The original microwave solvothermal synthesis and characteristics of the ZnO samples were described. Internodes were cultured on the MS medium with 0.6 mg∙L−1 6-benzylaminopurine (BAP) and 2 mg∙L−1 indole-3-acetic acid (IAA). In ‘UTP Burgundy Gold’, the highest shoot regeneration efficiency was obtained for 100 mg·L−1 ZnO SMPs and 500 mg·L−1 ZnO NPs treatments . These shoots had high or moderate chlorophyll and carotenoid contents. In ‘UTP Pinky Gold’, the highest shoot number was produced in the control (12.92), for 500 mg·L−1 ZnO SMPs (12.08) and 500 mg·L−1 ZnO NPs (10.42). These shoots had increased chlorophyll (a+b)-to-carotenoid ratios. In ‘UTP Pinky Gold’, the ZnO SMPs and ZnO NPs affected the anthocyanins biosynthesis, whereas ZnO + 1%Ag NPs decreased the phenolics accumulation. These results are important for the improvement of chrysanthemum micropropagation.Studies on nanoparticles’ effects on plants are relevant for horticulture. This study aimed to test the influence of zinc oxide submicron particles (ZnO SMPs), zinc oxide nanoparticles (ZnO NPs), and zinc oxide nanoparticles combined with silver nanoparticles (ZnO+1%Ag NPs) applied at 100 and 500 mg·L Nanoparticles (NPs), i.e., small particles of matter between 1 and 100 nanometers in diameter, are characterized by unique physicochemical properties that are directly related to their small size. These properties differ when compared to those possessed by material counterparts at the micrometric scale, often ensuring new applications of existing materials . HoweverMicropropagation is a clonal propagation method of plants performed under aseptic and fully controlled laboratory conditions. Inside the culture vessels, plants are grown on synthetic media that contain nutrient formulations of salts and vitamins, sugar, and growth regulator . In suchChrysanthemum × morifolium (Ramat.) Hemsl. (syn. Chrysanthemum × grandiflorum/Ramat./Kitam.) is one of the most economically important and favored floricultural crops worldwide, ranking second in the cut flower trade, following the rose. Chrysanthemum is also cultivated as a pot plant and used in gardening and ornamental landscaping. The market demand for chrysanthemum cultivars with new inflorescence characteristics, improved stress tolerance, or quality attributes is increasing annually, being a great challenge for chrysanthemum breeders [breeders . Chrysanbreeders .Zinc is one of the most significant micronutrients required in plant growth and development, playing an important role in many cellular metabolic processes, being the only metal found in all six enzyme classes . Zinc stimulates the biosynthesis of plant chlorophylls and carotenoids, enhancing photosynthetic activity and repairing photosystem II. This element is also an integral part of transcription factors of the zinc finger family. Cell division and differentiation, along with cellular repair and defense mechanisms, are also affected by zinc ion content in plant cells ,8,11.2+. However, determining the deficiency/sufficiency/toxicity thresholds of ZnO NPs in culture media is still under investigation [−1) to the culture medium stimulated callus proliferation, shoot multiplication, and rooting in date palm (Phoenix dactylifera L.) [−1 stimulated the in vitro germination of onion (Allium cepa L.) seeds, without negative effects on the further growth and development of seedlings [−1 increased the micropropagation efficiency, as well as the fresh and dry weight of olive (Olea europaea L.) microshoots [Zinc oxide nanoparticles (ZnO NPs) belong to the most broadly produced NPs worldwide ,12,13. Ttigation . The addfera L.) ,14. ZnO eedlings . The suproshoots . On the roshoots .−1, on the in vitro regeneration and biochemical activity of adventitious shoots in chrysanthemum ‘UTP Burgundy Gold’ and ‘UTP Pinky Gold’. The enhanced regeneration potential of internode explants resulting from nanoparticles application would be of great importance for multiplication improvement and breeding purposes in chrysanthemum.This study aimed to test, for the first time, the influence of ZnO SMPs, ZnO NPs, and zinc oxide nanoparticles combined with silver nanoparticles (ZnO+1%Ag NPs), used at the concentrations of 100 and 500 mg·L3COO)2∙2H2O, Avantor Performance Materials Poland S.A., Gliwice, Poland); silver acetate anhydrous (Ag(CH3COO), Chempur, Piekary Śląskie, Poland); ethylene glycol (C2H4(OH)2, Chempur, Piekary Śląskie, Poland); deionized water (H2O) (specific conductance below 0.1 μS·cm−1). All the chemical substances were analytically pure and used without further purification. Submicron particles of pharmaceutically pure zinc oxide (ZnO SMPs) were purchased from ZM SILESIA SA, Huta Oława, Oława, Poland [The following were used for the synthesis of ZnO NPs and ZnO+1%Ag NPs: zinc acetate dihydrate 2∙2H2O (35.00 g) was dissolved in C2H4(OH)2 (525 mL) with the use of the hot-plate magnetic stirrer . Subsequently, the solution was decanted into a polypropylene (PP) bottle and sealed. Once the solution reached the room temperature, a water content analysis was carried out (CpH2O = 1.03 wt%) and 2.8929 g of water was added to reach the final water concentration of 1.5 wt%. The precursor solution was subjected to microwave heating in the microwave reactor MSS2 , IHPP PAS , ITeE-PIB , ERTEC  [The original microwave solvothermal synthesis procedure applied for the synthesis of ZnO NPs was described in detail in our previous articles ,19. In s Poland) . After c3COO)2∙2H2O (35.0000 g) and Ag(CH3COO) (0.2664 g) were poured into C2H4(OH)2 (525 mL) and stirred with the use of the hot-plate magnetic stirrer  until the reagents dissolved. Subsequently, the solution was decanted into a PP bottle and sealed. Once the solution reached the room temperature, a water content analysis was carried out (CpH2O = 1.06 wt%) and 2.7249 g of water was added to reach the final water concentration of 1.5 wt%. The precursor solution was subjected to microwave heating in the microwave reactor, MSS2 , IHPP PAS , ITeE-PIB , ERTEC  [In order to obtain a sample with the nominal composition of 99%·ZnO+1%·Ag NPs, the microwave solvothermal co-synthesis procedure, described in detail in our previous article , was app Poland) . After cThe tests of the ZnO NPs, ZnO+1%Ag NPs and ZnO SMPs samples were carried out in the Laboratory of Nanostructures , which holds accreditation no. AB 1503 . A detai®, Norcross, GA, USA). The specific surface area was measured by the Brunauer-Emmett-Teller (BET) method with the use of a Gemini 2360 . The Zn and Ag content in the ZnO+1%Ag NPs was determined by the energy dispersive spectrometry (EDS) method with the use of a Quantax 400 . The presented results of Zn and Ag content are average values calculated based on six analyses of different areas of the sample, which was pressed to the form of pastille. The water content (wt%) in the glycol solution samples was measured with the use of a Cou-Lo AquaMAX KF , which applies the Karl Fischer method.X-ray powder diffraction (XRD) patterns were collected on an X-ray diffractometer X’Pert PRO with CuKα radiation . The morphology of the obtained samples was analyzed using the scanning electron microscope ULTRA PLUS . The skeleton density (pycnometric density) of NPs samples was tested using an AccuPyc II 1340 helium pycnometer . Plant growth regulators (PGRs): 0.6 mg∙L−1 6-benzylaminopurine (BAP) and 2 mg∙L−1 indole-3-acetic acid (IAA)  were added to the medium to stimulate the regeneration of adventitious shoots. The pH level of the medium was adjusted to 5.8 with the use of HCl and NaOH  prior to medium sterilization. Approximately 40 mL of the medium was poured into 350-mL glass jars, which were next sealed with a plastic lid, and autoclaved at 105 kPa and 121 °C for 20 min.The composition of the medium for the in vitro culture was optimized in our previous studies on adventitious organogenesis in various chrysanthemum cultivars ,4,10. A Chrysanthemum × morifolium (Ramat.) Hemsl. cultivars: ‘UTP Burgundy Gold’ and ‘UTP Pinky Gold’, were used in the experiment. Aseptic internodes, dissected from plantlets cloned previously with the single-node method on the modified MS medium without plant growth regulators, were used as explants. Four explants per each culture jar were placed horizontally on the medium. Immediately after the inoculation onto the medium, the explants were treated with zinc oxide submicron particles suspension (ZnO SMPs), zinc oxide nanoparticles suspension (ZnO NPs), or zinc oxide and silver nanoparticles suspension (ZnO+1%Ag NPs), at the concentration of 100 or 500 mg·L−1 selected on the basis of preliminary research (data not shown). The tested suspensions were sterilized in an autoclave, and before application, placed for 30 min in the Elmasonic S80(H) Ultrasonic Cleaner with the ultrasonic frequency of 37 kHz and the effective ultrasonic power of 150 W  to achieve proper dispersion of particles. Suspensions were poured onto the culture medium with an automatic pipette with a sterile tip, 2 mL of each suspension, at each tested concentration per culture jar. Non-treated explants were used as the control object.Two −2·s−1.In vitro cultures were kept in the growth room at ambient conditions: temperature 23 ± 1 °C, 16/8 h light/dark photoperiod provided by Philips TLD 36W/54 fluorescent lamps  emitting cool daylight with the photosynthetic photon flux density set at 35 μmol·mObservations of the dynamics of adventitious shoots regeneration were performed weekly, for eight successive weeks. Next, the share of explants forming shoots, and the mean number of shoots per one inoculated explant, were estimated in the ninth week of culture to assess the regeneration efficacy. a, chlorophyll b, carotenoids, anthocyanins, phenolic compounds). The whole shoots (1–3 cm in length) were used to prepare fresh weight (FW) samples. As for the cultivar ‘UTP Burgundy Gold’, the extraction of anthocyanins and phenolic compounds was not performed due to the limited amount of plant material obtained from some experimental treatments.The regenerated adventitious shoots were subjected to biochemical analysis to estimate the content of plant metabolites (chlorophyll v/v) , as described by Harborne [Chlorophylls and carotenoids were extracted using 100 mg FW samples and 100% acetone  according to Lichtenthaler’s  procedurHarborne . The samHarborne , based o® NP80  at specific wavelengths (λmax): 530 nm, 645 nm, 662 nm, 470 nm, and 765 nm for anthocyanins (cyanidin-3-glucoside), chlorophyll a, chlorophyll b, carotenoids, and phenolic compounds, respectively. The content of the plant metabolites was calculated in milligrams per one gram of sample fresh weight (mg·g−1 FW).The spectrophotometric analyses were performed in the NanoPhotometerp ≤ 0.05. For data expressed as a percentage, the Freeman–Tukey transformation was used. All statistical analyses were performed with the use of the Statistica 13.3 software .The experiment was set up in a completely randomized design. Each experimental object consisted of 3 jars . One explant was considered as one repetition. Biochemical analyses were repeated six times. The obtained data were presented as mean ± standard deviation (SD) and subjected to one-way analysis of variance (ANOVA) and a post hoc Fisher test at the significance level of The ZnO NPs sample a–c and tThe crystalline structure of the ZnO samples was tested by the XRD method, while the results of the analyses are presented in −3 and 5.05 ± 0.05 g·cm−3, respectively. Taking into account the value of the standard deviation for the obtained skeleton density results, it can be stated that no significant differences were observed in these results. The specific surface area values for ZnO NPs and ZnO+1%Ag NPs were 48.4 m2·g−1 and 44.4 m2·g−1, respectively. The smaller specific surface area of the ZnO+1%Ag NPs sample resulted from the presence of Ag NPs in its composition. Wu et al. [2·g−1, between the samples obtained by the solvothermal method Ag nanocomposite −75.9 m2·g−1). This might indicate that during the solvothermal co-synthesis of ZnO+Ag there is a close correlation between the nanoproducts, which should be explained by researching and verifying the co-synthesis mechanism. The average particle sizes, calculated on the basis of the specific surface area results for the ZnO NPs sample and the ZnO+1%Ag NPs sample, were 25 ± 2 nm and 27 ± 2 nm, respectively. The average ZnO crystallite sizes, calculated on the basis of the Scherrer equation for the ZnO NPs sample and the ZnO+1%Ag NPs sample, were 31 ± 8 nm and 22 ± 3 nm, respectively. The results based on the Scherrer equation coincided for these samples with the results obtained from the Nanopowder XRD Processor Demo application . However, the use of the same material sample at a lower concentration of 100 mg·L−1 yielded a significantly lower number of shoots (2.42). A high efficiency of shoot formation was also obtained when explants were treated with 100 mg·L−1 ZnO SMPs (6.50 shoots per explant). On the contrary, a low efficiency of shoot regeneration was found for the ZnO+1%Ag NPs sample (0.83–1.33) and for 500 mg·L−1 ZnO SMPs (1.42)  positively affected the ability of internode explants to form shoots and the efficiency of shoot regeneration as compared to the control object, where no shoot regeneration occurred. Nevertheless, the share of explants forming shoots ranged from 41.67% and 50% for 100 mg·Ls (1.42) .−1 ZnO+1% Ag NPs treatments, up to 100% in other experimental combinations. The highest efficiency of shoot regeneration was found for the control internodes (12.92 shoots per explant), with an application of 500 mg·L−1 ZnO SMPs (12.08) and 500 mg·L−1 ZnO NPs (10.42), whereas internodes in other experimental treatments produced 5.83–7.83 adventitious shoots  [Lamprocapnos spectabilis (L.) Fukuhara) [Streptocarpus × hybridus Voss.) [Interestingly, in both tested cultivars, the use of samples containing 1% AgNPs did not increase the explants’ regeneration efficiency considerably as compared to the other treatments. Silver nanoparticles, applied as a homogenous colloid at the concentration of 50 and 100 mg·Lpurposes ,4,10. Liukuhara) , gerberaa, chlorophyll b, total chlorophylls, and carotenoids was found in ‘UTP Burgundy Gold’ shoots regenerated on 100 mg·L−1 ZnO+1% Ag NPs-treated internodes. Nevertheless, the application of the same sample, but at 500 mg·L−1, resulted in a significant decrease in the content of these metabolites compared to the lower concentration. Shoots from the treatments, which provided the best results in terms of regeneration efficiency, i.e., 100 mg·L−1 ZnO SMPs and 500 mg·L−1 ZnO NPs, were characterized by a high or moderate capability for metabolites biosynthesis. Shoots formed on explants treated with 500 mg·L−1 ZnO SMPs or 100 mg·L−1 ZnO NPs had low contents of chlorophyll a, chlorophyll b, total chlorophylls, and carotenoids. Interestingly, compared to submicron particle treatments, nanoparticle treatments resulted in a significant increase in the values of the chlorophyll (a+b)-to-carotenoid ratio and decreasing chlorophyll a/b ratio  chlorophyll a/b ratios were found in the control object and as a result of 100 mg·L−1 ZnO SMPs, and 100 mg·L−1 ZnO+1%Ag NPs treatments. Simultaneously, the highest chlorophyll (a+b)/carotenoid ratios were identified for the control object, 500 mg·L−1 ZnO SMPs, and 500 mg·L−1 ZnO NPs samples. Treatment with ZnO SMPs and ZnO NPs, especially at a higher concentration, negatively affected the ability of shoots to synthesize anthocyanins compared to the control object and application of ZnO+1%Ag NPs. Interestingly, the content of phenolic compounds in the shoots was similar in the control and ZnO SMPs/ZnO NPs treatments, whereas the use of material samples with silver nanoparticles suppressed the biosynthesis of these compounds  shoots, as well as enhanced the chlorophyll a and b, carotenoids, anthocyanins, and total phenolic compound content [−1, significantly decreased the chlorophyll content in Vigna radiata (L.) Wilczek seedlings. As suggested by the authors, the decrease in chlorophyll synthesis might be due to the replacement of the central metal atom of chlorophyll (Mg2+) by Zn2+, leading to reduced photosynthetic efficiency [−1 ZnO NPs treatments reduced Arabidopsis growth by ∼20 and 80%, respectively, in comparison to the control. Pigments measurement showed that chlorophyll a and b contents were reduced more than 50%, whereas carotenoid content remained largely unaffected in 300 mg·L−1 ZnO NPs-treated Arabidopsis plants. Consistently, the net rate of photosynthesis, leaf stomatal conductance, intercellular CO2 concentration, and transpiration rate were all reduced more than 50% in 300 mg·L−1 ZnO NPs-treated plants.In a study performed by Al-Mayahi , date pan plants . Similar content . On the ficiency . Wang etficiency  found thPerilla frutescens var. crispa f. purpurea plants treated with 50 mg·L−1 than with 200 mg·L−1 ZnO NPs, whereas the treatment with ZnO NPs at 50 and 100 mg·L−1 enhanced anthocyanins content as compared with the control and 200 mg·L−1 [Capsicum annum L. showed that accumulation of phenolic compounds in response to 100, 200, and 500 mg·L−1 ZnO NPs application differed depending on the tested plant part. The polyphenols content in the plumule was not affected by ZnO NPs, but the increase from 100 to 500 mg·L−1 ZnO NPs stimulated the accumulation of these metabolites in the radicles [Apparently, chrysanthemum ‘UTP Pinky Gold’ is more tolerant to metal-induced biochemical response of cells, as the contents of chlorophylls and carotenoids did not vary in the plants of this cultivar, irrespectively of zinc form and concentration in the medium. On the other hand, the biosynthesis of anthocyanins, and to a lesser extent also of other polyphenols, was strongly affected by zinc and silver, as the profile of these metabolites has changed in ‘UTP Pinky Gold’ shoots in a wide range, depending on the experimental treatment. Our results are in line with some other studies presenting a varied influence of ZnO NPs on the non-enzymatic antioxidants profile in different plant species ,4,60. Fo0 mg·L−1 . A studyradicles .−1 ZnO SMPs and 500 mg·L−1 ZnO NPs. Simultaneously, shoots from these combinations had high or moderate contents of chlorophylls and carotenoids as compared to other treatments. On the other hand, in chrysanthemum ‘UTP Pinky Gold’, in shoots from the most efficient experimental treatments, i.e., the control, 500 mg·L−1 ZnO SMPs, and 500 mg·L−1 ZnO NPs, an increased chlorophylls (a+b)/carotenoids ratio was reported. Interestingly, in the latter cultivar, the application of ZnO SMPs and ZnO NPs affected negatively the anthocyanins biosynthesis, whereas the treatment with ZnO+1%Ag NPs decreased the accumulation of phenolic compounds. These findings open new research areas in terms of chrysanthemum micropropagation but can also be useful in mutation breeding or genetic transformation. Future studies will focus on a detailed analysis of the genetic stability of regenerants obtained after ZnO NPs and ZnO SMPs treatments. It will be interesting to verify whether the simultaneous application of engineered zinc nanomaterials with physical or chemical mutagens (particularly AgNPs at high concentration) can elevate the effectiveness of mutants regeneration and speed up the breeding process in chrysanthemum and other horticultural crops.This is a maiden study on micropropagation of two new valuable chrysanthemum cultivars: ‘UTP Burgundy Gold’ and ‘UTP Pinky Gold’. The present study confirmed the diversified regenerative potential of non-meristematic explants of even closely related chrysanthemum cultivars. By adding zinc nanoparticles or submicron particles on the surface of the culture medium, it is possible to overcome the recalcitrant potential of cultivars to adventitious organogenesis. For example, in chrysanthemum ‘UTP Burgundy Gold’, the best results in terms of regeneration efficiency were obtained after the treatments with 100 mg·L


