Impact of microbial-based biopreparations on soil quality, plant health, and fruit chemistry in raspberry cultivation.

Application of microbial-based biopreparations as a pre-harvest strategy offers a method to obtain sustainable agricultural practices and could be an important approach for advancing food science, promoting sustainability, and meeting global food market demands. The impact of a bacterial-fungal biopreparation mixture on soil-plant-microbe interactions, fruit chemical composition and yield of 7 raspberry clones was investigated by examining the structural and functional profiles of microbial communities within leaves, fruits, and soil. Biopreparation addition caused the enhancement of the microbiological utilization of specific compounds, such as d-mannitol, relevant in plant-pathogen interactions and overall plant health. The biopreparation treatment positively affected the nitrogen availability in soil (9-160%). The analysis of plant stress marker enzymes combined with the evaluation of fruit quality and chemical properties highlight changes inducted by the pre-harvest biopreparation application. Chemical analyses highlight biopreparations' role in soil and fruit quality improvement, promoting sustainable agriculture. This effect was dependent on tested clones, showing increase of soluble solid content in fruits, concentration of polyphenols or the sensory quality of the fruits. The results of the next-generation sequencing indicated increase in the effective number of bacterial species after biopreparation treatment. The network analysis showed stimulating effect of biopreparation on microbial communities by enhancing microbial interactions (increasing the number of network edges up to 260%) of and affecting the proportions of mutual relationships between both bacteria and fungi. These findings show the potential of microbial-based biopreparation in enhancing raspberry production whilst promoting sustainable practices and maintaining environmental homeostasis and giving inshght in holistic understanding of microbial-based approaches for advancing food science monitoring.

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Lost and Found: Misdiagnosis of AIDS-Related Bone Marrow Suppression As Neutropenic Fever and Benign Ethnic Neutropenia in a Patient With Congenital HIV.

Neutropenia is a relatively uncommon but notable secondary effect of HIV infection. While the various hematopoietic effects of HIV and AIDS are well-described in the literature, high-quality evidence directly linking neutropenia with mortality in HIV-infected patients remains limited. The multifactorial etiology of neutropenia complicates its diagnosis, particularly when it occurs secondary to HIV. We present the case of a 35-year-old African American male with congenital HIV, who presented with severe neutropenia accompanied by a fever in the context of untreated HIV. The initial differential diagnosis was broad, including benign ethnic neutropenia (given the patient's African American ethnicity), tuberculosis (given the potential for anti-tuberculosis therapy to cause neutropenia and its commonality as a co-infection in HIV patients), sepsis-related neutropenia, and AIDS-related bone marrow suppression. However, through further workup, it became apparent that HIV-related bone marrow suppression ultimately led to pancytopenia. This case highlights how HIV patient non-adherence to antiretroviral therapy (ART) and hematologic abnormalities complicate the diagnosis of hematopoietic abnormalities from HIV. It also discusses how vertical transmission and abrupt ART discontinuation create a new phenotype of HIV patients with delayed presentations of AIDS-related complications. This patient's presentation also provides insight into the consequences of untreated HIV following the self-discontinuation of long-term HIV management therapy due to low healthcare literacy and loss of follow-up. The patient's clinical course, laboratory findings, imaging studies, and treatment outcomes are discussed, emphasizing the need for timely diagnosis and a multidisciplinary approach to care while exploring potential barriers to care in different social contexts.

Study of the influence of disease duration on glutatione-dependent ensymes dynamics in patients with paranoid schizophrenia.

