Sulfated Polysaccharide-Based Nanocarrier Drives Microenvironment-Mediated Cerebral Neurovascular Remodeling for Ischemic Stroke Treatment.

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.

The positive effect of the enzyme inducer (MnSO4) on the formation of humic substance in rice straw composting by stimulating key microorganisms.

This study investigated the impact of adding enzyme inducer (MnSO4) on humic substance (HS) formation during straw composting. The results demonstrated that both enzyme inducer treatment group (Mn) and functional microorganism treatment group (F) led to an increase in the content of HS compared to the treatment group without enzyme inducer and functional microorganism (CK). Interestingly, the enzyme inducer exhibited a higher promoting effect on HS (57.80 % ~ 58.58 %) than functional microbial (46.54 %). This was because enzyme inducer stimulated the growth of key microorganisms and changed the interaction relationship between microorganisms. The structural equation model suggested that the enzyme inducer promoted the utilization of amino acids by the fungus and facilitated the conversion of precursors to humic substance components. These findings provided a direction for improving the quality of composting products from agricultural straw waste. It also provided theoretical support for adding MnSO4 to compost.

GDF1 ameliorates cognitive impairment induced by hearing loss.

Hearing loss is associated with an increased risk of Alzheimer disease (AD). However, the mechanisms of hearing loss promoting the onset of AD are poorly understood. Here we show that hearing loss aggravates cognitive impairment in both wild-type mice and mouse models of AD. Embryonic growth/differentiation factor 1 (GDF1) is downregulated in the hippocampus of deaf mice. Knockdown of GDF1 mimics the detrimental effect of hearing loss on cognition, while overexpression of GDF1 in the hippocampus attenuates the cognitive impairment induced by deafness. Strikingly, overexpression of GDF1 also attenuates cognitive impairment in APP/PS1 transgenic mice. GDF1 activates Akt, which phosphorylates asparagine endopeptidase and inhibits asparagine endopeptidase-induced synaptic degeneration and amyloid-ß production. The expression of GDF1 is downregulated by the transcription factor CCAAT-enhancer binding protein-ß. These findings indicate that hearing loss could promote AD pathological changes by inhibiting the GDF1 signaling pathway; thus, GDF1 may represent a therapeutic target for AD.

Assessment of blood one-carbon metabolism indexes during mid-to-late pregnancy in 397 Chinese pregnant women.

Objectives: One-carbon metabolism (OCM) significantly influences fetal growth and neurodevelopment through transferring methyl group to biomolecules, during which folate, methionine, choline and betaine function as methyl donor nutrients, while vitamin B2, B6, B12 function as enzyme cofactors, and homocysteine (Hcy) and S-adenosyl methionine (SAM) are functional metabolites. This study aimed to assess blood OCM index levels and explore their relationships among Chinese pregnant women. Methods: Data were obtained from the baseline of the Mother-Child Nutrition and Health Cohort Study. Pregnant women, voluntarily recruited from September 2020 to June 2022 during antenatal examinations in five Chinese cities at 24-32 gestational weeks, provided fasting venous blood samples. Measurements included RBC and serum folate, serum vitamin B2, B6, B12, choline, betaine, methionine, total Hcy (tHcy), and plasma SAM. Sociodemographic characteristics and pregnancy-related conditions were collected via a self-designed questionnaire. Results: Of 397 participants, 82.6% were in mid-pregnancy (24-27 gestational weeks) and 17.4% were in late-pregnancy (28-32 gestational weeks). Serum folate, vitamin B6, and B12 deficiencies were 2.5, 1.3, and 8.3%, respectively. Elevated tHcy (≥10 µmol/L) was observed in 1.8% of pregnant women. Elderly pregnant women (aged 35 and above) exhibited significantly lower serum methionine levels (p < 0.05), while multiparous women had lower RBC folate levels (p < 0.05), and lower serum methionine and vitamin B12 levels (p < 0.10, not statistically significant). Partial correlation analysis revealed positive associations between RBC folate and cofactor vitamin B12 (r = 0.244, p < 0.05) in the folate cycle, as well as significant correlations between two methyl donor paths [serum folate was significantly related to serum choline (r = 0.172) and betaine (r = 0.193)]. As functional biomarkers of OCM, serum tHcy exhibited negative associations with RBC folate (ß = -0.330, p < 0.05) and vitamin B6 (ß = -0.317, p < 0.05), and plasma SAM displayed a positive association with serum betaine (ß = 0.610, p < 0.05), while negatively associated with serum vitamin B6 (ß = -0.181, p < 0.05). Conclusion: The blood OCM exhibited imbalances during mid-to-late pregnancy, characterized by lower levels of folate, vitamin B6, and B12, alongside elevated tHcy levels. Adequate folate and vitamin B6 emerged as significant predictors of lower tHcy levels. Additionally, serum betaine showed a positive correlation with plasma SAM. This suggests the importance of not only ensuring sufficient folate but also optimizing other OCM-related nutrients throughout pregnancy.

