role in legal protection for product safety whereas also constrain the application of AP in food system. National regulations concerning Food Contact Materials (FCM) have been enacted worldwide, but they vary between countries and not all of them refer to AP specifically. Furthermore, when it comes to nanomaterials used within AP, the safety evaluation and approval process for the use of some nanoparticles  in food packaging remains challenging as there are difficulties in the evaluation of their safety and constraints associated with their assessment in the current policies. Therefore, to scale up and industrialize the AP technologies, legislative and regulatory issues must be addressed.FCM used in China are regulated by the Food Safety Law of the People’s Republic of China 2015. There are over 130 National Standards and 125 Industrial Standards for food packaging materials and containers in China which set specific safety requirements  for FCM including material groups , specific products and food contact additives. New regulations for FCM were introduced in 2017, of which requirements and standards regarding general safety, and the scope and restriction of various additives for producing FCM and products were included. All FCM and food contact articles made available in China must be compliant, properly labelled with the product name and material and provide a declaration of compliance according to the requirements of National Standards. New regulations which cover paper and paperboard for food contact use are more adequate and flexible, and provide a new basis for the general requirements and specific safety and marketing issues related to active and intelligent packaging in China. Besides, when manufacturing new materials and additives in food packaging materials (including resins and additives), they must pass the safety assessment of the National Health Commission of the People’s Republic of China and obtain the registration approval, the manufacturers then ensure the FCM complies with the food safety standards, conducts migration testing to verify compliance and provides product information to downstream users including the declaration of compliance and labelling .NZ regulates FCM through the binational agency Food Standards Australia NZ (FSANZ) under the joint Australia NZ Food Standards Code, enforced by the Ministry for Primary Industries. Under the code, FCM are regulated based on the intended function of the substance in three categories: food additive, processing aid and package. Under the regulation by FSANZ, the food packaging must be safe, and its contact with food should not result in the food exceeding the limit set for the level of toxicants in food. For instance, Standard 1.4.1 describes the contaminants and natural toxicants in food and establishes maximum levels of metal, non-metal and natural toxicants that are allowed in food (detailed in Schedule 19 of the Code) . FSANZ rExtensive research has been carried out in developing AP as novel packaging solutions in the food industry whereas their commercialisation and adoption in meat industry is scarce. To the best of our knowledge, both China and NZ food industries are interesting in incorporating AP into their products while the widely uptake of this technology remains to be seen. One example of AP application in horticulture industry in NZ is to include an ethylene (a ripening hormone) regulator to absorb or release ethylene in the packaging of fresh fruit, which can preserve its freshness through using ethylene absorber sachets or control the ripening process using ethylene release capsule. Coating prepared from chitosan, starch or gelatine has been used in China for fruit preservation . The major hurdles for the commercialisation of AP are related to the need for more evidence to show its effectiveness in-practice, perceived adverse effects on product quality, challenges in assuring their safety, and the challenges of producing AP on an industrial scale, including technology transfer issues, the cost of large-scale preparation or production, and rigorous legal and regulatory constraints. There are also concerns that using pouches or sachets may introduce new substances into the food as a result of migration, resulting in interactions between active agents and other packaging materials, or that active substances or their degradation and/or reaction products may migrate from packaging materials into the food, negatively impacting its toxicological properties. Consumers have also indicated that there is a perceived risk to health and safety with the introduction of nanotechnology, especially the antimicrobial substances like silver nanoparticles or ionic doped glass microparticles, which are generally toxic at low concentrations.Further, the use of some active compounds is still controversial. For instance, antioxidants like butylated hydroxytoluene  and butylated hydroxyanisole , which are GRAS compounds and permitted to be use at the concentrations observed in food preservation. In addition, some of the currently used active agents show limited efficacy against microorganisms, lipid oxidation, low thermal stability and mostly function via direct contact. Additionally, it remains a challenge to develop active materials that can maintain their original mechanical and barrier properties after addition of the active components. Finally, one major obstacle is that certain AP formats which show a high activity on in vitro systems do not present this activity when they are tested in meat. Therefore, the efficacy of the specialised packaging in the meat industry deserves further investigation and clarification.The future advancements of applying AP in meat industry could consider developing packaging materials with multifunctional approaches which incorporate different actives or a compound with several bioactive functions, to take advantages of their differing modes of action and efficacies over time. Such applications are especially relevant for processing and preservation of meat products, since the quality decay generally links with complex reactions between physical, biochemical and microbial activities. Further, the growing demands from consumers for high-quality convenient food  and flexitarian diet could impose the need to understand the interactions of different food components from plant and/or animal origins, and also lay a new ground for novel application of AP. Another emerging area of interest could be the application of AP for centralised packaging system of retail-ready meat products . This type of packaging approach may allow meat products to be shipped to the distant retail markets  in a master package or distributed directly to the consumers who place the purchase through e-commerce.Understanding consumer consumption habits, market composition and distribution channels for meat in China and NZ can assist with the customised design of packaging for improving processing efficiency, product quality and extending shelf-life of meat. AP is a promising technology for supporting the sustainability of the meat industry through improved packaging stewardship and the shelf-life of meat products. AP with antimicrobial activity may be utilised to extend shelf-life of pre-rigor meat through incorporation of natural antimicrobials into packaging formats like wrapping and vacuum-packaging. Further application of antimicrobial AP to tailor dry-ageing process through regulating the growth of microorganisms to facilitate the development of unique flavour profile and extend shelf-life. The moisture regulation system of AP combined with antimicrobial functions may have promising potentials for producing wet-aged meat with improved quality. Quality decay due to freezing and thawing of meat could also be improved using AP of antioxidant and antimicrobial functions. Continued innovation in both packaging materials and active compounds will be needed for AP applications in the meat industry in order to meet both technical and regulatory requirements for adoption.


