Polyphenols play a therapeutic role in vascular diseases, acting in inherent illness-associate conditions such as inflammation, diabetes, dyslipidemia, hypertension, and oxidative stress, as demonstrated by clinical trials and epidemiological surveys. The main polyphenol cardioprotective mechanisms rely on increased nitric oxide, decreased asymmetric dimethylarginine levels, upregulation of genes encoding antioxidant enzymes via the Nrf2-ARE pathway and anti-inflammatory action through the redox-sensitive transcription factor NF-κB and PPAR-γ receptor. However, poor polyphenol bioavailability and extensive metabolization restrict their applicability. Polyphenols carried by nanoparticles circumvent these limitations providing controlled release and better solubility, chemical protection, and target achievement. Nano-encapsulate polyphenols loaded in food grade polymers and lipids appear to be safe, gaining resistance in the enteric route for intestinal absorption, in which the mucoadhesiveness ensures their increased uptake, achieving high systemic levels in non-metabolized forms. Nano-capsules confer a gradual release to these compounds, as well as longer half-lives and cell and whole organism permanence, reinforcing their effectiveness, as demonstrated in pre-clinical trials, enabling their application as an adjuvant therapy against cardiovascular diseases. Polyphenol entrapment in nanoparticles should be encouraged in nutraceutical manufacturing for the fortification of foods and beverages. This study discusses pre-clinical trials evaluating how nano-encapsulate polyphenols following oral administration can aid in cardiovascular performance. Natural bioactive agents are attractive molecules, as their implicit safe status allows them to be tested as specific or multiple target regulators in signaling or functional human pathways, while also comprising promising therapeutic adjuvant candidates against multifactorial and complex physiopathological conditions, including degenerative diseases and metabolic dysfunctions. In food matrices, natural bioactive compounds contribute to color , bitternSeveral mechanisms are involved in the cardioprotective role of polyphenols. These compounds increase nitric oxide (NO) release and vasodilation in endothelial cells through several nitric oxide synthase (eNOS) effects, including gene expression, catalysis activation by phosphorylation of the eNOS Ser1179 residue, and decreased asymmetric dimethylarginine (ADMA) levels, and an eNOS inhibitor, by increasing dimethylarginine dimethylamino hydrolase (DDAH) activity ,19,20. IConversely, in vivo polyphenol performance may be limited due to the low hydrophilicity and poor intrinsic dissolution rate of these compounds or their physical or chemical instability ,28. In aNano-encapsulation is a submicroscopic technology used to carry active solid or liquid substances into a 10–1000 nm colloidal system, termed nanoparticles (NPs) . NPs canNano-encapsulation has been substantially applied in the formulation of novel drugs and as a high-technology food input in order to protect bioactive compounds such as polyphenols, essential oils, peptides, oligonucleotides, and antioxidants from oxidation or lysis by external factors, including pH, temperature variations, and exposure to light, ensuring their stability and increasing the half-lives of active principles. As a carrier system for therapeutic agents, nanoparticles can provide a controlled release of the active principle after oral, parenteral, or topical administration and, at the same time, guarantee better solubility and chemical structure stability, thus ensuring target achievement . Due to Foods can be enriched in polyphenols by adding NPs carrying pure and concentrated polyphenols obtained from edible plants or food grade microorganisms, such as yeast or acid lactic bacteria, in order to protect polyphenols from oxidative degradation and conferring all the aforementioned stability and advantages .The main natural (or food-grade) polymers obtained from plants and vegetables used to nano-encapsulate polyphenols are presented herein. The ability of these polymers to preserve polyphenol structure, bioactivity, and gastrointestinal bioaccessibility are addressed. The current framework concerning possible polyphenol gastrointestinal toxicity, bioavailability, and bioactivity addressed through clinical trials is reviewed and, finally, the projection of the performance of nano-encapsulated polyphenols in aiding cardiovascular impairments is discussed.Natural polymers, such as carbohydrates, proteins and lipids, are the most abundant organic matter in nature and essential for the existence of living organisms, as they perform vital functions such as comprising structural cell and tissue components and acting in transport and catalysis processes as energetic reserves and in energy transformation, among others . Due to Proteins such as gelatin, albumin, and casein are the most used proteins to obtain NPs. Gelatin is an encapsulant agent obtained from the partial hydrolysis of collagen and has been used to nano-encapsulate polyphenols alone or associated with surfactants and polysaccharides with opposite charges, such as cellulose, carboxymethylcellulose, chitosan, or arabic gum ,46,47,48−1 of each compound. Hydrogen bonds between the phenolic and aliphatic hydroxyls of catechin and gelatin, respectively, allowed for the spontaneous formation of NPs without the use of surfactants and crosslinkers. The gelatin-catechin NPs retained their antioxidant activity as evaluated by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays after 3 weeks stored at room temperature, indicating the effectiveness of gelatin, concerning the chemical and bioactive stability of catechin [w/v %) followed by the addition of glutaraldehyde , resulting in NPs with a uniform morphology and diameters ranging from 130 to 200 nm [Polyphenol adsorption onto gelatin NPs occurs through the formation of hydrogen linkages between phenolic rings and hydrophobic amino acids . Gelatincatechin . An enrio 200 nm . In that−1 and at temperature and incubation time above 20 °C and 24 h, respectively. The adsorption capacity of icariin was significantly higher than genistein, possibly due to the greater number of hydroxyl (–OH) groups. The amounts of adsorbed genistein and icariin were greater than their individual adsorptions, most likely due to the presence of more hydrogen linkages between phenolic rings and hydrophobic amino acids [Karthikeyan et al.  preparedno acids . This caOther proteins used as polyphenol nano-encapsulant agents consist of human or bovine serum albumins, HSA and BSA, both presenting a molecular mass of 66.5 kDa, synthesized in the liver and representing the most abundant proteins in plasma . AlbuminBSA-NPs loaded with rutin were formulated by nano-spray drying by dissolving 5 mg of rutin and 25 mg of BSA in water (6.6 mL), ethanol (3 mL), and Tween-80 (0.4 mL). The NPs were 316 nm in size and only 32% of the rutin was encapsulated due to low affinity to BSA and thermal polyphenol degradation due to high spray drying temperatures (100 °C). Conversely, BSA-rutin NPs comprised a homogeneous and stable nano-capsule population (PDI 0.27) with a surface charge of −32.1 mV. Rutin entrapment guaranteed a time control release and increased rutin IC50 by two-fold compared with free rutin for 72 h, as determined by ABTS+ assays . BSA-NPsThus, BSA-NPs maintain polyphenol molecule stability and allow for their controlled release, causing them to be gradually available to exert their physiological effects, while preserving their activity over time . Acetamiw/w) and chloroform/water (1:19), freeze-dried, and stored for 3 months at room temperature displayed no morphological alteration concerning 130–150 nm nano-capsules formulated in chloroform/water (1:19). The prepared HSA-NPs enhanced curcumin solubility by 300-fold and displayed cryoprotectant properties [Curcumin nano-encapsulated in HSA 2% (operties .v/v). Non-encapsulated curcumin displayed a 40-fold increased water dispersion, resulting in high antioxidant power as assayed by the Trolox assay (8.87 mM) when compared with the free form (<1 mM). The enhanced dispersion and uniform curcumin distribution in the reaction medium and surface area inherent to casein nano-capsules seem to facilitate the reaction kinetics and bioactivity of the active principle [Caseins, the major milk phosphoproteins, exhibit a micellar structure ranging from 50 to 300 nm, stabilized by hydrophobic interactions and bonds between calcium phosphate and serine residues, and have been applied in phenolic entrapment. Casein nanoparticles promote structural phenolic stability, enhancing their solubility and bioavailability ,67,68,69rinciple . A similrinciple .A novel approach in the production of stable NPs in the gastrointestinal environment has been developed using a liquid-liquid dispersion method applied in the encapsulation of ferulic acid in a zein-casein-lysine matrix. The NPs were 199 nm in diameter, displaying a slow and prolonged release of 4% of the polyphenol for 48 h at physiological pH (pH 7.4). The strong interaction between ferulic acid and the nano-capsule-matrix was a mandatory factor for its sustained release, maintaining polyphenol protection and, consequently, its biological effects for a long period of time. However, the lack of a kinetic profile determination at gastric pH comprises a study limitation regarding NP characterization and usage .w/w/w) in order to promote greater chemical stability. The NPs were 186 nm in size, displaying a high encapsulation efficiency (86.8%) and zeta potential (−35.8 mV) and were monodispersed (PDI 0.10), indicating feasibility in encapsulating a mixture of polyphenols. The formulation preserved 90% and 80% of EGCG for 15 and 45 days at 4 °C, respectively, while totally degrading at 25 °C. When nano-encapsulation was followed by freeze-drying, 90% of EGCG remained stable for 12 months at 25 °C without any physicochemical changes [Finally, caseins were used to encapsulate the flavonoid epigallocatechin gallate (EGCG) alongside glucosamine (GA) at a 1:2:8 ratio  particles through gelatinization and emulsification with Tween-80, forming 57 nm NPs. Resveratrol was efficiently encapsulated compared to curcumin (70.9 vs. 49.3%), while curcumin exhibited a slower release rate throughout 24 h (16.3 vs. 87%) and was better captured by cells compared resveratrol, demonstrating that alginate is a potential nanocarrier