OBJECTIVE: Aim: The objective of the research was to conduct a comprehensive longitudinal analysis of the temporal dynamics of glutathione system functionality in individuals diagnosed with paranoid schizophrenia. Specifically, the research was focused on investigating variations in the profiles of glutathione-dependent enzymes, with meticulous consideration given to the duration of the illness. PATIENTS AND METHODS: Materials and Methods: The study group comprised 300 individuals officially diagnosed with 'Paranoid Schizophrenia,' subdivided into five subgroups, each consisting of 60 patients. The subgroups were defined as follows: Subgroup I included 60 patients with a disease duration ranging from 3 to 5 years; Subgroup II comprised 60 patients with a duration of 6 to 10 years; Subgroup III consisted of 60 patients with a duration of 11 to 15 years; Subgroup IV included 60 patients with a duration of 16 to 20 years; and Subgroup V encompassed 60 patients with a duration of 21 years and older. The comparison group comprised 20 patients diagnosed with "Primary psychotic episode". RESULTS: Results: The research demonstrates a consistent and noteworthy reduction in the enzymatic activities of glutathione peroxidase, glutathione reductase, and glutathione-S-transferase in various Subgroups of paranoid schizophrenia patients. The observed declines are particularly prominent within the first 3-5 years of the illness, show casing statistically significant reductions. Patients with prolonged illness durations, especially surpassing 21 years, display substantial reductions in all three enzymes, suggesting a cumulative enzymatic impact associated with prolonged illness. CONCLUSION: Conclusions: The identification of critical periods of inhibition in the glutathione protection chain, provides valuable information about potential therapeutic interventions for individuals with paranoid schizophrenia.

Formononetin derivatives containing benzyl piperidine: A brand new, highly efficient inhibitor targeting Xanthomonas spp.

INTRODUCTION: Plant bacterial diseases take an incalculable toll on global food security. The indiscriminate use of chemical synthetic pesticide not only facilitates pathogen resistance of pathogenic bacteria, but also poses a major threat to human health and environmental protection. Therefore, it is of great economic value and scientific significance to develop a new antibacterial drug with environmental friendliness and unique mechanism of action. OBJECTIVES: To design and synthesize formononetin derivatives based on natural products, evaluate their in vitro and in vivo antibacterial activities and elucidate the mechanisms involved. METHODS: The synthesis was carried out by classical active group splicing method. The antibacterial activities were evaluated using turbidimetry and pot experiments. The antibacterial mechanism was further investigated using scanning electron microscopy (SEM), virulence factors, defense enzymes activities, proteomics and metabolomics. RESULTS: 40 formononetin derivatives containing benzyl piperidine were designed and synthesized. The antibacterial results demonstrated that H32 exhibited the most potent inhibitory effect against Xanthomonas oryzae pv. Oryzae (Xoo) with the EC50 of 0.07 µg/mL, while H6 displayed the highest inhibitory activity against Xanthomonas axonopodis pv. Citri (Xac) with the EC50 of 0.24 µg/mL. Furthermore, the control efficacy of H32 against rice bacterial leaf blight (BLB) and H6 against citrus canker (CC) was validated through pot experiments. SEM, virulence factors and host enzyme activities assay indicated that H32 could not only reduce the virulence of Xoo, but also activate the activities of defense enzymes and improve the disease resistance of host plants. The proteomics and metabolomics analysis demonstrated that H32 could inhibit the synthesis of branched-chain amino acids, make Xoo cells in a starvation state, inhibit its proliferation, weaken its virulence and reduce its colonization and infection of host cells. CONCLUSION: Formononetin derivatives containing benzyl piperidine could be used as potentially effective inhibitors against Xanthomonas spp.

Unraveling the role of ubiquitin-conjugating enzyme 5 (UBC5) in disease pathogenesis: A comprehensive review.

While certain members of ubiquitin-coupled enzymes (E2s) have garnered attention as potential therapeutic targets across diverse diseases, research progress on Ubiquitin-Conjugating Enzyme 5 (UBC5)-a pivotal member of the E2s family involved in crucial cellular processes such as apoptosis, DNA repair, and signal transduction-has been relatively sluggish. Previous findings suggest that UBC5 plays a vital role in the ubiquitination of various target proteins implicated in diseases and homeostasis, particularly in various cancer types. This review comprehensively introduces the structure and biological functions of UBC5, with a specific focus on its contributions to the onset and advancement of diverse diseases. It suggests that targeting UBC5 holds promise as a therapeutic approach for disease therapy. Recent discoveries highlighting the high homology between UBC5, UBC1, and UBC4 have provided insight into the mechanism of UBC5 in protein degradation and the regulation of cellular functions. As our comprehension of the structural distinctions among UBC5 and its homologues, namely UBC1 and UBC4, advances, our understanding of UBC5's functional significance also expands.

Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment.

Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the electron transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen and reactive nitrogen species (ROS and RNS). The associated progressive accumulation of molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger and indirect antioxidant, is synthesized in the mitochondrial matrix of neurons. Melatonin reduces electron leakage from the ETC and elevates ATP production; it also detoxifies ROS/RNS and via the SIRT3/FOXO pathway it upregulates activities of superoxide dismutase 2 and glutathione peroxidase. Melatonin also influences glucose processing by neurons. In neurogenerative diseases, neurons often adopt Warburg-type metabolism which excludes pyruvate from the mitochondria causing reduced intramitochondrial acetyl coenzyme A production. Acetyl coenzyme A supports the citric acid cycle and OXPHOS. Additionally, acetyl coenzyme A is a required co-substrate for arylalkylamine-N-acetyl transferase, which rate limits melatonin synthesis; therefore, melatonin production is diminished in cells that experience Warburg-type metabolism making mitochondria more vulnerable to oxidative stress. Moreover, endogenously produced melatonin diminishes during aging, further increasing oxidative damage to mitochondrial components. More normal mitochondrial physiology is preserved in aging neurons with melatonin supplementation.

Analysis of the genus B othrops snake venom: An inter and intraspecific comparative study.

The genus Bothrops are considered Category 1 of medical importance by the World Health Organization, responsible for approximately 85 % of snakebites occurring throughout Brazil. Main factors determining snake venom variations can be genetics, diet, gender, geographic distribution, age, or even seasonality. In this study, we compared the composition of protein profile, biochemical activities, and immunorecognition of toxins present in the venom of eight adults of Bothrops species (B. alternatus, B. atrox, B. jararaca, B. jararacussu, B. leucurus, B. moojeni, B. neuwiedi and B. pauloensis). The following methods were used to analyze the venoms: protein dosage; electrophoresis in polyacrylamide gel containing SDS; High Performance Liquid Chromatography - Reverse Phase; enzymatic activities, western blotting and Enzyme Linked Immuno Sorbent Assay. The results show inter and intraspecific differences in the electrophoretic profile. LAAO and PLA2 activities, in general, were higher in males than females and proteolytic activity was higher in females than males. The bothropic antivenom produced by Instituto Butantan recognized most of the protein bands in all Bothrops species analyzed, with only the regions between 37 and 25 kDa presenting lower intensity. A notable variability in the chromatograms was observed. Bothrops venom demonstrated inter-intraspecific disparities in protein composition and biochemical activity.

Spectroscopic and computational studies of a bifunctional iron- and 2-oxoglutarate dependent enzyme, AsqJ.

Iron and 2-oxoglutarate dependent (Fe/2OG) enzymes exhibit an exceedingly broad reaction repertoire. The most prevalent reactivity is hydroxylation, but many other reactivities have also been discovered in recent years, including halogenation, desaturation, epoxidation, endoperoxidation, epimerization, and cyclization. To fully explore the reaction mechanisms that support such a diverse reactivities in Fe/2OG enzyme, it is necessary to utilize a multi-faceted research methodology, consisting of molecular probe design and synthesis, in vitro enzyme assay development, enzyme kinetics, spectroscopy, protein crystallography, and theoretical calculations. By using such a multi-faceted research approach, we have explored reaction mechanisms of desaturation and epoxidation catalyzed by a bi-functional Fe/2OG enzyme, AsqJ. Herein, we describe the experimental protocols and computational workflows used in our studies.

Microcystin-LR induces histopathological injury and cell apoptosis in the hepatopancreas of white shrimp, Litopenaeus vannamei.

Microcystin-LR (MC-LR), a common hepatotoxin produced by bloom-forming cyanobacteria, presents a serious threat to the health of aquatic animals. In this study, we studied the impact of MC-LR on hepatopancreas histopathology, enzyme activity, transcriptome, and apoptosis of Litopenaeus vannamei. Thus, shrimp postlarvae (1.63 ± 0.5 g) exposed to MC-LR at 500 µg/kg caused morphological lesions in the histology of the shrimp hepatopancreas, which exhibited swollen, lighter coloration and unclear edges. Moreover, MC-LR significantly altered the hepatopancreas enzyme activities such as the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), acid phosphatase (ACP), alkaline phosphatase (AKP) and lysozyme (LZM), including the state of apoptosis in hepatopancreas. From the RNA-seq analysis of the hepatopancreas, a total of 728 differentially expressed genes (DEGs) were identified, and their functions in MC-LR treatment group were involved in cellular processes, metabolic processes, biological regulation, cellular components, catalytic activity and binding. The metabolic pathways primarily associated with the DEGs included reactive oxygen species, glycerophospholipid metabolism and the phospholipase D signaling pathway. Overall, q-PCR results indicated that MC-LR led to significant changes in multiple apoptosis genes of shrimp hepatopancreas. This study expand the understanding of the effect of microcystin-LR on commercially farmed crustaceans.