The unpredictable nature of new variants of coronavirus 2 (SARS-CoV-2)—highly transmissible and some with vaccine-resistance, have led to an increased need for feasible lifestyle modifications as complementary therapies. Systemic inflammation is the common hallmark of communicable diseases like severe coronavirus disease 2019 (COVID-19) and non-communicable chronic diseases (NCDs) such as obesity, cardiovascular diseases (CVD), diabetes mellitus, and cancers, all for which mitigation of severe outcomes is of paramount importance. Dietary quality is associated with NCDs, and intermittent fasting (IF) has been suggested as an effective approach for treatment and prevention of some NCDs, similar to that of caloric restriction. There is a paucity of high-quality data from randomized controlled trials regarding the impact of IF and the intake of specific nutrients on inflammation and post-infection outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current review of recent literature was performed to explore the immunomodulatory roles of IF regimens and supplements involving the intake of specific nutrients including vitamins , zinc, and nutraceuticals  on inflammatory and oxidative stress markers, with consideration of how they may be related to SARS-CoV-2. A new wave of a subvariant of concern of the “omicron” variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—which poses very high risk of infection—is spreading worldwide, continuing the evolving pandemic that is now in its third year . The effA key characteristic of severe presentations of acute SARS-CoV-2 infection involves overactive host inflammatory responses, with a substantial proportion of severe outcomes such as hospitalizations and deaths from COVID-19 linked to hyper-inflammation . InflammInterestingly, hs-CRP, IL-6, and many of the other inflammatory biomarkers mentioned above, are also markers of risk in NCDs such as coronary artery disease and diabetes ,14,15,16A literature search of the PubMed and Google Scholar databases was conducted to identify peer-reviewed articles published from January 2017 to March 2022 that involved assessments of markers of inflammation or oxidative stress. The search terms for dietary supplementation articles included the following: “vitamin”, “nutrient”, “mineral”, “antioxidant”, “nutraceuticals”, “polyphenols”, “resveratrol”, “quercetin”, “probiotic”, “omega-3”, combined with “infection”, “inflammation”, “inflammatory markers”, “immune response”, “immunity”, “oxidative stress”, “CVD”, “obese adults”, “obesity”, “overweight”, “‘SARS-CoV-2′”, and “COVID-19.” The search terms for intermittent fasting articles included the following: “intermittent fasting”, “alternate-day fasting”, “time-restricted eating”, “5:2 diet”, “Ramadan fasting”, combined with “infection”, “inflammation”, “inflammatory markers”, “immune response”, “immunity”, “oxidative stress”, “CVD”, “obese adults”, “obesity”, “overweight”, “SARS-CoV-2”, and “COVID-19.” Filters were set to allow only “human” studies, and studies written in the “English” language.Supplementation with vitamins such as A, B, C, D, and E is thought to play a significant role in the severity of COVID-19 infection by reducing inflammation, time to recovery, and preventing lung fibrosis ,40. To oAccumulating data highlight the immunomodulatory role of vitamin D, and link hypovitaminosis D (25 OHD ≤ 20 ng/mL) with hyperinflammation  and elevated risk of mortality in patients with COVID-19 ,44,45,46Evidence for the potential role of zinc supplementation for COVID-19 infection is inconclusive ,55,56; wIt is well known that n-3 PUFAs including eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory properties ,65,66. TQuercetin—a polyphenol with antioxidant and anti-inflammatory properties—is widely known to have favorable effects on inflammation and infection ,68,69. DHigh quality evidence from systematic reviews and meta-analyses of RCTs, indicates that probiotics may have a favorable role for responses to infections . In a reTo date, no RCTs have investigated the effects of IF on SARS-CoV-2 infection or severity of COVID-19 outcomes, although epidemiologic evidence regarding periodic fasting suggests that fasting in some forms may prevent severe COVID-19 outcomes such as hospitalization and death , perhapsCurrent evidence from RCTs reveals that time-restricted eating (TRE) may be effective for reducing interleukins IL-1β, IL-6 and IL-8 see . Of the Studies of the impact of different IF regimens on TNF-α have reported inconsistent results see . Early TThere has also been inconsistency in the results of various trials of IF regimens on hs-CRP levels, with most studies indicating no effects see . Of the IGF-1 levels remain unchanged with most IF trials that recruited participants with overweight and obesity. In athletes, however, two RCTs conducted by Moro et al. reported significant reductions in IGF-1 levels with TRE as compared to control and baseline after both 4 weeks and 12 months ,74. IGF-Interferon gamma (IFN-γ), a proinflammatory cytokine that plays a significant role in immune responses, has been investigated in only two 24-h prolonged fasting studies by Han and colleagues. These studies indicate that IFN-γ levels were significantly reduced when compared with 3 h after refeeding with isocaloric breakfast meal  in a total of adults who fasted for 24 h ,94. Matr8-Isoprostane is a marker of oxidative stress that is associated with COVID-19 . To dateEvidence suggests that intermittent fasting and supplementation with vitamin D, and nutraceuticals including quercetin, n-3 fatty acids, and probiotics, impact inflammation in canonical pathways related to both NCDs and infectious diseases including COVID-19 and, thus, should reduce COVID-19 severity. A lack of high-quality evidence exists for the support of such efficacy of supplementation with vitamins A, B, and C, as well as zinc in COVID-19 patients. Further investigation of these fasting and supplementation effects is indicated. Observational studies report that some diets  may reduce SARS-CoV-2 severity, potentially—at least in part—because the foods contain antioxidants and other components with anti-inflammatory properties ,102,103,Ultimately, the impact of intermittent energy restriction methods on inflammation during energy restriction may be acute but transient, contrasting with longer-term persistent changes to basal levels of inflammation. Future randomized controlled trials are needed to elucidate the effects of intermittent fasting on NCDs and on inflammatory host responses to infection.


Despite the extensive studies of topological states, their characterization in strongly nonlinear classical systems has been lacking. In this work, we identify the proper definition of Berry phase for nonlinear bulk waves and characterize topological phases in one-dimensional (1D) generalized nonlinear Schrödinger equations in the strongly nonlinear regime, where the general nonlinearities are beyond Kerr-like interactions. Without utilizing linear analysis, we develop an analytic strategy to demonstrate the quantization of nonlinear Berry phase due to reflection symmetry. Mode amplitude itself plays a key role in nonlinear modes and controls topological phase transitions. We then show bulk-boundary correspondence by identifying the associated nonlinear topological edge modes. Interestingly, anomalous topological modes decay away from lattice boundaries to plateaus governed by fixed points of nonlinearities. Our work opens the door to the rich physics between topological phases of matter and nonlinear dynamics. Topological phases are challenging to identify in systems with general, strong nonlinearities. Here, the authors establish the analytic methodology that defines the topological invariant of nonlinear normal modes. Strongly nonlinear topological boundary modes are guaranteed by the nontrivial topological index. In classical structures12, enormous efforts have been devoted to topological states that emulate their quantum analogs and enable many pioneering applications28. However, most studies of classical structures are limited to linear topological band theory, whereas nonlinear topological systems are not fully understood yet.The advent of topological band theory has led to the burgeoning field of “topological phases of matter” which manifest exotic properties, such as surface conduction of electronic states, and wave propagation insensitive to backscattering and disorder29, nonlinear elastic and mechanical structures34, nonlinear origami systems35, evolutionary dynamics of biological cycles37, second-harmonic generation of optic materials39, and cold atoms in optical lattices41. To date, few studies are addressed in nonlinear topological photonics45 and Bose-Einstein condensates47, but the interactions are limited to Kerr-like nonlinearities controlled by field intensities. These Kerr-like nonlinearities are the simplest ones that grant sinusoidal nonlinear bulk waves and thus the topological invariants48 are the same as those in linear theories.Nonlinear dynamics are more ubiquitous in nature, such as electrical circuits composed of nonlinear elements49, leading to topological invariants in these strongly nonlinear systems undefined. Though boundary modes remain topologically protected in the weakly nonlinear regime34, strong nonlinearities may destroy their topological nature by breaking the intrinsic symmetries47, and existing linear and weakly nonlinear topological theories are not always correct to predict their strongly nonlinear topological properties35. Moreover, it is intriguing to ask what exotic physics and unconventional attributes arise when topology meets universal strong nonlinearities. Thus, it is demanding to invoke the topological number that precisely describes the topological attributes of “beyond-Kerr” strongly nonlinear systems.However, the majority of classical structures are beyond Kerr-like nonlinearities, such as the aforementioned electrical, mechanical, biological, and optic systems. Nonlinear bulk modes cannot be solved analytically35, electrical circuits29, deep water waves50, and bio-physical cycles53, their dynamics are commonly described by generalized nonlinear Schrödinger equations, which we adopt to study theoretically, for future nonlinear topological experiments. The nonlinear parts of interactions are comparable to the linear ones and perturbation theory breaks down, which we designate the “strongly nonlinear