Melatonin-Mediated Molecular Responses in Plants: Enhancing Stress Tolerance and Mitigating Environmental Challenges in Cereal Crop Production.

Cereal crops are crucial for global food security; however, they are susceptible to various environmental stresses that significantly hamper their productivity. In response, melatonin has emerged as a promising regulator, offering potential benefits for stress tolerance and crop growth. This review explores the effects of melatonin on maize, sorghum, millet, rice, barley, and wheat, aiming to enhance their resilience to stress. The application of melatonin has shown promising outcomes, improving water use efficiency and reducing transpiration rates in millet under drought stress conditions. Furthermore, it enhances the salinity and heavy metal tolerance of millet by regulating the activity of stress-responsive genes. Similarly, melatonin application in sorghum enhances its resistance to high temperatures, low humidity, and nutrient deficiency, potentially involving the modulation of antioxidant defense and aspects related to photosynthetic genes. Melatonin also exerts protective effects against drought, salinity, heavy metal, extreme temperatures, and waterlogging stresses in maize, wheat, rice, and barley crops by decreasing reactive oxygen species (ROS) production through regulating the antioxidant defense system. The molecular reactions of melatonin upregulated photosynthesis, antioxidant defense mechanisms, the metabolic pathway, and genes and downregulated stress susceptibility genes. In conclusion, melatonin serves as a versatile tool in cereal crops, bolstering stress resistance and promoting sustainable development. Further investigations are warranted to elucidate the underlying molecular mechanisms and refine application techniques to fully harness the potential role of melatonin in cereal crop production systems.

Species-specific responses of C and N allocation to N addition: evidence from dual 13C and 15N labeling in three tree species.

Soil nitrogen (N) availability affects plant carbon (C) utilization. However, it is unclear how various tree functional types respond to N addition in terms of C assimilation, allocation, and storage. Here, a microcosm experiment with dual 13C and 15N labeling was conducted to study the effects of N addition (i.e., control, 0 g N kg-1; moderate N addition, 1.68 g N kg-1; and high N addition, 3.36 g N kg-1 soil) on morphological traits, on changes in nonstructural carbohydrates (NSC) in different organs, as well as on C and N uptake and allocation in three European temperate forest tree species (i.e., Acer pseudoplatanus, Picea abies and Abies alba). Our results demonstrated that root N uptake rates of the three tree species increased by N addition. In A. pseudoplatanus, N uptake by roots, N allocation to aboveground organs, and aboveground biomass allocation significantly improved by moderate and high N addition. In A. alba, only the high N addition treatment considerably raised aboveground N and C allocation. In contrast, biomass as well as C and N allocation between above and belowground tissues were not altered by N addition in P. abies. Meanwhile, NSC content as well as C and N coupling (represented by the ratio of relative 13C and 15N allocation rates in organs) were affected by N addition in A. pseudoplantanus and P. abies but not in A. alba. Overall, A. pseudoplatanus displayed the highest sensitivity to N addition and the highest N requirement among the three species, while P. abies had a lower N demand than A. alba. Our findings highlight that the responses of C and N allocation to soil N availability are species-specific and vary with the amount of N addition.

Elucidating the modulatory effect of melatonin on enzyme activity and oxidative stress in wheat: a global meta-analysis.