Treprostinil palmitil inhalation powder leverages endogenous lung enzymes to provide sustained treprostinil.

BACKGROUND: To determine key enzymes enabling treprostinil palmitil (TP) conversion to treprostinil and the main converting sites in the respiratory system. RESEARCH DESIGN AND METHODS: We performed in vitro activity assays to identify lung enzymes hydrolyzing TP, and cell-based assays and immunostainings to establish the likely locations within the lung. RESULTS: Lipoprotein lipase (LPL) had greater activity than the other tested lung enzymes. Excess LPL activity was present both in vitro and at the target TP dose in vivo. CONCLUSIONS: LPL is likely the key enzyme enabling TP conversion. The rate-limiting step is likely the accessibility of TP and not the enzyme activity.

Comparative analysis of cyto-genotoxicity of zinc using the comet assay and chromosomal abnormality test.

In this study, the toxicity of the trace element zinc (Zn) in Allium cepa L. test material was examined. Toxicity was investigated in terms of physiological, cytogenetic, biochemical, and anatomical aspects. Germination percentage, root length, weight gain, mitotic index (MI), micronucleus (MN) frequency, chromosomal abnormalities (CAs), malondialdehyde (MDA), proline and chlorophyll levels, superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and meristematic cell damage were used as indicators of toxicity. Additionally, the comet test was used to measure the degree of DNA damage. Four groups of A. cepa bulbs-one for control and three for applications-were created. While the bulbs in the treatment groups were germinated with Zn at concentrations of 35, 70, and 140 mg/L, the bulbs in the control group were germinated with tap water. Germination was carried out at room temperature for 72 h and 144 h. When the allotted time was over, the root tips and leaf samples were collected and prepared for spectrophotometric measurements and macroscopic-microscopic examinations. Consequently, Zn treatment led to significant reductions in physiological indicators such as weight gain, root length, and germination percentage. Zn exposure caused genotoxicity by decreasing the MI ratios and increasing the frequency of MN and CAs (p < 0.05). Zn promoted various types of CAs in root tip cells. The most observed of CAs was the sticky chromosome. Depending on the dose, Zn was found to cause an increase in tail lengths in comet analyses, which led to DNA damage. Exposure to Zn led to a significant decrease in chlorophyll levels and an increase in MDA and proline levels. It also promoted significant increases in SOD and CAT enzyme activities up to 70 mg/L dose and statistically significant decreases at 140 mg/L dose. Additionally, Zn exposure caused different types of anatomical damage. The most severe ones are epidermis and cortex cell damage. Besides, it was found that the Zn dose directly relates to all of the increases and decreases in physiological, cytogenetic, biochemical, and anatomical parameters that were seen as a result of Zn exposure. As a result, it has been determined that the Zn element, which is absolutely necessary in trace amounts for the continuation of the metabolic activities of the organisms, can cause toxicity if it reaches excessive levels.

Impact of dual Bt-transgenic maize (2A7) on soil microbial communities and enzyme activities: A comparative study with control variety Z58.