for hydrophobic polyphenols.The possibility of enriching NPs for the delivery of a mixture of hydrophobic polyphenols was tested by Saralkar and Dash . Curcumi−1 [In an optimized methodological approach, quercetin was encapsulated by chitosan gelatinization using sodium tripolyphosphate (TPP) as a crosslinker, followed by polyelectrolytic complexation with sodium alginate using alginate-chitosan at a 1:2 ratio and quercetin at 7.5 mg·mL−1 . NPs ranw/v) loaded with curcumin (0.25 mM) by nano-precipitation using ethanol, an oil mixture , and a surfactant, formed 87 nm NPs with 78% loading efficiency. Due to high starch hydrophilicity, greater surface area, and reduced size, NPs exhibited greater interaction with aqueous media and resulted in higher curcumin solubility compared to its free form. In addition, the use of starch NPs allowed for a controlled curcumin release of approximately 93% for 10 days under physiological pH [Starch has been applied as a wall material in nanotechnology, due to its solubility, emulsification, and biocompatibility characteristics. Its versatility relies on its structural-derivatives, maltodextrin and cyclodextrin, obtained by physical and chemical methods ,90. The gical pH .Pisum sativum), corn (Zea mays), and potato (Solanum tuberosum), have been applied in quercetin encapsulation by the nanoprecipitation method using 0.1 M HCL as the non-solvent. The higher the amylopectin content, the better the quercetin entrapment and antioxidant activity, as follows: potato (49% loading) > pea (44% loading) > corn (20% loading) [The loading capacity of starch depends on amylopectin content. Starch obtained from different edible vegetables such as pea (loading) .Eleocharis dulcis), horse chestnut (Aesculus hippocastanum), and lotus stem (Nelumbo nucifera), have been used to encapsulate resveratrol, producing 691, 419, and 797 nm NPs, respectively, with an average encapsulation efficiency of 79%. Nano-encapsulation provided thermal stability to resveratrol, observed by the increases in NP transition temperatures when exposed to 200 °C [Other starch sources, such as water chestnut  cross-linked with TPP (0.5 mg·mL−1), was used to encapsulate quercetin and myricetin (5 mg·mL−1), generating 123.75 nm and 153 nm NPs, respectively. Both NPs exhibited high retention capacity greater in myricetin (89% vs. 82%) due to the presence of an extra hydroxyl in ring B, allowing for greater interaction with the positively charged matrix. The chitosan-TPP NPs provided a controlled polyphenol release at physiological pH (7.4) during 96 h, contributing to their prolonged antioxidant effect in relation to free flavonoids [Recently, chitosan  cross-linked with CaClveratrol .−1, respectively, resulting in 219 nm sized NPs and 63% encapsulation. The anthocyanin-NPs were highly stable beverages, maintaining 84% encapsulation for 35 days at 4 °C, 68.4% for 12 days at 25 °C, and 30% for 9 days at 40 °C. However, free anthocyanins were less stable, at 71.2%, 49.7%, and 6.3% under the same conditions [Similarly, He et al.  applied nditions .Camellia sinensis) have also been tested as active agents in chitosan NPs [Other polyphenols, such as gallic acid, catechin, procyanidins, ferulic acid, quercetin, and polyphenols from green tea extract  are a colloidal system synthetized by the dispersion of two immiscible liquids, such as oil and water, stabilized by a surfactant compound, forming droplets ranging from 20 to 100 nm. In this system, the active principle, a hydrophilic or hydrophobic molecule, is dissolved in water or oil, and the active solvent is then emulsified in water (oil-in-water) or oil (water-in-oil) in the presence of surfactants  Figure . In the Peanut, corn, olive, and sesame oils and medium chain triglycerides (6 to 12 C) are commonly used as active principle-lipid coatings, while Tween-20, Tween-80, glycerol monooleate, soya lecithin, and polyoxyethylene can be employed as emulsifiers to stabilize the oil-water interface ,121. EncCamellia sinensis (400 mg) were encapsulated in corn oil using water and polysorbate 80 (oil-in-water), generating stable 99.4 nm NEs, which display no significant size modifications, aggregation, or pH after 20 days of storage at 4, 25, or 40 °C [In this sense, tea polyphenols from or 40 °C . Trans-ror 40 °C .According to Sessa et al. , the traBiocompatible NEs developed using isopropyl myristate combined to ionic and non-ionic surfactants  plus transcutol as an aqueous solvent (oil-in-water) were produced for curcumin encapsulation by emulsification at low energy. Curcumin-loaded NEs were 165 nm in size, with a low PDI of 0.072 and stable for 60 days at room temperature . This inLiposomes are used in the agricultural, food, and pharmaceutical industries as carriers for both nucleic acids and nutraceutical products such as vitamins, proteins and enzymes, and whole herbal extracts . Due to The main liposome components are lipids or phospholipids that can contain sterols incorporated in their structure. Cholesterol is the most widely used sterol in liposome syntheses, as it mimics the cell membrane and increases the stability of the lipid structure by modulating the lipid bilayer fluidity .In addition, niosomes, self-assembled vesicles, are formed by hydration of non-ionic surfactant, cholesterol, or other amphiphilic molecules and are able to transport both hydrophilic and hydrophobic molecules. Their chemical stability, easy preparation and low-cost production make them versatile nanocarriers for the delivery of drugs and bioactive compounds by several routes including oral, ocular, topical, pulmonary, parenteral, and transmucosal ,136,137.There is evidence that NLs may comprise good delivery nanodevices to supplement polyphenols in a safe and quick way to individuals presenting inflammatory and oxidative conditions .Nanoliposomes (NLs) and liposomes display identical chemical structures and thermodynamic properties, but the former exhibit greater surface area, stability, solubility, bioavailability, delayed body clearance, and precision targeting ,140. In w/w) ratio with chitosan (0.1%) by the ethanol injection method. These NLs displayed 123 nm average diameter, PDI reduced to 0.2 and stability at 4 °C and 25 °C during 3 months of storage. Furthermore, due to the inherent mucoadhesiveness of chitosan, NLs formulated with this polymer exhibit increased affinity for mucin (68%), the major mucus component, when compared to NLs prepared without chitosan, as revealed in a mucin adsorption model [Mucus is the first barrier for nutrients from the oral route. Curcumin-NLs with improved stability and mucoadhesive properties were synthesized through encapsulation in L-α-phosphatidylcholine at a 1:10 (on model . These ron model  and Andeon model .−1) in rice bran phospholipids (0.13 mg·mL−1) by the thin film-sonication method yielded spherical 157.33 nm NLs with an 84.9 % encapsulation efficiency. The NLs were stable at 4 °C and 27 °C for five months as indicated by the unchanged DPPH radical-scavenging assays and high quercetin NL retention (>97%). In addition, NLs displayed limited gastric degradation with a sustained release of 20% of quercetin after 4 h in gastric fluid, followed by a sustained intestinal release of 70% up to 24 h [Liposomal quercetin encapsulation (0.02 mg·mL to 24 h .−1), as evidenced by the γ value (0.91) [The nano-encapsulation of a mixture of bioactive substances in the same particle can be a good strategy for oral antioxidant co-supplementation with greater physicochemical potential and biological property retention . Chen ete (0.91) .This evidence indicates that nanoliposomes represent a promising tool for polyphenol delivery.Polyphenols display antioxidant and anti-inflammatory effects that play a preventive and therapeutic role in chronic diseases such as cardiovascular and neurodegenerative conditions, as well as neoplasms . To be eAs mentioned previously, the technological functionalities of NPs regarding polyphenols solubility, release kinetics, and chemical structure protection when exposed to different physicochemical conditions are well recognized. However, in vitro assays should also be performed to address the stability of nano-encapsulated phenolics under unfriendly gastrointestinal conditions. The oral bioavailability of nano-encapsulated phenolics must be evaluated in pre-clinical and clinical assays to reinforce and prove the advantage of nano-encapsulation concerning bioaccessibility and bioavailability gains, since they represent restrictions toward the effectiveness of polyphenols as supplements for well-being or as an adjuvant therapy to treat chronic diseases. Several reports regarding phenolic compound gastrointestinal stability, longer residence times, and increased oral bioavailability after nano-encapsulation, with no cell or tissue damage, are available in the literature.−1 for 14 days. The trans-resveratrol treatment may have provoked the development of gastrointestinal injuries due to inhibition of cyclooxygenase-1, while animals treated with trans-resveratrol nano-capsules exhibited lower lesion rates in the duodenum, jejunum, and ileum compared with free-resveratrol intake. It seems that an improvement in the safety usage of this antioxidant regarding gastrointestinal trait preservation can be achieved when this antioxidant is included in NPs [The trans-resveratrol-loaded into lipid core polymeric nano-capsules formed by poly(ε-caprolactone) and capric/caprylic-triglycerides allowed for increased accumulation of this antioxidant in the liver, kidney, and brain tissues of healthy rats compared to those supplemented with free resveratrol following intraperitoneal or gavage administration of 5 mg·kgd in NPs .Peanut oil and soy lecithin (oil in water) were used to encapsulate resveratrol and evaluate a simulated gastric and intestinal digestion, which resulted in resistance indicating that NEs allow full resveratrol availability for intestinal absorption. The size of the NEs of 250 nm enabled them to cross Caco-2 cell membranes and exert their intracellular antioxidant activity against hydrogen peroxide .−1 oral administration in Wistar rats compared with a 4 h plasma level maintenance observed for free resveratrol. A good correlation between in vitro bioaccessibility and the resveratrol fraction absorbed in vivo (R2 = 0.99) indicates that NPs are able to carry the resveratrol to the intestinal epithelium and promote a higher absorption rate of this polyphenol [The same simulated gastrointestinal fluid resistance is noted for casein-NPs. Resveratrol-casein-NPs exhibit a 10-fold higher resveratrol bioavailability and displayed stable plasma levels for 8 h after a single 15 mg·kglyphenol .