Novel melatonin-producing Bacillus safensis EH143 mitigates salt and cadmium stress in soybean.

Recently, microorganism and exogenous melatonin application has been recognized as an efficient biological tool for enhancing salt tolerance and heavy metal detoxification in agriculture crops. Thus, the goal of this study was to isolate and evaluate a novel melatonin-producing plant growth promoting bacterium. With high-throughput whole genome sequencing, phytohormone measurements, expression profiling, and biochemical analysis, we can identify a novel PGPB that produces melatonin and unravel how it promotes soybean growth and development and protects against salt and Cd stress. We identify the melatonin synthesis pathway (tryptophan→tryptamine→serotonin melatonin) of the halotolerant (NaCl > 800 mM) and heavy metal-resistant (Cd >3 mM) rhizobacterium Bacillus safensis EH143 and use it to treat soybean plants subjected to Cd and NaCl stresses. Results show that EH143 will highly bioaccumulate heavy metals and significantly improve P and Ca2+ uptake and the K+/Na+ (93%↑under salt stress) ratio while reducing Cd uptake (49% under Cd stress) in shoots. This activity was supported by the expression of the ion regulator HKT1, MYPB67, and the calcium sensors CDPK5 and CaMK1 which ultimately led to increased plant growth. EH143 significantly decreased ABA content in shoots by 13%, 20%, and 34% and increased SA biosynthesis in shoots by 14.8%, 31%, and 48.2% in control, salt, and Cd-treated plants, upregulating CYP707A1 and CYP707A2 and PAL1 and ICS, respectively. The melatonin content significantly decreased along with a reduced expression of ASMT3 following treatment with EH143; moreover, reduced expression of peroxidase (POD) and superoxide dismutase (SOD) by 134.5% and 39% under salt+Cd stress, respectively and increased level of total amino acids were observed. Whole-genome sequencing and annotation of EH143 revealed the presence of the melatonin precursor tryptophan synthase (trpA, trpB, trpS), metal and other ion regulators (Cd: cadA, potassium: KtrA and KtrB, phosphate: glpT, calcium: yloB, the sodium/glucose cotransporter: sgIT, and the magnesium transporter: mgtE), and enzyme activators (including the siderophore transport proteins yfiZ and yfhA, the SOD sodA, the catalase katA1, and the glutathione regulator KefG) that may be involved in programming the plant metabolic system. As a consequence, EH143 treatment significantly reduced the contents of lipid peroxidation (O2-, MDA, and H2O2) up to 69%, 46%, and 29% in plants under salt+Cd stress, respectively. These findings suggest that EH143 could be a potent biofertilizer to alleviate NaCl and Cd toxicity in crops and serve as an alternative substitute for exogenous melatonin application.

Enhanced use of chemical fertilizers and mitigation of heavy metal toxicity using biochar and the soil fungus Bipolaris maydis AF7 in rice: Genomic and metabolomic perspectives.

Chemical fertilizers are the primary source of crop nutrition; however, their increasing rate of application has created environmental hazards, such as heavy metal toxicity and eutrophication. The synchronized use of chemical fertilizers and eco-friendly biological tools, such as microorganisms and biochar, may provide an efficient foundation to promote sustainable agriculture. Therefore, the current study aimed to optimize the nutrient uptake using an inorganic fertilizer, sulfate of potash (SOP) from the plant growth-promoting fungus Bipolaris maydis AF7, and biochar under heavy metal toxicity conditions in rice. Bioassay analysis showed that AF7 has high resistance to heavy metals and a tendency to produce gibberellin, colonize the fertilizer, and increase the intake of free amino acids. In the plant experiment, the co-application of AF7 +Biochar+MNF+SOP significantly lowered the heavy metal toxicity, enhanced the nutrient uptake in the rice shoots, and improved the morphological attributes (total biomass). Moreover, the co-application augmented the glucose and sucrose levels, whereas it significantly lowered the endogenous phytohormone levels (salicylic acid and jasmonic acid) in the rice shoots. The increase in nutrient content aligns with the higher expression of the OsLSi6, PHT1, and OsHKT1 genes. The plant growth traits and heavy metal tolerance of AF7 were validated by whole-genome sequencing that showed the presence of the heavy metal tolerance and detoxification protein, siderophore iron transporter, Gibberellin cluster GA4 desaturase, and DES_1 genes, as well as others that regulate glucose, antioxidants, and amino acids. Because the AF7 +biochar+inorganic fertilizer works synergistically, nutrient availability to the crops could be improved, and heavy metal toxicity and environmental hazards could be minimized.