The impacts of transgenic crops on soil microbiology and fertility are critical in determining their biosafety. While transgenic crops can alter soil microbes, their effects are often context-dependent; therefore, the ecological importance of these changes remains a topic of ongoing research. Using high-throughput sequencing, we investigated the effects of Bacillus thuringiensis (Bt) maize expressing the mcry1Ab and mcry2Ab genes (2A7) on soil nutrient dynamics, as well as the diversity and function of soil microbial communities, including bacteria and fungi, within different soil compartments. Our findings revealed a plant-shaped rhizosphere (RS) microbial community as a result of the selective recruitment of microorganisms from the surrounding environment. The transgene insertion had a significant impact on the RS niche, and several species eventually became associated with Z58 and 2A7 plants. For example, Neocosmospora rubicola fungal and Pantoea dispersa bacterial microorganisms were significantly decreased in the dual Bt-transgenic 2A7 rhizosphere but enriched in the Z58 rhizospheres. The activity of soil enzymes such as urease, invertase, and alkaline phosphatase was boosted by Bt-transgenic 2A7. LefSe analysis identified significant bacterial and fungal biomarker species that were responsible for the differential effects of Bt-transgenic 2A7 and control Z58 within rhizosphere soils. Mantel analysis further demonstrated that the root exudates of 2A7 altered nutrient-acquisition enzymes by influencing biomarker taxa. PICRUSt2 functional characterization revealed a significantly higher abundance of the phosphate-starvation-inducible protein in control Z58 than in Bt-transgenic 2A7. Furthermore, taxonomy, alpha (Shannon diversity), and beta diversity analyses all revealed niche-driven microbial profile differentiation. Niche partitioning also had a significant impact on N- and P-related COGs as well. Our findings suggests that Bt-transgenic 2A7 modulates rhizosphere microbial communities by affecting biomarker taxa and soil enzyme activity. These findings will promote sustainable agriculture practices by advancing our knowledge of the ecological effects of Bt crops on soil microbial communities.

Toxicological effects of di(2-ethylhexyl)phthalate on dandelions: Insights into physiological, metabolic, and molecular docking perspectives.

Di(2-ethylhexyl)phthalate (DEHP) is one of the most widely used plasticizers in plastic manufacturing. However, the toxicological effects of DEHP on dandelions remain poorly understood. This study comprehensively analyzed and explored the response mechanisms of dandelions to 1, 10, 50, and 100 mg L-1 DEHP influencing the morphophysiological growth, metabolomics, and molecular docking. DEHP reduced chlorophyll synthesis, inhibited plant growth, and induced oxidative-state-associated stress, which was manifested by the excessive production of reactive oxygen species, an increase in antioxidant enzyme activities, and enhanced synthesis of some osmoregulatory compounds, including proline and soluble protein. An analysis of the integrated biological response index showed that the toxicity was dose-dependent. Molecular docking demonstrated that DEHP could bind stably to three enzymes, and the binding energy was peroxidase (POD) > catalase (CAT) > superoxide dismutase (SOD). Metabolomics revealed that metabolite abundance and metabolic pathways were altered by DEHP, with 88 and 72 primary metabolites identified in shoots and roots, respectively. Amino acid, sugar, and organic acid metabolism were severely disturbed, with the most significant effects being on carbohydrate metabolism, valine, leucine, and isoleucine biosynthesis. Our study elucidated the influence of DEHP exposure on dandelions, providing new insights into the toxicity mechanisms and toxicological risk assessment.

Stimulating action of sodium nitroprusside and vinasse on salicin and direct regeneration in Salix Safsaf Forssk.

The present study aimed to enhance salicin and direct regeneration in willow (Salix safsaf Forssk) using the sodium nitroprusside (SNP) regulation of nitric oxide (NO) and vinasse for its nutrition effect in culture medium. Internodes of Salix safsaf were cultured on Murashige and Skoog (MS) medium supplemented with benzyl adenine (BA) (0.25 mg L-1) and different concentrations of SNP (0, 5, 10, 15, and 20 mg L-1) or vinasse (0, 5, 10, and 20%) to examine shoot regeneration, antioxidant defense enzyme activity, total phenolic compounds, flavonoids, and salicine contents. The reported data revealed that application of SNP at 15 mg L-1 and vinasse at 10% induced a significant effect in vitro Salix safsaf shoot regeneration. To confirm that, nitric oxide is required for auxin-mediated activation of cell division in a dose-dependent manner. A concentration of 15 mg L-1 SNP promotes regeneration and salicin accumulation (3162.16 mg/100 g) during signaling action. On the other hand, the cross talk effect of nitric oxide and vinasse combination in Salix safsaf significantly induced a synergistic effect on direct propagation more than vinasse alone. SNP significantly stimulates salicylate accumulation in a dose-dependent manner, but the data on the association of vinasse and SNP on salicylate up-regulation showed a significant reduction in salicin accumulation when SNP was combined with 10% vinasse, which directly affected the signaling action of SNP as secondary product stimulators. Vinasse's phenolic compounds affect directly on the reduction activity of SNP to suppress its signaling action, or indirectly by inhibiting the sequence cascade of the SNP signaling transduction process to decrease the accumulation of salicin contents. Data confirmed that vinasse and SNP stimulated the antioxidant enzymes activity throw quenching the stimulated reactive oxygen species that produced via SNP. Results show that modified media with SNP administration at 15 mg L-1 and the combination of vinasse at 10% and SNP at 15 mg L-1 are recommended for modifying tissue culture media for induced direct regeneration and salicin accumulation in tissue culture applications, which will be very useful for commercial salicin overproduction as a biological active ingredient in willows.