−1, as demonstrated by a higher plasma half-life, mean residence time, and area under the curve (AUC), while free quercetin resulted in elevated plasma levels for only 8 h with a 4% bioavailability [Casein-hydroxypropyl-β-cyclodextrin NPs loaded with quercetin have been reported as resistant to gastrointestinal pH conditions and allow for the controlled release of 20% of quercetin in gastric fluid (pH 1.2), and 60% after 4 h in intestinal fluid (pH 6.8), while free quercetin is fully released when reaching gastric conditions. In rats, the plasma levels of nano-encapsulated polyphenols were prolonged for 72 h and 37% of bioavailability was reported after the oral ingestion of 25 mg·kglability .−1) and epigallocatechin (6.2 mg·mL−1) in the NPs were significantly better transported through jejunum tissue compared to non-encapsulated polyphenols . This bioavailability improvement was attributed to the stability afforded by NPs, resulting in higher available polyphenol concentrations to flux across the tissue [Ex vivo passive paracellular and transcellular transport models indicate that chitosan-TPP NPs enhance polyphenol absorption and transport across excised mouse jejunum in Ussing chambers. Catechin (3.6 mg·mLe tissue .−1 dose of chlorogenic acid entrapped in chitosan-TPP NPs (210 nm) was administered to Wistar rats, leading to a longer polyphenol residence time in plasma, extended time to reach maximum plasma concentration, and a greater area under the curve (p > 0.01), configuring a slow and prolonged chlorogenic acid release in plasma and superior oral bioavailability [In a pharmacokinetic assay, a single 100 mg·kglability .−1 of resveratrol encapsulated in carboxymethyl-chitosan NPs. The resveratrol-NPs offered in a single dose with an absorption time of 1.76 h, reaching a plasma peak after 6.83 h, and excreted in 20.5 h, while free resveratrol was rapidly absorbed at 1.12 h, with a plasma peak at 3.21 h, and excretion at 5.44 h. Resveratrol nano-encapsulation in carboxymethyl-chitosan NPs thus ensured a longer permanence of the antioxidant in the systemic environment, resulting in a substantial 3.5-fold increase in bioavailability [In another study, Wistar rats received an oral supplementation of 50 mg·kglability .−1 exhibited sustainable resveratrol release in plasma with a two-fold increased bioavailability and a maximum plasma resveratrol concentration of 0.42 μg·mL−1 and AUC 1.44 µg·h·mL−1 after 6 h, while free resveratrol was found at 0.33 μg·mL−1 at 30 min with an AUC of 0.633 µg·h·mL−1. In the same assay, nano-encapsulated resveratrol was found to be predominantly absorbed as the unmetabolized chemical structure (RSV-3-O-glucuronide), while free-resveratrol intake generated higher plasmatic metabolite levels [Distearoyl phosphatidyl choline and cholesterol liposomal formulations were used to load resveratrol (10 mg), improving gastrointestinal resistance against destabilization by bile salt and sodium taurocholate solutions. In addition, rats supplemented by resveratrol-NLs at 50 mg·kge levels , corroboIn short, poor polyphenol bioaccessibility and bioavailability can be overcome by their encapsulation in NPs or NEs obtained from natural food-grade polymers. Such benefits are the result of the chemical protection and enhanced solubility conferred by the polymeric matrices involving polyphenols, guaranteeing a greater number of intact polyphenol molecules able to reach absorption sites. In addition, the nanometric size of the particles, cell adhesion, and permeation properties facilitate polyphenol diffusion through membranes, increasing their absorption through the intestinal epithelium and ensuring bioavailability. Finally, the residence time of NPs containing polyphenols in biological compartments also increases their bioactive performance.The protective role that polyphenols play in pathophysiological disorders that lead to endothelial dysfunctions and cardiovascular events is strongly supported by scientific evidence. Polyphenols are pleiotropic compounds that exert epigenetic, antioxidant, and anti-inflammatory effects on various tissues, including vascular and cardiac tissues ,159,160.However, attempts to demonstrate the effect of isolated antioxidant molecules following oral intake on antioxidant status, lipid peroxidation, and inflammatory markers in humans have failed, perhaps due to the chemical instability of these molecules along the gastrointestinal trait alongside their low bioavailability in biological fluids ,164,165.−1 were superior to non-encapsulated curcumin and governed by inherent NP properties, which increase polyphenol bioavailability and delivery to the infarcted area, while also affecting pro-inflammatory cytokines and oxidative stress, as expected for curcumin, albeit enhanced by nano-encapsulation [−1 was successfully delivered to compromised myocardium, reducing cardiac hypertrophy and apoptosis in male Wistar rats.In general, clinical trials designed to evaluate the effects of polyphenol-loaded NPs on cardiovascular performance are scarce. Boarescu et al. ,167,168 sulation . In addisulation  also dem−1 doses for 7 days to C57BL/6J female mice [−1 for 1 week, which resulted in a significant TNF-α decrease when comparing animals treated with quercetin and the control group  [Resveratrol-loaded zein-NPs were able to reduce serum tumor necrosis factor (TNF-α) levels in 15% compared to free resveratrol after the orally administration of 15 mg·kgale mice . As TNF-ale mice . The samctively) .Prunus avium L.), which are rich in polyphenols (quercetin and cyanidin-3-glucoside), were encapsulated in quaternary ammonium chitosan-NPs. NPs displaying 2 µg·m−1 of gallic acid equivalents (GAE) were incubated with human endothelial cells after lipopolysaccharide-induced inflammation, significantly reducing TNF-α, interleukin-6 (IL-6), NO, and cyclooxygenase-2-dependent (COX-2) prostaglandin E2 levels and increasing anti-inflammatory IL-10 [Anti-inflammatory effects were also demonstrated when cherry extracts (ry IL-10 .Curcumin in micelle-NPs significantly reduced the mRNA expression and secretion of serum IL-1β and IL-6 cytokines in COVID-19 patients supplemented for 14 days with 160 mg of NPs . COVID-1−1) for 8 days after oxidative stress development induced by gentamicin. Concerning all the evaluated oxidative damage indicators, curcumin in NLs was more effective than free curcumin supplementation [As mentioned previously, polyphenols can protect macromolecules and tissues against oxidative damage due to their antioxidant properties, which can be enhanced by nano-encapsulation. Oxidative stress is a physiopathological condition enrolled in risk factors for cardiovascular diseases, and the monitoring of end products generated from the oxidation of biological macromolecules in biological fluids as well as intracellular antioxidant enzyme levels are used to assess the degree of cell damage and the therapeutic potential of drugs and bioactive compounds . Oxidatientation .2S2O8) at 25 µg·mL−1 [Oxidized amino acids (free or protein-bound) are typical oxidative stress markers, and dityrosine bonds formed in low density lipoprotein (LDL) particles comprise atherogenesis indicators . Protein µg·mL−1 .−1), displayed significant glycemic and insulinemic control in ß TC cells following diabetes induced by glucose and streptozotocin. In addition, cellular oxidative stress caused by long exposure periods to glucose and streptozotocin was mitigated following 24 h incubation with resveratrol-NLs, which significantly restored superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels compared to in-solution resveratrol administration [Resveratrol is known to protect the cardiovascular system by alleviating oxidative stress and controlling blood glucose . Synthesstration .−1 over a four-week period improved glucose tolerance and insulin sensitivity and led to a significant reduction in fasting glucose, insulin levels, and leptin. Furthermore, decreases in blood insulin levels of animals treated with anthocyanins-loaded niosomes were more effective than free-anthocyanin and as effective as metformin, demonstrating that niosomes may increase polyphenol carbohydrate metabolism effectiveness [Anthocyanins, the major polyphenol pigment in plants, can also reduce physiopathological damages associated with type 2 diabetes, but with limited effects due to poor chemical stability, aqueous solubility, and bioavailability ,183. Anttiveness .−1) displayed protective effects against peroxidation induced by iron/ascorbic acid in isolated rat liver microsomes, as determined by significant MDA level decreases. In addition, quercetin NPs containing a higher chitosan concentration (3 mg·mL−1) resulted in significant protection against t-BuOOH-induced GSH depletion, increasing the levels of this tripeptide by 183% [Quercetin loaded into alginate-chitosan NPs  status designated by the Food and Drug Administration (FDA) ,193. The®, Doxil®, and Zinostatin/stimalmar®, among others, are approved for commercialization [Currently, a number of food-grade NP coated drugs for use in medicine, such as Abraxanelization . To the Other formulations containing encapsulated curcumin in solid lipid NPs WO/2007/103435), oil emulsion NPs (CN1736369), and chitosan NPs (WO2010013224A2) have been formulated and patented for human applications. Several studies have demonstrated that curcumin may be beneficial in different disorders, such as Alzheimer’s disease, cardiovascular diseases, and psoriasis, due to its anti-inflammatory, antioxidant, and anti-cancer effects ,199. For7/103435,In vitro cytotoxicity assays are performed as part of product characterization during the formulation of NPs from natural polymers, in order to assess or rule out potential cell damage that can make their use unfeasible. Although pre-clinical and clinical trials are more appropriate, they are expensive and slower. In addition, pre-clinical trials in animal models have been discouraged due to animal sacrifice, as recommended by the European Commission, which guides the scientific community on the replacement of animal trials based on the “replacement, reduction, and refinement of animal use” principle . Cultures comprising Caco-2 intestinal cells, erythrocytes, respiratory tract cells, epithelial cells, hepatocytes, and embryonic cells are of the in vitro models applied in cytotoxicity food-grade NPs coated polyphenol assays .