Influence of N-Acetylglucosamine and Melatonin Interaction in Modeling the Photosynthetic Component and Metabolomics of Cucumber under Salinity Stress.

The application of N-acetylglucosamine (GlcNAc) and melatonin (Mel) in agriculture could be a promising avenue for improving crop resilience and productivity, especially under challenging environmental conditions. In the current study, we treated the cucumber plant with GlcNAc and Mel solely and combinedly under salt stress (150 mM) then studied photosynthetic attributes using the transient OJIP fluorescence method. The results showed that the combination of GlcNAc × Mel significantly improved the plant morphological attributes, such as root and shoot biomass, and also improved chlorophyll and photosynthetic components. The mineral elements such as K, Mg, Ca, and P were significantly elevated, whereas a lower influx of Na was observed in GlcNAc × Mel treated cucumber shoots. A significant reduction in abscisic acid was observed, which was validated by the reduction in proline content and the increase in stomatal conductance (Gs), transpiration rate (E), and substomatal CO2 concentration (Ci). Furthermore, the activities of antioxidants such as polyphenol and flavonoid were considerably improved, resulting in a decrease in SOD and CAT with GlcNAc × Mel treatment. In addition, GlcNAc × Mel treatment dropped levels of the toxic radical Malondialdehyde (MDA) and elevated amino acids in cucumber shoots. These findings suggest that the combination of GlcNAc × Mel could be an effective elicitor for modeling plant metabolism to confer stress tolerance in crops.

Hormones and the antioxidant transduction pathway and gene expression, mediated by Serratia marcescens DB1, lessen the lethality of heavy metals (As, Ni, and Cr) in Oryza sativa L.

Microorganisms have recently gained recognition as efficient biological tool for reducing heavy metal toxicity in crops. In this experiment, we isolated a potent heavy metal (As, Ni, and Cr) resistant rhizobacterium Serratia marcescens DB1 and detected its plant growth promoting traits such as phosphate solubilization, gibberellin synthesis, organic acid production and amino acid regulation. Based on these findings, DB1 was further investigated for application in a rice var. Hwayeongbyeo subjected to 1 mM As, 4 mM Ni, and 4 mM Cr stress. The rice plants treated with Cr and Ni appeared healthy but were lethal, indicating unfitness for consumption due to toxic metal deposition, whereas the plants treated with > 1 mM As instantaneously died. Our results showed that DB1 inoculation significantly decreased metal accumulation in the rice shoots. Particularly, Cr uptake dropped by 16.55% and 22.12% in (Cr + DB1) and (Cr + As + Ni + DB1), respectively, As dropped by 48.90% and 35.82% in (As + DB1) and (Cr + As + Ni + DB1), respectively, and Ni dropped by 7.95% and 19.56% in (Ni + DB1) and (Cr + As + Ni + DB1), respectively. These findings were further validated by gene expression analysis results, which showed that DB1 inoculation significantly decreased the expression of OsPCS1 (a phytochelatin synthase gene), OsMTP1 (a metal transporting gene), and OsMTP5 (a gene for the expulsion of excess metal). Moreover, DB1 inoculation considerably enhanced the morphological growth of rice through modulation of endogenous phytohormones (abscisic acid, salicylic acid, and jasmonic acid) and uptake of essential elements such as K and P. These findings indicate that DB1 is an effective biofertilizer that can mitigate heavy metal toxicity in rice crops.

Synergistic Effect of Melatonin and Lysinibacillus fusiformis L. (PLT16) to Mitigate Drought Stress via Regulation of Hormonal, Antioxidants System, and Physio-Molecular Responses in Soybean Plants.