Over the past few decades (covering 1972 to 2022), astounding progress has been made in the elucidation of structures, bioactivities and biosynthesis of polyene macrolactams (PMLs), but they have only been partially summarized. PMLs possess a wide range of biological activities, particularly distinctive fungal inhibitory abilities, which render them a promising drug candidate. Moreover, the unique biosynthetic pathways including β-amino acid initiation and pericyclic reactions were presented in PMLs, leading to more attention from inside and outside the natural products community. According to current summation, in this review, the chem- and bio-diversity of PMLs from marine and terrestrial sources are considerably rich. A systematic, critical and comprehensive overview is in great need. This review described the PMLs’ general structural features, production strategies, biosynthetic pathways and the mechanisms of bioactivities. The challenges and opportunities for the research of PMLs are also discussed. Streptomyces and Micromonospora in the Actinomycetes family showed great potential in the discovery of drug leads or drug candidates. For instance, Streptomyces, a Gram-positive bacteria, is a rich reservoir of natural products  cycloaddition by photocatalytic pathway  ,125 and  pathway . PTMs ar pathway   or  pathway  was inde34) was derived from its biosynthetic precursor vicenistatin through a selective epoxidation process in S. Sannanensis [34) was the same as vicenistatin (32). In some events, sugar affected their bioactivity and pharmacological application. For instance, vicenistatin D-vicenisamine replaced with D-mycarose completely lost activity [Antibacterial, fungal and cytotoxic activities were presented in glycosylated polyene macrolactams. Sannastatin (nanensis . The sugactivity . In the 37) containing a unique disaccharide motif was essential for its antimicrobial bioactivity. According to the putative sugar biosynthesis pathway, kasO*p was used and associated with CRISPR-Cas9-mediated genome editing by glycosyltransferase to regulate 3, 5-epi-lemonose biosynthesis [Auroramycin , the mode of the core structure with two sugar moieties were the same as auroramycin (37). In 2018, Mónica G. Malmierca et al. conducted an important experiment on the sipanmycin A and B’s route of biosynthesis and revealed that the cooperation of two different glycosyltransferases achieved the incorporation of the same sugar [In the structures of sipanmycin A and B  are a unique class of substances in microbial metabolism. Many of them have biological activities such as antibacterial, cytotoxicity, regulation of Bcl-XL function  and the 49) inhibited the synthesis of DNA, RNA and protein in yeast Saccharomyces cells in addition to causing holes on the surface of the cell membrane [Stubomycin (hitachimycin) (membrane . For spemembrane .48) belongs to the family of polyene macrolactams and had a wide range of antimicrobial and antitumor activities. LNM, in particular, was demonstrated to have a distinct DNA-damaging mechanism of action involving activation by cellular thiols [Leinamycin (LNM) (r thiols . In the r thiols . Individr thiols .37) was a rare member of polyene macrolactams with antifungal bioactivity. The action of auroramycin in yeast cells was that it disrupted the structural organization of the vacuolar and the integrity of membranes, which differed from amphotericin B. Auroramycin was able to cause ionic stress and hyperpolarization of the yeast plasma membrane, which resulted in the microcosmic phenomenon of cation leakage from the cytoplasm [Auroramycin (ytoplasm .25) may have potential antifungal activities due to its saturated hydrocarbon chain and its ability to be inserted into the phospholipid bilayer: that is to say, passing the corresponding membrane phospholipid target. In the study, the authors detected the morphological changes of yeast cells after the compound treatment and speculated that heronamide C might induce the abnormal accumulation of cell wall substances by regulating the lipid function of the cell membrane and activating the membrane protein, and this eventually results in the changes in cell morphology [Heronamide C  and analogues were different from other antifungal agents: that is, HASF interfering with sphingolipid biosynthesis in Candida albicans [The mechanisms of HASF , micromololactam (16), FW05328-1 (10) and other PMLs contain monocyclic polyene lactam structures. There were many hydroxyl and methyl groups in the rings, but there were no additional branched chains similar to fatty chains or carboxyl groups. To obtain such compounds, microorganic extracts experienced numerous and complicated isolation steps. Because the compounds were easily degraded in the stimulation of light, temperature, heat and oxygen, the acquisition of large-scale highly purified samples would become critical in future research and application.Sceliphrolactam  derived from the spores of the plant  in 2019 . The SpEWith further investigation, it was found that many natural small molecules or macromolecular proteins in the organic body were in a metastable/transition state. The molecule stayed in an inactive state as a complex with a protective agent (such as an amino group/protein); otherwise, the corresponding enzymes will remove the protective agent to activate the molecular. The extraction and purification of meta-stable molecular pose a challenge but we believed that with the acceleration of development and understanding of research on bio-macromolecule complexes, scientists will persistently approach and restore the truest condition and function of polyene macrolactams existing in vivo. In addition to the above-mentioned protective effect of artificial porous shell materials on polyene macrocyclic lactams, it is possible to combine protein substances and polyene macrocyclic lactam to form a stable complex for isolation, purification, preservation and application in the future.22), hitachimycin (49) and aureoverticillactam (29). These types of PMLs were difficult to use directly for the assessment of activities . The problem of polyene macrolactam solubility could be solved by chemical semi-synthetic approaches in which the -OH group was attached to the sugar group or PEG, etc., to increase the solubility of compounds in the future.Because the presence of hydrophobic groups such as medium and long aliphatic chains or amino acid phenylalanine in PMLs leading to their poor solubility, these affect BE-14106  technology has greatly broadened the scope of protein structure research, which will be no longer limited by the study of protein crystal structure but will be understood with the interface of protein interaction.Many PMLs draw much