[Identifying animal-derived components in camel milk and its products by ultra-high performance liquid chromatography-tandem mass spectrometry].

A method for identifying specific peptide biomarkers of animal-milk-derived components in camel milk and its products was established using proteomics. Samples were prepared by defatting, protein extraction, and trypsin hydrolysis, and proteins and peptides were identified using ultra-high performance liquid chromatography-quadrupole/electrostatic orbitrap-high resolution mass spectrometry (UHPLC-Q/Exactive-HRMS) and Protein Pilot software. Twenty two peptide biomarkers from eight species (i.e., Camelus, Bos taurus, Bubalus bubalis, Bos grunniens/Bos mutus, Capra hircus, Ovis aries, Equus asinus, Equus caballus) were identified by comparing the basic local alignment search tool (BLAST) with the Uniprot database. Verification of these marker peptides were performed quantitatively using a UHPLC-triple-quadrupole mass-spectrometry (QqQ-MS) system by multiple reaction monitoring (MRM). The pretreatment method of casein in camel milk was optimized, such as defatting, protein precipitation, and re-dissolving buffer solution. The effects of various mass-spectrometry parameters, such as atomization gas, heating- and drying-gas flow rates, and desolvation-tube (DL) and ion-source-interface temperatures on ion-response intensity were optimized. Camel milk signature peptides were detected in a mixture of milk from other seven species to ensure specificity for the selected biomarker peptides. The signature peptides of seven other species were also detected in camel milk. No mutual interference between the selected biomarker peptides of the various species was observed. Adulterated camel milk and milk powder were also quantitatively studied by adding 0, 2.5%, 5%, 10%, 25%, 50%, 75%, and 100% bovine milk or goat milk to camel milk. Similarly, the same mass proportion of bovine milk powder or goat milk powder was added to camel milk powder. A quantitative standard curve for adulteration was constructed by plotting the peak areas of characteristic cow or goat peptide segments in each mixed sample against the mass percentage of the added adulterant. The adulteration standard curves exhibited good linearity, with correlation coefficients (r2) greater than 0.99. The limits of detection and quantification (LODs and LOQs, respectively) of the method were determined as three- and ten-times the signal-to-noise ratio (S/N). The minimum adulteration LODs of bovine milk and goat milk in camel milk were determined to be 0.35% and 0.49%, respectively, and the minimum LOQs were 1.20% and 1.69%, respectively. The minimum adulteration LODs of bovine milk powder and goat milk powder in camel milk powder were determined to be 0.68% and 0.73%, respectively, and the minimum LOQs were 1.65% and 2.45%, respectively. The accuracy of the adulteration quantification method was investigated by validating the quantitative detection results for 1∶1∶1 (mass ratio) mixtures of camel milk, bovine milk, and goat milk, as well as camel-milk powder, bovine milk powder, and goat-milk powder, which revealed that this method exhibits good linearity, strong anti-interference, high sensitivity, and good repeatability for adulterated liquid-milk/solid-milk-powder samples. The adulteration results for both liquid milk and milk powder are close to the theoretical values. Finally, 11 actual commercially available samples, including five camel-milk and six camel-milk-powder samples were analyzed, which revealed that only camel signature peptides were detected in 10 samples, while camel and bovine signature peptides were both detected in one camel-milk-powder sample. The ingredient list of the latter sample revealed that it contained whole milk powder from an unidentified source; therefore, we infer that the bovine signature peptides originate from the whole milk powder. These signature peptides also demonstrate the necessity and practical significance of establishing this identification method.