Drought is one of the most detrimental factors that causes significant effects on crop development and yield. However, the negative effects of drought stress may be alleviated with the aid of exogenous melatonin (MET) and the use of plant-growth-promoting bacteria (PGPB). The present investigation aimed to validate the effects of co-inoculation of MET and Lysinibacillus fusiformis on hormonal, antioxidant, and physio-molecular regulation in soybean plants to reduce the effects of drought stress. Therefore, ten randomly selected isolates were subjected to various plant-growth-promoting rhizobacteria (PGPR) traits and a polyethylene-glycol (PEG)-resistance test. Among these, PLT16 tested positive for the production of exopolysaccharide (EPS), siderophore, and indole-3-acetic acid (IAA), along with higher PEG tolerance, in vitro IAA, and organic-acid production. Therefore, PLT16 was further used in combination with MET to visualize the role in drought-stress mitigation in soybean plant. Furthermore, drought stress significantly damages photosynthesis, enhances ROS production, and reduces water stats, hormonal signaling and antioxidant enzymes, and plant growth and development. However, the co-application of MET and PLT16 enhanced plant growth and development and improved photosynthesis pigments (chlorophyll a and b and carotenoids) under both normal conditions and drought stress. This may be because hydrogen-peroxide (H2O2), superoxide-anion (O2-), and malondialdehyde (MDA) levels were reduced and antioxidant activities were enhanced to maintain redox homeostasis and reduce the abscisic-acid (ABA) level and its biosynthesis gene NCED3 while improving the synthesis of jasmonic acid (JA) and salicylic acid (SA) to mitigate drought stress and balance the stomata activity to maintain the relative water states. This may be possible due to a significant increase in endo-melatonin content, regulation of organic acids, and enhancement of nutrient uptake (calcium, potassium, and magnesium) by co-inoculated PLT16 and MET under normal conditions and drought stress. In addition, co-inoculated PLT16 and MET modulated the relative expression of DREB2 and TFs bZIP while enhancing the expression level of ERD1 under drought stress. In conclusion, the current study found that the combined application of melatonin and Lysinibacillus fusiformis inoculation increased plant growth and could be used to regulate plant function during drought stress as an eco-friendly and low-cost approach.

Dynamics of Humic Acid, Silicon, and Biochar under Heavy Metal, Drought, and Salinity with Special Reference to Phytohormones, Antioxidants, and Melatonin Synthesis in Rice.

This study aimed to develop a biostimulant formulation using humic acid (HA), silicon, and biochar alone or in combination to alleviate the lethality induced by combined heavy metals (HM-C; As, Cd, and Pb), drought stress (DS; 30-40% soil moisture), and salt stress (SS; 150 mM NaCl) in rice. The results showed that HA, Si, and biochar application alone or in combination improved plant growth under normal, DS, and SS conditions significantly. However, HA increased the lethality of rice by increasing the As, Cd, and Pb uptake significantly, thereby elevating lipid peroxidation. Co-application reduced abscisic acid, elevated salicylic acid, and optimized the Ca2+ and Si uptake. This subsequently elevated the K+/Na+ influx and efflux by regulating the metal ion regulators (Si: Lsi1 and Lsi2; K+/Na+: OsNHX1) and increased the expressions of the stress-response genes OsMTP1 and OsNramp in the rice shoots. Melatonin synthesis was significantly elevated by HM-C (130%), which was reduced by 50% with the HA + Si + biochar treatment. However, in the SS- and DS-induced crops, the melatonin content showed only minor differences. These findings suggest that the biostimulant formulation could be used to mitigate SS and DS, and precautions should be taken when using HA for heavy metal detoxification.

Blood-based biomarker in Parkinson's disease: potential for future applications in clinical research and practice.

The clinical presentation of Parkinson's disease (PD) is both complex and heterogeneous, and its precise classification often requires an intensive work-up. The differential diagnosis, assessment of disease progression, evaluation of therapeutic responses, or identification of PD subtypes frequently remains uncertain from a clinical point of view. Various tissue- and fluid-based biomarkers are currently being investigated to improve the description of PD. From a clinician's perspective, signatures from blood that are relatively easy to obtain would have great potential for use in clinical practice if they fulfill the necessary requirements as PD biomarker. In this review article, we summarize the knowledge on blood-based PD biomarkers and present both a researcher's and a clinician's perspective on recent developments and potential future applications.

Clinical Profiles and Mortality of COVID-19 Inpatients with Parkinson's Disease in Germany.