regime”. We limit our considerations within the amplitude range33 that chaos does not occur. Consequently, nonlinear bulk modes54 are remarkably distinct from sinusoidal waves  for i = 1 and i = 2 stand for intracell and intercell nonlinear couplings, respectively. fi  are real-coefficient general polynomials of x, x*, y, and y* (* represents complex conjugate), which offer time-reversal symmetry3. Given a nonlinear solution Ψn (t), time-reversal symmetry demands a partner solution 56, 2 Ψ to enforce particle number conservation; in our case the fields do not correspond to particle densities and more general nonlinearities beyond Kerr-like interactions are thus permitted.The considered model is a nonlinear SSHfi  ≈ ciy  to have “gapped” two-band models when c1 ≠ c2. The bulk mode eigenfunctions are sinusoidal in time, and Berry phase is quantized by reflection symmetry. In the “strongly nonlinear regime” where nonlinear interactions become comparable to the linear ones, nonlinear bulk modes are significantly different from sinusoidal waves  as the frequencies of nonlinear bulk modes for given amplitude A. We consider the simple case that nonlinear bulk modes are always non-degenerate  unless they reach the topological transition amplitude when the nonlinear bands merge at the band-touching frequency. Hence, given the amplitude, frequency, and wave number, a nonlinear bulk mode is uniquely defined. Extended from gapped linear models, the lattice is a “gapped two-band nonlinear model”. In what follows, we define Berry phase for nonlinear bulk modes of the upper-band by adiabatically evolving the wave number across the Brillouin zone.In linear regime, the polynomials are approximated as 61 ,ω and q are the frequency and wave number, respectively. π-periodic wave components, where the phase conditions are chosen by asking eΨ(t = 0) = max(ReΨ(t)) adopted in Schrödinger equation in order to have the eigenfunctions Ψ(t) = |Ψ|eiϵt/ℏ−. Following this condition, ϕq in Eq. (∂t Ψq = H(Ψq), where H (Ψq) is the nonlinear function determined by Eq.  manifest non-dispersive, plane-wave like bulk modes in the strongly nonlinear regime. Finally, it is demonstrated in SI. 61 are characterized by the wave number q as well, as pictorially indicated in Fig. The ansatz in Eq.  correctlentclass1pt{minima63 and nonlinear localized modes31. Corresponding detailed discussions are addressed in SI. While the ansatz in Eq.  capturesq(t’) traversing the Brillouin zone from q(0) = q to q(t) = q + 2π, while the amplitude A remains unchanged during this process. According to the nonlinear extension of the adiabatic theorem67, a system H(Ψq) initially in one of the nonlinear modes Ψq will stay as an instantaneous nonlinear mode of H(Ψq(t)) throughout this procedure, provided that the nonlinear mode Ψq is stable67 within the amplitude scope of this paper. Due to the symmetry constraints of the nonlinear motion equations, we demonstrate that all nonlinear bulk states are marginally stable within Floquet analysis69  defines the phase shift of the nonlinear bulk mode in the adiabatic evolution. The dynamics of γ is depicted by (dγ/dt)(∂Ψq/∂θ) = (dq/dt)(∂Ψq/∂q). After q traverses the Brillouin zone, the wave function acquires an extra phase γ dubbed Berry phase of nonlinear bulk modes,j, j′ = 1, 2 denote the two wave components, and the mathematical derivations are displayed in SI. γ is not quantized unless additional symmetry properties are imposed on the model, which we will discuss below. We note that the eigenmodes of linear problems as well as Kerr-like nonlinear systems48 are sinusoidal in time, which reduces Eq.  and ω(ϕq = π) for q = 0 and π. γ = π if ω(ϕ0 = 0) and ω(ϕπ = π) belong to the same band, whereas γ = 0 if ω(ϕ0 = 0) and ω(ϕπ = 0) are in the same band. Interestingly, γ encounters a topological transition induced by the critical amplitude A = Ac if the frequencies merge at ω = ω. This transition is exemplified by the minimal model of nonlinear topological lattice in Sec.III. It is worth emphasizing that despite all the discussions of nonlinear Schrödinger equations and the quantization of Berry phase, the model is purely classical in the sense of ℏ being zero.Thus, the Fourier components of nonlinear bulk modes satisfy with Eq. , is the with Eq.   to induce topological-to-non-topological phase transition  as amplitudes increase. We abbreviate them as “T-to-N” and “N-to-T” transitions, and they are converted to one another by simply flipping intracell and intercell couplings. In the remainder of this paper, a semi-infinite lattice subjected to open boundary condition (OBC) is always considered whenever we refer to topological edge modes.We are interested in attributes unique to nonlinear systems, in particular the topological phase transition induced by bulk mode amplitudes. Thus, the parameters yield c1 < c2 and d1 > d2, in which a T-to-N transition occurs. Figure ϵ0 = 1.5, c1 = 0.25, c2 = 0.37, d1 = 0.22, and d2 = 0.02. Given that Berry phase γ(A = 0) = π, the lattice is topologically nontrivial in the linear limit. As amplitudes rise, the topological invariant γ(A < Ac) = π cannot change until it becomes ill-defined when the nonlinear band gap closes at the transition amplitude Ac. The band gap reopens above Ac, allowing the well-defined Berry phase to take the trivial value γ(A > Ac) = 0, as depicted in the inset of Fig. Ac is numerically computed by solving the band gap-closing equation ω = ω. We propose a convenient approximation72We first study the case 26 and Schrödinger71 systems by showing topological boundary modes guaranteed by topologically non-trivial Berry phase. In the strongly nonlinear problem, we utilize analytic approximation and numerical experiment, to doubly confirm this correspondence by identifying nonlinear topological edge modes. In the former, the lattice is composed of N = 45 unit cells with OBCs on both ends to mimic semi-infinite lattice, and the parameters are carried over from Fig. ωT, respectively. Analogous to linear SSH chain55, the analytic scheme is to approximate ωT = ϵ0, andBulk-boundary correspondence has been extended to weakly nonlinear Newtonian70. The numerical scenario is accomplished by applying a Gaussian profile signal ωext = ϵ0 = 1.5, T = 2π/ωext, τ = 3T controls Gaussian spread, and t0 = 15T denotes trigger time. Figure 71 by identifying the presence and absence of topological boundary excitations below and above the critical amplitude Ac, respectively. In Fig. From Eq. , the sem see SI. , and theωT = ϵ0 are independent of amplitudes, although this result is in agreement with Refs. 48 in weakly nonlinear regime and is proved in SI. 55 demands the tail of the mode to be ωT = ϵ0, which in turn requires the frequency of the nonlinear topological mode to be independent of the amplitude.One may find it unusual that the frequencies of topological modes Topological protection is featured in multiple aspects. As visualized in Fig. c1 > c2 and d1 < d2, N-to-T  transition occurs as amplitudes rise. We exemplify boundary excitations in Fig. ϵ0 = 8, c1 = 0.37, c2 = 0.25, d1 = 0.02, and d2 = 0.22. A Gaussian signal is applied on the first site of the lattice, where the carrier frequency ωext = ϵ0 = 8, T = 2π/ωext, Gaussian spread τ = 10T, and trigger time t0 = 25T. In the small-amplitude regime, we consider a chain of N = 45 unit cells. As shown in Fig. N = 120 unit cells. Anomalous topological edge modes emerge when Ac governed by the stable fixed point of Eq. , but this fixed point becomes unstable in N-to-T transition (T-to-N transition).Although T-to-N and N-to-T transitions are converted to one another by choosing the unit cell, topological modes behave qualitatively different Fig. d and 3h ϵ0 with ϵA = (1 + 5%)ϵ0 and ϵB = (1–5%)ϵ0 for A and B-sites, respectively, leading to the disappearance of in-gap nonlinear boundary excitations. Instead of violating reflection symmetry, we introduce disorders by changing the coupling coefficients to ci,n = ci + δci,n and di,n = di + δdi,n, where δci,n/ci and δdi,n/di ∈ are random variables for different unit cells. As shown in Fig. Finally, it is important to emphasize that these strongly nonlinear in-gap states are symmetry-protected topological modes, in the sense that they cannot exist in systems with broken reflection symmetry. Berry phase cannot be derived from Eq.  to Eq.  and is n73 extends the study of topological mechanics to strongly nonlinear regime and manifests strongly nonlinear topological boundary dynamics. Here we discuss an alternative example, namely the active topoelectrical circuit, that manifests topological nonlinear boundary excitations. This experimental proposal is modified from the cascaded circuit ladder by Hadad, et. al., where the nonlinear capacitors in Ref. 7 are now replaced by linear ones, and the nonlinearity in our model is introduced by active voltage sources , the linear circuit system manifests topological boundary voltage excitations due to the reflection-symmetric nature of the dynamics. Thus, it is intuitive to expect that topological boundary voltages also arise as long as the nonlinear voltage sources respect reflection symmetry. To this end, we demand that the nonlinear sources yield the constraints Without these nonlinear voltage sources  of topological modes is associated with a change in the Berry phase to its topological  value. As amplitudes increase, T-to-N  and N-to-T  transitions take place for different choices of unit cells. Anomalous topological modes decrease away from lattice boundaries to a plateau controlled by the stable fixed point of nonlinearities. These two unconventional properties stem from the interplay between nonlinear dynamics and topological physics.53, we discuss future directions of nonlinear topological physics. These existing literature mainly belong to two classes, namely the topological numbers and properties in Kerr-nonlinear systems47, and stochastic topological dynamics in bio-physical cycles53.By comparing our results with recent developments regarding topological attributes in classical structures47 study the nonlinear effects in adiabatic geometric phases. Besides the common interest in nonlinear