In our comprehensive meta-analysis, we initially collected 177 publications focusing on the impact of melatonin on wheat. After meticulous screening, 40 published studies were selected, encompassing 558 observations for antioxidant enzymes, 312 for reactive oxygen species (ROS), and 92 for soluble biomolecules (soluble sugar and protein). This analysis revealed significant heterogeneity across studies (I2 > 99% for enzymes, ROS, and soluble biomolecules) and notable publication bias, indicating the complexity and variability in the research field. Melatonin application generally increased antioxidant enzyme activities [superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX)] in wheat, particularly under stress conditions, such as high temperature and heavy-metal exposure. Compared to control, melatonin application increased SOD, POD, CAT, and APX activities by 29.5, 16.96, 35.98, and 171.64%, respectively. Moreover, oxidative stress markers like hydrogen peroxide (H2O2), superoxide anion (O2), and malondialdehyde (MDA) decreased with melatonin by 23.73, 13.64, and 21.91%, respectively, suggesting a reduction in oxidative stress. The analysis also highlighted melatonin's role in improving carbohydrate metabolism and antioxidant defenses. Melatonin showed an overall increase of 12.77% in soluble sugar content, and 22.76% in glutathione peroxidase (GPX) activity compared to the control. However, the effects varied across different wheat varieties, environmental conditions, and application methods. Our study also uncovered complex relationships between antioxidant enzyme activities and H2O2 levels, indicating a nuanced regulatory role of melatonin in oxidative stress responses. Our meta-analysis demonstrates the significant role of melatonin in increasing wheat resilience to abiotic stressors, potentially through its regulatory impact on antioxidant defense systems and stress response.

Catabolism of phenolics from grape peel and its effects on gut microbiota during in vitro colonic fermentation.

BACKGROUND: Grape peels, the main by-products of wine processing, are rich in bioactive ingredients of phenolics, including proanthocyanidins, flavonoids and anthocyanins. Phenolics have the function of regulating intestinal microbiota and promoting intestinal health. From the perspective of the dietary nutrition of grape peel phenolics (GPP), the present study aimed to investigate the influence of GPP on the composition and metabolism of human gut microbiota during in vitro fermentation. RESULTS: The results indicated that GPP could decrease pH and promote the production of short-chain fatty acids. ACE and Chao1 indices in GPP group were lower than that of the Blank group. GPP enhanced the levels of Lachnospiraceae UCG-004, Bacteroidetes and Roseburia, but reduced the Firmicutes/Bacteroidetes ratio. Kyoto Encyclopedia of Proteins and Genome enrichment pathways related to phenolic acid metabolism mainly included flavonoid, anthocyanin, flavone and flavonol biosynthesis. Gut microbiota could accelerate the release and breakdown of phenolic compounds, resulting in a decrease in the content of hesperetin-7-O-glucoside, delphinidin-3-O-glucoside and cyanidin-3-rutinoside etc. In vitro antibacterial test found that GPP increased the diameters of the inhibition zones of Escherichia coli and Staphylococcus aureus in a dose-dependent manner. CONCLUSION: The results of the present study revealed that GPP might be a potential prebiotic-like to prevent diseases by improving gut health. The findings could provide a theoretical basis for the potential to exploit GPP as dietary nutrition to maintain intestinal function. © 2024 Society of Chemical Industry.

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Mixing native broadleaved tree species is a widely used method for renovating Pinus massoniana plantations. Soil microbial necromass carbon and organic carbon fractions are important parameters for evaluating the impacts of tree species mixing and soil organic carbon (SOC) stability. However, their responses to the mixing and renovation of P. massoniana plantation has not been understood yet. Here, we selected a pure P. massoniana plantation (PP) and a mixed P. massoniana and Castanopsis hystrix plantation, with ages of 16 (MP16) and 38 years (MP38), respectively, as the research objects. We quantified soil physical and chemical properties, microbial necromass carbon content, and organic carbon components at different soil layers to reveal whether and how the introduction of C. hystrix into P. massoniana plantation affected soil microbial necromass carbon and organic carbon components. The results showed that the mixed P. massoniana and C. hystrix plantation significantly reduced fungal necromass carbon content and the ratio of fungal/bacterial necromass carbon in the 0-20 cm and 20-40 cm soil layers. There were no significant differences in microbial necromass carbon contents, bacterial necromass carbon contents, and their contributions to SOC among the different plantations. The contribution of fungal necromass carbon to SOC was higher than that of bacterial necromass carbon in all plantation types. The contribution of soil mineral-associated organic carbon (MAOC) to SOC was higher than that of occluded particulate organic carbon (oPOC) and light-free particulate organic carbon (fPOC) for all plantation types. Mixing the precious broadleaved tree species (i.e., C. hystrix) with coniferous species (P. massoniana) significantly increased MAOC content and the contribution of MAOC, oPOC, and fPOC to SOC in the 0-20 cm and 20-40 cm soil layers. The MAOC of MP38 was significantly higher than that of PP in all soil layers and the MAOC of MP38 stands were significantly higher than MP16 stands in the 20-40 cm, 40-60 cm, and 60-100 cm soil layers, indicating that hybridization enhanced SOC stability and that the SOC of MP38 stands were more stable than MP16 stands. SOC and total nitrogen contents were the main environmental factors driving the changes in soil microbial necromass carbon, while soil total nitrogen and organically complexed Fe-Al oxides were the primary factors affecting organic carbon fraction. Therefore, SOC stability can be enhanced by introducing native broadleaved species, such as C. hystrix, during the management of the P. massoniana plantation.