−1) [Das et al.  reported−1) . No mortHowever, tests on healthy cells are scarce due to the emphasis placed on the effects of NPs on tumor cells in different tissues, i.e., gastrointestinal and respiratory tracts and the brain ,87,204.Although they do not clarify the mechanisms of toxicity or cell death, the colorimetric methods thiazolyl blue tetrazolium bromide (MTT) and -5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) concerning mitochondrial function and lactate dehydrogenase (LDH) regarding cell membrane integrity are the most applied techniques to assess NP cytotoxicity . ResultsDespite the scarcity of clinical trials with NPs, their oral and topical use in humans is well tolerated, with no severe side effects or toxicity in administration periods ranging from 4 to 12 weeks ,207,208.The biological effects of polyphenols on cardiovascular health are irrefutable, although their effectiveness in clinical trials in humans may be compromised due to the physiological variabilities among individuals that can compromise polyphenol physical-chemical integrity. However, the major challenge is to delivery these bioactive molecules through distinct routes i.e., oral, parenteral, or topical, to fulfill therapeutic needs. Polyphenol effectiveness depends on antioxidant characteristics, which requires that their chemical structure be preserved along the gastrointestinal tract during intestinal absorption, when in the bloodstream, when reaching the target cell these compounds, and when crossing plasmatic or intracellular membranes in order to exert their bioactivity. The incorporation of polyphenols into NPs may keep these compounds protected from hydrolytic enzymes, oxidation, and other stringent physicochemical conditions throughout the gastrointestinal and systemic pathways, and, at the same time, overcome polyphenol bioaccessibility and bioavailability. Distinct, efficient, and safe nanocarriers have been described and seem to be able to deliver polyphenols in an adequate kinetic release guaranteeing a sustained pharmacological concentration of polyphenols for several hours. Pre-clinical assays have demonstrated that nano-encapsulated polyphenols such as ferulic acid, quercetin, gallic acid, resveratrol, catechin, epicatechin, epigallocatechin, proanthocyanidin, and curcumin, as well as whole extracts from grape seeds and cherries, exhibit no toxicity to human cell lineages. The use of polyphenols in NPs should be encouraged for the incorporation and fortification of foods and beverages, in addition to their application in the manufacturing of nutraceuticals in order to conveniently assist in the prevention of and in adjuvant therapies against multifactorial and physiopathological complex conditions, such as cardiovascular diseases and other chronic health impairments.2S2O8, potassium persulfate; LDH, lactate dehydrogenase; LDL, low density lipoprotein; MDA, malondialdehyde; MTS, -5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; MTT, thiazolyl blue tetrazolium bromide; mV, millivolt; NEs, nanoemulsions; NF-κB, factor nuclear kappa B; NLs, nanoliposomes; NNI, National Nanotechnology Initiative; NO, nitric oxide; Nrf2-ARE, nuclear factor erythroid-2-related factor—antioxidant response element; NPs, nanoparticles; OECD, Organization for Economic Co-operation and Development; PEG, Polyethylene glycol; PDI, polydispersity index; PPAR-γ, peroxisome proliferator-activated gamma receptor; ROS, reactive oxygen species; SOD, superoxide dismutase;. TNF-α, tumor necrosis factor; TPP, sodium tripolyphosphate; UV, ultraviolet.Abbreviations: ABTS, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid; ADMA, asymmetric dimethylarginine; AUC, area under the curve; BSA, bovine serum albumin; CHC, chitosan chloridate; CMC, carboxymethyl chitosan; COX, cyclooxygenase; DDAH, dimethylarginine dimethylamino hydrolase; DPPH, 2,2-diphenyl-1-picrylhydrazyl; EFSA, European Food Safety Authority; EGCG, epigallocatechin gallate; EMA, European Medicine Agency; eNOS, nitric oxide synthase; FDA, Food and Drug Administration; GRAS, generally recognized as safe; GSH-Px, glutathione peroxidase; HSA, serum albumin; IL, interleukin; K


To examine the clinical characteristics of autoimmune encephalitis associated with the contactin-associated protein-2 (CASPR2) antibody.Medical records of all patients diagnosed with CASPR2 antibody-associated encephalitis were retrospectively analysed. Data regarding demographic features, neurological symptoms and signs, laboratory tests, imaging results, treatments, and prognosis were collected.A total of 25 patients aged from 3 to 79 years old were enrolled in this study, with a median age of 43. Eight of 25 (32%) were female, and 17 of 25 (68%) were male. The median age of symptom onset was 42 years old with the course of disease from onset to hospital admission ranging from 2 days to 6 months (median was 17 days). Six patients (6/25) had fever as an onset symptom. During the course of disease, cognitive disturbance was the most common symptom, which was observed in 17 patients (17/25) in total. Eight patients (8/25) met the criteria for limbic encephalitis. Epileptic seizure occurred in six of these eight patients. Four patients (4/25) were diagnosed as Morvan syndrome. All patients were positive for anti-CASPR2 antibody in the serum (1:10–1:300). In six patients, antibodies were detected both in the blood and CSF (1:32–1:100). White blood cell (WBC) counts in the CSF were elevated in eight patients (8/25). The concentration of proteins in CSF increased in 10 patients , decreased in seven patients (ranging from 23.2 to 130.5 mg/dl) and remained at a normal range in the other eight patients (ranging from 150 to 450 mg/dl). Abnormal electroencephalogram (EEG) activities included slow background activity and epileptic patterns. Abnormal signals in the bilateral hippocampus were detected by magnetic resonance imaging (MRI) in three patients presenting cognitive disturbance. In one patient who had limbic encephalitis, increased metabolism of bilateral basal ganglia and the mesial temporal lobe was revealed by PET-CT. Eleven of 15 patients receiving immunotherapy experienced varying degrees of improvement. Relapse occurred in four of 25 patients (4/25) after 2 months.CASPR-antibody-mediated autoimmune encephalitis is characterized by diverse clinical manifestations. The most prominent conclusion revealed by this retrospective analysis is the involvement of both central and peripheral nerve systems, as well as a lower relapse rate, a good response to immunotherapy, and favorable short-term prognosis after treatment was also demonstrated. Besides, additional work is necessary to evaluate the long-term prognosis. Autoimmune encephalitis was first recognized as early as 1968 when Corsellis et al. came up with the concept “limbic encephalitis” . In 2007 (AMPAR) , anti-re (GABAR)  has been (GABAR) , 13.CASPR2 is a cellular adhesion molecule (CAM) and part of the neurexin family . It reguAnti-CASPR2 antibodies have been reported in various clinical conditions  Supple, 5, 6. OThe pathogenesis in anti-CASPR2 antibody-associated disease is believed to be due to the blocking action of the interaction between CASPR2 and Contactin-2 , 8 Sup, and in The contactin-associated protein-2 (CASPR2) is a transmembrane protein which is located adjacent to VGKC on the cell membrane. The CASPR2-antibodies could be detected by immunoprecipitation on account of CASPR2 which is a site where most VGKC-antibodies bind to , 17, andIn conclusion, the great variability of syndromes associated with anti-CASPR2 antibodies, despite its rarity, should be noted in clinical practice as a differential diagnosis of conditions, such as limbic encephalitis and epilepsy, especially in older patients, newly onset psychiatric symptoms; neuropathic pain; and idiopathic ataxia, as immunotherapy has been identified to be associated with improved outcomes in patients with CASPR2-associated encephalitis.This study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University. The study was conducted in accordance with the declaration of Helsinki, and all patients provided informed consent for the use of their medical records.Twenty-five patients were enrolled in our cohort as CASPR2 antibody-associated encephalitis, all with positive results for CASPR2 antibody in the serum. Meanwhile, the same positive results were reported in part of the CSF sample as well. Our patients were collected from multiple centers, including Beijing Tiantan Hospital, Henan Provincial People’s Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Brain Hospital and the Affiliated Hospital of Ningxia Medical University. In this study, we retrospectively analyzed their clinical features, including present and past history , manifestations, laboratory tests (including antibody titer), electrophysiology and imaging examinations, treatments, and prognosis.All the patients included in the study met the criteria as follows: (1) Subacute onset (rapid progression of less than 3 months) of one or more of the ten major groups of manifestations, including psychosis, memory deficit, speech disturbance, seizure, movement disorder, loss of consciousness, autonomic dysfunction, and central hypoventilation; or Morvan syndrome(2)with or without CSF pleocytosis, encephalitis MRI features or EEG epileptic or slow-wave activity; (3) cerebrospinal fluid (CSF) or blood serum antibody testing positive for AE antibodies based on a cell-based assay (CBA) ; (4) reasonable exclusion of other disorders.