BACKGROUND: Comprehensive, nationwide data regarding Parkinson's disease (PD) hospitalizations, coronavirus disease 2019 (COVID-19) in-hospital frequency, and COVID-19-associated inpatient mortality during the first wave of the COVID-19 pandemic are not available. OBJECTIVE: To provide a nationwide analysis on hospitalized PD patients in Germany and evaluate the impact of the COVID-19 pandemic. METHODS: We conducted a cross-sectional study using an administrative claims database covering 1468 hospitals and 5,210,432 patient hospitalizations including a total of 30,872 COVID-19+ cases between January 16 and May 15, 2020. RESULTS: Compared to 2019, hospitalizations for PD transiently decreased by up to 72.7% in 2020. COVID-19 frequency was significantly higher in the population of 64,434 PD patients (693 being COVID-19+ ) than in non-PD patients (1.1% vs. 0.6%, P < 0.001), especially in subjects with advanced age (≥ 65 years). Regarding established COVID-19 risk comorbidities, COVID-19+ inpatients with PD showed higher incidences than non-PD COVID-19+ subjects, particularly hypertension and chronic kidney disease. Advanced age and male sex were significantly more frequent in COVID-19+ than in COVID-19- PD patients. The COVID-19 inpatient mortality rate was much higher in PD patients than in non-PD patients (35.4% vs. 20.7%, P < 0.001), especially in patients aged 75-79 years. Of note, overall inpatient mortality of PD patients was significantly higher in 2020 than in 2019 (5.7% vs. 4.9%, P < 0.001). CONCLUSIONS: PD inpatients are more frequently affected by COVID-19 and suffer from increased COVID-19-associated mortality in comparison to non-PD patients. More comprehensive studies are needed to assess the significance of associated comorbidities for COVID-19 risk and mortality in PD. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Chitosan-GSNO Nanoparticles and Silicon Priming Enhance the Germination and Seedling Growth of Soybean (Glycine max L.).

Soybean, a major legume crop, has seen a decline in its production owing to challenges in seed germination and the development of seedlings. Thus, in this study, we systematically investigated the influence of various chitosan-S-nitrosoglutathione (chitosan-GSNO) nanoparticle (0, 25, 50, and 100 µM) and Si (0, 0.5, and 1 mM) priming concentrations on soybean seed germination and seedling growth over five different priming durations (range: 1-5 h at each concentration). Significant differences were observed in all parameters, except seedling diameter, with both treatments. Seed germination was significantly enhanced after 3 h of priming in both treatments. The final germination percentage (FGP), peak germination percentage (PGP), vigor index (VI), seedling biomass (SB), hypocotyl length (HL), and radical length (RL) of 100 µM chitosan-GSNO-nanoparticle-primed seeds increased by 20.3%, 41.3%, 78.9%, 25.2%, 15.7%, and 65.9%, respectively, compared with those of the control; however, the mean germination time (MGT) decreased by 18.43%. Si priming at 0.5 mM increased the FGP, PGP, VI, SB, HL, and RL by 13.9%, 55.17%, 39.2%, 6.5%, 22.5%, and 25.1%, respectively, but reduced the MGT by 12.29% compared with the control treatment. Chitosan-GSNO and Si treatment up-regulated the relative expression of gibberellic acid (GA)-related genes (GmGA3ox3 and GmGA2ox1) and down-regulated that of abscisic acid (ABA)-related genes (GmABA2, GmAAO3, and GmNCED5). Chitosan-GSNO and Si application increased bioactive GA4 levels and simultaneously reduced ABA content. Hence, the use of exogenous chitosan-GSNO nanoparticles and Si as priming agents had a beneficial effect on seed germination and seedling growth because of the up-regulation in the expression of GA and down-regulation in the expression of ABA. Additional research is needed to understand the combined impact of Si and chitosan-GSNO nanoparticles, including their effects on the expression levels of other hormones and genes even in the later growth stage of the crop.

Combined application of melatonin and Bacillus sp. strain IPR-4 ameliorates drought stress tolerance via hormonal, antioxidant, and physiomolecular signaling in soybean.

