Sorbitol Levels Research Articles

Automatic periodical negative air ions reduce postharvest decay and maintain texture and flavor quality of ‘Fuji’ apple during long-term cold storage

The aim of this study was to explore the effect of periodical negative air ions (NAI) on the quality of ‘Fuji’ apple fruit after treatment at 0, 30, 60, and 90 min every 4 weeks. NAI for 60 min decreased weight loss, mitigated decay, and maintained hardness of the apple fruit during the 40 weeks of storage. Treatment of fruits with NAI for 60 min enhanced the apple defense ability against pathogens by maintaining the cell wall integrity and improving the related-enzyme activities as well as accumulation of total phenols and flavonoids. Reverse-phase HPLC and solid-phase microextraction GC–MS analysis showed that NAI treatment for 60 min increased the levels of fructose, sucrose, sorbitol, malic acid and volatiles, such as 2-hexenal, 2-methylbutyl acetate, hexyl acetate, and ethyl butanoate. Taken together, NAI is promising for improving the quality ‘Fuji’ apples during the cold storage.

Mechanism of ginsenoside Rb3 against OGD/R damage based on metabonomic and PCR array analyses.

In order to study the mechanisms of ginsenoside Rb3 (G-Rb3) against oxygen-glucose deprivation/reoxygenation (OGD/R) injury in HT22 cells based on metabolomics and PCR array, HT22 cells were randomly divided into control group, model group, G-Rb3 high-dose group (10 µmol/l) and G-Rb3 low-dose group (5 µmol/l). Except for the control group, which was left untreated, the remaining groups were incubated with 10 mmol/l Na2S2O4 in sugar-free DMEM medium for 2 h and then replaced with serum-free high-sugar DMEM medium for 2 h in order to replicate in vitro OGD/R model. Trypan blue staining was used to detect the cell viability; flow cytometry was used to detect apoptosis; western blotting was used to detect the protein expression levels of Bax, Bcl-2 and caspase-3. The metabolomics were used to analyze the differential metabolites of G-Rb3 affecting OGD/R in order to find the relevant metabolic pathways. PCR array assay was performed to identify the expression of the differential genes. G-Rb3 could inhibit HT22 apoptosis according to the result of cell morphology, trypan blue staining and flow cytometry. The levels of Bax and caspase-3 protein expression were decreased, whereas the level of Bcl-2 protein expression was increased after the treatment of G-Rb3. Metabolomics results showed that a total of 31 differential metabolites between OGD/R group and G-Rb3 group, such as guanosine level, was downregulated, the levels of enalaprilat and sorbitol were upregulated, affecting ABC transporters, galactose metabolism, citrate cycle and other related metabolic pathways; according to the result of PCR array, it was observed that G-Rb3 significantly downregulated Trp63, Trp73, Dapk1, Casp14 and Cd70 pro-apoptotic genes. In conclusion, G-Rb3 has a significant protective effect on the OGD/R model simulated in vitro, and the mechanism may be related to the inhibition of apoptosis by affecting metabolites.

GC-MS validation and analysis of targeted plasma metabolites related to carbonyl stress in type 2 diabetes mellitus patients with and without acute coronary syndrome.

Methylglyoxal (MG) is responsible for advanced glycation end-product formation, the mechanisms leading to diabetes pathogenesis and complications like acute coronary syndrome (ACS). Sugar metabolites, amino acids and fatty acids are possible substrates for MG. The study aimed to measure plasma MG substrate levels using a validated gas chromatography-mass spectrometry (GC-MS) method and explore their association with ACS risk in type 2 diabetes mellitus (T2DM). The study included 150 T2DM patients with ACS as cases and 150 T2DM without ACS as controls for the analysis of glucose, fructose, ribulose, sorbitol, glycerol, pyruvate, lactate, glycine, serine, threonine, C16:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:0 and C22:6 by GC-MS. Validated GC-MS methods were accurate, precise and sensitive. Cases significantly differed in plasma MG and metabolite levels except for lactate, C16:0, C18:0, C18:2, and C18:3 levels compared with controls. On multivariable logistic regression, plasma C20:0, C18:1, glycine and glycerol levels had increased odds of ACS risk. On multivariate receiver operating characteristic analysis, a model containing plasma C20:0, C16:1, C18:1, C18:2, serine, glycerol, lactate and threonine levels had the highest area under the curve value (0.932) for ACS diagnosis. In conclusion, plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol levels were associated with ACS risk in T2DM.