α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), and γ-aminobutyric acid type B (GABAB). Serum or CSF antibody tested positive for AE antibodies based on a cell-based assay (CBA) . CASPR2-positive patients were enrolled with dilution of antibodies . Patients who were then diagnosed with viral encephalitis were excluded. We conducted a complete immunological evaluation, consisting of anti-neuronal antibodies , autoantibody series, anti-neutrophil cytoplasmic antibodies (ANCA), anti-nuclear antibody spectrum, anti-cardiolipin antibody, rheumatoid factor, anti-streptolysin O; serum level of complement was also tested as complement is involved in immune response and inflammation which might underlie autoimmune encephalitis. Thyroid function analysis included total T3 (TT3), total T4 (TT4), free T3 (FT3), free T4 (FT4), thyroid-stimulating (TSH), thyroglobulin (TG), anti-thyroglobulin antibody (TG Ab), anti-thyroperoxidase antibody (TPO Ab), and thyrotropin receptor antibody (TRAb). All patients accepted tumor screening by detecting tumor markers, and anti-neuronal antibodies. Whole-body PET-CT was completed in only five patients due to the limitation of individual financial capacity, medical insurance policies, and examination ability of some centers.Serum and CSF tests for autoantibody were routine for each patient suspected of autoimmune encephalitis. The spectrum of specific antibodies included D-aspartate receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), GAD65, contactin-associated protein-2 (CASPR2), A video electroencephalogram (VEEG) was undertaken using EEG-1200C (Nippon Optoelectronics Corporation), EEG-V32 , EMU40EX , and Micromed-SD . Magnetic resonance imaging (MRI), with or without gadolinium injection, was undertaken using an NT 3.0-T Philips Gyroscan , GE-SIGNA , Vantage Tian 3.0 T , and Magnetom Lumina . In addition, 18 F-FDG positron emission tomography (PET) images were acquired using a PET/CT scanner .The modified Rankin scale (mRS) was adopted for outcome evaluation. For all patients, except a 3-year-old and an 8-year-old, the Montreal Cognitive Assessment (MOCA) and the Mini-Mental State Examination (MMSE) were used to measure cognitive impairment. MMSE<24 or MOCA<26 was defined as cognitive disturbance.An extensive literature search was performed for the terms “CASPR-2” and “encephalitis” from January 2007 to October 2020. The reported results were reviewed and summarized. The primary search identified 94 topic-related publications on PubMed, and any studies and case reports that included more than five patients were included. Ultimately, five studies and case series were reviewed in discussion . Eight of 25 (32%) were female, and 17 of 25 (68%) were male.Data for symptoms presenting at onset and during the course are summarized in During the course of the disease, cognitive disturbance was the most common symptom observed in 17 patients . Among them, five patients (5/17) had amnesia, five (5/17) had behavioral disorders, five (5/17) had hallucinations, and seven (7/17) had psychosis. Two or more symptoms occurred in four patients. Five (5/25) patients had epilepsy. Two presented generalized tonic–clonic seizures, and one only had focal seizures with automatisms. Autonomic dysfunction occurred in six patients (6/25), three had constipation, four had urinary retention of hesitation, three had hyperhidrosis, and one presented with tachycardia. Moreover, weight loss was seen in two patients, and insomnia was seen in four.Eight patients (8/25) met the criteria for limbic encephalitis, presenting with cognitive disturbance and mental or behavior disorders. Short-term memory impairment was most common (4/8), with MMSE scores of 25, 5, 26, and 26. Some experienced meaningless speech or mis-actions such as washing hands in the toilet or wearing the wrong clothes. Epileptic seizures occurred in six of the eight patients. Four patients (4/25) had Morvan syndrome, which is characterized by involuntary muscle cramping and stiffness accompanied by insomnia, hallucinations, and autonomic symptoms. Two of them experienced weight loss of 12 and 15 kg. Tumor screening showed slightly elevated tumor markers. Three patients (3/25) had cerebellum symptoms, and their chief complaints were walking instability. Relapse was recorded in four patients, among which three experienced both sleep disorders and epileptic seizures.The results of laboratory tests and imaging are summarized in Approximately 65% of patients reported an abnormal electroencephalogram (EEG) including slow background activity and epileptic patterns. ), while in one patient, the right hippocampus appeared to be smaller than the left hippocampus. One patient presenting weakness in both lower limbs at onset had a remote infarction in the bilateral basal ganglia on MRI. Moreover, non-specific white matter disease and lacunar infarction were common, though not directly related to AE. In one patient who had limbic encephalitis, increased metabolism of bilateral basal ganglia and the mesial temporal lobe was revealed by PET-CT .In three patients presenting cognitive disturbance, abnormal signals were observed in bilateral hippocampus (Immunoglobulin and corticosteroid were the most common therapy. Immunoglobulin plus intravenous methylprednisolone pulse (IVMP) was adopted in 15 of 25 patients. In our cohort, a standard protocol was intravenous immunoglobulin for 5 days, followed by steroid sequential therapy. Meanwhile, five patients (5/25) received IVMP therapy alone, while two (2/25) were given immunoglobulin alone. One of each of the other three patients was treated with circulation improving, anti-tuberculotic, and anti-viral therapies Table 3.Comparing the modified Rankin scale (mRS) before and after treatment, 11 patients experienced varying degrees of improvement. For seven patients who were assessed as requiring external help in life (mRS ≥3), they were able to take care of themselves independently after treatment. However, six patients failed to respond to therapy, including one who remained severely disabled (mRS = 4). No patient reported disability progression. Three patients underwent lumber puncture again after treatment, showing decreased protein and WBC in CSF after treatment. Relapse occurred in four of 25 patients (4/25) after 2 months. Insomnia and epileptic seizures both appeared in three of them Table 3.vs 38 years old). This result is similar to those of other studies in Asia . An  neurons , which m neurons . For ins neurons . Interes neurons . It may In our study, five patients (5/25) claimed to present epileptic seizures during the course of disease. This incidence is lower than that previously published, which was reported to be 30% by Husari and 53% by Agnes van Sonderen , 27. HowAdditionally, tumors usually present as a comorbid to autoimmune encephalitis, mostly in anti-GABAB encephalitis . In our Immunotherapy was initiated once the diagnosis was confirmed. Intravenous immunoglobulin (IVIG) and/or corticosteroid were applied to 22/25 patients. The response rate was relatively satisfying compared with previously published data , 33. MorTo our knowledge, the incidence of autoantibody encephalitis is low and compared to that of NMDA, lgI1 or GABAB, and anti-CASPR2 antibodies are rarely detected. We first analyzed a retrospective cohort of anti-CASPR2 encephalitis in a Chinese population. Moreover, our study is based on a multi-center population. For comparison, we screened published cohorts about anti-CASPR2 encephalitis to date and then listed those with integrated clinical data in , Capital Healthy Development Research Funding (2016-1-2011), Beijing Postdoctoral Research Foundation , China Postdoctoral Science Foundation (No.2019M660719), Beijing-Tianjin-Hebei Cooperative Basic Research Program (H2018206435), and Beijing Natural Science Foundation (Z200024).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.


Myocardial ischemia is a disease with high morbidity and mortality, for which reperfusion is currently the standard intervention. However, the reperfusion may lead to further myocardial damage, known as myocardial ischemia/reperfusion injury (MI/RI). Oxidative stress is one of the most important pathological mechanisms in reperfusion injury, which causes apoptosis, autophagy, inflammation, and some other damage in cardiomyocytes through multiple pathways, thus causing irreversible cardiomyocyte damage and cardiac dysfunction. This article reviews the pathological mechanisms of oxidative stress involved in reperfusion injury and the interventions for different pathways and targets, so as to form systematic treatments for oxidative stress-induced myocardial reperfusion injury and make up for the lack of monotherapy. Myocardial ischemia is the most frequent form of cardiovascular disease with high morbidity and mortality , for whi2O2) [OS refers to an imbalance between normal oxidant scavenging enzyme systems, such as superoxide dismutase, catalase, and glutathione, and intracellular reactive oxygen species (ROS) production, which leads to toxic accumulations of reactive oxygen intermediates like hydrogen peroxide (H2O2) , 12. Und2O2) –15 and r2O2) , 17. Lim2O2) . In the 2O2) , which a2O2) , 19–21. 2O2) . However2O2) , 24. TheHere, through summarizing pathogenesis of oxidative stress involved in MI/RI, including sources of ROS, ROS-mediated MI/RI, and its related pathways and signaling molecules, as well as various interventions targeting them, we expect systematic treatments against oxidative stress-induced myocardial reperfusion injury to be formed, complications like arrhythmias, myocardial stunning, microvascular obstruction and myocardial remodeling to be inhibited, and mortality following reperfusion to be reduced.Amounts of potential sources of ROS in the postischemic heart are most attributed to one or more enzymes like xanthine oxidase , NADPH o2− [2− instead of reduction to H2O [2− can be converted into H2O2 and O2 either spontaneously or enzymatically catalyzed by superoxide dismutase (SOD) [2O2) can be fully reduced to water or partially reduced to the hydroxyl radical (•OH) [2O2 oxidizes Fe2+to Fe3+ to generate hydroxyl radicals through the Fenton reaction [2− to generate •OH in the Haber-Weiss reaction [2O2 to form nonradical water and oxygen [Mitochondria are deemed the major intracardiac source of ROS RI, impaired autopha/RI . There a2− , that isn to H2O , and, amn to H2O , 39. O2−se (SOD) , 40. Hydal (•OH) . H2O2 oxreaction , 35 and reaction , 35. Glu+ as an electron acceptor and xanthine oxidase (XO) using O2 as the terminal electron acceptor [2−or H2O2 generation as by-products [+ to NADH, and the higher proportion of NADH, the more enhanced O2− production [+ to NADH ratio) during reperfusion period in the heart could be a feasible treatment to protect against MI/RI.Xanthine oxidoreductase, the major source of superoxide in postischemic tissue too , consistacceptor . Xanthinproducts , 42. Morproducts . Therefoproducts . For insproducts  and humaproducts  cannot pproducts . Perhapsproducts , and theoduction , researc2 and incorporating it into l-arginine to produce l-citrulline and NO [2− instead of NO [2O2 could potentially induce and activate the eNOS [−) that causes further cell and tissue damage [Different effects of NO from various sources on MI/RI have been reported. NO derived from endothelial nitric oxide synthase and neuronal nitric oxide synthase are thought to protect against MI/RI, while inducible nitric oxide synthase-derived ones aggravate MI/RI and can also cause cardiac hypertrophy and oxidative stress . NOS aree and NO , 49. Howe and NO . In the ad of NO , 51, thuthe eNOS , 53 thatthe eNOS , 55. NO e damage , 56, 57.2, leading to the generation of O2−.