Effect of NH4+ and NO3- cooperatively regulated carbon to nitrogen ratio on organic nitrogen fractions during rice straw composting.

The purpose of this study was to examine the effects of replacing urea with inorganic nitrogen on the organic nitrogen sequestration process and the mitigation of nitrogen loss during rice straw composting. These groups include a control group with urea addition (CK), a group with (NH4)2SO4 addition (NH), a group with KNO3 addition (NO), and a group with (NH4)2SO4 + KNO3 addition (NN). The results demonstrated that adding NH, NO, and NN significantly increased the content of bioavailable organic nitrogen in the composting. Furthermore, compared to the CK, the NH treatment reduced nitrogen loss by 8.41 %. Structural equation modeling revealed the correlation between bacterial communities and organic nitrogen fractions in different treatment groups. Comparisons of nitrogen efficacy and nitrogen loss indicated that adding (NH4)2SO4 was more effective during composting, which provided a meaningful research basis for rice straw composting.

The yeast prion protein Sup35 initiates α-synuclein pathology in mouse models of Parkinson's disease.

Parkinson's disease (PD) is characterized by the pathologic aggregation and prion-like propagation of α-synuclein (α-syn). Emerging evidence shows that fungal infections increase the incidence of PD. However, the molecular mechanisms by which fungi promote the onset of PD are poorly understood. Here, we show that nasal infection with Saccharomyces cerevisiae (S. cerevisiae) in α-syn A53T transgenic mice accelerates the aggregation of α-syn. Furthermore, we found that Sup35, a prion protein from S. cerevisiae, is the key factor initiating α-syn pathology induced by S. cerevisiae. Sup35 interacts with α-syn and accelerates its aggregation in vitro. Notably, injection of Sup35 fibrils into the striatum of wild-type mice led to α-syn pathology and PD-like motor impairment. The Sup35-seeded α-syn fibrils showed enhanced seeding activity and neurotoxicity compared with pure α-syn fibrils in vitro and in vivo. Together, these observations indicate that the yeast prion protein Sup35 initiates α-syn pathology in PD.

Qualitative and Quantitative Changes of Oligosaccharides in Human and Animal Milk over Lactation.

The aim of this study was to investigate the changes in human and animal milk oligosaccharides over lactation. In total, 89, 97, 115, and 71 oligosaccharides were identified in human, bovine, goat, and camel milk. The number of common oligosaccharides between camel and human milk was the highest (16 and 17 in transitional and mature milk). With respect to the absolute concentration of eight oligosaccharides (2'-FL, 3-FL, α3'-GL, LNT, LNnT, 3'-SL, 6'-SL, and DSL), 2'-FL, 3'-FL, LNT, and LNnT were much higher in human than three animal species. 3'-SL had a similar concentration in bovine colostrum (322.2 µg/mL) and human colostrum (321.0 µg/mL), followed by goat colostrum (105.1 µg/mL); however, it had the highest concentration in camel mature milk (304.5 µg/mL). The ratio of 6'-SL and 3'-SL (1.77) in goat colostrum was similar to that in human colostrum (1.68), followed by bovine colostrum (0.13). In terms of changes of eight oligosaccharides over lactation, they all decreased with the increase of lactation in bovine and goat milk; however, α3'-GL, 2'-FL, and 3-FL increased in camel species, and LNT increased first and then decreased over lactation in human milk. This study provides a better understanding of the variation of milk oligosaccharides related to lactation and species.

Effects of Human Milk Fat Substitutes on Lipid Metabolism in First-Weaned Rats.