The Role of Aldose Reductase in Polyol Pathway: An Emerging Pharmacological Target in Diabetic Complications and Associated Morbidities.

The expression of aldose reductase leads to a variety of biological and pathological effects. It is a multifunctional enzyme which has a tendency to reduce aldehydes to the corresponding sugar.alcohol. In diabetic conditions, the aldose reductase enzyme converts glucose into sorbitol using nicotinamide adenine dinucleotide phosphate as a cofactor. It is a key enzyme in polyol pathway which is a surrogate course of glucose metabolism. The polyol pathway has a significant impact on the aetiology of complications in individuals with end-stage diabetes. The exorbitant level of sorbitol leads to the accumulation of intracellular reactive oxygen species in diabetic heart, neurons, kidneys, eyes and other vasculatures, leading to many complications and pathogenesis. Recently, the pathophysiological role of aldose reductase has been explored with multifarious perspectives. Research on aldose reductase suggest that besides implying in diabetic complications, the enzyme also turns down the lipid-derived aldehydes as well as their glutathione conjugates. Although aldose reductase has certain lucrative role in detoxification of toxic lipid aldehydes, its overexpression leads to intracellular accumulation of sorbitol which is involved in secondary diabetic complications, such as neuropathy, cataractogenesis, nephropathy, retinopathy and cardiovascular pathogenesis. Osmotic upset and oxidative stress are produced by aldose reductase via the polyol pathway. The inhibition of aldose reductase alters the activation of transcription factors like NF-ƙB. Moreover, in many preclinical studies, aldose reductase inhibitors have been observed to reduce inflammation-related impediments, such as asthma, sepsis and colon cancer, in diabetic subjects. Targeting aldose reductase can bestow a novel cognizance for this primordial enzyme as an ingenious strategy to prevent diabetic complications and associated morbidities. In this review article, the significance of aldose reductase is briefly discussed along with their prospective applications in other afflictions.

Assessment of sorbitol clearance in induced acute liver failure

The study of substance clearance plays an important role in the diagnosis of liver pathologies. Increased or decreased clearance of certain substances may indicate hepatobiliary disorders, including at the initial stages of the development of such pathologies, which allows us to evaluate the predictive potential of these assessment methods as high. The scientific literature provides detailed and statistically proven data on the use of substances such as galactose, amidopyrine, sorbitol and others in diagnostic protocols. Each substance is characterized by its own level of clearance, which allows one to obtain a comprehensive picture of the functioning of the hepatobiliary system. However, for most of the above exogenous substances, information in the scientific literature is either indicated in relation to humane medicine, or consists of pilot studies on a small number of animals, which requires additional testing of this kind to develop a statistically reliable array of data obtained. The purpose of this study is to conduct an experimental study aimed at studying changes in the pharmacokinetics of exogenous sorbitol in the blood plasma of laboratory animals with acute liver failure. The level of sorbitol was determined by the colorimetric Corcoran and Page method with modification (using potassium periodate and chromotropic acid, the method takes into account the calculated sorbitol indicator from the sum of polyols) using a UV-100 spectrophotometer (manufacturer – Shanghai Mapada Instruments Co., Ltd., China) for 12 hours (step – 2 hours) in blood plasma deproteinized using 0.4 M lithium perchlorate, obtained by venipuncture of the tail vein. Comparing pharmacokinetic curves with each other, it should be noted that in animals with acute liver failure, the graphical representation of sorbitol levels is similar to the inverse exponential, characterized by a sharp systematic decrease, while in clinically healthy animals the graphical representation of sorbitol levels is similar to the branch of a parabola, characterized by “smoothness” » reduction. The pharmacokinetic curves obtained in this study, which describe the levels of exogenous sorbitol in the blood plasma, can be used in the future as one of the methods for the early diagnosis of such pathologies.