A small molecule MST1/2 inhibitor accelerates murine liver regeneration with improved survival in models of steatohepatitis.

Dysfunctional liver regeneration following surgical resection remains a major cause of postoperative mortality and has no therapeutic options. Without targeted therapies, the current treatment paradigm relies on supportive therapy until homeostasis can be achieved. Pharmacologic acceleration of regeneration represents an alternative therapeutic avenue. Therefore, we aimed to generate a small molecule inhibitor that could accelerate liver regeneration with an emphasis on diseased models, which represent a significant portion of patients who require surgical resection and are often not studied. Utilizing a clinically approved small molecule inhibitor as a parent compound, standard medicinal chemistry approaches were utilized to generate a small molecule inhibitor targeting serine/threonine kinase 4/3 (MST1/2) with reduced off-target effects. This compound, mCLC846, was then applied to preclinical models of murine partial hepatectomy, which included models of diet-induced metabolic dysfunction-associated steatohepatitis (MASH). mCLC846 demonstrated on target inhibition of MST1/2 and reduced epidermal growth factor receptor inhibition. The inhibitory effects resulted in restored pancreatic beta-cell function and survival under diabetogenic conditions. Liver-specific cell-line exposure resulted in Yes-associated protein activation. Oral delivery of mCLC846 perioperatively resulted in accelerated murine liver regeneration and improved survival in diet-induced MASH models. Bulk transcriptional analysis of regenerating liver remnants suggested that mCLC846 enhanced the normal regenerative pathways and induced them following liver resection. Overall, pharmacological acceleration of liver regeneration with mCLC846 was feasible, had an acceptable therapeutic index, and provided a survival benefit in models of diet-induced MASH.

Effects of dietary D-lactate levels on rumen fermentation, microflora and metabolomics of beef cattle.

Introduction: Excessive intake of lactate caused by improper use of silage in animal husbandry has adverse effects on rumen fermentation, such as rumen acidosis. The speed of absorption and metabolism of D-lactate in rumen epithelial cells was slower than that of L-lactate, making D-lactate more prone to accumulate and induce rumen acidosis. Therefore, this study was conducted to explore the effects of dietary D-lactate levels on rumen fermentation of beef cattle and its mechanism in an in vitro system. Methods: This experiment was adopted in single-factor random trial design, with 5 days for adaptation and 3 days for sample collection. Three treatments (n = 8/treatment) were used: (1) D-LA (0.3%), basal fermentation substrate with 0.3% (dry matter, DM basis) D-lactate; (2) D-LA (0.75%), basal fermentation substrate with 0.75% (DM basis) D-lactate; and (3) D-LA (1.2%), basal fermentation substrate with 1.2% (DM basis) D-lactate. Results: With the dietary D-lactate levels increased, the daily production of total gas, hydrogen and methane, as well as the ruminal concentrations of acetate, propionate, butyrate, isobutyrate, valerate, isovalerate, total volatile fatty acid and D-lactate increased (p < 0.05), but the ruminal pH and acetate/propionate ratios decreased (p < 0.05). Principle coordinate analysis based on Bray-Curtis distance showed that increasing dietary D-lactate levels could significantly affect the structure of rumen bacterial community (p < 0.05), but had no significant effect on the structure of rumen eukaryotic community (p > 0.05). NK4A214_group, Ruminococcus_gauvreauii_group, Eubacterium_oxidoreducens_group, Escherichia-Shigella, Marvinbryantia and Entodinium were enriched in D-LA (1.2%) group (p < 0.05), as well as WCHB1-41, vadinBE97, Clostridium_sensu_stricto_1, Anaeroplasma and Ruminococcus were enriched in D-LA (0.3%) group (p < 0.05). Changes in the composition of ruminal microorganisms affected rumen metabolism, mainly focus on the biosynthesis of glycosaminoglycans (p < 0.05). Discussion: Overall, feeding whole-plant corn silage with high D-lactate content could not induce rumen acidosis, and the metabolization of dietary D-lactate into volatile fatty acids increased the energy supply of beef cattle. However, it also increased the ruminal CH4 emissions and the relative abundance of opportunistic pathogen Escherichia-Shigella in beef cattle. The relative abundance of Verrucomicrobiota and Escherichia-Shigella may be influenced by glycosaminoglycans, reflecting the interaction between rumen microorganisms and metabolites.