Although numerous studies indicate that formula-fed infants are more prone to obesity than breastfed ones, the underlying reasons have not been fully elucidated. This study aimed to determine the impact of human milk fat substitutes (HMFS) on the lipid metabolism of first-weaned Sprague Dawley rats. The findings revealed that administering HMFS did not affect the body weight of the rats (control: 298.38 ± 26.73 g, OPO (1,3-dioleic acid-2-palmitoyl triglyceride): 287.82 ± 19.85 g and HMFS: 302.31 ± 19.21 g), but it significantly decreased their body fat content (control: 28.70 ± 1.17 cm3, OPO: 22.51 ± 1.10 cm3 and HMFS: 14.90 ± 0.95 cm3) (p < 0.05). Lipidome analysis revealed that glycerophospholipid was the primary differentiating lipid present in the liver of HMFS-fed rats. The abundance of Bacteroides significantly increased in the intestine of HMFS-fed rats (p < 0.05), and their short-chain fatty acid (SCFA) content significantly increased (p < 0.05). The multi-omics correlation analysis established the "Bacteroidetes-SCFAs-Glycerophospholipid pathway" as a potential mechanism by which administering HMFS affects body fat buildup in first-weaned rats. Additionally, it was found that HMFS administration significantly promoted lipid metabolism in the rat liver at both the gene and protein levels (p < 0.05). These findings serve to underscore the nutritional benefits of HMFS for infants.

A New Nomogram for Predicting 30-Day In-Hospital Mortality Rate of Acute Cholangitis Patients in the Intensive Care Unit.

Purpose: Acute cholangitis (AC) is a widespread acute inflammatory disease and the main cause of septic shock, which has a high death rate in hospitals. At present, the prediction models for short-term mortality of AC patients are still not ideal. We aimed at developing a new model that could forecast the short-term mortality rate of AC patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0). There were a total of 506 cases of AC patients that were included. Patients were given a 7 : 3 split between the training set and the validation set after being randomly assigned to one of the groups. Multivariate logistic regression was used to create an AC patient predictive nomogram for 30-day mortality. The overall efficacy of the model is evaluated using the area under the receiver operating characteristic curve (AUC), the calibration curve, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA). Results: Out of 506 patients, 14.0% (71 patients) died. The training cohort had 354 patients, and the validation cohort had 152 patients. GCS, SPO2, albumin, AST/ALT, glucose, potassium, PTT, and peripheral vascular disease were the independent risk factors according to the multivariate analysis results. The newly established nomogram had better prediction performance than other common scoring systems (such as SOFA, OASIS, and SAPS II). For two cohorts, the calibration curve demonstrated coherence between the nomogram and the ideal observation (P > 0.05). The clinical utility of the nomogram in both sets was revealed by decision curve analysis. Conclusion: The novel prognostic model was effective in forecasting the 30-day mortality rate for acute cholangitis patients.

Effects of dietary patterns on the all-cause mortality and cardiovascular disease mortality in patients with hypertension: A cohort study based on the NHANES database.

BACKGROUND: Hypertension (HTN) patients have higher risk of all-cause and cardiovascular disease (CVD)-specific mortality. Dietary patterns have been reported related to the risk of mortality, but their roles in HTN patients is unclear. HYPOTHESIS: To explore the relationships between different dietary patterns and all-cause/CVD-specific mortality and provide dietary guidance for HTN patients' prognosis improvement. METHODS: Data of 27 618 HTN patients were extracted from the National Health and Nutrition Examination Survey (NHANES) database in this retrospective cohort study. The associations between Healthy Eating Index (HEI)-2015, Alternate Healthy Eating Index (AHEI)-2010, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean (MED) diet and all-cause and CVD-specific mortality were explored using univariate and multivariate Cox regression analyses with hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses of age, gender, body mass index, and comorbidity were also performed. RESULTS: The median follow-up time was 83 months. A total of 3462 patients died for all-cause and 1064 died due to CVD. After adjusting for covariates, we found that high adherence to AHEI-2010 (HR = 0.84 for all-cause; HR = 0.72 for CVD), and MED (HR = 0.84 for all-cause; HR = 0.77 for CVD) diet were associated with decreased risks of both all-cause and CVD-specific mortality. In patients who aged ≥65 years old, were normal/overweight, without complications, the relationships between different dietary patterns and risk of mortality were different. CONCLUSION: High scores of AHEI-2010 and MED may be associated with decreased risks of all-cause and CVD-specific mortality in patients with HTN.

