Unidirectional mannitol synthesis of Acinetobacter baumannii MtlD is facilitated by the helix-loop-helix-mediated dimer formation.

Persistence of Acinetobacter baumannii in environments with low water activity is largely attributed to the biosynthesis of compatible solutes. Mannitol is one of the key compatible solutes in A. baumannii, and it is synthesized by a bifunctional mannitol-1-phosphate dehydrogenase/phosphatase (AbMtlD). AbMtlD catalyzes the conversion of fructose-6-phosphate to mannitol in two consecutive steps. Here, we report the crystal structure of dimeric AbMtlD, constituting two protomers each with a dehydrogenase and phosphatase domain. A proper assembly of AbMtlD dimer is facilitated by an intersection comprising a unique helix­loop­helix (HLH) domain. Reduction and dephosphorylation catalysis of fructose-6-phosphate to mannitol is dependent on the transient dimerization of AbMtlD. AbMtlD presents as a monomer under lower ionic strength conditions and was found to be mainly dimeric under high-salt conditions. The AbMtlD catalytic efficiency was markedly increased by cross-linking the protomers at the intersected HLH domain via engineered disulfide bonds. Inactivation of the AbMtlD phosphatase domain results in an intracellular accumulation of mannitol-1-phosphate in A. baumannii, leading to bacterial growth impairment upon salt stress. Taken together, our findings demonstrate that salt-induced dimerization of the bifunctional AbMtlD increases catalytic dehydrogenase and phosphatase efficiency, resulting in unidirectional catalysis of mannitol production.

Function analysis of transcription factor OSR1 regulating osmotic stress resistance in maize.

BACKGROUND: Maize is a major cereal crop world widely, however, the yield of maize is frequently limited by dehydration and even death of plants, which resulted from osmotic stress such as drought and salinity. Dissection of molecular mechanisms controlling stress tolerance will enable plant scientists and breeders to increase crops yield by manipulating key regulatory components. METHODS: The candidate OSR1 gene was identified by map-based cloning. The expression level of OSR1 was verified by qRT-PCR and digital PCR in WT and osr1 mutant. Electrophoretic mobility shift assay, transactivation activity assay, subcellular localization, transcriptome analysis and physiological characters measurements were conducted to analyze the function of OSR1 in osmotic stress resistance in maize. RESULTS: The osr1 mutant was significantly less sensitive to osmotic stress than the WT plants and displayed stronger water-holding capacity, and the OSR1 homologous mutant in Arabidopsis showed a phenotype similar with maize osr1 mutant. Differentially expressed genes (DEGs) were identified between WT and osr1 under osmotic stress by transcriptome analysis, the expression levels of many genes, such as LEA, auxin-related factors, PPR family members, and TPR family members, changed notably, which may primarily involve in osmotic stress or promote root development. CONCLUSIONS: OSR1 may serve as a negative regulatory factor in response to osmotic stress in maize. The present study sheds new light on the molecular mechanisms of osmotic stress in maize.

Enhancing salt stress tolerance in wheat (Triticum aestivum) seedlings: insights from trehalose and mannitol.

Salinity stress, an ever-present challenge in agriculture and environmental sciences, poses a formidable hurdle for plant growth and productivity in saline-prone regions worldwide. Therefore, this study aimed to explore the effectiveness of trehalose and mannitol induce salt resistance in wheat seedlings. Wheat grains of the commercial variety Sakha 94 were divided into three groups : a group that was pre-soaked in 10 mM trehalose, another group was soaked in 10 mM mannitol, and the last was soaked in distilled water for 1 hour, then the pre soaked grains cultivated in sandy soil, each treatment was divided into two groups, one of which was irrigated with 150 mM NaCl and the other was irrigated with tap water. The results showed that phenols content in wheat seedlings increased and flavonoids reduced due to salt stress. Trehalose and mannitol cause slight increase in total phenols content while total flavonoids were elevated highy in salt-stressed seedlings. Furthermore, Trehalose or mannitol reduced salt-induced lipid peroxidation. Salt stress increases antioxidant enzyme activities of guaiacol peroxidase (G-POX), ascorbate peroxidase (APX), and catalase (CAT) in wheat seedlings, while polyphenol oxidase (PPO) unchanged. Trehalose and mannitol treatments caused an increase in APX, and CAT activities, whereas G-POX not altered but PPO activity were decreased under salt stress conditions. Molecular docking confirmed the interaction of Trehalose or mannitol with peroxidase and ascorbic peroxidase enzymes. Phenyl alanine ammonia layase (PAL) activity was increased in salt-stressed seedlings. We can conclude that pre-soaking of wheat grains in 10 mM trehalose or mannitol improves salinity stress tolerance by enhancing antioxidant defense enzyme and/or phenol biosynthesis, with docking identifying interactions with G-POX, CAT, APX, and PPO.