Anti-inflammatory mechanism of the non-volatile ingredients originated from Guanghuoxiang () based on high performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope and cell metabolomics.

To explore the anti-inflammatory components and mechanism of the non-volatile ingredients of patchouli. High performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope (HPLC-HESI-HRMS) was used to analyze the chemical constituents of the non-volatile ingredients of patchouli. The anti-inflammatory activity of ingredients was evaluated using lipopolysaccharide (LPS) induced RAW264.7 cell inflammation model, and the anti-inflammatory mechanism was investigated using multivariate statistical analysis of cell metabolomics. The non-volatile ingredients of patchouli were characterized by HPLC-HESI-HRMS, and 36 flavonoids and 18 other components were identified. These ingredients of patchouli not only had a good protective effect on the LPS-induced inflammation model of RAW264.7 cells, but also regulated the expression levels of arginine, L-leucine, cholesterol, fructose and sorbitol by down-regulating arginine metabolism, aminoacyl-tRNA biosynthesis, polyol/sorbitol pathway, so as to reduce inflammation and reduce cell damage. The non-volatile ingredients of patchouli had good anti-inflammatory effect and exerted its curative effect by regulating endogenous metabolic pathway to reduce inflammatory response.

SORD-deficient rats develop a motor-predominant peripheral neuropathy unveiling novel pathophysiological insights.

Biallelic SORD mutations cause one of the most frequent forms of recessive hereditary neuropathy, estimated to affect ∼10 000 patients in North America and Europe alone. Pathogenic SORD loss-of-function changes in the encoded enzyme sorbitol dehydrogenase result in abnormally high sorbitol levels in cells and serum. How sorbitol accumulation leads to peripheral neuropathy remains to be elucidated. A reproducible animal model for SORD neuropathy is essential to illuminate the pathogenesis of SORD deficiency and for preclinical studies of potential therapies. Therefore, we have generated a Sord knockout (KO), Sord-/-, Sprague Dawley rat, to model the human disease and to investigate the pathophysiology underlying SORD deficiency. We have characterized the phenotype in these rats with a battery of behavioural tests as well as biochemical, physiological and comprehensive histological examinations. Sord-/- rats had remarkably increased levels of sorbitol in serum, CSF and peripheral nerve. Moreover, serum from Sord-/- rats contained significantly increased levels of neurofilament light chain, an established biomarker for axonal degeneration. Motor performance significantly declined in Sord-/- animals starting at ∼7 months of age. Gait analysis evaluated with video motion-tracking confirmed abnormal gait patterns in the hindlimbs. Motor nerve conduction velocities of the tibial nerves were slowed. Light and electron microscopy of the peripheral nervous system revealed degenerating myelinated axons, de- and remyelinated axons, and a likely pathognomonic finding-enlarged 'ballooned' myelin sheaths. These findings mainly affected myelinated motor axons; myelinated sensory axons were largely spared. In summary, Sord-/- rats develop a motor-predominant neuropathy that closely resembles the human phenotype. Our studies revealed novel significant aspects of SORD deficiency, and this model will lead to an improved understanding of the pathophysiology and the therapeutic options for SORD neuropathy.

Toward Translational Impact of Low-Glucose Strategies on Red Blood Cell Storage Optimization.

Transfusion of stored red blood cells (RBCs) to patients is a critical component of human healthcare. Following purification from whole blood, RBCs are stored in one of many media known as additive solutions for up to 42 days. However, during the storage period, the RBCs undergo adverse chemical and physical changes that are often collectively known as the RBC storage lesion. Storage of RBCs in additive solutions modified to contain physiological levels of glucose, as opposed to hyperglycemic levels currently used in most cases, reduces certain markers of the storage lesion, although intermittent doses of glucose are required to maintain normoglycemic conditions. Here, we describe an electrically actuated valving system to dispense small volumes of glucose into 100 mL PVC storage bags containing packed RBCs from human donors. The RBCs were stored in a conventional additive solution (AS-1) or a normoglycemic version of AS-1 (AS-1N) and common markers of stored RBC health were measured at multiple time points throughout storage. The automated feeding device delivered precise and predictable volumes of concentrated glucose to maintain physiological glucose levels for up to 37 days. Hemolysis, lactate accumulation, and pH values of RBCs stored in AS-1N were statistically equivalent to values measured in AS-1, while significant reductions in osmotic fragility and intracellular sorbitol levels were measured in AS-1N. The reduction of osmotic fragility and oxidative stress markers in a closed system may lead to improved transfusion outcomes for an important procedure affecting millions of people each year.