Increased precipitation alters the effects of nitrogen deposition on soil bacterial and fungal communities in a temperate forest.

Anthropogenic nitrogen (N) deposition and increased precipitation are known to alter soil microbial communities. However, the combined effects of elevated N deposition and increased precipitation on soil microbial community dynamics and co-occurrence networks in temperate forests remain elusive. In this study, we conducted a field manipulation experiment by applying N solution and water to the forest canopy to simulate natural N deposition and increased precipitation in a temperate forest. We collected samples in the litter layer, organic soil layer, and mineral soil layer in 2018-2019 after 6-7 years of N and water treatments, and explored how elevated N deposition and increased precipitation regulate soil microbial diversity, community composition, and co-occurrence networks in different soil layers and at different sampling times. We found that the effects of N deposition and increased precipitation on soil microbial communities varied with soil layers and sampling times. Compared to the ambient environment, single canopy N addition (CN) or single canopy water addition (CW) did not affect bacterial Shannon diversity in the mineral soil layer in 2018, but the combined canopy N and water additions (CNW) decreased it in this layer at this time. CN increased fungal OTU richness in the organic and mineral soil layers in 2018; however, CW and CNW did not have an effect on it in the same layer at the same time. CW and CNW, but not CN, significantly affected bacterial and fungal community compositions in the litter layer in 2018 and in the organic soil layer in 2019. In contrast, CN, but not CW or CNW, significantly affected fungal community composition in the litter layer in 2019. CNW exhibited higher complexities of bacterial and fungal co-occurrence networks than CN and the ambient environment, indicating increased precipitation can strengthen the effect of N deposition on the complexity of bacterial and fungal co-occurrence networks. Our findings suggest that increased precipitation alters the effects of atmospheric N deposition on soil bacterial and fungal communities in this temperate forest, depending on soil layer and sampling time. Moreover, both bacterial and fungal community compositions are sensitive to increased precipitation, but the bacterial community composition is more sensitive to N deposition than the fungal community composition in the organic and mineral soil layers in this forest.

Divergent role of nutrient availability in determining drought responses of sessile oak and Scots pine seedlings: evidence from 13C and 15N dual labeling.

Increased soil nutrient availability can promote tree growth while drought impairs metabolic functioning and induces tree mortality. However, limited information is available about the role of nutrients in the drought responses of trees. A greenhouse experiment was conducted with sessile oak (Quercus petraea (Matt.) Liebl) and Scots pine (Pinus sylvestris L.) seedlings, which were subjected to three fertilization treatments in the first year and two water regimes in the second year. Old and newly fixed carbon (C) and nitrogen (N) allocation were traced by dual labeling with 13C and 15N tracers, respectively, at two time points. Leaf gas exchange, biomass, as well as N and nonstructural carbohydrate (NSC) concentrations of all organs were measured. Fertilization predisposed sessile oak to drought-induced mortality, mainly by prioritizing aboveground growth, C and N allocation, reducing root NSC concentrations and decreasing old C contribution to new growth of leaves. In contrast, fertilization did not additionally predispose Scots pine to drought, with minor effects of fertilization and drought on newly fixed and old C allocation, tissues N and NSC concentrations. The role of nutrients for drought responses of trees seems to be species-specific. Therefore, we suggest nutrient availability and species identity to be considered in the framework of physiological mechanisms affecting drought-induced mortality.