The role of melatonin and plant growth-promoting rhizobacteria (PGPR) in enhancing abiotic stress tolerance has been widely investigated. However, the mechanism underlying the interaction between melatonin and PGPR in drought stress tolerance is poorly understood. In this study, we investigated the role of Bacillus sp. strain IPR-4 co-inoculated with melatonin (IPR-4/MET) to ameliorate drought stress response in soybean. Initially, 16 random isolates were selected from a previously pooled collection of isolates from soil at plant physiology lab, and were screesn for plant growth promoting (PGP) traits and their survival rate polyethylene glycol (PEG6000) (5%, 10%, and 15%). Among these isolate Bacillus sp. strain IPR-4 were selected on base of its significant PGP traits such as the survival rate gradient concentrations of PEG6000 (5%, 10%, and 15%) compared to other isolates, and produced high levels of indole-3-acetic acid and organic acids, coupled with exopolysaccharide, siderophores, and phosphate solubilization under drought stress. The Bacillus sp. strain IPR-4 were then validated using 16S rRNA sequencing. To further investigate the growth-promoting ability of the Bacillus sp. IPR-4 and its potential interaction with MET, the bacterial inoculum (40 mL of 4.5 × 10-8 cells/mL) was applied alone or in combination with MET to soybean plants for 5 days. Then, pre-inoculated soybean plants were subjected to drought stress conditions for 9 days by withholding water under greenhouse conditions. Furthermore, when IPR-4/MET was applied to plants subjected to drought stress, a significant increase in plant height (33.3%) and biomass (fresh weight) was observed. Similarly, total chlorophyll content increased by 37.1%, whereas the activity of peroxidase, catalase, ascorbate peroxidase, superoxide dismutase, and glutathione reductase increased by 38.4%, 34.14%, 76.8%, 69.8%, and 31.6%, respectively. Moreover, the hydrogen peroxide content and malondialdehyde decreased by 37.3% and 30% in drought-stressed plants treated with IPR-4 and melatonin. Regarding the 2,2-diphenyl-1-picrylhydrazyl activity and total phenolic content, shows 38% and 49.6% increase, respectively. Likewise, Bacillus-melatonin-treated plants enhanced the uptake of magnesium, calcium, and potassium by 31.2%, 50.7%, and 30.5%, respectively. Under the same conditions, the salicylic acid content increased by 29.1%, whereas a decreasing abscisic acid content (25.5%) was observed. The expression levels of GmNCED3, GmDREB2, and GmbZIP1 were recorded as the lowest. However, Bacillus-melatonin-treated plants recorded the highest expression levels (upregulated) of GmCYP707A1 and GmCYP707A2, GmPAL2.1, and GmERD1 in response to drought stress. In a nutshell, these data confirm that Bacillus sp. IPR-4 and melatonin co-inoculation has the highest plant growth-promoting efficiency under both normal and drought stress conditions. Bacillus sp. IPR-4/melatonin is therefore proposed as an effective plant growth regulator that optimizes nutrient uptake, modulates redox homeostasis, and enhances drought tolerance in soybean plants.

Exogenous SA Applications Alleviate Salinity Stress via Physiological and Biochemical changes in St John's Wort Plants.

The plant St. John's wort contains high levels of melatonin, an important biochemical that has both beneficial and adverse effects on stress. Therefore, a method for increasing melatonin levels in plants without adversely affecting their growth is economically important. In this study, we investigated the regulation of melatonin levels in St. John's wort by exposing samples to salinity stress (150 mM) and salicylic acid (0.25 mM) to augment stress tolerance. The results indicated that salinity stress significantly reduced the plant chlorophyll content and damaged the photosystem, plant growth and development. Additionally, these were reconfirmed with biochemical indicators; the levels of abscisic acid (ABA) and proline were increased and the activities of antioxidants were reduced. However, a significant increase was found in melatonin content under salinity stress through upregulation in the relative expression of tryptophan decarboxylase (TDC), tryptamine 5-hydroxylase (T5H), serotonin N-acetyltransferase (SNAT), and N-acetylserotonin methyltransferase (ASMT). The salicylic acid (SA) treatment considerably improved their photosynthetic activity, the maximum photochemical quantum yield (133%), the potential activity of PSⅡ (294%), and the performance index of electron flux to the final PS I electron acceptors (2.4%). On the other hand, SA application reduced ABA levels (32%); enhanced the activity of antioxidant enzymes, such as superoxide dismutase (SOD) (15.4%) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (120%); and increased polyphenol (6.4%) and flavonoid (75.4%) levels in salinity-stressed St. John's wort plants. Similarly, SA application under NaCl stress significantly modulated the melatonin content in terms of ion balance; the level of melatonin was reduced after SA application on salt-treated seedlings but noticeably higher than on only SA-treated and non-treated seedlings. Moreover, the proline content was reduced considerably and growth parameters, such as plant biomass, shoot length, and chlorophyll content, were enhanced following treatment of salinity-stressed St. John's wort plants with salicylic acid. These findings demonstrate the beneficial impact of salt stress in terms of a cost-effective approach to extract melatonin in larger quantities from St. John's wort. They also suggest the efficiency of salicylic acid in alleviating stress tolerance and promoting growth of St. John's wort plants.