High incidence of sebaceous gland inflammation in aldose reductase-deficient mice

Aldose reductase is a member of the 1B1 subfamily of aldo-keto reductase gene superfamily. The action of aldose reductase (AR) has been implicated in the pathogenesis of a variety of disease states, most notably complications of diabetes mellitus including neuropathy, retinopathy, nephropathy, and cataracts. To explore for mechanistic roles for AR in disease pathogenesis, we established mutant strains produced using Crispr-Cas9 to inactivate the AKR1B3 gene in C57BL6 mice. Phenotyping AR-knock out (ARKO) strains confirmed previous reports of reduced accumulation of tissue sorbitol levels. Lens epithelial cells in ARKO mice showed markedly reduced epithelial-to-mesenchymal transition following lens extraction in a surgical model of cataract and posterior capsule opacification. A previously unreported phenotype of preputial sebaceous gland swelling was observed frequently in male ARKO mice homozygous for the mutant AKR1B3 allele. This condition, which was shown to be accompanied by infiltration of proinflammatory CD3+ lymphocytes, was not observed in WT mice or mice heterozygous for the mutant allele. Despite this condition, reproductive fitness of the ARKO strain was indistinguishable from WT mice housed under identical conditions. These studies establish the utility of a new strain of AKR1B3-null mice created to support mechanistic studies of cataract and diabetic eye disease.

Metabolomics and Physiological Changes Underlying Increased Tolerance to Salt Stress Induced by Applied Nitric Oxide in Fatsia japonica Seedlings

Fatsia japonica (Thunb.) Decne. et Planch. is an important woody landscape plant, and its distribution is commonly limited by salt stress. Although the application of exogenous nitric oxide (NO) has been known to be effective in alleviating abiotic stress in plants, the underlying mechanism by which NO induces salt resistance in F. japonica remains unknown. In this study, the physiological and metabolic characteristics of F. japonica seedlings with the application of NO under salt stress conditions were investigated. We demonstrated that exogenous NO (0.1 mM sodium nitroprusside, SNP) mitigated the growth inhibition caused by 0.4% NaCl. This alleviation could be attributed to NO-induced enhancement in photosynthesis, osmotic adjustment, antioxidant enzyme activities, and a reduction in oxidative damage when exposed to salt stress. Furthermore, the metabolomic analysis revealed that salt stress significantly disrupts the growth of F. japonica by downregulating sugars, sugar alcohols, amino acids, and organic acids. However, the application of exogenous NO improves sugar metabolism, enhancing the levels of fructose, glucose, mannose, galactose, xylose, ribose, inositol, and sorbitol, as well as the metabolism of amino acids and organic acids. These findings provide new insights into the physiological and metabolic homeostasis adjustments induced by NO that promote salt stress tolerance in F. japonica, enhancing our understanding of plant resilience mechanisms.

Synthesis and Characterization of Bioplastic Derived from Chlorella sp. Residue Biomass