Physiological, transcriptomic and metabolomic insights of three extremophyte woody species living in the multi-stress environment of the Atacama Desert.

MAIN CONCLUSIONS: In contrast to Neltuma species, S. tamarugo exhibited higher stress tolerance, maintaining photosynthetic performance through enhanced gene expression and metabolites. Differentially accumulated metabolites include chlorophyll and carotenoids and accumulation of non-nitrogen osmoprotectants. Plant species have developed different adaptive strategies to live under extreme environmental conditions. Hypothetically, extremophyte species present a unique configuration of physiological functions that prioritize stress-tolerance mechanisms while carefully managing resource allocation for photosynthesis. This could be particularly challenging under a multi-stress environment, where the synthesis of multiple and sequential molecular mechanisms is induced. We explored this hypothesis in three phylogenetically related woody species co-occurring in the Atacama Desert, Strombocarpa tamarugo, Neltuma alba, and Neltuma chilensis, by analyzing their leaf dehydration and freezing tolerance and by characterizing their photosynthetic performance under natural growth conditions. Besides, the transcriptomic profiling, biochemical analyses of leaf pigments, and metabolite analysis by untargeted metabolomics were conducted to study gene expression and metabolomic landscape within this challenging multi-stress environment. S. tamarugo showed a higher photosynthetic capacity and leaf stress tolerance than the other species. In this species, a multifactorial response was observed, which involves high photochemical activity associated with a higher content of chlorophylls and ß-carotene. The oxidative damage of the photosynthetic apparatus is probably attenuated by the synthesis of complex antioxidant molecules in the three species, but S. tamarugo showed the highest antioxidant capacity. Comparative transcriptomic and metabolomic analyses among the species showed the differential expression of genes involved in the biosynthetic pathways of key stress-related metabolites. Moreover, the synthesis of non-nitrogen osmoprotectant molecules, such as ciceritol and mannitol in S. tamarugo, would allow the nitrogen allocation to support its high photosynthetic capacity without compromising leaf dehydration tolerance and freezing stress avoidance.

Elucidation of triacylglycerol catabolism in Yarrowia lipolytica: How cells balance acetyl-CoA and excess reducing equivalents.

Yarrowia lipolytica is an industrial yeast that can convert waste oil to value-added products. However, it is unclear how this yeast metabolizes lipid feedstocks, specifically triacylglycerol (TAG) substrates. This study used 13C-metabolic flux analysis (13C-MFA), genome-scale modeling, and transcriptomics analyses to investigate Y. lipolytica W29 growth with oleic acid, glycerol, and glucose. Transcriptomics data were used to guide 13C-MFA model construction and to validate the 13C-MFA results. The 13C-MFA data were then used to constrain a genome-scale model (GSM), which predicted Y. lipolytica fluxes, cofactor balance, and theoretical yields of terpene products. The three data sources provided new insights into cellular regulation during catabolism of glycerol and fatty acid components of TAG substrates, and how their consumption routes differ from glucose catabolism. We found that (1) over 80% of acetyl-CoA from oleic acid is processed through the glyoxylate shunt, a pathway that generates less CO2 compared to the TCA cycle, (2) the carnitine shuttle is a key regulator of the cytosolic acetyl-CoA pool in oleic acid and glycerol cultures, (3) the oxidative pentose phosphate pathway and mannitol cycle are key routes for NADPH generation, (4) the mannitol cycle and alternative oxidase activity help balance excess NADH generated from ß-oxidation of oleic acid, and (5) asymmetrical gene expressions and GSM simulations of enzyme usage suggest an increased metabolic burden for oleic acid catabolism.

Systems metabolic engineering of the primary and secondary metabolism of Streptomyces albidoflavus enhances production of the reverse antibiotic nybomycin against multi-resistant Staphylococcus aureus.