Recent progress on the microbial mitigation of heavy metal stress in soybean: overview and implications.

Plants are adapted to defend themselves through programming, reprogramming, and stress tolerance against numerous environmental stresses, including heavy metal toxicity. Heavy metal stress is a kind of abiotic stress that continuously reduces various crops' productivity, including soybeans. Beneficial microbes play an essential role in improving plant productivity as well as mitigating abiotic stress. The simultaneous effect of abiotic stress from heavy metals on soybeans is rarely explored. Moreover, reducing metal contamination in soybean seeds through a sustainable approach is extremely needed. The present article describes the initiation of heavy metal tolerance mediated by plant inoculation with endophytes and plant growth-promoting rhizobacteria, the identification of plant transduction pathways via sensing annotation, and contemporary changes from molecular to genomics. The results suggest that the inoculation of beneficial microbes plays a significant role in rescuing soybeans under heavy metal stress. They create a dynamic, complex interaction with plants via a cascade called plant-microbial interaction. It enhances stress metal tolerance via the production of phytohormones, gene expression, and secondary metabolites. Overall, microbial inoculation is essential in mediating plant protection responses to heavy metal stress produced by a fluctuating climate.

Gibberellin-Producing Bacteria Isolated from Coastal Soil Enhance Seed Germination of Mallow and Broccoli Plants under Saline Conditions.

Salinity hinders plant growth, posing a substantial challenge to sustainable agricultural yield maintenance. The application of plant growth-promoting rhizobacteria (PGPR) offers an emerging strategy to mitigate the detrimental effects of high salinity levels. This study aimed to isolate and identify gibberellin-producing bacteria and their impact on the seed germination of Malva verticillata (mallow) and Brassica oleracea var. italica (broccoli) under salt stress. In this study, seven bacterial isolates (KW01, KW02, KW03, KW04, KW05, KW06, and KW07) were used to assess their capacity for producing various growth-promoting traits and their tolerance to varying amounts of salinity (100 mM and 150 Mm NaCl). The findings revealed that KW05 and KW07 isolates outperformed other isolates in synthesizing indole-3-acetic acid, siderophores, and exopolysaccharides and in solubilizing phosphates. These isolates also enhanced phosphatase activity and antioxidant levels, including superoxide dismutase and catalase. Both KW05 and KW07 isolate highlight the growth-promoting effects of gibberellin by enhancing of growth parameters of Waito-C rice. Further, gas chromatography-mass spectrometry validation confirmed the ability of KW05 and KW07 to produce gibberellins (GAs), including GA1, GA3, GA4, and GA7. Seed germination metrics were enhanced due to the inoculation of KW05 and KW07. Moreover, inoculation with KW05 increased the fresh weight (FW) (7.82%) and total length (38.61%) of mallow under salt stress. Inoculation with KW07 increased the FW (32.04%) and shoot length of mallow under salt stress. A single inoculation of these two isolates increased broccoli plants' FW and shoot length under salt stress. Gibberellin-producing bacteria helps in plant growth promotion by improving salt tolerance by stimulating root elongation and facilitating enhanced absorption of water and nutrient uptake in salty environments. Based on these findings, they can play a role in boosting agricultural yield in salt-affected areas, which would help to ensure the long-term viability of agriculture in coastal regions.

Monogenetic Forms of Parkinson's Disease - Bridging the Gap Between Genetics and Biomarkers.

The therapy of neurodegenerative diseases such as Parkinson's disease (PD) is still limited to the treatment of symptoms and primarily aimed at compensating for dopaminergic hypofunction. Numerous disease-modifying therapies currently in the pipeline attempt to modify the underlying pathomechanisms. In recent decades, the results of molecular genetics and biomarker research have raised hopes of earlier diagnosis and new neuroprotective therapeutic approaches. As the disease-causing processes in monogenetic forms of PD are better understood than in sporadic PD, these disease subsets are likely to benefit first from disease-modifying therapies. Recent studies have suggested that disease-relevant changes found in genetically linked forms of PD (i.e., PARK-LRRK2, PARK-GBA) can also be reproduced in patients in whom no genetic cause can be found, i.e., those with sporadic PD. It can, therefore, be assumed that as soon as the first causal therapy for genetic forms of PD is approved, more patients with PD will undergo genetic testing and counseling. Regarding future neuroprotective trials in neurodegenerative diseases and objective parameters such as biomarkers with high sensitivity and specificity for the diagnosis and course of the disease are needed. These biomarkers will also serve to monitor treatment success in clinical trials. Promising examples in PD, such as alpha-synuclein species, lysosomal enzymes, markers of amyloid and tau pathology, and neurofilament light chain, are under investigation in blood and CSF. This paper provides an overview of the opportunities and current limitations of monogenetic diagnostic and biomarker research in PD and aims to build a bridge between current knowledge and association with PD genetics and biomarkers.