Nitrogen deposition raises temperature sensitivity of soil organic matter decomposition in subtropical forest.

Subtropical ecosystems are strongly affected by nitrogen (N) deposition, impacting soil organic matter (SOM) availability and stocks. Here we aimed to reveal the effects of N deposition on i) the structure and functioning of microbial communities and ii) the temperature sensitivity (Q10) of SOM decomposition. Phosphorus (P) limited evergreen forest in Guangdong Province, southeastern China, was selected, and N deposition (factor level: N (100 kg N ha-1 y-1 (NH4NO3)) and control (water), arranged into randomized complete block design (n = 3)) was performed during 2.5 y. After that soils from 0 to 20 cm were collected, analyzed for the set of parameters and incubated at 15, and 25, and 35 °C for 112 days. N deposition increased the microbial biomass N and the content of fungal and Gram-positive bacterial biomarkers; activities of beta-glucosidase (BG) and acid phosphatase (ACP) also increased showing the intensification of SOM decomposition. The Q10 of SOM decomposition under N deposition was 1.66 and increased by 1.4 times than under control. Xylosidase (BX), BG, and ACP activities increased with temperature under N but decreased with the incubation duration, indicating either low production and/or decomposition of enzymes. Activities of polyphenol-(PPO) and peroxidases (POD) were higher under N than in the control soil and were constant during the incubation showing the intensification of recalcitrant SOM decomposition. At the early incubation stage (10 days), the increase of Q10 of CO2 efflux was explained by the activities of BX, BQ, ACP, and POD and the quality of the available dissolved organic matter pool. At the later incubation stages (112 days), the drop of Q10 of CO2 efflux was due to the depletion of the labile organic substances and the shift of microbial community structure to K-strategists. Thus, N deposition decoupled the effects of extracellular enzyme activities from microbial community structure on Q10 of SOM decomposition in the subtropical forest soil.

Comparison of the effects of rumen-protected and unprotected L-leucine on fermentation parameters, bacterial composition, and amino acids metabolism in in vitro rumen batch cultures.

This study was conducted to compare the effects of rumen-protected (RP-Leu) and unprotected L-leucine (RU-Leu) on the fermentation parameters, bacterial composition, and amino acid metabolism in vitro rumen batch incubation. The 5.00 g RP-Leu or RU-Leu products were incubated in situ in the rumen of four beef cattle (Bos taurus) and removed after 0, 2, 4, 6, 12, 16, and 24 h to determine the rumen protection rate. In in vitro incubation, both RP-Leu and RU-Leu were supplemented 1.5 mmol/bottle (L-leucine HCl), and incubated after 0, 2, 4, 6, 8, 12, and 16 h to measure gas production (GP), nutrient degradability, fermentation parameters, bacterial composition, and amino acids metabolism. Results from both in vitro and in situ experiments confirmed that the rumen protection rate was greater (p < 0.01) in RP-Leu than in RU-Leu, whereas the latter was slow (p < 0.05) degraded within incubation 8 h. Free leucine from RP-Leu and RU-Leu reached a peak at incubation 6 h (p < 0.01). RU-Leu supplementation increased (p < 0.05) gas production, microbial crude protein, branched-chain AAs, propionate and branched-chain VFAs concentrations, and Shannon and Sobs index in comparison to the control and RP-Leu supplementation. RU-Leu and RP-Leu supplementation decreased (p < 0.05) the relative abundance of Bacteroidota, which Firmicutes increased (p < 0.05). Correlation analysis indicated that there are 5 bacteria at the genus level that may be positively correlated with MCP and propionate (p < 0.05). Based on the result, we found that RP-Leu was more stable than RU-Leu in rumen fluid, but RU-Leu also does not exhibit rapid degradation by ruminal microbes for a short time. The RU-Leu was more beneficial in terms of regulating rumen fermentation pattern, microbial crude protein synthesis, and branched-chain VFAs production than RP-Leu in vitro rumen conditions.