Nybomycin is an antibiotic compound with proven activity against multi-resistant Staphylococcus aureus, making it an interesting candidate for combating these globally threatening pathogens. For exploring its potential, sufficient amounts of nybomycin and its derivatives must be synthetized to fully study its effectiveness, safety profile, and clinical applications. As native isolates only accumulate low amounts of the compound, superior producers are needed. The heterologous cell factory S. albidoflavus 4N24, previously derived from the cluster-free chassis S. albidoflavus Del14, produced 860 µg L-1 of nybomycin, mainly in the stationary phase. A first round of strain development modulated expression of genes involved in supply of nybomycin precursors under control of the common Perm* promoter in 4N24, but without any effect. Subsequent studies with mCherry reporter strains revealed that Perm* failed to drive expression during the product synthesis phase but that use of two synthetic promoters (PkasOP* and P41) enabled strong constitutive expression during the entire process. Using PkasOP*, several rounds of metabolic engineering successively streamlined expression of genes involved in the pentose phosphate pathway, the shikimic acid pathway, supply of CoA esters, and nybomycin biosynthesis and export, which more than doubled the nybomycin titer to 1.7 mg L-1 in the sixth-generation strain NYB-6B. In addition, we identified the minimal set of nyb genes needed to synthetize the molecule using single-gene-deletion strains. Subsequently, deletion of the regulator nybW enabled nybomycin production to begin during the growth phase, further boosting the titer and productivity. Based on RNA sequencing along the created strain genealogy, we discovered that the nyb gene cluster was unfavorably downregulated in all advanced producers. This inspired removal of a part and the entire set of the four regulatory genes at the 3'-end nyb of the cluster. The corresponding mutants NYB-8 and NYB-9 exhibited marked further improvement in production, and the deregulated cluster was combined with all beneficial targets from primary metabolism. The best strain, S. albidoflavus NYB-11, accumulated up to 12 mg L-1 nybomycin, fifteenfold more than the basic strain. The absence of native gene clusters in the host and use of a lean minimal medium contributed to a selective production process, providing an important next step toward further development of nybomycin.

Investigation of the Solid-State Interactions in Lyophilized Human G-CSF Using Hydrogen-Deuterium Exchange Mass Spectrometry.

Hydrogen/deuterium exchange mass spectrometry (HDX-MS) previously elucidated the interactions between excipients and proteins for liquid granulocyte colony stimulating factor (G-CSF) formulations, confirming predictions made using computational structure docking. More recently, solid-state HDX mass spectrometry (ssHDX-MS) was developed for proteins in the lyophilized state. Deuterium uptake in ssHDX-MS has been shown for various proteins, including monoclonal antibodies, to be highly correlated with storage stability, as measured by protein aggregation and chemical degradation. As G-CSF is known to lose activity through aggregation upon lyophilization, we applied the ssHDX-MS method with peptide mapping to four different lyophilized formulations of G-CSF to compare the impact of three excipients on local structure and exchange dynamics. HDX at 22 °C was confirmed to correlate well with the monomer content remaining after lyophilization and storage at -20 °C, with sucrose providing the greatest protection, and then phenylalanine, mannitol, and no excipient leading to progressively less protection. Storage at 45 °C led to little difference in final monomer content among the formulations, and so there was no discernible relationship with total deuterium uptake on ssHDX. Incubation at 45 °C may have led to a structural conformation and/or aggregation mechanism no longer probed by HDX at 22 °C. Such a conformational change was observed previously at 37 °C for liquid-formulated G-CSF using NMR. Peptide mapping revealed that tolerance to lyophilization and -20 °C storage was linked to increased stability in the small helix, loop AB, helix C, and loop CD. LC-MS HDX and NMR had previously linked loop AB and loop CD to the formation of a native-like state (N*) prior to aggregation in liquid formulations, suggesting a similar structural basis for G-CSF aggregation in the liquid and solid states.

Comparative Assessment of Mitochondria Isolation Buffers for Optimizing Tissue-Specific Yields in Buffalo.