SARS-CoV-2, COVID-19 and Parkinson's Disease-Many Issues Need to Be Clarified-A Critical Review.

Neurological manifestations during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are of interest, regarding acute treatment and the so-called post-COVID-19 syndrome. Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders worldwide. Hence, the influence of SARS-CoV-2 and the COVID-19 syndrome on PD patients has raised many questions and produced various publications with conflicting results. We reviewed the literature, with respect to symptoms, treatment, and whether the virus itself might cause PD during the SARS-CoV-2 pandemic in SARS-CoV-2-affected symptomatic PD patients (COVID-19 syndrome). In addition, we comment on the consequences in non-symptomatic and non-affected PD patients, as well as post-COVID syndrome and its potential linkage to PD, presenting our own data from our out-patient clinic.

Update on CSF Biomarkers in Parkinson's Disease.

Progress in developing disease-modifying therapies in Parkinson's disease (PD) can only be achieved through reliable objective markers that help to identify subjects at risk. This includes an early and accurate diagnosis as well as continuous monitoring of disease progression and therapy response. Although PD diagnosis still relies mainly on clinical features, encouragingly, advances in biomarker discovery have been made. The cerebrospinal fluid (CSF) is a biofluid of particular interest to study biomarkers since it is closest to the brain structures and therefore could serve as an ideal source to reflect ongoing pathologic processes. According to the key pathophysiological mechanisms, the CSF status of α-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes and markers of neuroinflammation provide promising preliminary results as candidate biomarkers. Untargeted approaches in the field of metabolomics provide insights into novel and interconnected biological pathways. Markers based on genetic forms of PD can contribute to identifying subgroups suitable for gene-targeted treatment strategies that might also be transferable to sporadic PD. Further validation analyses in large PD cohort studies will identify the CSF biomarker or biomarker combinations with the best value for clinical and research purposes.

COVID-19 outcomes in hospitalized Parkinson's disease patients in two pandemic waves in 2020: a nationwide cross-sectional study from Germany.

BACKGROUND: The individualized clinical and public health management of the COVID-19 pandemic have changed over time, including care of people with PD. The objective was to investigate whether in-hospital COVID-19 outcomes and hospital care utilization of people with PD differed between the first two pandemic waves (W) 2020 in Germany. METHODS: We conducted a nationwide cross-sectional study of inpatients with confirmed COVID-19 and PD between March 1 and May 31 (W1), and October 1 and December 31 (W2), 2020 and 2019, using an administrative database. Outcomes were in-hospital mortality, ICU admission rate, change in hospital care utilization, demographical data, PD clinical characteristics, and selected comorbidities. Differences were assessed between waves, PD/non-PD groups, and years. RESULTS: We identified 2600 PD COVID-19 inpatients in W2 who in total showed higher in-hospital mortality rates and lower ICU admission rates, compared to both W1 (n = 775) and W1/W2 non-PD COVID-19 inpatients (n = 144,355). Compared to W1, W2 inpatients were more long-term care-dependent, older, more of female sex, and had less advanced disease. During both waves, PD inpatients were older, more frequently male and long-term care-dependent, and showed more risk comorbidities than non-PD COVID-19 inpatients. Decreases in hospital care utilization were stronger than average for PD inpatients but relatively weaker during W2. Non-COVID-19 PD inpatients showed poorer in-hospital outcomes in 2020 than in 2019 with better outcomes during W2. CONCLUSIONS: In-hospital COVID-19 outcomes and hospital care utilization of PD patients in Germany differed between the two pandemic waves in 2020 with increased in-hospital mortality for PD COVID-19. Overall hospital care utilization for PD was increased during W2. TRIAL REGISTRATION: No trial registration or ethical approval was required because data were publicly available, anonymized, and complied with the German data protection regulations.