topological phases, there are several differences between Refs. 47 and our work. In particular, Ref. 46 conducts a 2D Kerr-nonlinear Chern insulator, where the geometric Zak phase is naturally un-quantized due to the lack of symmetry. Interestingly, Ref. 46 figures the quantized Aharonov-Bohm phase that characterizes nonlinear Dirac cones. It is therefore intriguing to ask if “beyond-Kerr” interactions can also realize nonlinear Dirac cones protected by quantized Aharonov-Bohm phase and enable novel designs of nonlinear mechanical and electrical metamaterials. Ref. 47 studies the interplay between chiral symmetry and topological attributes in 1D Kerr-nonlinear systems. Following this idea, it is worth asking how chiral symmetry quantizes Berry phase and reveals novel topological physics in general nonlinear systems. Ref. 43 studies the topological phases of Kerr-nonlinear 3D photonic metamaterial, where the topological invariant is the 3-form Chern-Simons theory. Following this idea43, it is worth exploring 3D topological insulators with general nonlinearities using the formalism of our work.With regards to Kerr-nonlinear topological systems, previous works53 studies topological properties in a linear non-equilibrium stochastic process, where complex eigenfrequencies manifest themselves in the non-Hermitian system. Thus, it is exciting to investigate how topologically robust nonlinear edge flow arises in nonlinear active biological cycles, which demands a systematic construction of non-Hermitian, nonlinear topological band theory. Moreover, bulk-boundary correspondence and edge distribution of biomass75 may be further identified using the invariant derived in this work.We now discuss the interplay between nonlinear topological physics and biological dynamics. Ref. Our primary methods were analytical theories accompanied by computer-aided simulations on MATLAB interface. Nonlinear bulk modes were numerically computed by shooting method. The stability of nonlinear modes were confirmed by the analytic Floquet analysis and the numerical integration algorithm. The algorithmic details are displayed in the supplementary information.Supplementary InformationPeer Review File


Predicting that a stimulus is painful facilitates action to avoid harm. But how distinct are the neural processes underlying the prediction of upcoming painful events vis-à-vis those taking action to avoid them? Here, we investigated brain activity as a function of current and predicted painful or nonpainful thermal stimulation, as well as the ability of voluntary action to affect the duration of upcoming stimulation. Participants performed a task which involved the administration of a painful or nonpainful stimulus (S1), which predicted an immediately subsequent very painful or nonpainful stimulus (S2). Pressing a response button within a specified time window during S1 either reduced or did not reduce the duration of the upcoming stimulation. Predicted pain increased activation in several regions, including anterior cingulate cortex (ACC), midcingulate cortex (MCC), and insula; however, activation in ACC and MCC depended on whether a meaningful action was performed, with MCC activation showing a direct relationship with motor output. Insula’s responses for predicted pain were also modulated by potential action consequences, albeit without a direct relationship with motor output. These findings suggest that cortical pain processing is not specifically tied to the sensory stimulus, but instead, depends on the consequences of that stimulus for sensorimotor control of behavior. The cerebral cortex plays a major role in generating predictions about internal and external events and in comparing and adjusting those predictions against incoming sensory information . But prebefore a stimulation occurs  plays a key role in supporting voluntary action to avoid harm. It is well-situated for this role through its involvement in the cortical control of voluntary movement during nonpainful  and painIf prediction and meaningful, motivated action are critical component functions of pain, how can they be disentangled for investigation of their underlying functional neuroanatomy? To do so requires experimentally dissociating acute pain processing (what is happening now) from predictive processing (what happens next) and probing the effects of motivated action (what can be done) on these processes. We pursued this aim by using functional magnetic resonance imaging (fMRI) to measure hemodynamic changes during an experimental paradigm in which participants were administered acute painful or nonpainful thermal stimulation (“current”) which predicted upcoming suprathreshold painful or nonpainful stimulation (“predicted”) later in the trial.This experimental task required participants to make a timed button-press response during the stimulation in each trial regardless of whether the current stimulus was painful or nonpainful. At the start of each trial, participants were informed of the current stimulus’ (S1) predictive relationship to an upcoming stimulus (S2) as well as whether a successfully timed button-press within a 450-ms window would shorten the upcoming stimulation by 3 s . This paradigm allowed dissociation of immediate from predicted effects of pain processing (current and predicted pain during S1) as well as any general effects of action from task-related processing (button-presses which would or would not affect S2). It also allowed dissociation of the effects of action execution (button-press) from action consequence (shortening upcoming stimulation).With this paradigm, we tested for any pain-specific neural modulation of, and any interactions among, 3 major factors during the “current” stimulation in S1: (i) current pain in S1 regardless of whether it predicts upcoming pain in S2, (ii) predicted pain in S2 regardless of current stimulation in S1; and (iii) the ability to affect S2 by making an accurately timed action during S1. In (i), “predicted” pain is held constant, potentially revealing activations selective for current stimulation; a lack of modulation here might indicate that current stimulation has no specific influence on predictive pain processing. Likewise, in (ii), “current” pain is held constant, potentially revealing activations selectively modulated by the predicted stimulation. A lack of modulation here might indicate that current pain processing outweighs predicted pain.In its operationalization of the factors pain, prediction, and action, this paradigm pulls apart in time functions which may normally be “bundled” in a less attenuated way during real-life acute pain processing. In ecological acute pain, the cortical process that corresponds to the “prediction” factor in this experiment is not necessarily a forecast of a future painful event. Rather, it may reflect a broader apprehension of the immediate consequences of ongoing sensations, handled by the brain in terms of the scope for limiting potential or actual tissue damage via behavioral adjustment. What you sense now depends on what you just did; by the same token, what you will sense soon depends on what you are doing now. In this perspective, such a broadly predictive or apprehensive process would facilitate behavioral responses more likely to aid escape or avoidance of tissue damage in the moment while also adapting to the particular circumstances of the painful event, for example, with regard to prior experience, current goals, and situational context.https://osf.io/8p7rq).We hypothesized that AI would distinguish between predicted painful and nonpainful stimulation regardless of whether or not the upcoming stimulus was controllable by action, whereas MCC would selectively respond to predicted stimulation that was controllable by action regardless of whether or not it was painful. The methods, analysis plan, and specific hypotheses for each contrast of interest were preregistered on the Open Science Framework (M ± standard deviation {SD}]) in the final sample. Due to technical issues, 2 participants only have data from 1 of 2 functional runs.Forty participants were recruited from a student subject pool at Linköping University, Sweden, using the Online Recruitment System for Experiments in Economics . InclusiM = 44.86, SD = 1.77) and very painful stimuli ranged from 45 °C to 49 °C . Nonpainful stimuli corresponded to baseline temperature, 32 °C.Physical pain was delivered using a 3 × 3-cm thermal stimulator probe  on the dorsal part of the left forearm. Prior to the experiment, thresholds for warmth, cold, and heat pain as well as heat pain limits were determined using a procedure adapted from The experiment had a 2 × 2 × 2 within-subjects design with the following factors: S1 (current stimulation: painful or nonpainful), S2 (predicted stimulation: very painful or nonpainful), and action (effective or ineffective). The trial structure is shown in The experiment was programmed in Matlab and included 96 trials, separated into 2 blocks of 48 trials each. The order of the 2 blocks was counterbalanced between participants. The order of trials within each block was pseudorandomized using a Latin square (and its reverse) balancing the 4 combinations of S1 and S2 to help avoid first-order carryover effects. The action factor was folded in as an additional Latin square (and its reverse). This resulted in “mini-blocks” in which the task changed every four trials. The start of each trial was triggered by the Pathway. The interstimulus interval  was 4–6 s, randomly jittered by the Matlab script. The intertrial interval  varied depending on trial duration and Pathway ramping time (ITI range 3.56–16.86 s).2 × 476 mm2; in-plane voxel resolution: 3 mm2; flip angle: Ernst angle [59°]).  