attention due to the multiple types of physiological activities and immunomodulatory activities. However, the mechanism for the bioactivity of PMLs remains insufficiently understood. Research on PMLs is also dependent on the progress and development of physics observation methods. With the advancement of bioinformatics and chemical informatics, biological fluorescein, isotope labelling technology, marking biological macromolecular protein via fluorescence microscope, microscope principle and scanning electron microscopy (SEM), drugs and proteins exist in the signal pathways of living organisms and can be visually and dynamically observed. This accelerates the understanding of the new compound structure and the mode of attachment of small molecules to a macromolecular protein, promoting the progress of mechanism research and providing assistance in new drug research and development processes. It is important to study the development of antifungal PMLs lead-drugs, which are currently in short supply in clinical trials.This paper reviewed the discoveries, structural characteristics, producing strains, mechanism of actions, biosynthetic pathways and problems in the research of PMLs, as well as some possible solutions and research orientation. Hopefully, this paper will help scientists in exploring PMLs in the future.In summary, due to the existence of active double-bond groups in PMLs, PMLs have fused into multiple groups to form a variety of structural classes and correspond to a variety of biological activities. Although the isolation and structural elucidation of these compounds have a long history, their biosynthesis pathways, especially those forming intramolecular cyclization, are still not clear. The study on in vivo peri-cyclic reactions and intramolecular cycloaddition chemical reaction mechanisms can better guide their chemical synthesis modification, as well as bionic synthesis.


Viruses are strictly intracellular parasites requiring host cellular functions to complete their reproduction cycle involving virus infection of host cell, viral genome replication, viral protein translation, and virion release. Ribosomes are protein synthesis factories in cells, and viruses need to manipulate ribosomes to complete their protein synthesis. Viruses use translation initiation factors through their own RNA structures or cap structures, thereby inducing ribosomes to synthesize viral proteins. Viruses also affect ribosome production and the assembly of mature ribosomes, and regulate the recognition of mRNA by ribosomes, thereby promoting viral protein synthesis and inhibiting the synthesis of host antiviral immune proteins. Here, we review the remarkable mechanisms used by RNA viruses to regulate ribosomes, in particular, the mechanisms by which RNA viruses induce the formation of specific heterogeneous ribosomes required for viral protein translation. This review provides valuable insights into the control of viral infection and diseases from the perspective of viral protein synthesis. Viruses are intracellular parasitic organisms with infectious potential and are divided into two categories, namely DNA viruses and RNA viruses, according to their genomic characteristics. In recent years, RNA viruses have attracted the increasing attention of researchers because of their high adaptability, high variability, and strong pathogenicity . DependiThe ribosome is the host protein synthesis factory, and it is formed by the assembly of rRNA, the 40S ribosomal subunit, and the 60S ribosomal subunit. There are more than 80 known ribosomal proteins (RPs), the 40S subunit comprises about 30 proteins, while the 60S subunit contains 50 proteins, but it has been found that not all RPs are involved in the formation of mature ribosomes. However, not all RPs are involved in the formation of mature ribosomes . TherefoIn this review, we focus on the regulation of the host ribosome following viral invasion of the host cell. Including how viruses shut down ribosomal translation of the host genome and how viruses use the host ribosome to preferentially translate the viral genome.Viral infection is a dynamic process in which viruses and organisms compete with each other. Depending on the mechanism of infection, viruses can be classified as those that cause cell-killing, stable, and integrated infections . CompareDuring viral infection, the virus regulates the expression of host proteins through the control of ribosomes. The main pathways include remodeling the host mRNA pool and inhibiting the recognition of host mRNA by ribosomes. Currently, some viruses can remodel the host mRNA library by encoding viral proteins that interfere with host pre-mRNA synthesis, induce host mRNA degradation, or block host mRNA nuclear export pathway. Among these approaches, interference with host mRNA synthesis is mainly achieved by strategies such as inhibition of pre-mRNA splicing by the incorporation of poly(A) or direct inhibition of pre-mRNA polyadenylation. For example, the Vpr protein of human immunodeficiency virus (HIV) was identified to inhibit pre-mRNA splicing, and the NS1 protein of avian influenza virus (AIV) inhibits pre-mRNA splicing and polyadenylation . MoreoveIn recent years, some viruses were found to prevent ribosomes from recognizing host mRNA, resulting in the inhibition of normal cellular physiological functions and providing a more supportive environment for virus proliferation. In studies of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes the worldwide coronavirus disease 2019 (COVID-19) pandemic affecting millions of people, it was found that the viral non-structural protein 1 (NSP1) encoding the virus early in infection binds with high affinity to the ribosomal mRNA entry channel, preventing recognition of host and viral mRNA by the ribosome . The intRibosome biogenesis is primarily in the nucleolus, where rRNA precursors (pre-rRNA) are processed into mature molecules with mature RPs that assemble into 40S ribosomal subunits and 60S ribosomal subunits for release into the cytoplasm. The 40S ribosomal subunit forms a 48S pre-initiation complex with the translation initiation complex and mRNA, which subsequently recruits the 60S ribosomal subunit to eventually form the translationally functional 80S ribosome. Viruses cannot carry their protein synthesis machinery and need to manipulate ribosomes to complete their protein translation. Hence, the viral genome competitively utilizes ribosomes with host mRNA. Viruses have evolved mechanisms to influence the assembly and maturation of ribosomes.Some viral proteins interact directly with the host 40S or 60S, thereby preventing the formation of the 43S initiation complex and the assembly of the 60S and 40S subunits. For example, SARS-CoV NSP1 protein interacts with the 40S ribosomal subunit to inhibit the formation of the 80S ribosome . NotablyThe modification and splicing of eukaryotic translation initiation factors required for ribosome assembly by viruses lead to ribosome-mediated translation barriers. Most RNA viruses inhibit host protein translation by preventing the binding of ribosomal subunits through strategies such as promoting phosphorylation or dephosphorylation modification of translation initiation factors, cleaving eukaryotic translation initiation factors, or cleaving poly(A)-PABP . The coaIn contrast, viruses can use the diversity of genomes