Branched-Long-Chain Monomethyl Fatty Acids: Are They Hidden Gems?

Branched-long-chain monomethyl fatty acids (BLCFA) are consumed daily in significant amounts by humans in all stages of life. BLCFA are absorbed and metabolized in human intestinal epithelial cells and are not only oxidized for energy. Thus far, BLCFA have been revealed to possess versatile beneficial bioactivities, including cytotoxicity to cancer cells, anti-inflammation, lipid-lowering, reducing the risk of metabolic disorders, maintaining normal ß cell function and insulin sensitivity, regulation of development, and mitigating cerebral ischemia/reperfusion injury. However, compared to other well-studied dietary fatty acids like eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), BLCFA has received disproportionate attention despite their potential importance. Here we outlined the major food sources, estimated intake, absorption, and metabolism in human cells, and bioactive properties of BLCFA with a focus on the bioactive mechanisms to advocate for an increased commitment to BLCFA investigations. Humans were estimated to absorb 6-5000 mg of dietary BLCFA daily from fetus to adult. Notably, iso-15:0 inhibited the growth of prostate cancer, liver cancer and T-cell non-Hodgkin lymphomas in rodent models at the effective doses of 35-105 mg/kg/day, 70 mg/kg/day, and 70 mg/kg/day, respectively. Feeding formula prepared with 20% w/w BLCFA mixture to neonatal rats with enterocolitis mitigated the intestine inflammation. Iso-15:0 at doses of 10, 40, and 80 mg/kg relieved brain ischemia/reperfusion injury in rats. In the future, it is crucial to conduct research to establish the epidemiology of BLCFA intake and their impacts on health outcomes in humans as well as to fully uncover the underlying mechanisms for their bioactivities.

Appropriate particle size of rice straw promoted rumen fermentation and regulated bacterial microbiota in a rumen simulation technique system.

The purpose of this study is to reveal the effects of different particle sizes of rice straw on the rumen protozoa count, nutrient disappearance rate, rumen fermentation, and microbial community in a rumen simulation technique (RUSITEC) system. In this experiment, a single-factor random trial design was adopted. According to the different particle sizes of rice straw, there were three treatments with three replies in each treatment. Three kinds of goat total mixed ration (TMR), with the same nutrients were used to carry out a 10 days in vitro fermentation experiment using the rumen simulation system developed by Hunan Agricultural University, including 6 days the pretrial period and 4 days formal period. This study found that the organic matter disappearance rate, concentrations of total volatile fatty acids (VFAs), acetate, propionate, and iso-butyrate were greatest in the 4 mm group (p < 0.05). There were no significant differences in the alpha diversity, among the three groups (p > 0.05). The relative abundance of Treponema and Ruminococcus of the 2 mm group increased; the relative abundance of Butyrivibrio and Prevotella in samples increased in the 4 mm group. In addition, the results of correlation analysis showed that Prevotella and Ruminococcus was positively correlated with butyrate, ammonia-N, dOM and d ADF (p < 0.05) and negatively correlated with valerate (p < 0.05); Oscillospira was positively correlated with valerate (p < 0.01) and negatively correlated with propionate, butyrate, ammonia-N, dOM and dADF (p < 0.05). The present results imply that compared to the other groups, rice straw particle size of 4 mm may improve the disappearance rate of nutrients and promote the production of volatile fatty acids by regulating ruminal microorganisms.

Resveratrol inhibits LPS-induced apoptosis in bovine mammary epithelial cells: the role of PGC1α-SIRT3 axis.