Three dummy volumes were acquired before each run  to ensure that data collection started after the longitudinal magnetization reached steady state. A high-resolution 3D T1-weighted (MP-RAGE) anatomical image was acquired before the first EPI .fMRI data were acquired using a 3.0 Tesla Siemens scanner  with a 64-channel head coil . We collected data in 2 functional runs (1 for each task block), each lasting for 20 min and 51 s. For each run, 1,389 T2*-weighted echo-planar images (EPIs) containing 45 multiband slices were acquired  software v20.0.12. Blood oxygen level–dependent (BOLD) images were despiked and slice-time-corrected. For motion correction and coregistration purposes, each EPI volume was registered to the volume with the minimum outlier fraction (using the AFNI outlier definition). Functional images were then warped to Montreal Neurological Institute (MNI) template space using a combination of affine and nonlinear transformations. Nuisance effects due to head motion (estimated from the motion correction procedure) were accounted for by adding the motion parameters as regressors of no interest in the main regression. A motion censoring threshold of 0.3 mm per TR was implemented in combination with an outlier fraction threshold of 0.05 . Volumes violating either of these thresholds were subsequently ignored in the time-series regression.A general linear model (GLM) analysis was performed to capture differences across conditions. Whole-brain, voxel-wise GLM statistical analysis was carried out on the BOLD time-series data using 3dmvm in AFNI. We conducted GLM-based analysis of a 1-s time window from the onset of S1. Predictors (convolved with a standard model of the hemodynamic response function) were created for each of the 8 combinations of current stimulation, predicted stimulation, and action effectiveness. Following P-value threshold of P = 0.002, which is in accordance with recommendations from the maintainers of AFNI  analysis in MCC and left and right insula. For the insula, we used activation clusters from a main effect of pain during S2 see . Any voxF = 19.15, P < 0.001, ηp2 = 0.398, indicating that participants responded faster when the button-press action was effective  than when it was ineffective  = 0.002, P = 0.963, ηp2 < 0.001) or predicted stimulation  = 2.06, P = 0.162, ηp2 = 0.066) and no significant interactions  = 2.38, P = 0.134, ηp2 = 0.076; current × action: F = 0.004, P = 0.949, ηp2 = < 0.001; predicted × action: F = 0.14, P = 0.713, ηp2 = 0.005; current × predicted × action: F = 1.99, P = 0.169, ηp2 = 0.064).On average, participants responded within the 450-ms response window (and thus successfully reduced the duration of the upcoming stimulation when the response button was enabled) on 85.9% of trials , predicted stimulation (pain or nonpain), and action (effective or ineffective). Results of any significant main effects or interactions were further explored with general linear tests.t-tests) that were of particular interest. First, we compared activation on trials in which pain predicted pain to trials in which pain predicted nonpain in order to discover any selective activation for pain predicted by congruent current stimulation. Here, we expected increased activation in AI. This analysis revealed greater activation for predicted pain than predicted nonpain in bilateral putamen, right pallidum, bilateral insula, bilateral inferior frontal gyrus, left postcentral gyrus, right MCC, right ACC, and right rolandic operculum  = 25.02, P < 0.001, ηp2 = 0.463, indicating greater activation when predicted stimulation was painful compared to nonpainful. There were no other main effects or interactions  = 3.06, P = 0.091, ηp2 = 0.095; predicted stimulation × action: F = 2.98, P = 0.095, ηp2 = 0.093).In right insula, there was a main effect of predicted stimulation, ions see , althougF = 17.69, P < 0.001, ηp2 = 0.379, and a 3-way interaction between current stimulation, predicted stimulation, and action effectiveness, F = 5.70, P = 0.024, ηp2 = 0.164. Pairwise comparisons with Bonferroni correction indicated that activation was lower when pain predicted nonpain for which action was ineffective than when (i) pain predicted pain for which action was ineffective (t(106) = 3.26, P = 0.042), (ii) pain predicted pain for which action was effective (t(103) = 3.70, P = 0.010), and (iii) nonpain predicted pain for which action was effective (t(105) = 3.64, P = 0.012).In left insula, there was a main effect of predicted stimulation, F = 3.42, P = 0.075, ηp2 = 0.105.In MCC, there were no statistically significant main effects or interactions see , althougr = −0.49, P = 0.005) and when it was nonpainful  nor when it was nonpainful . This pattern of results in MCC and insula remained regardless of whether current stimulation was painful or nonpainful , although the correlation between response times and activation in the MCC when current stimulation was painful and predicted stimulation was nonpainful was only significant at α = 0.10 . This analysis revealed increased activation in right insula, right ACC, and right MCC , preceding the feedback on the outcome of the button press (shortening the stimulation). The resulting activation is shown in This study was also designed to hold constant the effects of current pain by testing for main effects of painful versus nonpainful stimulation in S2 (regardless of whether S1 was painful or nonpainful), allowing detection of any selective BOLD modulation by the predicted stimulation. This revealed that activation in ACC, MCC, and bilateral anterior and midinsula was influenced by the noxious nature of predicted events over and above that of current stimulation.https://osf.io/8p7rq). Contrary to our hypothesis, selective responses for predicted pain in AI were also modulated by potential action consequences, especially in a cluster in the left hemisphere.These regions were also modulated by the possibility of shortening the duration of upcoming stimulation in S2 by making an accurately timed, effective action during S1. In particular, ACC and MCC activation for predicted pain depended on whether a meaningful action was performed, with signal changes in a MCC ROI showing a direct relationship with motor output, which we had expected , both ACC and MCC ROIs showed nonselective, above-baseline activation, followed by below-baseline responses across conditions in S1 . This suIn macaque monkeys and humans, ACC and MCC contain premotor fields (cingulate motor areas/zones), with both output to and input from motoneurons in the spinal cord, well-situated for a role in action selection and control . The orgThe rostral midcingulate region has been specifically implicated in pain-motor relationships, for example, tracking individual variance in motor reflex reactivity, with nearby areas tracking autonomic variance . MacaqueCaudal to RCZa lies a posterior rostral cingulate motor zone, corresponding approximately to the predefined MCC ROI . The motp2 = 0.104 and ηp2 = 0.175 in each pilot, respectively, but did not replicate in the main study; see Consistent with these premotor and motor roles and with previous results , MCC resAn exploratory plot of group-level, unsmoothed data  pointed Such rostral regions, such as the RCZa, may be enlisted when the situation involves higher levels of conditional information like those involved in the present task, such as increased task complexity , internaAlongside the anterior portions of cingulate cortex, AI has been centrally implicated in acute pain processing . Here, bPrevious findings have indicated that AI responses to pain are independent of overt action when executing a button-press is compared to refraining from a button-press . Such evDespite such influence of the behavioral relevance of S2 during S1, BOLD responses in AI did not correlate with RTs either here or in a previous study . This subefore the painful experience occurred  pain on pain-related BOLD changes in S2, as well as any effects of the action task factor, an exploratory analysis investigated the factors “previous pain” (painful vs. nonpainful stimulation in S1), “predicted pain” (painful vs. nonpainful stimulation in S2), and action effectiveness postresponse (expectation of an action consequence on S2 duration) .For the main effect of pain during S2, whole-brain regional activation was consistent with that expected from painful stimulation , includiInstead, a cluster in the pre-SMA/SMA was engaged by the main effect of action at the whole-brain level. The engagement of the pre-SMA/SMA may reflect feedback monitoring . BilaterExamination of BOLD responses in ROIs during cue, S1, and S2 trial segments  suggesteIn experimental pain paradigms in which a pain factor can be either controllable or uncontrollable, AI may be involved in both facilitatory and inhibitory signaling by virtue of its participation in a network that includes insular and prefrontal areas . The finThis study temporally separated functional processes of sensory pain processing, stimulus relevance, and prediction in terms of action consequences. These processes likely occur in parallel and in a less attenuated fashion during ecological acute pain. BOLD activation in the ACC/MCC and AI/midinsula was preferentially modulated by whether an upcoming, predicted stimulus would be painful but not by whether a current stimulus was painful. ACC/MCC and AI/midinsula were more strongly engaged when the upcoming stimulation could be affected by the possibility that a button-press would shorten it, but this action factor also influenced AI responses to innocuous stimulation that predicted pain. These findings imply that cortical pain processing in these and other cortical regions is not specifically tied to the sensory stimulus but instead is processed in “consequence-level” terms based on what the stimulus implies for sensorimotor control of behavior.This study was supported by Distinguished Young Investigator grant FYF-2013-687 from the Swedish Research Council to I.M.Conflict of interest statement. None declared.https://osf.io/ghxzy/. Unthresholded statistical maps of the fMRI results are available in NeuroVault at https://neurovault.org, and can be accessed with https://identifiers.org/neurovault.collection:11088.Behavioral data and beta values extracted for the ROIs are available on the Open Science Framework and can be accessed at I.M. designed the research. L.K. and M.S. performed the research. L.K., G.N., and R.K. analyzed the data. I.M. and L.K. wrote the paper.Predict_act_supplementary_revised_220202_bhac102Click here for additional data file.