INTRODUCTION: Mitochondrial studies are crucial for assessing livestock health and performance. While extensive research has been done on cattle and pigs, the influence of mitochondria in Indian buffalo remains unexplored. Therefore, in order to understand functions of mitochondria, their energy-related processes, or any additional mitochondrial traits in buffaloes, it is imperative to isolate high-yield mitochondria with purity and functionality. Mitochondria are extracted by few conventional buffers. These buffers were previously characterized for their effectiveness in isolating mitochondria from rodent and human tissues. Therefore, the present study is to assess the performance of mitochondria isolation buffers specifically in buffalo tissues. METHODS: The study involved isolation of mitochondria from four different tissues, i.e., liver, brain, heart and muscles of slaughtered buffalo (n = 3), using: (i) Tris-Mannitol buffer (ii) Tris-Sucrose buffer, and (iii) MOPS-Sucrose buffer. Buffer efficiency in preserving high fidelity during mitochondria isolation was assessed by comparison with Cayman's MitoCheck® Mitochondrial Isolation Kit (control). Further mitochondrial purity and functionality was assessed through comparative estimation of protein concentration and marker enzyme assays, respectively. RESULTS: Our results revealed insights into the suitability of specific buffer for functional mitochondria isolation from specific type of buffalo tissue. Notably for obtaining high quality functional mitochondria from buffalo, MOPS-Sucrose buffer appeared optimal for soft tissues (liver and brain), while Tris-Mannitol buffer was efficient for hard tissues (muscles and heart). CONCLUSIONS: Thus, our research highlights the influence of buffer composition and tissue-specific variations in buffer effectiveness on mitochondrial activity in different tissues, leading to improved mitochondrial isolation in buffalo.

How Metarhizium robertsii's mycelial consciousness gets its conidia Zen-ready for stress.

This memoir takes a whimsical ride through my professional adventures, spotlighting my fungal stress research on the insect-pathogenic fungus Metarhizium robertsii, which transformed many of my wildest dreams into reality. Imagine the magic of fungi meeting science and me, a happy researcher, arriving at Utah State University ready to dive deep into studies with the legendary insect pathologist, my advisor Donald W. Roberts, and my co-advisor Anne J. Anderson. From my very first "Aha!" moment in the lab, I plunged into a vortex of discovery, turning out research like a mycelium on a mission. Who knew 18 h/day, seven days a week, could be so exhilarating? I was fueled by an insatiable curiosity, boundless creativity, and a perhaps slightly alarming level of motivation. Years later, I managed to bring my grandest vision to life: the International Symposium on Fungal Stress-ISFUS. This groundbreaking event has attracted 162 esteemed speakers from 29 countries to Brazil, proving that fungi can be both fun and globally fascinating. ISFUS is celebrating its fifth edition in 2024, a decade after its 2014 debut.

Sugar alcohol degradation in Archaea: uptake and degradation of mannitol and sorbitol in Haloarcula hispanica.

The halophilic archaeon Haloarcula hispanica utilizes the sugar alcohols mannitol and sorbitol as carbon and energy sources. Genes, enzymes, and transcriptional regulators involved in uptake and degradation of these sugar alcohols were identified by growth experiments with deletion mutants and enzyme characterization. It is shown that both mannitol and sorbitol are taken up via a single ABC transporter of the CUT1 transporter family. Then, mannitol and sorbitol are oxidized to fructose by two distinct dehydrogenases. Fructose is further phosphorylated to fructose-1-phosphate by a haloarchaeal ketohexokinase, providing the first evidence for a physiological function of ketohexokinase in prokaryotes. Finally, fructose-1-phosphate is phosphorylated via fructose-1-phosphate kinase to fructose-1,6-bisphosphate, which is cleaved to triosephosphates by a Class I fructose-1,6-bisphosphate aldolase. Two distinct transcriptional regulators, acting as activators, have been identified: an IclR-like regulator involved in activating genes for sugar alcohol uptake and oxidation to fructose, and a GfcR-like regulator that likely activates genes involved in the degradation of fructose to pyruvate. This is the first comprehensive analysis of a sugar alcohol degradation pathway in Archaea.

Metabolic engineering of Corynebacterium crenatum for enhanced L-tyrosine production from mannitol and glucose.

BACKGROUND: L-Tyrosine (L-Tyr) is a significant aromatic amino acid that is experiencing an increasing demand in the market due to its distinctive characteristics. Traditional production methods exhibit various limitations, prompting researchers to place greater emphasis on microbial synthesis as an alternative approach. RESULTS: Here, we developed a metabolic engineering-based method for efficient production of L-Tyr from Corynebacterium crenatum, including the elimination of competing pathways, the overexpression of aroB, aroD, and aroE, and the introduction of the mutated E. coli tyrAfbr gene for elevating L-Tyr generation. Moreover, the mtlR gene was knocked out, and the mtlD and pfkB genes were overexpressed, allowing C. crenatum to produce L-Tyr from mannitol. The L-Tyr production achieved 6.42 g/L at a glucose-to-mannitol ratio of 3:1 in a shake flask, which was 16.9% higher than that of glucose alone. Notably, the L-Tyr production of the fed-batch fermentation was elevated to 34.6 g/L, exhibiting the highest titers among those of C. glutamicum previously reported. CONCLUSION: The importance of this research is underscored by its pioneering application of mannitol as a carbon source for the biosynthesis of L-Tyr, as well as its examination of the influence of mannitol-associated genes in microbial metabolism. A promising platform is provided for the production of target compounds that does not compete with human food source.