Resveratrol (Res) is a bioactive dietary component and alleviates apoptosis in multiple cell types. However, its effect and mechanism on lipopolysaccharide (LPS)-induced bovine mammary epithelial cells (BMEC) apoptosis, which commonly happens in dairy cows with mastitis, is unknown. We hypothesized that Res would inhibit LPS-induced apoptosis in BMEC through SIRT3, a NAD + -dependent deacetylase activated by Res. To test the dose-response effect on apoptosis, 0-50 µM Res were incubated with BMEC for 12 h, followed by 250 µg/mL LPS treatment for 12 h. To investigate the role of SIRT3 in Res-mediated alleviation of apoptosis, BMEC were pretreated with 50 µM Res for 12 h, then incubated with si-SIRT3 for 12 h and were finally treated with 250 µg/mL LPS for 12 h. Res dose-dependently promoted the cell viability and protein levels of Bcl-2 (Linear P < 0.001) but decreased protein levels of Bax, Caspase-3 and Bax/Bcl-2 (Linear P < 0.001). TUNEL assays indicated that cellular fluorescence intensity declined with the rising doses of Res. Res also dose-dependently upregulated SIRT3 expression, but LPS had the opposite effect. SIRT3 silencing abolished these results with Res incubation. Mechanically, Res enhanced the nuclear translocation of PGC1α, the transcriptional cofactor for SIRT3. Further molecular docking analysis revealed that Res could directly bind to PGC1α by forming a hydrogen bond with Tyr-722. Overall, our data suggested that Res relieved LPS-induced BMEC apoptosis through the PGC1α-SIRT3 axis, providing a basis for further in vivo investigations of applying Res to relieve mastitis in dairy cows.

α/Sulfono-γ-AA peptide hybrids agonist of GLP-1R with prolonged action both in vitro and in vivo.

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t 1/2 > 14 days) compared to t 1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

Inactivated vaccine-elicited potent antibodies can broadly neutralize SARS-CoV-2 circulating variants.

A full understanding of the inactivated COVID-19 vaccine-mediated antibody responses to SARS-CoV-2 circulating variants will inform vaccine effectiveness and vaccination development strategies. Here, we offer insights into the inactivated vaccine-induced antibody responses after prime-boost vaccination at both the polyclonal and monoclonal levels. We characterized the VDJ sequence of 118 monoclonal antibodies (mAbs) and found that 20 neutralizing mAbs showed varied potency and breadth against a range of variants including XBB.1.5, BQ.1.1, and BN.1. Bispecific antibodies (bsAbs) based on nonoverlapping mAbs exhibited enhanced neutralizing potency and breadth against the most antibody-evasive strains, such as XBB.1.5, BQ.1.1, and BN.1. The passive transfer of mAbs or their bsAb effectively protected female hACE2 transgenic mice from challenge with an infectious Delta or Omicron BA.2 variant. The neutralization mechanisms of these antibodies were determined by structural characterization. Overall, a broad spectrum of potent and distinct neutralizing antibodies can be induced in individuals immunized with the SARS-CoV-2 inactivated vaccine BBIBP-CorV, suggesting the application potential of inactivated vaccines and these antibodies for preventing infection by SARS-CoV-2 circulating variants.

Evaluation of stirring time through a rumen simulation technique: Influences on rumen fermentation and bacterial community.