[2O2 [2O2, while the remaining NOX isoenzymes largely produce superoxide [2− and H2O2 in the heart, which promote oxidative stress RI, impaired autopha/RI [NADPH oxidases (NOXs) are a family of seven transmembrane electron transporters, respectively, named NOX1 to NOX5 and dual oxidase- (DUOX-) 1 and DUOX-2 , 59 thatO2−.[2O2 –62. To bperoxide , 27, 60.peroxide . The othperoxide , 63. NOXtopha/RI . NADPH otopha/RI , 66.Oxidative stress causes cell death either through directly destroying proteins, DNA, lipids, and other macromolecules or acting as a signal molecule in the cell death signaling pathway . In thisApoptosis, a unique form of gene-regulated cell death, has been shown to be triggered or accelerated primarily during reperfusion or reoxygenation , 69. Sec2+ is induced by ROS to influx into the cytoplasm and then influx into the mitochondria, resulting in the opening of MPTP, the collapse of mitochondrial membrane potential, and release of apoptotic signaling molecules such as cytochrome c and apoptosis-inducing factor (AIF) from the intermembrane space [Apoptosis triggered by disruption of mitochondrial homeostasis. Cane space , 78–80. ne space , 79. Evine space , 82. Beyne space , decreasκB from its inhibitor IκB and upregulate activated NF-κB [κB in the cytoplasm influx into the nucleus, contributing to synthesis of TNF-α that releases to extracellular matrix, combines with membrane surface receptors (TNFR1 and Fas), activates caspase-8 and caspase-3, and then triggers an extrinsic death cascade [κB. H2O2 may directly mediate the dissociation of IκB from NF-κB and upregulate NF-κB [κB via tyrosine phosphorylation of IκBα [κB activation by oxidative stress have also been described by Bowie and O'Neill [κB by H2O2 is cell-specific [Apoptosis triggered by MAPK family. ROS activate MAPKs (primary p38 and JNK MAPKs), which mediate the dissociation of the NF-ed NF-κB . NF-κB i cascade . ROS coute NF-κB . H/R-ind of IκBα . Evidenc O'Neill . Howeverspecific , and it 2+ homoeostasis interfere with endoplasmic reticulum (ER) function, causing unfolded protein response with unfolded/misfolded protein accumulation, the condition referred to as ER stress [Apoptosis induced by endoplasmic reticulum stress. RI, impaired autopha/RI, deficiency of glucose and nutrient supply, ATP depletion, ROS accumulation, and destruction of CaR stress , 88. NumR stress . ProlongR stress , 90. Sim2+ overload may be caused via multiple pathways that involved oxygen free radicals. Sarcolemmal Ca2+-ATPase related to the extrusion of Ca2+ from cardiac cells [2+, Mg2+-ATPase sequestering Ca2+ from the cytoplasm into the lumen of sarcoplasmic reticulum [2+ overload is also reported to be caused via the activation of Na+/H+ exchanger [+-K+ ATPase [+/Ca2+ exchange  [2+ into the intracellular space. Besides, increased extracellular Ca2+ influx is caused by ROS through membrane lipid peroxidation and the voltage-sensitive Ca2+ channel opening [Intracellular Caac cells  and sarceticulum  are altexchanger , inhibit+ ATPase , 93, and efflux) , which a opening , 95.2+ and ROS but inhibited by low pH in ischemia. However, during reperfusion, restoration of pH, along with mitochondrial calcium overload and excessive ROS generation, causes the pore to form [2+ efflux disorder in mitochondria after CyP-D-mediated MPTP opening is inhibited [2+accumulation in the mitochondrial matrix. As for cyclosporine toxicity, more specific and novel CyP-D inhibitors may be explored.The formation of mitochondrial permeability transition pore (MPTP), an inner membrane nonselective pore, can cause ATP depletion, enhanced ROS production, membrane ion pump failure, solute entry, and then mitochondrial swelling, rupture, and release of apoptotic signaling molecules such as cytochrome c from the intermembrane space; this eventually leads to cardiomyocytes apoptosis, causing irreversible damage to the heart , 18. The to form , leading to form –102. In  to form . CyP-D c to form  and evennhibited , 106 limnhibited  and may κB/TNF-α apoptotic signaling pathway [Mitogen-activated protein kinases (MAPKs) are a protein family including extracellular signal-regulated kinases (ERK1 and ERK2), c-Jun N-terminal kinases (JNK1 and JNK2), and p38 MAPK, among which JNK and p38 MAPK promote apoptotic cell death, while ERK1/ERK2 exerts a protective effect . However pathway  previous pathway . TUNEL a pathway . On the  pathway . ERKs al pathway . The dyn pathway .2+ homeostasis, and lipid synthesis [2+ overload, deficiency of glucose and nutrient supply, and ATP depletion, homeostasis is impaired with the accumulation of unfolded/misfolded proteins, as described above [2+ depletion, then leading to protein misfolding [The ER, under physiological conditions, regulates many biological processes, including protein folding, assembly, modification and secretion, Caynthesis , 124. Hoed above , 88, 123ed above . It has sfolding . MI/RI-asfolding . Howeversfolding , 90, 1272+ overload [L inhibit autophagy through binding and inhibiting Beclin1 [Autophagy is a major pathway for eukaryotic cells to degrade and recycle organelles and macromolecules by which cytosolic long-lived proteins and damaged organelles can be removed . Organeloverload , releaseoverload , mitochooverload , and CyPoverload . As mentoverload . The ant Beclin1 , while d Beclin1 .Autophagy is characterized by the protection of cell function under normal conditions, whereas autophagy under pathophysiological conditions can either protect against cell damage or serve as another form of programmed cell death, known as PCD type II . Findingβ through the NLRP3 inflammasome activation and caspase-1 expression [β [κB, activated by ROS, regulates the expression of inflammatory genes, like IL-1β, IL-6, and TNF-α [Oxidative stress and inflammatory response are mutually promoting pathological processes , 65, 95.pression . IL-6 wossion [β . It was ssion [β . In addind TNF-α , 162.β, and TNF-α [α exerts a negative effect via inducing the expression of adhesion molecules and chemokines, promoting the adhesion and interaction of leukocytes with endothelial cells, and increasing leukocyte infiltration [β aggravate myocardial injury through promoting the adhesion of endothelial cells and neutrophils [κB activation, increase of endothelial cell adhesion molecules, and leukocyte/endothelial cell interaction [The severe inflammatory conditions during MI/RI have been thought to occur due to the increased cytokines, that is, IL-6, IL-1nd TNF-α . During ltration , 164. Sitrophils . Beyond trophils . The inftrophils . ROS caneraction . Besideseraction .κB and thereby inhibit the Nrf2-ARE pathway to promote oxidative stress-induced necrosis [−, exerts cytotoxic effects that cause cell and tissue damage [As for oxidative stress-induced MI/RI, there are still other pathological changes that need to be further explored in addition to the frequently studied mechanisms mentioned above. For instance, ROS is believed to be involved in necrotic cardiomyocyte death via MPTP opening that is deemed as a main cause of the necrotic cell death rather than just inducing apoptosis . Anothernecrosis . In addinecrosis . As was necrosis . Therefoe damage , 56, 57.As mentioned above, based on the multiple sources of ROS, the effects of oxidative stress on MI/RI and the mutual influence of various pathways, it is extremely important to explore multiple targets and systematic intervening measures including traditional Chinese medicine to overcome the limitations of single therapy.It was demonstrated that oxidative stress to cardiomyocyte may lead to detrimental cellular effects like necrosis, apoptosis, or autophagy  and elicAmounts of potential sources of ROS have been researched, such as xanthine oxidase , NADPH o(1) Mitochondria. Paraoxonase 2 binds specifically to the complex III in inner mitochondrial membrane, and its deficiency alters mitochondrial function partly by reducing the activities of mitochondrial complexes I/III, thus resulting in the superoxide generation and exacerbating the development of atherosclerosis [2O2 causing oxidative damage and the cell death, is a core pathological mechanism of MI/RI [clerosis . A reseaclerosis . Based oof MI/RI , mitochoof MI/RI . In adulof MI/RI . The H9cof MI/RI . Dapagliof MI/RI .(2) Xanthine Oxidoreductase. Xanthine oxidase inhibitors, which include purines  and nonpurines (febuxostat and topiramate), exert antioxidant effects by reducing purine-derived ROS production [oduction . In partoduction , 174–176oduction . Clinicaoduction , 179.(3) NOS. As mentioned above, the decreased bioavailability of NO caused by eNOS uncoupling and the cytotoxicity of NO synthesized by iNOS are the cause of myocardial damage induced by NOS. The depletion of tetrahydrobiopterin (BH4), an important cofactor of NOS, in MI/RI resulted in increased eNOS uncoupling and ROS production, but preischemia administration of liposomal BH4 can reduce the dysfunction of eNOS secondary to BH4 depletion during reperfusion, thus protecting cardiac function [−-triggered oxidative/nitrative stress and that they both improved cardiac functions, as well as reduced myocardial infarction, apoptosis, and creatine kinase/lactate dehydrogenase release. Studies have shown that the exogenous donor of NO, NO-aspirin, releases NO at a rate similar to the endogenous NO derived from L-arginine, which limits infarct size, improves myocardial contractile dysfunction, and reduces the mortality rate, during MI/RI [function . To invefunction . The profunction . Insulinfunction  and pterfunction  can not ng MI/RI . In adding MI/RI , it may ng MI/RI .