The accumulation of plastic waste is a significant global pollution issue in the age of globalization. Despite their irreplaceable properties and multiple applications, conventional fossil-based plastics cannot decompose naturally in the environment, resulting in exponential accumulation over time. To address this problem, biodegradable and biobased plastics have been introduced as alternatives to fossil-based plastics. This study aimed to characterize bioplastics formulated from <i>Chlorella</i> sp. microalgae biomass. Various formulations of biodegradable plastics were developed using microalgae <i>Chlorella</i> sp. and tapioca starch, with varying levels of plasticizer glycerol or sorbitol (25 wt%, 50 wt%, or 75 wt% based on the weight of starch) and the addition of chitosan as a filler. The physical, mechanical, and chemical properties of bioplastics were characterized. The study found that the chlorella bioplastics were ductile and had low elasticity, despite the addition of glycerol or sorbitol. However, the bioplastic exhibited an exceptional rate of biodegradability, with 100% weight loss when buried in loamy soil for 7 days. Furthermore, the <i>Chlorella </i>bioplastic with 75 wt% of glycerol, without the addition of chitosan, exhibited the highest solubility at 62.35%. The results indicated that increasing the amount of plasticizer tended to increase solubility, with glycerol having a more significant effect than sorbitol. Meanwhile, chitosan loading reduced bioplastic solubility.

Harvest maturity stage affects watercore dissipation and postharvest quality deterioration of watercore 'Fuji' apples

Watercore 'Fuji' apples, with their special watercore shape and unique flavor and texture, are a very popular specialty fruit in the Asian markets. However, watercore disappearance and quality deterioration of apples during postharvest storage are serious problems. In this study, we compared the differences among three harvest maturity stages of apples in watercore dissipation and fruit quality deterioration. In this study, the physiochemical attributes (visual quality, watercore incidence, and firmness), flavor substances (TSS content, TA content, and TSS/TA), aroma volatiles, and cellular structure were analyzed in 'Fuji' apple fruits of low maturity (LM) at early harvest stage, medium maturity (MM) at mid harvest stage, and high maturity (HM) at late harvest stage, during a cold storage at 0 ± 1 °C for 120 d. The results showed that harvest maturity stage had a significant effect on postharvest storage quality parameters of watercore 'Fuji' apples. Specifically, L*, b*, firmness, and TA values of the flesh decreased significantly from the LM to the HM levels. However, the watercore incidence of apples significantly increased from LM to HM levels. Moreover, the parameters including L*, b*, firmenss, TA, and watercore incidence of apples with different harvest maturity stages gradually decreased as the storage time increased. In contrast, the TSS, TSS/TA, and a* values showed an increasing trend from LM to HM apples. In particular, the TSS tended to increase first and decrease after 60 d of storage. Moreover, the microstructure and cellular structure gradually deformed as the structural porosity and cell size decreased from LM to HM apples. Furthermore, the microstructure of the watercore and non-watercore sites is significantly different. Meanwhile, the content of soluble sugars and aroma volatiles increased with the advancing maturity. Non-watercore sites of apples with the same level of maturity contained higher levels of sucrose, fructose, maltose, and sorbitol than watercore sites. Furthermore, the MM apples maintained better sensory qualities during the shelf life after cold storage. Overall, the MM apples showed higher quality and were more acceptable to consumers, which suggested watercore 'Fuji' apples from mid harvest stage showed the optimal harvest-ready maturity for post-harvest long-term cold storage.

Changes in the Fruit Quality Parameters of Medlar Fruit (Mespilus germanica L.) after Heat Treatment, Storage, Freezing or Hoarfrost.

The present study deals with the comparison of traditional fruit processing methods on medlar fruits and their effects on sugar content, organic acids, and phenolic composition in the medlar fruit variety 'Domača nešplja'. The study aimed to analyze which processing methods can be used to make technologically mature medlar fruits that are not yet suitable for consumption edible and to maintain their good chemical quality. The two major sugars in medlars are fructose (59.30 g/kg FW) and glucose (54.43 g/kg FW), and the most abundant organic acids present are malic (8.44 g/kg FW) and quinic acid (8.77 g/kg FW). A total of 38 different phenolic compounds were identified in the medlar fruits: 13 phenolic acids, 9 flavanols, 1 flavone, 3 flavanones, and 12 flavonol glycosides. To explicate: phenolic acids (532.85 mg/kg FW) and flavanols (375.21 mg/kg FW) predominated; neochlorogenic acid had the highest content among phenolic acids; and procyanidins were the most abundant flavanols. The analysis observed statistical differences in metabolite content amongst fruits treated differently (technologically ripe fruits (harvested from the three fruits), edible fruits (technologically ripe fruits stored at 8 °C for 25 days), fruits exposed to the hoarfrost (temperature -1 °C to -4 °C), fruits heated at 60 °C (3 h), and frozen fruits (at -20 °C for 2 months). The lowest levels of fructose (191.77-195.1 g/kg DW) and sorbitol (29.35-31.3 g/kg DW) were detected in the heated and edible fruits. Edible fruits had a 30% lower content of organic acids than technologically ripe fruits and a five times lower content of flavanols, whereas flavonols had an 18.7 times lower content of phenolic acids than technologically ripe fruits. Heating the fruits to 60 °C resulted in a 40% increase in total phenolic compounds in medlars. The results of the study indicate that exposure of medlar fruit to hoarfrost does not significantly affect the chemical quality of the fruit and only minimally alters the composition of sugars, acids, and phenolic compounds. The processing of medlar fruit with hoarfrost, therefore, remains the most suitable method of fruit bletting.