and the expression of viral proteins to promote the assembly of ribosomal subunits and facilitate the formation of heterogeneous ribosomes to selectively translate the viral genome . The ribIn summary, RNA viruses manipulate the functional ribosome to translate the viral mRNA. However, the biosynthesis and assembly mechanism of ribosomes are very complex and elusive. As shown in Viral infection induces a comprehensive stress response in cells that stimulates the phosphorylation of eIF2α and inhibits viral proliferation . To defeMutation or recombination of the viral genome can increase its diversity, thereby allowing viruses to easily adapt to a new host and to mediate immune escape and exhibit resistance to gene therapy . This evDiscovered in 1988 by Jang and Pelletier et al., IRES is a secondary structure of the untranslated region (UTR) at the 5′ end of PV mRNA that binds directly to 40S and remodels the ribosome structure to form a heterogeneous ribosome that preferentially translates the viral genome . NotablyIGR IRES of double-stranded viruses represent the simplest class of IRES . Each OREukaryotic mRNAs are usually monocistronic, while some viral mRNAs are polycistronic. Thus, in order to survive and reproduce in the host cell, viruses have a superior means of solving the problems of time, space and quality of genetic information expression than cells. The strategies include leaky scanning, translation termination re-initiation, ribosomal shunting, ribosome hopping, and frameshifting. As summarized in Viral genomes take advantage of diverse translation strategies not only to facilitate the production of two or more proteins but also to regulate the ratio of viral proteins generated. Viruses regulate gene expression by modulating the arrangement of nucleotides on mRNA, for example by forming specific Kozak sequences or relatively complex secondary structures such as DPL sequences, TURBS sequences and 2A sequences, which affect the rate and mode of translation of the ribosome. As found in both Sendai and parainfluenza viruses, the viral genome can cleverly hijack ribosomal initiation for translation by using different initiation codons through nucleotide changes at specific sites of mRNA . NotablyViral infection induces ribosome aggregation. RNA viruses induce ribosomal localization to recruit viral mRNA. In eukaryotes, some transcripts could be assembled into specific RNA condensates to form ribonucleoprotein (RNP) particles . These pHeavy is more infectious than SINVLight because of its ribosomal component  infects hosts with viral particles that contain host-derived ribosomal components, and SINVomponent . SINVHeatebrates . This meWith the development of cryo-electron microscopy, the delicate structure of the ribosome is gradually being revealed. Numerous studies have found that viral infection affects ribosome biogenesis, modification of ribosomal components, and changes in ribosome conformation.The biosynthesis of ribosomes occurs mainly in the nucleolus, and disturbances in the process at any point can potentially lead to nucleolar stress, is also known ribosomal stress . To manaSome RNA virus infections are accompanied by viral proteins that need to be transported to the nucleolus and possibly affect ribosome biogenesis. The HCV NS5B protein and core protein upregulate the expression of rRNA, thereby mediating the production of heterogeneous ribosomes and promoting viral protein translation . It is wThe host is a whole interconnected organism, and viral infections can affect the metabolic functions of the organism in various ways. Viruses and host cells are in a constant state of battle, and an increasing number of mechanisms and countermeasures are gradually being revealed that play an important role in maintaining an effective infection process and the stability of the internal environment of the host cell.rRNA and RPs are the main components of ribosomes. Presently, we know that viral infection induces post-translational modifications of RPs, but it remains unknown whether rRNA changes occur due to viral infection. rRNAs are the main effectors of ribosome dynamics during mRNA decoding, peptide bond formation, and translation . In addiMutations, amplicon changes, and post-transcriptional modifications of rRNA alleles not only affect the fidelity of ribosomal translational mRNA, but are also a major aspect that contributes to ribosomal heterogeneity . HoweverDifferences in post-translational modifications of RPs, such as phosphorylation, acylation, methylation, or glycosylation, contribute to ribosomal heterogeneity. Recent studies have shown that the deletion of RPs that constitute the subunits of the ribosome alters the level of translation of cellular proteins . DiffereCurrently, it is known that the different translation strategies used by the viral genome to manipulate the ribosome cause changes in ribosomal conformation . HoweverTo date, there are no reports that identify viral-induced heterogeneous ribosomal components. Therefore, it is crucial to conduct more studies on heterogeneous ribosomes to clarify the translation mechanism of viral proteins.Viruses antagonize the antiviral immune response of the host and promote virus replication through complex interactions with the host. At present, several studies have shown that ribosomes have non-ribosomal functions in addition to translation after virus infection.Ribosomal proteins positively regulate viral proliferation, mainly by promoting the replication, transcription, and assembly of viral genomes or by serving as viral receptors. The lymphocytic choriomeningitis virus (LCMV) Z protein interacts with the ribosomal protein RPLP0 and plays an important role in virion assembly . MoreoveSome RPs have antiviral functions. RPs interact with viral proteins to directly inhibit viral transcription or translation. During CSFV infection, the viral protein Npro interacts with uS10 and induces Npro degradation by the proteasome . BecauseIn summary, the biological significance of many RPs in the infection of different viruses is gradually being revealed. In recent years, the interaction between viral and host proteins has been analyzed by high-throughput quantitative mass spectrometry where over 50 RPs interact with SFV capsid proteins . HoweverRibosomes are protein synthesis factories not only for eukaryotic mRNA but also for viral mRNA. After the virus infects the host cell, it needs to manipulate the ribosome to complete the translation of viral protein. The control of the ribosome by viruses involves two main aspects. First, viruses shut down the ribosome to translate host mRNA. For example, some viral proteins regulate the compartmentalization of organelles or recruit translation initiation factors to facilitate the assembly of the translation machinery and viral protein translation. To inhibit host mRNA translation by the ribosome, viruses also promote the assembly of large/small ribosomal subunits by regulating the secondary structure of viral mRNAs. Second, viruses manipulate the ribosome to complete viral protein translation. The viral mRNA secondary structure not only influences the assembly rate of the large and small subunits of the ribosome, but it also regulates how ribosomes move on the viral mRNA during different translation stages. Viral infection also induces changes in the composition and conformation of