Purification and characterization of α-fucosidase from Dichostereum sordulentum 1488.

Biological glycans mediate several physiological processes, thus altered glycosylation patterns can lead to different diseases such as autoimmune, infectious, chronic anti-inflammatory diseases, or even cancer. In fact, alterations in fucosylation in either N- or O-glycans are among the most frequent changes in glycosylation patterns associated with cancer. Therefore, elucidation of the role of glycoconjugate glycans is essential for understanding the development of pathologies where they are involved. In this sense glycosidases are excellent tools, since they catalyse the selective removal of sugar residues, allowing the evaluation of changes in their biological role due to glycan removal. This work describes the purification and characterization of a α-fucosidase from the fungus Dichostereum sordulentum 1488. It is a homodimer with a molecular weight of 214 kDa and optimum pH and temperature of 4.0 and 70 °C respectively. It has a KM of 0.27 mM and VMax of 3.3 µmoles PNP/min per mg for the substrate p-nitrophenyl-α-l-fucopyranoside, showing a substrate inhibition profile. It showed high specificity for the hydrolysis of fucose linked by α-(1,2) bonds. The identification, purification, and characterization of this new α-fucosidase is highly relevant for enlarging the availability of glycosidases for use as tools for glycan elucidation.

Chemical tools for probing the Ub/Ubl conjugation cascades.

Conjugation of ubiquitin (Ub) and structurally related ubiquitin-like proteins (Ubl's), essential for many cellular processes, employs muti-step reactions orchestrated by specific E1, E2 and E3 enzymes. The E1 enzyme activates the Ub/Ubl C-terminus in an ATP-dependent process that results in the formation of a thioester linkage with the E1 active site cysteine. The thioester activated Ub/Ubl is transferred to the active site of an E2 enzyme which then interacts with an E3 enzyme to promote conjugation to the target substrate. The E1-E2-E3 enzymatic cascades utilize labile intermediates, extensive conformational changes, and vast combinatorial diversity of short-lived protein-protein complexes to conjugate Ub/Ubl to various substrates in a regulated manner. In this review, we discuss various chemical tools and methods used to study the consecutive steps of Ub/Ubl activation and conjugation, which are often too elusive for direct studies. We focus on methods developed to probe enzymatic activities and capture and characterize stable mimics of the transient intermediates and transition states thereby providing insights into fundamental mechanisms in the Ub/Ubl conjugation pathways.

Drug metabolizing enzymes pharmacogenetic variation-informed antidepressant therapy approach for common mental disorders: A systematic review and meta-analysis.