Metabolite Diversity in Pulp Segments, Peel, Leaves, and Bark of a Red-Fleshed ‘Baya Marisa’ Apple Cultivar

This study investigated the composition of sugars, organic acids, individual and total phenolic compounds in the pulp, peel, leaves, and bark of a red-fleshed ‘Baya Marisa’ apple cultivar. As the fruit is known for its red pulp color, the study focused on comparing the profiles of primary and selected secondary metabolites in three sections along the equatorial fruit plane. The analyses were carried out using HPLC–MS system, and compositional differences were compared among fruit segments. Inner fruit segments accumulated higher levels of sorbitol and the sum of sugars and lower levels of citric acid. However, no differences in the sum of organic acids could be determined among segments. The phenolic composition differed among pulp (hydroxycinnamic acids > dihydrochalcones ≈ anthocyanins ≈ flavanols > flavonols), peel (flavanols > anthocyanins > dihydrochalcones > flavonols > hydroxycinnamic acids), leaves (flavonols > dihydrochalcones > hydroxycinnamic acids > anthocyanins), and bark (dihydrochalcones > flavonols > flavanols > anthocyanins > hydroxycinnamic acids). The greatest phenolic diversity was detected in bark (25), followed by leaves (18), peel (17) and finally, pulp (11). Three anthocyanins (cyanidin-3-O-galactoside > cyanidin-3-O-arabinoside > peonidin-3-O-galactoside) were determined in all ‘Baya Marisa’ tissues with their content highest in the peel. The innermost sections of the fruit were characterized by higher levels of dihydrochalcones and lower levels of most flavanols, flavonols and anthocyanins. These were predominant in the apple pulp nearest to the peel, with cyanidin-3-O-galactoside being the prevalent representative. Accumulation of anthocyanins in pulp is a rare trait in apples, and therefore, the distinct distribution and diversity of metabolites in this cultivar highlights its potential for high-nutrient products such as juices, apple chips or purees.

Interplay of Impaired Cellular Bioenergetics and Autophagy in PMM2-CDG.

Congenital disorders of glycosylation (CDG) and mitochondrial disorders are multisystem disorders with overlapping symptomatology. Pathogenic variants in the PMM2 gene lead to abnormal N-linked glycosylation. This disruption in glycosylation can induce endoplasmic reticulum stress, contributing to the disease pathology. Although impaired mitochondrial dysfunction has been reported in some CDG, cellular bioenergetics has never been evaluated in detail in PMM2-CDG. This prompted us to evaluate mitochondrial function and autophagy/mitophagy in vitro in PMM2 patient-derived fibroblast lines of differing genotypes from our natural history study. We found secondary mitochondrial dysfunction in PMM2-CDG. This dysfunction was evidenced by decreased mitochondrial maximal and ATP-linked respiration, as well as decreased complex I function of the mitochondrial electron transport chain. Our study also revealed altered autophagy in PMM2-CDG patient-derived fibroblast lines. This was marked by an increased abundance of the autophagosome marker LC3-II. Additionally, changes in the abundance and glycosylation of proteins in the autophagy and mitophagy pathways further indicated dysregulation of these cellular processes. Interestingly, serum sorbitol levels (a biomarker of disease severity) and the CDG severity score showed an inverse correlation with the abundance of the autophagosome marker LC3-II. This suggests that autophagy may act as a modulator of biochemical and clinical markers of disease severity in PMM2-CDG. Overall, our research sheds light on the complex interplay between glycosylation, mitochondrial function, and autophagy/mitophagy in PMM2-CDG. Manipulating mitochondrial dysfunction and alterations in autophagy/mitophagy pathways could offer therapeutic benefits when combined with existing treatments for PMM2-CDG.