(4) NAD(P)H Oxidase. The NOX family of NADPH oxidase may produce superoxide and other ROS by transporting electrons through the biological membranes from NADPH to O2 during MI/RI, especially NOX2 and NOX4 [2O2-responsive antioxidant PVAX nanoparticles was used to evaluate the therapeutic effect of PVAX on MI/RI in mice. The results of dihydroethidium staining showed that PVAX effectively inhibited MI/RI-caused ROS production, and PVAX targeted the production site of ROS, reducing the expression levels of NOX2 and NOX4 that are the main NOX subtypes in the heart, thus protecting against MI/RI [and NOX4 . Injectist MI/RI . By suppst MI/RI . In addist MI/RI .The endogenous antioxidant systems can protect cells against the potential injury through regulating the balance of individual ROS and their reactants, maintaining “redox homeostasis” . Major eSince endogenous antioxidant levels are not sufficient to prevent reperfusion injury , it is aAntioxidants that are neither targeted nor accumulated in the mitochondria may be ineffective . Mitocho(1) Nuclear Factor Erythroid-Related Factor 2 (Nrf2). Nrf2, a nuclear transcription factor, plays an indispensable regulatory role in the defensive genes that encode detoxifying enzymes and antioxidant proteins, contributing to cellular resistance to oxidants [oxidants , 210 andoxidants . Nrf2 bioxidants . HO-1, aoxidants . The Nrfoxidants . Many droxidants  and tripoxidants , inhibitoxidants . Upstreaoxidants , 217, proxidants . Glycogeoxidants –221, whioxidants .(2) Hypoxia-Inducible Factor-1 (HIF-1). HIF-1 is a critical regulator of the transcriptional response to hypoxia conditions of mammalian cells [α mediates ischemic preconditioning [α signaling pathway [α/HO-1 signaling pathway [an cells . Evidencan cells , 225 andan cells , 227. HIitioning , 228, reitioning , which,  pathway . Besides pathway .(3) PI3K/Akt. Activation of phosphatidylinositol-3-kinase (PI3Ks) and its downstream target protein kinase B (Akt) regulates myocardial oxidative stress and promotes myocardial protection against MI/RI [st MI/RI . The regst MI/RI . GSK-3, st MI/RI , inhibitst MI/RI , and prost MI/RI –221, is st MI/RI . Pretreast MI/RI . In addist MI/RI . Signalist MI/RI , 235, exst MI/RI , or Achyst MI/RI , then enst MI/RI , 239, myst MI/RI , and advst MI/RI .2+ overload, as mentioned above, can be triggered by ROS in a variety of ways [2+ overload in cardiomyocytes also leads to cell death by causing excessive contraction of cardiomyocytes during reperfusion [2+ overload may provide new ideas for the prevention and treatment of oxidative stress-induced reperfusion injury. For example, intracardiac injection of 4(RS)-4-F4t-neuroprostane before ischemia, a nonenzymatic oxidized metabolite of cardiac protective docosahexaenoic acid, can limit myocardial infarction and reduce the incidence of ventricular arrhythmias [2+ overload, which is related to decreased MPTP opening, but also suggest that its antiarrhythmic properties seem related to reduced Ca2+ release from sarcoplasmic reticulum, diastolic membrane hyperpolarization, and action potentials shortening [2+ overload and scavenging OFRs, among other beneficial pathways [ATP) can reduce mitochondrial Ca2+ overload, increase ATP synthesis, and increase protective ROS production during preconditioning but decrease ROS generation during reperfusion [2+ accumulation in the matrix, then reducing MPTP opening and apoptosis [2S donor 4-carboxyphenyl isothiocyanate can prevent Ca2+ accumulation in the mitochondrial matrix, and the mitoKATP may be a relevant pharmacological target of it [2+ has been reported to ameliorate complications associated with MI/RI. In a model simulating MI/RI, Salvia miltiorrhiza was showed to improve antioxidant and calcium regulation in cardiomyocytes during MI/RI and reduce arrhythmias and apoptosis [2+ ATPase pump improves mechanical and electric stability in the heart through reducing Ca2+ overload and then inhibits ventricular arrhythmias [Intracellular Ca of ways , 91–94. erfusion . Therefohythmias . The resortening . Tetramepathways . Mitochoerfusion , 245. Acpoptosis . The novet of it . Regulatpoptosis . In a pohythmias . In addihythmias .2+ overload and excessive ROS production, along with some other factors, can trigger MPTP opening [2+ overload caused by oxidative stress, thereby inhibiting MPTP opening [Mitochondria-mediated apoptosis is recognized as a key part in MI/RI . During  opening . Myocard opening , 254. MP opening . It has  opening . In addi opening . Schaffe opening . It has  opening . Inhibit opening . Besides opening , and CyP opening . However opening . Newer C opening  and poly opening  may over opening , rather  opening , and tre opening , which m opening .ROS triggers the initiation of apoptosis, which is related to the decrease of antiapoptotic Bcl-2 and proapoptotic Bax ratio during MI/RI . The ratκB/TNF-α signaling pathway. Interventions targeting p38 MAPK or JNK have been shown to protect against oxidative stress-induced MI/RI. Dual-specificity phosphatase is upregulated by N-acetylcysteine pretreatment [2+ overload, inhibiting the activation of caspase-3, and downregulating the phosphorylated JNK (p-JNK) and p38 MAPK (p-p38 MAPK) protein expression [Activated by ROS, MAPKs (mainly p38 and JNK MAPKs) initiate exogenous cell death cascades through the MAPK/NF-reatment . And thereatment . Betulinreatment . Syringireatment . Injectipression .β-activated protein kinase 1, a key regulator of cell death, may trigger MI/RI as an upstream signaling molecule of the ROS/ER stress pathway, and inhibition of it significantly decreased MI/RI-induced infarct size, reduced cell death, and improved cardiac function [κB pathway so as to reduce inflammation, and inhibiting procoagulant-related factors to reduce thrombosis [During MI/RI, prolonged or excessive ER stress triggered by oxidative stress and other causes acts as a target for intervening in oxidative stress-induced reperfusion injury; in that, it causes apoptosis of the cardiomyocytes. Transforming growth factor function . It has function . In vitrfunction  and tourfunction  may exerfunction . Shuxuenrombosis .2S donor 5-(4-methoxyphenyl)-3H-1, 2-dithiole-3-thione [The decline of LAMP2 and upregulation of BECN1 mediate the damage of autophagosome clearance during MI/RI, forming a vicious cycle of increased ROS production and enhanced mitochondrial permeability, which eventually leads to cell death , 155. Th3-thione , and sev3-thione  restore 3-thione  and cilo3-thione  protect 3-thione . In a MI3-thione . Since e3-thione . Trimeta3-thione . Sevoflu3-thione . Phellin3-thione .κB may be an ideal target for the treatments against reperfusion injury; in that, it plays an important role in cardiomyocyte apoptosis and inflammatory injury triggered by oxidative stress during MI/RI. Apart from inhibition of ER stress, silibinin also exerts cardioprotective effect against MI/RI through alleviating inflammatory response via deactivating the NF-κB pathway [κB to relieve the MI/RI-induced inflammatory injury [α, IL-6, and IL-1β are also indispensable in ROS-induced inflammatory injury. Dietary selenium intake, for example, reduces myocardial infarct size of rats and reduces adverse remodeling, and beneficial effect of it might be partly related to the inhibition of proinflammatory cytokine overexpression [Phyllanthus species, has also been reported to diminish IL-6, IL-1β, and TNF-α in the mice during MI/RI, as well as suppress the overexpression of NF-κB [The nuclear transcription factor- pathway . Researcy injury . Cytokinpression . The supof NF-κB . In addiof NF-κB .Reperfusion following myocardial ischemia may lead to accelerated myocardial injury and worsening clinical outcomes. One of the most important pathological mechanisms in reperfusion injury is oxidative stress, which is the imbalance between the antioxidant system and the excessive production of ROS, leading to the toxic accumulation of reactive oxygen intermediates.Multiple sources of ROS have been reported, including electron leakage from the ETC in mitochondria, the conversion of hypoxanthine and xanthine to uric acid catalyzed by xanthine oxidoreductase, “being uncoupled” of NOS to their primary role of NO synthesis, the transfer of electrons from NADPH catalyzed by NADPH oxidase, and other sources like the monoamine oxidases, lipoxygenases, cyclooxygenases, cytochrome P450, neutrophils, and catecholamine.2+ overload and decreased ratio of Bcl-2 to Bax, then formation of MPTP, mitochondrial membrane potential collapse, release of apoptotic signaling molecules, and finally activation of caspase-3. On the other hand, ROS initiate exogenous apoptotic pathway by activating MAPK family, upregulating activated NF-κB, promoting the synthesis and release of TNF-α, binding of TNF-α to membrane surface receptors, and activating caspase-8 and caspase-3. Besides, ROS trigger ER-related apoptosis with the increased expression of CHOP and the activation of caspase-12. As for autophagic pathway, ROS induce decrease of LAMP2 and upregulation of BECN1, leading to impaired autophagic flux and excessive autophagy. About inflammation, ROS lead to pathological injury through inflammatory response with cytokine release, NF-κB activation, increased adhesion molecules, and leukocyte/endothelial cell interaction. The inflammatory response also induces MMPs activation, then leading to collagen degradation, myofibril slippage, and left ventricular dilatation. Finally, NO synthesized by iNOS and ONOO− produced by NO and O2− cause cardiomyocyte death through cytotoxicity.ROS mainly cause cardiomyocyte death through apoptotic pathway, autophagic pathway, inflammatory pathway, and cytotoxic effect. On the one hand, ROS initiate one apoptotic pathway through CaFortunately, some interventions are currently available for ROS-induced reperfusion injury, including antioxidant therapy, along with regulation of apoptosis-related pathways, autophagy-related pathways, and inflammatory response. Researches have shown that these interventions can reduce reperfusion-mediated complications such as remodeling, arrhythmias, myocardial stunning, microvascular obstruction, and heart failure to a certain extent, as well as reduce mortality.However, researches on the mechanisms of reperfusion injury caused by oxidative stress still need to be further improved, and more measures targeting various pathways and targets need to be explored. In addition, many of the current studies are based on animal or molecular level while fewer clinical studies have been done. Therefore, in future studies, (i) it may be of additional value to develop a comprehensive understanding of the oxidative stress involved in MI/RI and its associated signaling pathways, thereby reducing the risk of exposure. (ii) In terms of treatments, in addition to antioxidant therapies, systematic interventions targeting various pathways may overcome the limitations of single measures and targets. (iii) In addition to more abundant and mature laboratory research, more clinical research should be performed appropriately.