Melatonin ameliorates atherosclerosis by suppressing S100a9-mediated vascular inflammation.

Atherosclerosis (AS)-associated cardiovascular diseases are predominant causes of morbidity and mortality worldwide. Melatonin, a circadian hormone with anti-inflammatory activity, may be a novel therapeutic intervention for AS. However, the exact mechanism is unclear. This research intended to investigate the mechanism of melatonin in treating AS. Melatonin (20 mg/kg/d) was intraperitoneally administered in a high-fat diet (HFD)-induced AS model using apolipoprotein E-deficient (ApoE-/-) mice for 12 weeks. Immunohistochemical and immunofluorescence analyses, data-independent acquisition (DIA)-based protein profiling, ingenuity pathway analysis (IPA), and western blotting were employed to investigate the therapeutic effects of melatonin in treating HFD-induced AS. An adeno-associated virus (AAV) vector was further used to confirm the antiatherosclerotic mechanism of melatonin. Melatonin treatment markedly attenuated atherosclerotic lesions, induced stable phenotypic sclerotic plaques, inhibited macrophage infiltration, and suppressed the production of proinflammatory cytokines in ApoE-/- mice with HFD-induced AS. Notably, DIA-based quantitative proteomics together with IPA identified S100a9 as a pivotal mediator in the protective effects of melatonin. Moreover, melatonin significantly suppressed HFD-induced S100a9 expression at both the mRNA and protein levels. The overexpression of S100a9 significantly activated the NF-κB signaling pathway and markedly abolished the antagonistic effect of melatonin on HFD-induced vascular inflammation during atherogenesis. Melatonin exerts a significant antiatherogenic effect by inhibiting S100a9/NF-κB signaling pathway-mediated vascular inflammation. Our findings reveal a novel antiatherosclerotic mechanism of melatonin and underlie its potential clinical use in modulating AS with good availability and affordability.

Parasitoids as taxonomists: how does the parasitoid Chouioia cunea distinguish between a host and a non-host?

BACKGROUND: How parasitoids distinguish hosts from non-hosts remains an unknown question. Chouioia cunea Yang (Eulophidae) is an important fall webworm parasitoid that attacks many forest and agricultural pests. To study the differences in the chemical clues used by C. cunea to distinguish host and non-host plants, we used gas chromatography-mass spectrometry (GC-MS) to identify volatile compounds of two C. cunea hosts (Hyphantria cunea and Helicoverpa armigera) and two non-hosts (Spodoptera exigua and Spodoptera frugiperda). Additionally, we used behavioral assays to compare the attraction of C. cunea to various compounds. RESULTS: The two natural host species were more attractive than the two non-host species, in the following order: Hyphantria cunea > Helicoverpa armigera > S. exigua = S. frugiperda. The pupae of the natural hosts contained 1-dodecene, which was not produced by the two natural non-hosts. When the 'attractants' based on the difference between the species-specific blend emitted by pupae and the optimal blend were sprayed onto the natural non-host pupae, they significantly improved the attraction of C. cunea to the non-host pupae. CONCLUSION: These results revealed that specific host-produced volatile compounds guide C. cunea to distinguish between natural hosts and non-hosts. Overall, this study provides a foundation for developing a behavior-modifying strategy to re-direct C. cunea attacks to control important non-host pests. © 2023 Society of Chemical Industry.

Study of Oncolytic Virus Preservation and Formulation.

In recent years, oncolytic viruses (OVs) have emerged as an effective means of treating cancer. OVs have multiple oncotherapeutic functions including specifically infecting and lysing tumor cells, initiating immune cell death, attacking and destroying tumor angiogenesis and triggering a broad bystander effect. Oncolytic viruses have been used in clinical trials and clinical treatment as drugs for cancer therapy, and as a result, oncolytic viruses are required to have long-term storage stability for clinical use. In the clinical application of oncolytic viruses, formulation design plays a decisive role in the stability of the virus. Therefore, this paper reviews the degradation factors and their degradation mechanisms (pH, thermal stress, freeze-thaw damage, surface adsorption, oxidation, etc.) faced by oncolytic viruses during storage, and it discusses how to rationally add excipients for the degradation mechanisms to achieve the purpose of maintaining the long-term stability of oncolytic viral activity. Finally, the formulation strategies for the long-term formulation stability of oncolytic viruses are discussed in terms of buffers, permeation agents, cryoprotectants, surfactants, free radical scavengers, and bulking agent based on virus degradation mechanisms.