Photoperiodic Induction of Diapause Character and Sorbitol Level in the Silkworm Eggs of APM1, MU303 and PM Strains/Races

Embryonic diapause is the suspended animation responsible for the onset of Voltinism in the silkworm. The embryo is completely arrested during the developmental event to overcome unfavourable environmental conditions. This further results in the synthesis of sorbitol from glucose and examines the differences between sorbitol levels in the diapause-induced silkworm eggs of APM1, MU303 and PM strains by exposure to photoperiodic regime of 16L:08D, 14L:10D and 12L:12D. The results obtained revealed the fact that the sorbitol level is high during the 6th day in all the selected strains at their 7th and 8th generation. This indicates that the enhancement of the sorbitol is independent of the induced diapause in all three strains of the mulberry silkworm. Further, it is also clear that the enhancement of sorbitol concentration is devoid of a photoperiodic regime.

Sorbitol reduction via AT-007 (govorestat) ameliorates synaptic dysfunction and neurodegeneration in models of sorbitol dehydrogenase deficiency.

Sorbitol dehydrogenase (SORD) deficiency has been identified as the most frequent autosomal recessive form of hereditary neuropathy. Loss of SORD causes high sorbitol levels in tissues due to the inability to convert sorbitol to fructose in the two-step polyol pathway, leading to degenerative neuropathy. The underlying mechanisms of sorbitol-induced degeneration have not been fully elucidated, and no current FDA-approved therapeutic options are available to reduce sorbitol levels in the nervous system. Here, in a Drosophila model of SORD deficiency, we showed synaptic degeneration in the brain, neurotransmission defect, locomotor impairment, and structural abnormalities in the neuromuscular junctions. In addition, we found reduced ATP production in the brain and reactive oxygen species accumulation in the central nervous system (CNS) and muscle, indicating mitochondrial dysfunction. Applied Therapeutics, Inc has developed a CNS-penetrant next-generation aldose reductase inhibitor (ARI), AT-007 (govorestat), which inhibits the conversion of glucose to sorbitol. AT-007 significantly reduced sorbitol levels in patient-derived fibroblasts, iPSC-derived motor neurons, and Drosophila brains. AT-007 feeding in Sord-deficient Drosophila mitigated synaptic degeneration and significantly improved synaptic transduction, locomotor activity, and mitochondrial function. Moreover, AT-007 treatment significantly reduced ROS accumulation in Drosophila CNS, muscle, and patient-derived fibroblasts. These findings uncover the molecular and cellular pathophysiology of SORD neuropathy and provide a potential treatment strategy for patients with SORD deficiency.

SORD-related peripheral neuropathy in a French and Swiss cohort: Clinical features, genetic analyses, and sorbitol dosages.