Introduction: Rumen motility is a key element that influences ruminant nutrition, whereas little is known about the effects of rumen contraction duration on rumen fermentation and ruminal microbiome. We previously reported that proper rotation speed of a rumen simulation technique (RUSITEC) system enhanced rumen fermentation and microbial protein (MCP) production. In the present study, different contraction durations and intervals were simulated by setting different stirring times and intervals of the stirrers in a RUSITEC system. The objective of this trial was to evaluate the influences of stirring time on rumen fermentation characteristics, nutrient degradation, and ruminal bacterial microbiota in vitro. Methods: This experiment was performed in a 3 × 3 Latin square design, with each experimental period comprising 4 d for adjustment and 3 d for sample collection. Three stirring time treatments were set: the constant stir (CS), the intermittent stir 1 (each stir for 5 min with an interval of 2 min, IS1), and the intermittent stir 2 (each stir for 4 min with an interval of 3 min, IS2). Results: The total volatile fatty acid (TVFA) concentration, valerate molar proportion, ammonia nitrogen level, MCP density, protozoa count, disappearance rates of dry matter, organic matter, crude protein, neutral detergent fiber, and acid detergent fiber, emissions of total gas and methane, and the richness index Chao 1 for the bacterial community were higher (p < 0.05) in the IS1 when compared to those in the CS. The greatest TVFA, MCP, protozoa count, nutrient disappearance rates, gas productions, and bacterial richness indices of Ace and Chao 1 amongst all treatments were observed in the IS2. The relative abundance of the genus Treponema was enriched (p < 0.05) in CS, while the enrichment (p < 0.05) of Agathobacter ruminis and another two less known bacterial genera were identified in IS2. Discussion: It could be concluded that the proper reduction in the stirring time might help to enhance the feed fermentation, MCP synthesis, gas production, and the relative abundances of specific bacterial taxa.

Fatal multisystem inflammatory syndrome in a 78-year-old adult after severe COVID-19 pneumonia during 2022 Omicron variant epidemic in Shanghai, China.

Multisystem inflammatory syndrome adult type (MIS-A) is a rare type of post-acute COVID-19 syndrome which more frequently occurred in younger population. Here we present a 78-year-old Chinese female, the oldest case reported, diagnosed with MIS-A who had severe SARS-CoV-2 infection. She was diagnosed with severe COVID-19 and experienced an unexpected sudden hemodynamic collapse in the recovery period within three weeks. Her platelet count was sharply dropped, accompanied with sustained cardiac, kidney and liver injury. She was diagnosed with MIS-A according to criteria established by Center of Disease Control and Prevention. Though her condition was improved under administrating with high dose of methylprednisolone and intravenous immunoglobulin, methylprednisolone was unable to withdraw till two weeks as her partial pressure of oxygen/fraction of inspiration oxygen ratio and platelet count dropped on the heels of decreasing dosage. Unfortunately, the patient's condition gradually deteriorated with the development of severe nosocomial pneumonia. We presented this rare case in order to emphasize that MIS-A could occur in the elderly and the management of this population might be more difficult as the condition of the elderly with SARS-CoV-2 infection and MIS-A might be more severe.

Effect of mulberry leaf or mulberry leaf extract on glycemic traits: a systematic review and meta-analysis.

Mulberry leaf (ML) and mulberry leaf extract (MLE) have numerous biological properties, such as regulating sugar and lipid metabolism, reducing blood glucose, and increasing insulin secretion. The aim of this study was to perform a systematic review and meta-analysis of randomized clinical trials to examine the effect of ML/MLE supplementation on glycemic traits in adults, including fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), and fasting plasma insulin (FPI). Twelve clinical trials (615 participants) fulfilled the eligibility criteria for the present meta-analysis, which included sensitivity analysis and GRADE (grading of recommendations assessment, development, and evaluation) certainty. Based on the heterogeneity between included studies, a random effects model was applied in the meta-analysis, and the results are expressed as WMD (weighted mean differences) with 95% CI (confidence intervals). Meta-analysis showed that ML/MLE supplementation resulted in a significant reduction in FBG by -0.47 mmol L-1, HbA1c by -2.92 mmol mol-1, and FPI by -0.58 µIU mL-1. In addition, subgroup analysis indicated that long-term supplementation of ML/MLE (≥8 weeks) was more effective for regulation of the glycemic traits in the non-healthy and baseline FPG >6.1 mmol L-1 subgroups. Glycemic regulation by ML/MLE may be attributed to the phytochemicals they contain, which are mainly 1-deoxynojirimycin, flavonoids, phenolics, and polysaccharides.