The development of light-electricity conversion in nanomaterials has drawn intensive attention to the topic of achieving high efficiency and environmentally adaptive photoelectric technologies. Besides traditional improving methods, we noted that low-temperature cooling possesses advantages in applicability, stability and nondamaging characteristics. Because of the temperature-related physical properties of nanoscale materials, the working mechanism of cooling originates from intrinsic characteristics, such as crystal structure, carrier motion and carrier or trap density. Here, emerging advances in cooling-enhanced photoelectric performance are reviewed, including aspects of materials, performance and mechanisms. Finally, potential applications and existing issues are also summarized. These investigations on low-temperature cooling unveil it as an innovative strategy to further realize improvement to photoelectric conversion without damaging intrinsic components and foresee high-performance applications in extreme conditions. To meet the emergent requirement of the development of sustainable and clean energy, solar energy, recognized as the best potential alternative to fossil-fuel power, has been intensively investigated regarding its effective harvesting, conversion and storage in past decades ,6,7,8,9.To realize improvements through low-temperature cooling, the underlying function mechanism deserves investigation. Similar to coupling effects or surface modification ,24,25,26Here, we summarize the cooling-enhanced effect on the photoelectric process in various nanoscale semiconductors from near room temperature (300 K) to liquid nitrogen temperature (77 K). First, low-temperature-enhanced photoelectric parameters, materials and their corresponding devices’ structures are classified for further analysis with the underlying photoelectric mechanism. On this basis, the cooling-enhanced photoelectric performance and corresponding physical mechanism are demonstrated in different photoelectric processes. In this section, we also symmetrically discuss the related characteristics of cryogenic-enhanced optoelectronic devices from carrier movement to device optimization. Finally, the future opportunities and potential application of cooling-enhancing effects in optoelectronics are discussed for further scientific research and practical utilization.The influence of temperature on the photoelectric process is closely related to nanomaterials and their structures. The working range of the cooling method includes nanomaterials from elemental semiconductors to organic-inorganic complexes. The reported works on cryogenic-enhanced optoelectrical performance are based on various photoelectric structures, summarized as photovoltaic photodiodes, photoconductors, phototransistors and photogating transistors, as depicted on the right side of 2-based photodetectors’ performance from 77 K to 300 K and found higher effective electron mobilities up to 520 cm2 V−1s−1 at 77 K, further improving photoresponse [OC increased when cooling to 230 K without sacrificing current, resulting from temperature-dependent reverse saturation current [10 Jones under low temperature for raised carrier intensity and mobility [3 [3 [−1 at 150 K for low-temperature enhanced diffusion [3(THT)2(NH4)3 MOF-based photodetector presenting an improved photoresponse with declining temperature [OC of several CZTS devices and discovered that all of them increase with decreasing temperature [2−xIx has been reported with cooling-enhanced photodetection performance caused by less phonon scattering under low temperature [In photovoltaic photodiodes, effective electron-hole pairs are activated by absorbed phonons, and then separated by built-in electric fields to transport to specific electrodes for collection. In this case, Ohmic contact, Schottky contact, the p-n junction or more complex p-i-n junction are required driving forces. Solar cells ,59,60, Iresponse . In addiresponse ,90,91, Presponse ,51 and Presponse , have be current . Chusnutmobility . Weng etmobility . As depiility [3 ,96,97,98ty [3 [3  inspiredty [3 [3 , comparety [3 [3 . Due to iffusion . For theperature . Hadke eperature , resemblperature ,103,104.perature . It is wThe interplay between temperature and the photoelectric process varies along with the specific design of devices. We divided low-temperature-enhanced performance into three parts to analyze the specific function of cooling effects: common physical parameters represented by absorption, photodetector performance, and solar-cell performances. Moreover, the related formulas of temperature-dependent photoelectric parameters are listed in g(0) is the bandgap of the semiconductor at 0 K, while α and β are empirical constants. According to the Varshni equation, the cutoff wavelength of devices based on single semiconductors tends to monotonous blueshift. As shown in 3)0.85(MAPbBr3)0.15 perovskite thin films show a red-shift trend [g/dT effect [2 [2/p-Si [Despite photoelectric investigations over past decades, optical properties like absorption are bottlenecks restricting semiconductor candidates in both photodetectors and solar cells. Unlike traditional tuning methods by doping or sensitizing ,111,112,ft trend . Thus, aft trend ,115,116 ft trend  caused rft trend ,118,119 ft trend , consistT effect  in PbS qT effect ,122,123 ffect [2  and SnS2 [2/p-Si .According to the Varshni equation  , defined cooling , directlto 600 K . As extreratures .2 photoconductor [D is Debye temperature, WH and WD represent hopping energy and disorder energy, respectively. As the temperature drops further, the optical phonons’ energy becomes inadequate to maintain high conduction. Thus, the variable hopping mechanism, assisted by single acoustic phonons, is suitable for low temperature. There are a handful of experiments that evidenced this conduction-temperature model as accounting for temperature-dependent sensing performance, such as HgTe QDs [To comprehend the underlying mechanisms of temperature variation and photoconductive performance, temperature-dependent conductivity (σ), which is dominated by the interaction between phonons and carriers or polarons, has been widely investigated. As show in onductor , the neaonductor ,132, as HgTe QDs , PbS/polHgTe QDs , boron sHgTe QDs , InI [13HgTe QDs  and monoHgTe QDs . What deHgTe QDs .3(THT)2(NH4)3 MOF-based photodetectors  have observed increasing Voc and decreasing dark current due to the temperature-influenced resistance of the Schottky barrier at ferroelectric-electrode interfaces [Furthermore, cooling-enhanced photovoltaic devices with lateral photovoltaic effect (LPV) and bulk voltaic effect (BPV) are investigated. The position responsivity of ITO/Si has been researched by Qiao et al. showing 7.47 mV/mm at 80 K. This is about 1.91 times of performance at 295 K , attributerfaces .For 2D layered materials and their hybrid nanostructures, the photogating effect is a common mechanism that modulates structures’ photoconductivity through photogenerated local electric fields. Different from the linear relationship of photocurrent and light intensity in photoconductive mode, the photogating sensor performs with a sublinear tendency due to the underlying long-lived trap states . TemperaIn conclusion, the cooling method is an effective way to enhance photodetection performance with impacts on absorption, photoconductivity, photogenerated carriers’ movement and more. Herein, we summarize the reported low-temperature-enhanced photoresponse in OC varies with the temperature of CZTS-type solar cells [OC and fill factor (FF) on CZTSe solar cells during cooling to 240 K [The capability of converting solar energy to applicable electronic energy renders great attention to solar cells, especially for low-cost solution-processed types . Thin-fiar cells , owing tto 240 K . As illuto 240 K . Tempera3, MAPbBr3 and MAPbI3 from a cubic to an orthorhombic crystal structure [3)0.85(MAPbBr3)0.1 at different temperatures and observed sudden changes in absorption [0.4I0.6)3. They also reported that β-phase, which possess fewer defects and a narrower band gap, appears at low temperature [3, showing less trap concentration at low temperatures and obvious turning points during the phase transition region [xPb1−xI3, with x = 0.25 and 1, which increased with temperature reductions at each crystal-structure region, based on temperature-regulated recombination mechanisms [3 at low temperature through the addition of SnF2, since hole-doping reduced recombination [3 showed remnant PbI2 contributing to higher photocurrent, especially at low temperatures [3 solar cells and proposed the insulating nature of a charge-extraction layer, rather than an absorption layer restricting performance at low temperature [3−xClx [−8 cm3s−1 at room temperature to ~10−9 cm3s−1 at low temperature due to less phonon-mediated recombination. Another experiment by Zhou et al. claimed the impact of surface passivation by PASP benefiting the reduction of trap states during temperature-dependent measurements [k1), biomolecular recombination (k2) and Auger recombination (k3) dominate the recombination mechanisms of perovskite solar cells. Depicted in k1 decreased from 4.6 × 107 s−1 at 340 K to 2.3 × 106 s−1 at near 10 K in MAPbI3 devices. Since the low temperature passivates and freezes the dopant site, perovskite materials weakened by defects have promise of significant improvement at lower temperature. Different from k1, k2, which was evaluated with the Langevin model [k2, providing a feasible way to improve biomolecular recombination-restricted performance at low temperature [k3 reveals it is strongly dependent on carrier density [J-V scans, plotted in Among thin-film solar cells, organic-inorganic hybrid perovskite solar cells have been reported to have advantages in a superior absorption coefficient, less excitons banding energy and an optimal energy level . The cootructure , referretructure ,169,170,sorption  and carrperature . Moreoveperature . Landi en region . Anotherchanisms . Neverthchanisms . Milot ebination . As Figueratures . Similarperature . Represeperature . Neverthperature  PCBM as perature . Subsequperature . The fou [3−xClx . The raturements . The temin model , general density  and mono density . The flu density ,179,180,In general, low-temperature operation for solar cells is a rare but effective attempt. This method is connected with temperature-dependent changes in morphology, structure and overall carrier-charge motion. Development of cooling method can improve light-electricity conversion efficiency and application in extremely cool circumstances.1), summarised by Wang et al., typical high-resolution photodetectors in the infrared field are dominated by materials with low-temperature operating requirements [2,a3), the III-V group photodetector acquires accuracy to distinguish details such as vessels when the temperature further drops to 60 K [1,c2). For this planar structure photodetector, significant enhancement (~500%) of the ratio of pyroelectric to total signal was achieved as temperature declined to 77 K [3 [3,c4). Under low-temperature operation, shallow trap levels play a more important role in photoinduced response. At room temperature, the function of shallow traps has been suppressed. However, the temperature dependence of piezo-photoelectric effect showed that cooling weakens piezoelectric and photoelectric performance [Advances in cooling-enhanced photoelectronic processes bring new opportunities to conventional photoelectrical nanomaterials, based on superiority in tuneable band alignment, suppressed noise current, a different mechanism of charge motion and so on, hence, enabling more innovative optoelectronic applications. The cooling method has been widely used in the photodetection field, especially for background-limited infrared photodetectors. As shown in irements . In addi to 60 K . Despite to 60 K . The enh to 60 K ,192,193. to 77 K . Further to 77 K  and p-Si to 77 K  verified 77 K [3 , shown iformance ,199; theIn this review, we propose a low-temperature operation method with huge potential in photodetectors and solar cells without altering nanostructures or configurations and summarize the relevant advances of cooling methods in improving optoelectrical performance. Advances on cooling-enhanced photoelectric performance have proven its benefits to various materials and structures, for example, 2D photoconductors, III-Vs group infrared photodetectors and perovskite solar cells. In addition to the summary of cooling-enhanced photoelectric performance, in-depth mechanisms have been discussed in terms of different application types, represented by photodetectors and solar cells. Through analysis from materials to performance, the cooling method is based on the integration of bandgap optimization, recombination suppression, phase transition and so on. Moreover, there is also plenty of room to further improve photoelectric performance and realize practical applications of properly lowering temperature. Overall, the low-temperature cooling method, which lacked attention in recent decades, is capable of pushing forward photoelectric applications in harsh environments and featuring highly improved optoelectronic performance without complex modification.