The prevalence of diabetes mellitus (DM) was higher in primary aldosteronism (PA) patients. We aimed to evaluate the outcome of DM after adrenalectomy and determine the factors associated with that in PA patients.PA patients with DM (PA + DM patients) who received adrenalectomy were recruited into the study. The patients were classified into 3 groups based on their DM conditions after treatment, including “remission”, “improved” and “unchanged” groups. Univariate and multivariate logistic regression analysis was conducted to uncover the preoperative factors affecting the outcome of DM after adrenalectomy.P = 0.029). Higher concentration of urinary magnesium (P = 0.031) and higher 24 h urinary potassium (P = 0.049) were factors negatively associated with the “remission” from DM after adrenalectomy.A total of 54 PA + DM patients received adrenalectomy. After adrenalectomy, 16.7%, 33.3% and 50.0% of patients were classified into the “remission”, “improved” and “unchanged” groups, respectively. The factors negatively associated with remission or improvement from DM after adrenalectomy were longer duration of hypertension (Adrenalectomy was beneficial for the remission and improvement from DM in the half of PA patients with DM. Longer duration of hypertension, higher concentration of urinary magnesium and higher 24 h urinary potassium may prevent the remission and improvement from DM after adrenalectomy in PA patients. Examination of urinary electrolyte could be considered in PA patients with DM for predicting the outcome of DM after adrenalectomy.The online version contains supplementary material available at 10.1186/s12902-022-01254-6. Primary aldosteronism (PA) is characterized by hypertension, excessive aldosterone excretion and low serum potassium. Its prevalence in hypertensive populations ranges from 4–10% . The preThis retrospective study was conducted following the Strengthening the Reporting of Observational Studies in Epidemiology guideline . The WesWe selected PA patients with DM who received adrenal venous sampling from January 2018 to January 2021 at our institute. PA was diagnosed using the American Endocrine Society guideline . DM was Demographics, medical history information, and preoperative laboratory test results were extracted from the medical records of PA patients with DM. Demographic factors included body mass index (BMI), gender and age. Medical history information included the maximal systolic blood pressure, duration of hypertension and DM, side and size of tumor and clinical symptoms. The results of laboratory tests before adrenalectomy were also collected, including renin-angiotensin-aldosterone system factors, urinary and blood electrolytes, factors of glucocorticoid metabolism, routine blood tests, hepatic and renal function factors, lipids and glucose metabolism indices. Fasting blood glucose and glycosylated hemoglobin (HbA1C) before surgery were also examined. Biochemical examinations were performed with a Roche Cobas 8000. Renin and aldosterone were examined with radioimmunoassay. Briefly, serum was incubated with a solid phase anti-aldosterone or anti-renin monoclonal antibody at 37℃ for 1 h. Then, unbound material was removed. The concentrations of renin and aldosterone were calculated according to standard curves. The intra-assay coefficient of variation (CV) was < 10.4%, and the inter-assay CV was < 15.6%.PA patients with DM were followed up to obtain DM and hypertension conditions one year after adrenalectomy. They also received examinations of fasting blood glucose and HbA1C. First, we separated the patients into 3 groups according to the use of antidiabetic medications. Patients in the “remission” group were not taking antidiabetic medications any longer and the fasting blood glucose and HbA1C were within the normal range. The following conditions were considered as “improved”. First, patients had fewer types of antidiabetic medications than before or fewer doses of medications (without any change of types of medications), while the fasting blood glucose or HbA1C was the same or lower than before. Second, the types of antidiabetic medications did not change, but the fasting blood glucose or HbA1C was within the normal range after treatment. The remaining patients were classified as “unchanged”. Similarly, they were also divided into three groups according to their antihypertensive medications after treatment. The “remission”, “improved” and “unchanged” groups included patients having no, less, and the same or more medications to maintain blood pressure within a normal range after treatment, respectively.P values < 0.05 was considered significantly different.Categorical variables were presented as quantity (percentage) and were analyzed using Fisher’s exact test or Chi-square test. Quantitative variables were reported as the mean (standard deviation) if they were symmetrically distributed; otherwise, they were presented as median (interquartile range). Quantitative variables were analyzed by the Kruskal-Wallis test or analysis of variance (ANOVA) between three groups and by Mann-Whitney test or Student’s t-test between two groups. Univariate and multivariate logistic regression analyses were conducted to identify the parameters affecting the remission and improvement from DM. Statistical analyses were conducted using AKIBM SPSS Statistics 24.0 . 2. The number of males (n = 34) accounted for 63% of all the PA patients with DM. One year after adrenalectomy, 9 (16.7%) “remission” patients did not need antidiabetic medications any longer, and their fasting blood glucose and HbA1C levels were within the normal ranges; 18 (33.3%) “improved” patients had lower fasting blood glucose or HbA1C levels after surgery, while they needed fewer types or doses of antidiabetic medications. The remaining 27 (50.0%) “unchanged” patients maintained the same therapy for DM as before and their fasting blood glucose and HbA1C levels did not decrease after surgery (Supplementary Table P = 0.428). After adrenalectomy, both the median fasting blood glucose  and median HbA1C  levels were lower than those before surgery. The median fasting blood glucose (P = 0.398) and median HbA1C (P = 0.068) before surgery were not significantly different between three groups. However, the median fasting blood glucose was lower in the “remission” group (5.23 mmol/L), followed by the “improved” group (6.15 mmol/L) and “unchanged” (7.08 mmol/L) group after surgery (P = 0.001). Median HbA1C was also lower in the “remission” group (5.70%) than in the “improved” group (6.45%) and “unchanged” group (6.50%) (P = 0.001). After surgery, the mean serum potassium levels of all patients were higher than 3.5 mmol/L. All the patients’ median plasma aldosterone levels (lying or standing position) and median ARRs dropped below the upper limit of normal.In all, 321 PA patients received adrenal venous sampling at our institute. Among them, 63 (19.6%) PA patients had DM, and 54 (85.7%) of them were available for follow-ups (Table P < 0.05). Then, variables with P < 0.10 were entered into the multivariate logistic regression analysis, including duration of hypertension, red blood cell, platelet, alkaline phosphatase, concentration of urinary sodium and 24 h urinary phosphorus. Fasting blood glucose before surgery was also taken into consideration when multivariate logistic regression analysis was performed because it was lower in the “remission” patients. The results showed that PA + DM patients with longer duration of hypertension (odds ratio (OR) = 1.020, 95% confidence interval (CI) 1.002–1.039, P = 0.029) were less likely to achieve remission or improvement from DM after adrenalectomy.The remission and improved groups were considered as a whole group and compared with the unchanged group Table . VariablP < 0.10, including age, red blood cell, eGFR, concentration of urinary potassium, concentration of urinary magnesium and 24 h urinary potassium by multivariate logistic regression analysis, we found that higher concentration of urinary magnesium  and higher 24 h urinary potassium  were factors negatively associated with the “remission” from DM after adrenalectomy in PA patients.We also compared the remission group with the other two groups Table . UnivariSome studies have analyzed the changes in blood glucose and insulin sensitivity in PA patients after adrenalectomy. Most studies found that blood glucose did not decrease , 9, 10. Our study found that 16.7% of PA + DM patients have achieved remission from DM, and 33.3% of patients were considered “improved” from DM after adrenalectomy, which emphasized the importance of the early identification of PA in DM patients who need adrenalectomy to achieve remission or improvement from DM. Similarly, some studies reported that fasting plasma glucose decreased and insulin sensitivity increased after adrenalectomy , 10, 16.Apart from high blood aldosterone, low blood potassium was another typical feature of PA. Our study revealed that higher 24 h urinary potassium (K) was a factor negatively associated with the “remission” from DM after adrenalectomy in PA patients. However, the blood potassium was not statistically different between three groups. The reason for this phenomenon might be that PA patients would receive oral supplement of potassium before preoperative examination, while low blood potassium induced by high blood aldosterone had lasted for a long time. Some studies reported that there was an inverse relationship between blood potassium level and risk of DM , 21. RowOur study found that the duration of hypertension was much longer in the unchanged group, indicating that a longer duration of hypertension prevented the remission or improvement from DM after adrenalectomy in PA patients. However, the remission or improvement from hypertension did not influence the remission or improvement from DM after adrenalectomy. Although PA can affect patients at any age, studies have reported that PA was commonly diagnosed approximately 50 years old, which indicated the late recognition of PA and its negative effects on DM . PatientMultivariate logistic regression analyses revealed that higher 24 h urinary magnesium prevented the remission from DM after adrenalectomy. The possible mechanism may be associated with the expansion of the extravascular space, which prevents the reabsorption of magnesium in the proximal tubules, resulting in their excessive excretion from urine . To mainThere were some limitations to the study. First, the sample size was small, and the age was statistically lower in remission group, all which may cause biases and affect the statistical analysis. Second, this was a retrospective study, which may cause biases when analyzing the factors affecting the outcome of DM after adrenalectomy. More prospective randomized studies are needed to verify whether adrenalectomy could improve glucose metabolism and which factors are associated with the blood glucose after adrenalectomy.Adrenalectomy was beneficial for the remission and improvement from DM in the half of PA patients with DM. Longer duration of hypertension, higher concentration of urinary magnesium and higher 24 h urinary potassium may prevent the remission and improvement from DM after adrenalectomy in PA patients. Examination of urinary electrolyte could be considered in PA patients with DM for predicting the outcome of DM after adrenalectomy.Additional file 1:Table 1. The drugs used to treat diabetes mellitus before and after adrenalectomy.