Biopriming of Maize Seeds with a Novel Bacterial Strain SH-6 to Enhance Drought Tolerance in South Korea.

Maize is the third most common cereal crop worldwide, after rice and wheat, and plays a vital role in preventing global hunger crises. Approximately 50% of global crop yields are reduced by drought stress. Bacteria as biostimulants for biopriming can improve yield and enhance sustainable food production. Further, seed biopriming stimulates plant defense mechanisms. In this study, we isolated bacteria from the rhizosphere of Artemisia plants from Pohang beach, Daegu, South Korea. Twenty-three isolates were isolated and screened for growth promoting potential. Among them, bacterial isolate SH-6 was selected based on maximum induced tolerance to polyethylene glycol-simulated drought. SH-6 showed ABA concentration = 1.06 ± 0.04 ng/mL, phosphate solubilizing index = 3.7, and sucrose concentration = 0.51 ± 0.13 mg/mL. The novel isolate SH-6 markedly enhanced maize seedling tolerance to oxidative stress owing to the presence of superoxide dismutase, catalase, and ascorbate peroxidase activities in the culture media. Additionally, we quantified and standardized the biopriming effect of SH-6 on maize seeds. SH-6 significantly increased maize seedling drought tolerance by up to 20%, resulting in 80% germination potential. We concluded that the novel bacterium isolate SH-6 (gene accession number (OM757882) is a biostimulant that can improve germination performance under drought stress.

A Review on the Role of Endophytes and Plant Growth Promoting Rhizobacteria in Mitigating Heat Stress in Plants.

Among abiotic stresses, heat stress is described as one of the major limiting factors of crop growth worldwide, as high temperatures elicit a series of physiological, molecular, and biochemical cascade events that ultimately result in reduced crop yield. There is growing interest among researchers in the use of beneficial microorganisms. Intricate and highly complex interactions between plants and microbes result in the alleviation of heat stress. Plant-microbe interactions are mediated by the production of phytohormones, siderophores, gene expression, osmolytes, and volatile compounds in plants. Their interaction improves antioxidant activity and accumulation of compatible osmolytes such as proline, glycine betaine, soluble sugar, and trehalose, and enriches the nutrient status of stressed plants. Therefore, this review aims to discuss the heat response of plants and to understand the mechanisms of microbe-mediated stress alleviation on a physio-molecular basis. This review indicates that microbes have a great potential to enhance the protection of plants from heat stress and enhance plant growth and yield. Owing to the metabolic diversity of microorganisms, they can be useful in mitigating heat stress in crop plants. In this regard, microorganisms do not present new threats to ecological systems. Overall, it is expected that continued research on microbe-mediated heat stress tolerance in plants will enable this technology to be used as an ecofriendly tool for sustainable agronomy.

Melatonin and nitric oxide: Dual players inhibiting hazardous metal toxicity in soybean plants via molecular and antioxidant signaling cascades.

Melatonin (MT), a ubiquitous signaling molecule, is known to improve plant growth. Its regulatory function alongside nitric oxide (NO) is known to induce heavy metal (Cd and Pb) stress tolerance, although the underlying mechanisms remain unknown. Here, we observed that the combined application of MT and NO remarkably enhanced plant biomass by reducing oxidative stress. Both MT and NO minimized metal toxicity by significantly lowering the levels of endogenous abscisic acid and jasmonic acid via downregulating NCED3 and upregulating catabolic genes (CYP707A1 and CYP707A2). MT/NO-induced mitigation of Cd and Pb stress was associated with increased endo-melatonin and variable endo-S-nitrosothiol levels caused by enhanced expression of gmNR and gmGSNOR mRNAs. Remarkably, the combined application of MT/NO reduced soil Cd and Pb mobilization by increasing the uptake of Ca2+ and K+ and increasing the exudation of organic acids into the rhizosphere. These results correlated with the upregulation of MTF-1 and WARKY27 during metal translocation. MT/NO regulates the MAPK and CDPK cascades to promote plant cell survival and Ca2+ signaling, thereby imparting resistance to heavy metal toxicity. In conclusion, MT/NO modulates the stress-resistance machinery to mitigate Cd and Pb toxicity by regulating the activation of antioxidant and molecular transcription factors.