Risk factors for acute kidney injury associated with intravenous vancomycin in neurosurgical inpatients: a retrospective study.

PURPOSE: Vancomycin (VAN) is widely used in neurosurgical patients for intracranial infections. We aimed to assess the incidence and risk factors for VAN-associated acute kidney injury (VA-AKI) in this population. METHODS: A case-control study of patients who treated with vancomycin in neurosurgery from January 2020 to December 2022 was conducted. Demographics and potential risk factors were collected. Multivariate logistic regression analyses were performed to identify risk factors for VA-AKI. AKI was defined according to the Kidney Disease Improving Global Outcomes Guidelines (KDIGO). RESULTS: A total of 345 patients participated with a VA-AKI incidence of 17.1% (59 cases). Among them, 15 patients had renal impairment (Stage 2 or higher), and 2 required dialysis. With univariate analysis and binary logistic regression analysis, we found that the use of mannitol (OR: 4.164; 95% CI: 1.606-10.792; P = 0.003), loop diuretics (OR: 3.371; 95% CI: 1.633-6.958; P = 0.001), three or more antimicrobial applications (OR: 3.623; 95% CI: 1.600-8.206; P = 0.002), diastolic blood pressure 80-89 mm Hg (OR: 5.532; 95% CI: 1.677-18.250; P = 0.005) and diastolic blood pressure ≥ 90 mm Hg (OR: 6.845; 95% CI: 1.518-30.866; P = 0.012) were independent risk factors for VA-AKI. In addition, according to the Youden Index, the trough concentration of vancomycin should not exceed 15.845 mg/L. CONCLUSION: The incidence of VA-AKI in neurosurgical patients was 17.1%. The concomitant use of mannitol and loop diuretics, along with higher diastolic blood pressure and the combined use of more than three antimicrobial agents, were associated with an increased risk of neurosurgical VA-AKI.

Photoperiod and temperature interactions drive the latitudinal distribution of Laminaria hyperborea (Laminariales, Phaeophyceae) under climate change.

Due to global rises in temperature, recent studies predict marine species shifting toward higher latitudes. We investigated the impact of interacting abiotic drivers on the distribution potential of the temperate kelp Laminaria hyperborea. The ecosystem engineering species is widespread along European coasts but has not yet been observed in the High Arctic, although it can survive several months of low temperatures and darkness. To investigate its ability to extend northward in future, we conducted a long-term multifactorial experiment with sporophytes from Porsangerfjorden, Norway-close to the species' documented northernmost distribution margin. The samples were exposed to three different photoperiods (PolarDay, LongDay, and PolarNight) at 0°C, 5°C, and 10°C for 3 months. Optimum quantum yield of photosynthesis (Fv/Fm), dry weight, pigments, phlorotannins, and storage carbohydrates were monitored. Both physiological and biochemical parameters revealed that L. hyperborea was strongly influenced by the different photoperiods and their interaction with temperature, while temperature alone exerted only minor effects. The Fv/Fm data were integrated into a species distribution model to project a possible northward expansion of L. hyperborea. The combination of extended day lengths and low temperatures appeared to be the limiting reason for northward spread of L. hyperborea until recently. However, with water temperatures reaching 10°C in summer, this kelp will be able to thrive also in the High Arctic. Moreover, no evidence of stress to Arctic winter warming was observed. Consequently, L. hyperborea has a high potential for spreading northward with further warming which may significantly affect the structure and function of Arctic ecosystems.

Impact of Mannitol Bladder Distension in the Intraoperative Detection of Ureteral Kinking During Pelvic Floor Surgery.