IMPORTANCE: Currently, 30-50 % of individuals with depression and 40 % with anxiety-collectively referred to as common mental disorders (CMDs), exhibit inadequate responses to antidepressant treatments. OBJECTIVE: To assess the effectiveness and safety of drug-metabolizing enzyme pharmacogenetic variation informed treatment (PGxIT) versus usual antidepressant treatment (UT) in patients with CMDs. DATA SOURCES: A literature search was conducted in the MEDLINE, Scopus, and Cochrane Library databases from inception until January 30, 2024. STUDY SELECTION: Studies were selected based on CMD diagnoses, reporting on the genetic variations of drug-metabolizing enzyme (DME) genes in relation to antidepressants, involving PGxIT and UT groups with human subjects, and published in English. DATA EXTRACTION AND SYNTHESIS: Data extraction and quality assessment were performed independently by two authors. A pooled risk ratio (RR) with 95 % CI was estimated using both random and fixed-effect models, and heterogeneity was assessed using Cochran's Q test and the I2 statistic. The publication bias of eligible studies was assessed using post hoc Doi plots and the LFK index. RESULTS: This systematic review included 18 studies (n = 7021). The PGxIT demonstrated greater efficacy in the remission of symptoms of depressive disorder at 8 weeks (RR 1.523 [95 % CI: 1.255-1.843]; I2 = 48 %) and 12 weeks (RR 1.631 [95 % CI: 1.001-2.657]; I2 = 86 %; p < 0.01), and symptoms of anxiety disorder compared to UT. Additionally, the risk of adverse drug events (ADEs) was significantly lower in the PGxIT group (RR = 0.65 [95 % CI: 0.52-0.82]; I2 = 0 %) than in the UT group. The certainty of evidence for both outcomes was moderate. CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis suggest that pharmacogenetically guided antidepressant treatment, based on genetic variation in drug-metabolizing enzymes, is associated with superior efficacy in the remission of symptoms for patients with depressive disorders and a reduction in ADEs compared to usual treatment and the findings of the systematic review for remission in anxiety disorders indicate that, PGx guided treatment is also associated with increased remission of symptoms in anxiety disorders compared to usual treatment.

Effects of long-term continuous cultivation on the structure and function of soil bacterial and fungal communities of Fritillaria Cirrhosa on the Qinghai-Tibetan Plateau.

Fritillaria cirrhosa, an endangered medicinal plant in the Qinghai-Tibet Plateau, is facing resource scarcity. Artificial cultivation has been employed to address this issue, but problems related to continuous cultivation hinder successful transplantation. Imbalanced microbial communities are considered a potential cause, yet the overall changes in the microbial community under continuous cropping systems remain poorly understood. Here, we investigated the effects of varying durations of continuous cropping on the bacterial and fungal communities, as well as enzymatic activities, in the rhizospheric soil of F. cirrhosa. Our findings revealed that continuous cropping of F. cirrhosa resulted in soil acidification, nutrient imbalances, and increased enzyme activity. Specifically, after 10 years of continuous cropping, there was a notable shift in the abundance and diversity (e.g., Chao1 index) of soil bacteria and fungi. Moreover, microbial composition analyses revealed a significant accumulation of harmful microorganisms associated with soil-borne diseases (e.g., Luteimonas, Parastagonospora, Pseudogymnoascus) in successively cropped soils, in contrast to the significant reduction of beneficial microorganisms (e.g., Sphingomonas, Lysobacter, Cladosporium) that promote plant growth and development and protect against diseases such as Fusarium sp.These changes led to decreased connectivity and stability within the soil microbial community. Structural equation modeling and redundancy analysis revealed that alkaline hydrolytic nitrogen and available phosphorus directly influenced soil pH, which was identified as the primary driver of soil microbial community changes and subsequently contributed to soil health deterioration. Overall, our results highlight that soil acidification and imbalanced rhizosphere microbial communities are the primary challenges associated with continuous cropping of F. cirrhosa. These findings establish a theoretical foundation for standardized cultivation practices of F. cirrhosa and the bioremediation of continuously cultivated soils.

Effect of withering/spreading on the physical and chemical properties of tea: A review.

Withering and spreading, though slightly differing in their parameters, share the same aim of moisture reduction in tea leaves, and they have a strong impact on the physical and chemical properties of tea. Even though researchers tend to pay close attention to the characteristic crafts of different teas, increasing investigations begin to focus on the withering process due to its profound effects on the composition and content of quality-related compounds. This review provides an overview of tea withering process to address questions comprehensively during withering. Hence, it is expected in this review to figure out factors that affect withering results, the way withering influences the physical and chemical properties of withered leaves and tea quality, and intelligent technologies and devices targeted at withering processes to promote the modernization of the tea industry. Herein, several key withering parameters, including duration, temperature, humidity, light irradiation, airflow, and more, are tailored to different tea types, demanding further exploration of advanced withering devices and real-time monitoring systems. The development of real-time monitoring technology enables objective and real-time adjustment of withering status in order to optimize withering results. Tea quality, including taste, aroma, and color quality, is first shaped during withering due to the change of composition and content of quality-related metabolites through (non)enzymatic reactions, which are easily influenced by the factors above. A thorough understanding of withering is key to improving tea quality effectively and scientifically.