ribosomes, resulting in the formation of heterogeneous ribosomes. Therefore, analyzing the mechanism of viral control of ribosomes and studying the properties and assembly mechanisms of heterogeneous ribosomes required for viral protein translation will help us to fully understand the mechanism of viral protein translation.With the development of science and technology, especially proteomics and cryo-EM, the structure of eukaryotic ribosomes has been gradually revealed. The crystal structure of the human 80S ribosome and the crystal structure of the yeast 90S ribosomal precursor has been reported, thereby opening a new door for designing small-molecule drugs targeting the ribosome . Some reGL and JZ: conceptualization and review and editing. XW and JZ: writing original draft preparation. GL: supervision and project administration. DZ and XW: visualization. All authors have read and agreed to the published version of the manuscript.This study was sponsored by the Natural Science Foundation of Shanghai (22ZR1476300), the National Natural Science Foundation of China (32000109 and 32172832), the Shanghai Sailing Program (20YF1457700), Shanghai Municipal Science and Technology Major Project (ZD2021CY001), and the Central Public-interest Scientific Institution Basal Research Fund (2022JB01).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In response to the global call for emission reduction, China has assumed international responsibility for energy conservation and emission reduction by enacting several environmental policies to save energy and reduce consumption. However, it is debatable whether the increased uncertainty in environmental policies negatively affects firms’ emission reduction. Few studies have examined this relationship based on micro-level data. Therefore, this study constructs a theoretical framework of environmental policy uncertainty affecting firms’ pollution emissions. Based on comprehensive data from the Chinese Industrial Enterprise Database, the Chinese Industrial Enterprise Pollution Emission Database, and the Chinese Patent Database from 2002 to 2014, we empirically analyzed the impact of environmental policy uncertainty on firms’ pollution emissions. The results show that (1) environmental policy uncertainty significantly aggravates the pollution emission intensity of industrial enterprises; (2) environmental policy uncertainty inhibits the improvement of enterprises’ innovation capacity, reduces their human capital stock and foreign investment, and aggravates their pollution emission; (3) environmental policy uncertainty has significant heterogeneity on enterprise pollution emissions, that is, environmental policy uncertainty has a greater impact on non-export enterprises, large enterprises, young enterprises, capital-intensive enterprises, state-owned enterprises, and enterprises in polluting industries and central regions. This study provides a useful reference for the improvement of environmental policy and the green transformation of enterprises. Approximately four decades of economic growth made China the world’s second-largest economy in 2010. However, this economic development brought in its wake serious resource constraints, high levels of pollution by enterprises, and the degradation of the ecosystem. According to the 2020 Report on China’s Ecological and Environmental Conditions, only 59.9% of cities across the country have acceptable air standards, high pollution emissions cause 1.2–1.4 million deaths annually , the ImpIn the context of the green transformation and development of enterprises, enterprise pollution emission has become a hot topic in academia. Additionally, government regulation policy has an immense impact on enterprise pollution emission. If environmental policies are stringent or frequent, the technological progress of enterprises will be hindered, which will eventually lead to the development of enterprises . BurtrawRegarding the influencing factors of enterprise pollution discharge, the existing literature mainly focuses on technological innovation, human capital, and foreign investment. The development experience of developed countries shows that technological innovation can fundamentally solve the problem of excessive pollution emissions of enterprises and improve the competitiveness of enterprises’ products, and the improvement of green innovation ability can help enterprises occupy market share . When thHuman capital—an important aspect of economic efficiency and green development—influences the maximization of resource utilization efficiency and breaking through the constraint of diminishing marginal returns. Investing in enterprise human capital enhances the quality of managers and laborers, thereby improving the energy utilization efficiency of enterprises. When enterprise human capital stock is high, it can significantly improve the absorption capacity and application ability of energy-saving technologies . Kurtz eThe influence of foreign investment on enterprises’ pollution emissions has not been determined yet, and research has mainly focused on the “pollution paradise hypothesis” and “pollution halo hypothesis.” The pollution paradise hypothesis holds that foreign-funded enterprises tend to move to countries with weak environmental regulations. Here, local enterprises engage in a vicious competition with transferring enterprises—most of which are pollution-intensive industries—reducing investment in green technology to save costs and increasing pollution emission intensity . The polExisting studies on environmental policy uncertainty focus on its connotations and impacts on enterprise investment, technological innovation, and economic development. Uncertainty implies that actors make decisions without access to complete information, and therefore, the specific impact of their decisions cannot be accurately predicted. When the object of uncertainty is environmental policy, then environmental policy uncertainty is formed . EnvironTo date, studies have been conducted on enterprises’ pollution emissions from the perspectives of government regulation policies, influencing factors, the connotations of environmental policy uncertainty, and its influence on foreign investment, employment, and enterprise innovation. However, little research has been performed on whether increasing environmental policy uncertainty impacts enterprise pollution emissions. Additionally, due to the lack of an effective micro-basis of macro-level research, the emission reduction path of the macro-level influence mechanism acting on micro-enterprises is not clear. In fact, how to deal with the increasing uncertainty of environmental policy is the basis and key to understand the relationship between policy fluctuation and emission reduction at the macro level. Therefore, based on the combined data of the China Industrial Enterprise Database, China Industrial Enterprise Pollution Emission Database, and China Patent Database from 2002 to 2014, this study illustrates the impact and mechanism of environmental policy uncertainty on enterprise pollution emissions from the perspective of micro-enterprises.Based on the research by Bloom, Bond, and Van Reenen , this stIn Formula (1), B is the demand shock faced by the enterprise. Based on the relationship between demand and supply, the income function of the enterprise is as follows:At this point, the demand