INTRODUCTION AND HYPOTHESIS: Ureteral injuries are the most feared complications of gynecological surgery and therefore intraoperative recognition is of the utmost importance. Intraoperative cystoscopy represents the diagnostics of choice to investigate ureteral patency thanks to the direct visualization of ureteral flows after administration of infusion mediums. In this study, we aimed to compare the diagnostic performance of saline versus mannitol intraoperative cystoscopy in terms of false negatives in a large cohort of patients. METHODS: We retrospectively analyzed data of patients who underwent vaginal hysterectomy and high uterosacral ligament suspension for POP. Patients were divided in two groups based on the use of saline or mannitol medium for intraoperative cystoscopy. Postoperative daily control of serum creatinine was performed until discharge, as well as urinary tract imaging, in symptomatic patients. RESULTS: A total of 925 patients underwent vaginal hysterectomy followed by high USL suspension for POP. Saline and mannitol medium were used in 545 patients and 380 patients respectively. Postoperative ureteral injuries were identified in 12 patients, specifically in 2% of the saline group and in 0.3% of the mannitol group. CONCLUSIONS: The use of mannitol instead of saline as a bladder distension medium was able to significantly reduce the occurrence of postoperative ureteral sequelae.

Preoperative intravenous mannitol administration and its rationale before cataract surgery.

BACKGROUND: The purpose of this study is to assess the variations in anterior chamber depth (ACD), axial length (AXL), and intraocular pressure (IOP) in both phakic and pseudophakic eyes undergoing preoperative intravenous mannitol infusion. The study was conducted at the Ophthalmology Department of IRCSS Humanitas in Milan, Italy. This is a prospective and non-randomized study. METHODS: 40 patients with phakic eyes and 40 patients with pseudophakic eyes scheduled for cataract surgery in their fellow eye were included. Prior to the surgery, comprehensive ophthalmic examinations were conducted, including IOP measurement, and bilateral biometry performed with Anterion® (Heidelberg Engineering GmbH, 69,115, Heidelberg, Germany). All patients received intravenous infusion of mannitol before the surgery. One hour after cataract extraction, the patients underwent the same set of examinations. We analyzed the changes AXL, ACD and IOP in the eye opposite to the one that underwent surgery. RESULTS: The comparison between preoperative and postoperative parameters showed no differences in AXL (p = 0.34 and p = 0.53) and in ACD (p = 0.38 and p = 0.31) in the phakic and in the pseudophakic group, respectively. Instead, a statistically significant difference was found between the mean preoperative and postoperative IOP (p = 0.02) for the phakic group and (p = 0.03) for the pseudophakic group. CONCLUSIONS: The administration of mannitol does not lead to any changes in the ACD and AXL, regardless of whether the eyes are phakic or pseudophakic. However, there is a statistically significant reduction in IOP. Nonetheless, it is important to consider the various side effects associated with mannitol infusion.

Enhancing chlamydospore production in Duddingtonia flagrans on solid substrate: The impact of mannitol and varied cultivation conditions.

Duddingtonia flagrans is a nematophagous fungus which has shown promising results as a non-chemical parasitic control tool. The fungus disrupts the parasite's life cycle by trapping larvae in the environment through the networks generated from chlamydospores, thus preventing the reinfection of animals. One barrier to the development of a commercial product using this tool is the need to increase chlamydospore production in the laboratory for its administration to livestock. The purpose of this study was to evaluate the addition of mannitol to an enriched culture medium and the effect of adverse cultivation conditions on chlamydospore production. D. flagrans was cultivated on Petri dishes with corn agar for 4 weeks at 27 °C and 70% relative humidity (RH). Four groups were then formed, all with Sabouraud agar as a base, to which different growth inducers were added: GSA (glucose Sabouraud agar), GSA-MI (glucose Sabouraud agar + meso inositol), GSA-E (enriched glucose Sabouraud agar), and AE-M (enriched agar + mannitol). After 4 weeks, chlamydospores were recovered by washing the surface of each plate with distilled water and then quantified. The medium that yielded the highest amount of chlamydospores was subjected to different cultivation conditions: NC (normal conditions): 70% RH and 27 °C, AC (adverse conditions) 1: 20% RH and 40 °C, CA2: 60% RH and 27 °C, and CA3: 55% RH and 24 °C. It was determined that mannitol increases chlamydospore production (65x106 chlamydospores/plate), and when reducing humidity by 10% under cultivation conditions it resulted in an approximately 10% increase in chlamydospore production compared to the control group. These results suggest that the addition of polyols, as well as its cultivation under certain environmental conditions, can improve chlamydospore production on a laboratory scale.

Efficacy of postoperative analgesia with intravenous paracetamol and mannitol injection, combined with thoracic paravertebral nerve block in post video-assisted thoracoscopic surgery pain: a prospective, randomized, double-blind controlled trial.