R), Schmidt number (Sc), and chemical reaction parameter (Kr), on fluid velocity, concentration, and thermal radiation within the boundary layer has been examined. The outcomes indicate that enhancing values of the Soret and Dufour numbers reduce the thermal boundary layer thickness. Uplifting values of the thermal radiation (0.5-3.5) enhance the local skin friction coefficient and mass transfer rate by approximately 15% and 78% but decrease the heat transfer rate by 47%. The local skin friction coefficient enhances about 21%, and the mass transfer rate reduces about 64% due to an increase in the chemical reaction parameter (0.5-2.0). Finally, we compared our numerical results with previously published literature and observed them to have a good agreement.The unsteady magneto-convective heat-mass transport passing in a vertical porous sheet with the thermal radiation and the chemical reaction effects has been examined numerically. The governing PDEs have been transferred into ODEs by applying the local similarity transformation. The nondimensional governing equations including the boundary conditions are solved by applying the superposition method with the help of the “MATLAB ODE45” software numerically. The influence of emerging nondimensional numbers/parameters, for example, the Prandtl number (Pr), thermal radiation parameter ( The MHD (hydromagnetic) free convective and heat transfer flow problems in a permeable medium play an important role in various industrial and scientific processes, for example, problems of boundary layer flow control, plasma studies, thermo nuclear fusion, furnace design, metallurgy, mineral and petroleum engineering, geothermal energy extraction, chemical engineering, and solar power technology. These types of problems act on the different engineering devices applying electrically conducting fluids, for example, MHD generators, plasma jet engines, MHD accelerators, MHD pumps, nuclear reactors, and MHD flow meters. The free magneto-convective heat-mass transport passing a permeable medium restricted by a vertical permeable sheet with constant heat flux has been examined by Raptis and Kafousias . The infWith the combination of mass and heat transfer procedures, the flow is run by density differences created by concentration gradient, temperature gradient, and material composition simultaneously. The Dufour (diffusion-thermo) effect is the concentration differences which create the energy flux. The Soret  effect is the temperature gradient which creates the mass flux. The Soret influence, for example, has been used in mixture and for isotope separation between gases with medium molecular weight and gases with very light molecular weight. The Dufour and Soret influences are faced in numerous practical applications, for example, in the fields of chemical engineering and geosciences. The effects of the Dufour number and Soret number on the hydromagnetic mixed convection-radiation interaction along a porous surface submerged in a permeable medium have been studied by Chamkha and Ben-Nakhi . Alam anThe main result of this current research is to suppose the above problems passing a vertical permeable sheet taking into account the chemical reaction and thermal radiation effects. The mail novelty of this study is to compare our results with a published paper. Another novelty of this paper is also enhanced by assuming the chemical reaction and thermal radiation under the Runge-Kutta-Merson integration technique which is not explained yet. Computations have been performed for a vast range of the dimensionless numbers/parameters; for example, thermal radiation parameter, Soret number, suction parameter, chemical reaction parameter, Prandtl number, Dufour number, Schmidt number, and magnetic number on temperature, concentration, and velocity profiles are discussed graphically and analyzed. Besides, the properties of the heat and mass transfer and skin friction coefficient have been explained in the tabular forms.y = 0 is considered. The direction of an upward sheet is the x-axis. The y-axis is the normal of the plane sheet in the fluid. When a uniform magnetic field B is imposed on the sheet, then the permeable sheet is supposed to be electrically nonconducting along the y-axis as shown in The two-dimensional unsteady free magneto-convective heat-mass transport of an electrically conducting viscous fluid passing in a vertical permeable sheet at B = . The current density is J = , and the continuity equation of charge is ∇.J = 0 which implies that Jy = constant. The propagation direction is presumed only along the y-axis. This propagation direction does not have any change along the y-axis. So the differentiation of Jy with respect to y must be zero such as ∂Jy/∂y = 0. Since this constant of integration is zero when the sheet is electrically nonconducting, Jy = 0 at the sheet and it is zero everywhere.We presume that the induced magnetic field is insignificant for a very small flow magnetic Reynolds number compared with one of the research projects . Then, tThe one-dimensional problem under the Boussinesq approximation and the above assumptions may be used in the below form :The continuity equation:The momentum equation:The energy equation:The concentration equation:u and v are the components of the velocity in the x and y directions, respectively. The fluid density is ρ, υ is the kinematic viscosity, the coefficient of concentration expansion is β∗, the coefficient of thermal expansion is β, the fluid temperature is T, the wall temperature is Tw, the fluid temperature in the free stream is T∞, the component of radiative heat flux is qr, C is the fluid concentration, the wall concentration is Cw, the free stream concentration is C∞, the thermal conductivity of the sheet is k, the concentration susceptibility is Cs, the specific heat at constant pressure is Cp, the mean temperature of the fluid is Tm, kT is the thermal diffusion ratio, the mass diffusivity coefficient is Dm, g is the gravitational acceleration, and the chemical reaction rate of species concentration is K′.The boundary conditions are given byσ,σ. The solution of equation , eq, eq11), Gr = gβ(Tw − T∞)σ2/U0υ, the magnetic force parameter is M = σ′B02σ2/ρυ, the Prandtl number is Pr = ρυCp/k, Gm = gβ∗(Cw − C∞)σ2/U0υ is the modified local Grashof number, the Dufour number is Df = DmkT(Cw − C∞)/CsCpυ(Tw − T∞), the Soret number is S0 = DmkT(Tw − T∞)/υTm(Cw − C∞), the Schmidt number is Sc = υ/Dm, the thermal radiation parameter is R = 16σ∗TW2/3K∗K, the chemical reaction parameter is Kr = K′σ2/υ, and ξ = η + (v0/2).The converted boundary conditions are given byτ), the Nusselt number (Nu), and the local Sherwood number (Sh) which are defined asThe flow parameters are the skin-friction coefficient (f(η), θ(η), and ϕ(η) are, respectively, decomposed toδ, μ, and λ are arbitrary constants. Now, putt equations  and andf(η),f1(η), f2(η), f3(η), f4(η), ⋯ are now got passing in the boundary conditions f1(η), f2η⟶∞, using the boundary conditions η⟶∞, usinnditions , we obtaIn –18), al, al18), The missing slopes are given byNow, assuming the values of the missing slopes:τ are, respectively, denoted as the Sherwood number, the Nusselt number, and the local skin friction coefficient which are proportionate to −∂ϕ(0)/∂η, −∂θ(0)/∂η, and ∂f(0)/∂η, respectively.the initial conditions for the missing slopes of the decomposed functions are observed easily. Integrate equations –14) by  by 14) b2v0), the Dufour number (Df), the magnetic force parameter (M), the Soret number (So), the radiation parameter (R), the Schmidt number (Sc), the chemical reaction parameter (Kr), and the Prandtl number (Pr) on temperature, concentration, and velocity distributions are displayed in Figures 20 and 0.71 for air at 200). The values 0.75, 0.60, and 0.22 are also supposed for Sc . The remaining nondimensional parameter/number values are however taken arbitrarily.The impact of thermal radiation on unsteady magneto-convective heat-mass transport passing in a vertical permeable sheet under the chemical reaction effect has been analyzed numerically in this research. By applying the superposition technique, we have solved the set ODEs –12) wit wit12) wM). From M). With increasing values of the magnetic force parameter, a resistive kind of force, for example, a drag force, is generated. This resistive type of force is called Lorentz force. This is due to the fact that the magnetic force parameter produces a resistive kind of force (Lorentz force) which causes reduction in the fluid velocity. v0) on the velocity profile. When v0 > 0, then the whole system fluid suction event has happened. It can be concluded from v0 > 0), the mass of the fluid in the computational domain decreases. For this reason, the frictional force reduces. So the velocity of fluid reduces for increasing values of the suction. This is because suction stabilizes the boundary layer growth. The velocity distribution is observed to enhance and reaches the highest value in a region close to the leading edge of the sheet and then reduces to zero gradually. The Prandtl number (Pr = ρυCp/k) is the proportional to the kinematic viscosity. From graph 4, it is noticed that when the Prandtl number enhances, then the fluid kinematic viscosity increases. For this reason, the fluid particles cannot move freely. So the fluid velocity reduces. Physically, due to enhancement of the Prandtl number (Pr), the kinematic viscosity of the fluid increases which in turn makes the fluid much thicker. For this reason, the velocity of the fluid reduces. The behavior of thermal radiation parameter (R) on the velocity distribution is displayed in R = (16σ∗TW2)/(3k∗k) and shaped in the increased thermal diffusion term in equation (R)θ″(η). The comparative contribution of the thermal radiation heat transfer to the thermal conduction heat transfer is defined by the thermal radiation parameter. The thermal radiation dominates over thermal conduction when R > 1, but the thermal conduction dominates for R < 1. The thermal radiation contributions and thermal conduction both are equal for R = 1.equation , i.e., 1R > 1 for the present simulations. R. The energizing of the flow increases thermal diffusion and then decreases momentum diffusion. This leads to a decrease in the thickness of the momentum boundary layer. υ). From graph 6, it is found that when the Schmidt number enhances, then the kinematic viscosity of the fluid increases. For this reason, the fluid particles cannot move freely. So the fluid velocity diminishes. The thickness of the momentum boundary layer is also decreased with a greater Schmidt number. Kr). The impact of chemical reaction parameter is very momentous in the concentration distribution. Chemical reaction decreases the interfacial mass transfer rate. Reaction enhances the local concentration, hence decreasing its flux and its concentration gradient.We constrict attention to the case of v0) on the temperature distribution is plotted in R) on the temperature profile. From R. The thermal radiation parameter is accountable for the thermal boundary thickening. The fluid loses the heat energy from the flow region, and for this reason, the system cools. This is due to the fact that the Rosseland approximation increases the temperature. DmkT(Cw − C∞)/CsCpυ(Tw − T∞), on the temperature profile. The Dufour effect mentions heat flux produced by a solutal (concentration) gradient. The temperature distribution accentuates for increasing the diffusion-thermo parameter (Df) as shown in The impact of the suction parameter (v0) on the concentration distribution. Sucking decelerated fluid particles past the permeable wall decreases the concentration boundary layer growth. DmkT(Tw − T∞)/υTm(Cw − C∞); i.e., the Soret number is inversely proportional to the mass diffusivity coefficient (Dm). The Soret effect rises where large heavy molecules and small light molecules separate under a temperature gradient. The Soret number enhancement means that the mass diffusivity coefficient increases. For this reason, the concentration distribution increases significantly as the Soret number increases. This outcome is an important enhancement in concentration boundary layer thickness. The impact of the chemical reaction parameter (Kr) on the concentration profile is displayed in The authors have investigated not only the velocity, temperature, and concentration fields but also the values of the local skin friction coefficient and heat and mass transfer rates. The authors gave the local skin friction coefficient and mass and heat transfer rates in Tables 1Tables 11The present research results have been compared with Alam et al. . The comThe local skin friction enhances about 15%, 13%, 28%, 56%, and 21% due to increasing thermal radiation parameter (0.5-3.5), Soret number (1.0-3.0), local Grashof number (5.0-10.0), modified Grashof number (5.0-10.0), and the chemical reaction parameter (0.5-1.0), respectively. Besides, rising values of the magnetic force number (0.5-4.0), suction parameter (0.5-1.5), Prandtl number (0.71-1.0), and Schmidt number (0.22-1.0) reduce the local skin friction by 48%, 7%, 20%, and 15%, respectivelyUplifting values of the suction parameter (0.5-1.5) and Prandtl number (0.71-1.0) enhance the heat transfer rate by 64% and 23%, respectively, but decrease about 47% for enhancing the thermal radiation parameter (0.5-3.5)The mass transfer rate enhances about 5% due to enhancing the suction parameter (0.0-1.5). Besides, increasing the Soret number (1.0-3.0), Schmidt number (0.22-1.0), and chemical reaction parameter (0.5-2.0) decreases the mass transfer rate by 82%, 14%, and 64%, respectivelyThe unsteady free magneto-convective heat-mass transport passing in a vertical permeable sheet has been analyzed numerically under the thermal radiation and the chemical reaction effects. From the above numerical simulations, the below conclusions can be illustrated:The result of this paper can be helpful for suspensions, production of paper, plasma studies, thermo nuclear fusion, furnace design, metallurgy, mineral and petroleum engineering, geothermal energy extraction, chemical engineering, solar power technology, etc.