function faced by the enterprise is:X indicates that the production and investment of enterprises are affected by the uncertainty of environmental policies, making K and labor L are completely flexible and their variable costs are 0. We substituted Formula (2) into Formula (4), and the return function is:We defined n Reenen , assuminTo a homogeneous equation:S is the influence coefficient of enterprise innovation capacity on enterprise emission reduction (0 < s < 1). Additionally, the technological innovation of enterprises reduces the cost of enterprises’ pollution emission; e is the proportion of the impact of technological innovation on the cost of enterprises’ emission reduction (0 < e < 1). Additionally, the innovation cost of enterprises is affected by the uncertainty of environmental policy and innovation capability.The emission reduction in enterprise pollution is not only affected by the original pollutant discharge Assume that the total cost of the enterprise is In Formula (8), The total profit function of the enterprise is:When profit is maximized, the first derivative of profit is 0, then:According to Formula (12), the relationship between environmental policy uncertainty According to Formula (13), the uncertainty of environmental policy will inhibit the improvement of enterprises’ innovation ability, whereas the technological innovation of enterprises will promote the upgrading of industrial structure, improve energy utilization efficiency, and further reduce enterprises’ pollution emissions ,26. TherThe production function is adjusted on the basis of Formula (1), and the meaning of the letters remains unchanged. The specific function form is as follows:The larger the inflow of labor, the larger the stock of human capital . The spes1 is the influence coefficient of the stock of human capital on emission reduction (0 < s1 < 1). Human capital can internalize technical knowledge to overcome the diminishing marginal returns of production and reduce the cost of enterprise pollution emission. e1 is the proportion of human capital affecting enterprise emission reduction cost (0 < e1 < 1). The cost of introducing human capital is affected by environmental policy uncertainty and the effect of human capital promoting emission reduction.There is a positive correlation between the stock of human capital and emission reduction, and Assume that the total cost of the enterprise is According to Formula (18), the uncertainty of environmental policy will inhibit the improvement of enterprise human capital stock. The new economic growth theory states that human capital can overcome the law of diminishing marginal returns on means of production and then realize economic growth and enterprise emission reduction ,29. TherThe production function is adjusted on the basis of Formula (1), and the meaning of the letters remains unchanged. The specific function form is as follows:As foreign investment will increase the production and working capital of enterprises, it is assumed that s2 is the influence coefficient of foreign investment on emission reduction (0 < s2 < 1). Foreign investment can expand the production scale of enterprises to produce scale effect and reduce the pollution emission cost of enterprises. e2 (0 < e2 < 1) is the proportion of foreign investment affecting enterprise emission reduction cost, which is affected by both environmental policy uncertainty and foreign investment income.The increase in foreign investment makes enterprises strict in the formulation of environmental standards, and most multinational companies will implement international environmental standards, thus reducing the pollution emissions of enterprises. The amount of foreign investment is positively correlated with emission reduction, and Assume that the total cost of the enterprise is Increased foreign investment can significantly improve financial support for enterprises to reduce emissions. Additionally, foreign enterprises bring advanced emission reduction technologies that facilitate the implementation of international environmental standards in China. Moreover, by introducing green cleaning products from the home country, foreign investment has a clean technology spillover effect on its upstream and downstream industries, which is conducive to promoting emission reduction in domestic enterprises. Therefore, environmental policy uncertainty can inhibit foreign investment and aggravate the pollution emission of enterprises.Currently, China’s economy is in a transition phase, and the government’s policy environment is experiencing significant fluctuations. The main feature of this phase is the increasing fluctuations and uncertainty of environmental policy. On the one hand, advanced production and pollution discharge technologies require enormous human and material investment, whereas the positive externality of technological innovation reduces the willingness of enterprises to invest in innovation. Additionally, environmental policy uncertainty intensifies the severe fluctuation of micro-enterprise performance, which increases the difficulty of operation. Enterprise managers will avoid the uncertainty of investment returns as much as possible because of their risk-averse and profit-oriented mindset and pay more attention to short-term investment and investment with definite returns. Then, they will reduce the investment in R&D . AdditioHypothesis 1 (H1).Environmental policy uncertainty can inhibit the improvement of enterprises’ innovation ability and aggravate enterprises’ pollution emission.When the uncertainty of environmental policy increases, it induces enterprise managers to make investments with definite short-term benefits. The tendency of enterprises to choose investment projects with higher risks and less obvious short-term returns will be weakened. The human capital investment of enterprises has the characteristic of not having an obvious income effect, and relative to other factors of production, human capital adjustment cost is low . In ordeHypothesis 2 (H2).The uncertainty of environmental policy increases the pollution emission of enterprises by inhibiting the increase in human capital stock of enterprises.The fundamental purpose of foreign investments is profit. When the uncertainty of environmental policy increases, it becomes difficult to accurately predict the income of foreign investment. To maximize interests and avoid risks, investors tend to invest in enterprises with clear and stable returns; they may even reduce investments in domestic companies because it is difficult to accurately control the risk of investment returns. The uncertainty of environmental policies has aggravated the fluctuation of enterprise performance and raised the financing difficulty of enterprises, which has hindered the production and operation of domestic enterprises. In the case of uncertain returns, foreign enterprises further reduce investment to reduce risks, so the increase in environmental policy uncertainty reduces foreign investment. Foreign investment has been a key component of economic growth and an important means of transferring modern technology and providing employment to host countries. Especially in recent years, inflows of foreign investment have become more important than international trade . ForeignHypothesis 3 (H3).Environmental policy uncertainty worsens pollution emissions by inhibiting