BACKGROUND: Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain. METHODS: This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events. RESULTS: In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method. CONCLUSIONS: Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS. TRIAL REGISTRATION: The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).

Ascophyllum nodosum (Linnaeus) Le Jolis from Arctic: Its Biochemical Composition, Antiradical Potential, and Human Health Risk.

Ascophyllum nodosum is a brown seaweed common in Arctic tidal waters. We have collected A. nodosum samples from the Barents Sea (BS), Irminger Sea (IS), and Norwegian Sea (NS) in different reproductive stages and have evaluated their biochemical composition, radical scavenging potential, and health risks. The total content of dominating carbohydrates (fucoidan, mannitol, alginate, and laminaran) ranged from 347 mg/g DW in NS to 528 mg/g DW in BS. The proportion of two main structural monosaccharides of fucoidan (fucose and xylose) differed significantly between the seas and reproductive phase, reaching a maximum at the fertile phase in the BS sample. Polyphenols and flavonoids totals were highest in NS A. nodosum samples and increased on average in the following order: BS < IS < NS. A positive correlation of free radical scavenging activity for seaweed extracts with polyphenols content was observed. The concentration of elements in A. nodosum from the Arctic seas region was in the following order: Ca > Mg > Sr > Fe > Al > Zn > As total > Rb > Mn > Ba > Cu > Co. Seaweeds from BS had the lowest metal pollution index (MPI) of 38.4. A. nodosum from IS had the highest MPI of 83. According to the calculated target hazard quotient (THQ) and hazard index (HI) values, Arctic A. nodosum samples pose no carcinogenic risk to adult and child health and are safe for regular consumption. Our results suggest that the Arctic A. nodosum has a remarkable potential for food and pharmaceutical industries as an underestimated source of polysaccharides, polyphenols, and flavonoids.

Blood-brain barrier opening by intracarotid artery hyperosmolar mannitol induces sterile inflammatory and innate immune responses.

Intracarotid arterial hyperosmolar mannitol (ICAHM) blood-brain barrier disruption (BBBD) is effective and safe for delivery of therapeutics for central nervous system malignancies. ICAHM osmotically alters endothelial cells and tight junction integrity to achieve BBBD. However, occurrence of neuroinflammation following hemispheric BBBD by ICAHM remains unknown. Temporal proteomic changes in rat brains following ICAHM included increased damage-associated molecular patterns, cytokines, chemokines, trophic factors, and cell adhesion molecules, indicative of a sterile inflammatory response (SIR). Proteomic changes occurred within 5 min of ICAHM infusion and returned to baseline by 96 h. Transcriptomic analyses following ICAHM BBBD further supported an SIR. Immunohistochemistry revealed activated astrocytes, microglia, and macrophages. Moreover, proinflammatory proteins were elevated in serum, and proteomic and histological findings from the contralateral hemisphere demonstrated a less pronounced SIR, suggesting neuroinflammation beyond regions of ICAHM infusion. Collectively, these results demonstrate ICAHM induces a transient SIR that could potentially be harnessed for neuroimmunomodulation.

Effectiveness of hypertonic saline infusion in management of traumatic brain injury: an updated systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to find out the efficacy of using Hypertonic saline solution (HSS) over mannitol in the management of TBI by comparing their performance in improving different outcomes. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing the impact of HSS vs. mannitol on ICP in patients who suffered TBI. Outcomes of interest were mortality, neurologic functional outcomes, risk ratio (RR) of successful ICP treatment, reduction in ICP after 30-60 and 90-120 min, improvement in cerebral perfusion pressure (CPP) at 30-60 and 90-120 min, and also treatment failure. Evaluations were reported as RR or mean difference (MD) with 95% confidence intervals (CIs) using weighted random-effects models. RESULTS: The analysis included 624 patients from 15 RCTs. HSS infusion had a significant impact on the improvement of CPP at 30-60 min [MD = 5.54, 95% CI (3.04, 8.03),p < 0.001] compared to mannitol. However, results yielded no significant difference between HSS and mannitol in terms of mortality, neurologic functional outcomes, successful ICP treatment, reduction in ICP after 30-60 min and 90-120 min, improvement in CPP at 90-120 min, and treatment failure. CONCLUSION: HSS and mannitol are both effective treatments for elevated ICP due to TBI. However, further research is required to derive a better comparison.