Biallelic variants in SORD have been reported as one of the main recessive causes for hereditary peripheral neuropathies such as Charcot-Marie-Tooth disease type 2 (CMT2) and distal hereditary motor neuropathy (dHMN) resulting in lower limb (LL) weakness and muscular atrophy. In this study, phenotype and genotype landscapes of SORD-related peripheral neuropathies were described in a French and Swiss cohort. Serum sorbitol dosages were used to classify SORD variants. Patients followed at neuromuscular reference centres in France and Switzerland were ascertained. Sanger sequencing and next generation sequencing were performed to sequence SORD, and mass spectrometry was used to measure patients' serum sorbitol. Thirty patients had SORD peripheral neuropathy associating LL weakness with muscular atrophy, foot deformities (87%), and sometimes proximal LL weakness (20%) or distal upper limb weakness (50%). Eighteen had dHMN, nine had CMT2, and three had intermediate CMT. Most of them had a mild or moderate disease severity. Sixteen carried a homozygous c.757delG (p.Ala253Glnfs*27) variant, and 11 carried compound heterozygous variants, among which four variants were not yet reported: c.403C > G, c.379G > A, c.68_100 + 1dup, and c.850dup. Two unrelated patients with different origins carried a homozygous c.458C > A variant, and one patient carried a new homozygous c.786 + 5G > A variant. Mean serum sorbitol levels were 17.01 mg/L ± 8.9 SD for patients carrying SORD variants. This SORD-inherited peripheral neuropathy cohort of 30 patients showed homogeneous clinical presentation and systematically elevated sorbitol levels (22-fold) compared to controls, with both diagnostic and potential therapeutic implications.

The Morpho-Anatomy of Nectaries and Chemical Composition of Nectar in Pear Cultivars with Different Susceptibility to Erwinia amlylovora

The topography and morpho-anatomical characteristics of floral nectaries and the chemical analysis of nectar have been studied in seven pear cultivars with different susceptibility to Erwinia amylovora. The susceptible cultivar Williams, the moderately resistant cultivars Bella di guigno, Poire de Cure and the low susceptible cultivar Alexander Lucas originated from Pyrus communis, while highly resistant cultivars Chojuro and Nijisseiki from P. pyraster and Kieffer as interspecies hybrid P. communis × P. pyraster were included in this experiment and studied for the first time. Large differences in size and structure of the nectaries were observed in these seven pear cultivars. The epidermal cells were with cuticle being more or less striated in Alexander Lucas, Kieffer and Williams. Resistant cultivars had a narrow, elongated cell shape of epidermal cells while those susceptible had an isodiametric. Stomata were mesomorphic in all cultivars except in Poire de Cure and Williams, being slightly xeromorphic since they were situated in deep hollows. Guard cells of the modified stomata were much larger in resistant cultivars. Hypanthium cells were larger in resistant compared to susceptible cultivars. The most abundant sugars were glucose, fructose, sorbitol and sucrose in nectar of all studied pear cultivars. The resistant cultivars (Chojuro, Kieffer and Nijisseiki) had a ~2-fold higher level of sorbitol and galactose, ~2.2-fold higher isomaltose, ~2.7-fold turanose, ~3.35-fold maltose, ~4.4-fold melibiose and ~12.7-fold higher melesitose compared to susceptible cultivars. The sum of quantified phenolic acids varied from 0.049 (Williams) up to 4.074 µg CAE/mL (Kieffer), while flavonoid glycosides levels ranged from 1.224 (Williams) up to 11.686 µg RE/mL (Nijisseiki). In the nectar of the resistant cultivars, rutin, apigetrin, together with patuletin and luteolin glycosides were detected but not in susceptible cultivars, which could be considered as the markers of resistance.

1-Methylcyclopropene treatment delays the softening of Actinidia arguta fruit by reducing cell wall degradation and modulating carbohydrate metabolism

The rapid softening of hardy kiwifruit (Actinidia arguta) fruit significantly reduces its marketing potential. Therefore, the effect of 1-methylcyclopropene (1-MCP) on the softening of A. arguta fruit was investigated. Results indicated that A. arguta fruit treated with 1-MCP maintained a higher level of firmness, titratable acidity, ascorbic acid, total phenolics, and flavonoids content, relative to non-treated fruit. Fruit treated with 1-MCP and placed in long-term cold storage had higher sensory scores, as determined by a taste panel and supported by electronic nose and tongue data. Notably, 1-MCP delayed the degradation of cell wall components, including pectin, cellulose, and hemicellulose, by reducing the activity of cell-wall-modifying enzymes. In addition, 1-MCP reduced the activity of carbohydrate metabolism-related enzymes, resulting in fruit with higher levels of starch and sucrose and lower levels of glucose, fructose and sorbitol. Collectively, these results indicate that 1-MCP can be used to delay the softening of A. arguta fruit and extend its storage and shelf life.