foreign investment.To verify the impact of environmental policy uncertainty on enterprise productivity, the benchmark model is set as follows:To measure the enterprise pollution emission intensity comprehensively and accurately, in this study, the comprehensive index method was used. Based on data availability and the harmfulness of pollutants, we mainly selected five individual indicators of industrial wastewater: chemical oxygen demand, industrial waste gas, sulfur dioxide, smoke, and dust emissions to measure the intensity of enterprise pollution emission . First, Then, The higher the value of The change in both external and internal environment increases the uncertainty of environmental policy, which causes a fluctuation in the enterprise’s sales revenue . TherefoThe ordinary least squares method was used in this study to estimate the abnormal sales income of enterprises in the past three years.The moderating variables are enterprise innovation, human capital, and foreign investment. Enterprise innovation  and (2) of Enterprises can be categorized as large- and small- and medium-sized enterprises based on whether the number of employees exceeds 1000 according to the classification standards of “Measures for The Classification of Statistically Large, Small and Medium-sized Enterprises (2017).” We aimed to investigate whether the impact of environmental policy uncertainty on enterprise pollution emissions is heterogeneous because of different enterprise sizes. Columns (3) and (4) of Based on the median time of establishment, enterprises are divided into young and old enterprises. Columns (1) and (2) of Based on the median capital labor ratio of enterprises, they are categorized as labor-intensive and capital-intensive enterprises. Columns (3) and (4) of Enterprises are divided into state-owned and non-state-owned enterprises depending on whether they are state holding enterprises or not. Columns (1) and (2) of Companies are divided into clean and polluting enterprises according to their industry. Columns (3) and (4) of China is divided into eastern, central, and western regions to study whether the environmental policy uncertainty in different regions has different effects on enterprises’ pollution emission intensity. The results are shown in In this section, the uncertainty of environmental policy is re-measured to verify whether its impact on enterprise pollution emission intensity is robust. The previous article mainly refers to the Ghosh and Olsen  algorithThe pollution emission intensity of enterprises mentioned above was measured using the comprehensive index method. In this section, five single pollution emissions of enterprises are used to measure the pollution emission intensity of enterprises. The regression results are shown in The entry and exit of enterprises in the sample period interferes with the impact of environmental policy uncertainty on enterprise pollution emissions. Therefore, this section deletes entering and exiting enterprises in the sample period for robustness tests. The regression results are shown in Column (1) of In this study, macro-variables were controlled to eliminate the influence of time factor on empirical results, but time factors may still have had an impact on the results. Robustness was analyzed from two perspectives. (1) The sample period of this study was 2002–2014. The State Environmental Protection Administration set up six inspection centers in 2006. The Environmental Protection Law was introduced in 2008, and ecological progress was proposed at the 18th National Congress of the Communist Party of China in 2012. To control the influence of these factors, only samples from 2012 to 2014 are used for regression in this section. (2) We considered deleting the time dummy variable and substituting the rest of the dummy variables into the regression model to control the influence of the time effect. The results are shown in Columns (2) and (3) of To eliminate the influence of outliers on regression results, variables were treated with Winsor at the level of 1%. The regression results are shown in Column (4) of As environmental policy uncertainty is caused by the fluctuation of national macro-policy, and the micro-behavior of individual enterprises can hardly affect the macro-environmental policy, there is almost no reverse causality between enterprise pollution emissions and environmental policy uncertainty. Additionally, the fixed effects of enterprises, industries, regions, and years are strictly controlled in the empirical analysis of this study, which effectively avoids the endogenous problems caused by omitted variables. As eliminating the lag term of enterprise pollution emission intensity may affect the results, referring to Fang et al. (2015), this study added the variable  Formula ; the resBased on the above theoretical analysis, environmental policy uncertainty can affect the pollution emission intensity of enterprises in three ways: enterprise innovation, human capital, and foreign investment. This section empirically tests the impact of environmental policy uncertainty on enterprise pollution emission intensity through these three channels. The specific model is as follows:Formula (29) shows that environmental policy uncertainty affects enterprise pollution emission intensity through firm innovation, Formula (30) shows that environmental policy uncertainty affects enterprise pollution emission intensity through human capital, and Formula (31) shows that environmental policy uncertainty affects enterprise pollution emission intensity through foreign investment. The regression results are shown in The purpose of enterprise investment is profit maximization. With an increase in environmental policy uncertainty, the silent risk of enterprise investment and innovation also increases. Moreover, innovation investment is a project with high risk and a long cycle, so enterprise innovation investment needs sufficient capital guarantee. When the uncertainty of the environmental policy facing enterprises increases, the uncertainty of enterprise innovation investment income increases, and to reduce risks, enterprise managers decrease investment in innovation. This lowers the innovation capacity of enterprises. As can be seen from Column (1) of According to the classical financial theory, when an enterprise faces greater uncertainty in the external environment, it reserves more cash to cope with unknown shocks . When thThe change in external environment is an important factor affecting foreign investment, the main purpose of which is profit. When the uncertainty of investors’ profit expectation increases, the opportunity cost of enterprise investment also increases, and foreign capital flows to projects with more definite investment returns. Therefore, the increased uncertainty of environmental policy reduces foreign investment expectations. Column (3) of Based on the combined data of the China Industrial Enterprise Database, China Industrial Enterprise Pollution Emission Database, and China Patent Database from 2002 to 2014, we empirically analyzed the impact of environmental policy uncertainty on enterprise pollution emission.The marginal contributions of this study are as follows: First, at the research level, the existing literature mainly discusses the impact of environmental regulations on regional environmental pollution emissions from a macro-perspective; the micro-viewpoint is the basis and key to understand the macro-perspective. From the perspective of micro-enterprises, this study was mainly based on the Chinese Industrial Enterprise Pollution Emission Database, and chemical oxygen demand, industrial waste gas, sulfur dioxide, smoke, and dust emissions were selected to measure the intensity of enterprise pollution emission. The composite index method makes the measurement result closer to the real enterprise pollution emission intensity. It also systematically discusses the influence of environmental policy uncertainty on enterprise pollution emissions to further refine the existing research and establishes the micro-basic cognition of the relationship between environmental policy uncertainty and enterprise pollution emissions. Thus, it makes up for the deficiencies of existing research in the field of micro-enterprises.Second, in terms of research content and perspectives: (1) from the perspective of increasing environmental policy uncertainty, this article discussed the impact and mechanism of environmental policy uncertainty on enterprise pollution emissions and provides a new research perspective for enterprise pollution emissions; and (2) there is often summing bias in regional summing data, which may cover up or change the real relationship between variables in empirical tests, and as macro-research ignores the heterogeneity of enterprises, it is difficult to investigate how enterprises’ emission reduction behaviors with different characteristics respond to environmental policy uncertainties. This article discussed the heterogeneity of enterprise export status, enterprise size, enterprise age, enterprise type, enterprise ownership, and enterprise industry category, which helps to form a comprehensive understanding of the relationship between environmental policy uncertainty and enterprise pollution emissions.Third, regarding the mechanism of action, the existing literature on the mechanism of enterprise emission reduction is increasingly mature. However, from a new perspective of environmental policy uncertainty and micro level, the effectiveness of these mechanisms is questionable. Based on the theoretical model, this study revealed that environmental policy uncertainty affects enterprise pollution emissions through three channels: technological innovation, human capital, and foreign investment. It further deepened the understanding of the complete logical chain of environmental policy uncertainty to enterprise pollution discharge.Forth, ordinary least squares was selected as the analysis method, and the interference of time, industry, region, and individual was controlled, so that the correlation coefficient between environmental policy uncertainty and enterprise pollution emission intensity was closer to the reality.The research still has certain limitations and should be further deepened. First, in view of the limitations of research methods, this paper selected panel data to analyze the heterogeneity of the Enterprise Pollution Emission Intensity and influencing factors in China; however, it lacked an analysis of the dynamic evolution of space. In the future, appropriate research methods will be selected to conduct a more in-depth spatial dynamic analysis of the Enterprise Pollution Emission Intensity. Second, since the latest data were only collected in 2014, if there are updated data in the future, we will further update the data in the following study.Based on the combined data of the China Industrial Enterprise Database, China Industrial Enterprise Pollution Emission Database, and China Patent Database from 2002 to 2014, we empirically analyzed the impact of environmental policy uncertainty on enterprise pollution emission. The results show that:First, the impact of environmental policy uncertainty on enterprise emission reduction was discussed theoretically and empirically. Second, the heterogeneity of environmental policy uncertainty on enterprise pollution emission was discussed from the perspectives of enterprise export status, enterprise size, enterprise age, enterprise type, enterprise ownership, enterprise industry category, and different region. Finally, we empirically examined whether environmental policy uncertainty can increase enterprise pollution emissions by inhibiting enterprise innovation, human capital, and foreign investment.The conclusions of this study are as follows: (1) The uncertainty of environmental policy significantly intensifies the pollution emission intensity of enterprises and aggravates regional environmental pollution. (2) Environmental policy uncertainty intensifies enterprises’ pollution emission intensity through three transmission channels: enterprise innovation, human capital, and foreign investment. In other words, environmental policy uncertainty intensifies enterprises’ pollution emission intensity by inhibiting the improvement of their innovation ability, reducing their human capital stock, and discouraging foreign investment. (3) Environmental policy uncertainty has significant heterogeneity on enterprise pollution emissions, that is, environmental policy uncertainty has a greater impact on non-export enterprises, large enterprises, young enterprises, capital-intensive enterprises, state-owned enterprises, and enterprises in polluting industries and central regions.The conclusions of this study have enlightening significance for the adjustment of environmental policy and enterprise green transformation. (1) The government should give full play to the decisive role of the market in resource allocation, strengthen macro-regulation, and reduce uncertainties in environmental policies. Currently, China needs enormous external capital, new talent, and green technology to promote economic transformation and upgradation. The government should build a stable economic environment to help enterprises acquire foreign capital, advanced technology, and new talents, and accelerate the transformation or elimination of high-pollution, high-consumption enterprises. (2) The government should construct a stable and efficient compound environmental regulation policy system. Although the government’s environmental regulation measures can curb pollution emission by enterprises, the frequent introduction of environmental policies increases environmental policy uncertainty, which inhibits enterprise innovation, human capital, and foreign investment. Therefore, the government should maintain the sustainability of local environmental regulation policies, effectively promote the coordination and cooperation of heterogeneous environmental regulation tools, and reduce the negative impact of environmental policy uncertainty on enterprise emission reduction. (3) In the process of policy formulation and implementation, the government needs to further refine specific measures. Due to the significant heterogeneity of environmental policy uncertainty on enterprise pollution emission, the government needs to formulate detailed measures. As such, we will focus on monitoring pollution emissions of non-export enterprises and small enterprises, so as to minimize the negative impact of environmental policy uncertainty on enterprise emission reduction. In general, this study introduced a new research perspective and microscopic evidence for the green transformation development of Chinese enterprises.