Islet amyloid polypeptide triggers α-synuclein pathology in Parkinson's disease.

Pathologic aggregation and prion-like propagation of α-synuclein (α-syn) are the hallmarks of Parkinson's disease (PD). Emerging evidence shows that type 2 diabetes mellitus (T2DM) is a risk factor for PD. Interestingly, T2DM is characterized by the amyloid deposition of islet amyloid polypeptide (IAPP) in the pancreas. Although T2DM and PD share pathological similarities, the underlying molecular mechanisms bridging these two diseases remain unknown. Here, we report that IAPP co-deposits with α-syn in the brains of PD patients. IAPP interacts with α-syn and accelerates its aggregation. In addition, the IAPP-seeded α-syn fibrils show enhanced seeding activity and neurotoxicity compared with pure α-syn fibrils in vitro and in vivo. Strikingly, intravenous injection of IAPP fibrils into α-syn A53T transgenic mice or human SNCA transgenic mice accelerated the aggregation of α-syn and PD-like motor deficits. Taken together, these findings support that IAPP acts as a trigger of α-syn pathology in PD, and provide a mechanistic explanation for the increased risk and faster progression of PD in patients with T2DM.

Comparative analysis of whey proteins in yak milk from different breeds in China using a data-independent acquisition proteomics method.

Yak milk is rich in essential milk proteins of nutritional and therapeutic value. In this study, whey proteins of milk from 3 yak breeds (Gannan, GN; Huanhu, HH; Maiwa, MW) in China were comprehensively identified and compared using a data-independent acquisition quantitative proteomics approach. A total of 632 proteins were identified in yak milk whey samples, in which immune-related proteins were abundant. Compared with other milks, more proteins were involved in oxidation-reduction process and with ATP binding. In addition, we identified 96, 155, and 164 differentially expressed proteins (DEP) for GN versus HH, GN versus MW, and HH versus MW, respectively. "Phagosome" and "complement and coagulation cascades" were the most significant pathways for DEP of GN versus HH and GN or HH versus MW yak milk based on the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Protein-protein interaction network analysis showed that DEP for the 3 comparisons had significant biological interactions but were associated with different functions. The results provide useful information on yak milk from different breeds in China, and elucidate the biological functions of yak milk proteins.

Characteristics of intestinal microbiota in infants with late-onset breast milk jaundice.

Introduction: In this paper, microbiota analysis was determined to analyze the structure and difference of intestinal microbiota between LBMJ (late-onset breast milk jaundice) infants and healthy individuals. Methods: We collected fresh fecal samples from 13 infants with LBMJ and 13 healthy individuals, then determined the intestinal microbiota by 16 s rRNA sequencing. The differences of microbiota structure, diversity and functional characteristics between the two groups were analyzed, and the correlation between dominant genus and TcB (transcutaneous bilirubin) value was calculated. Results: In this study, there were no significant differences in maternal demographic characteristics, neonatal status and macronutrients in breast milk between the two groups (p > 0.05). There are differences in the structure of intestinal microbiota between LBMJ and the control group. At the genus level, the relative abundance of Klebsiella in the case group is high (p < 0.05). At the same time, correlation analysis indicates that the abundance of Klebsiella is positively correlated with TcB value. The intestinal microbiota richness and diversity (Alpha diversity and Beta diversity) of the two groups were significantly different (p < 0.05). LEfSe analysis showed that 25 genera including Klebsiella was significantly enriched in the LBMJ infants, and the other 17 species are enriched in the control group. Functional prediction analysis indicated that 42 metabolic pathways may be related to the occurrence of LBMJ. Conclusion: In conclusion, characteristic changes are seen in intestinal microbiota compositions between LBMJ infants and the healthy controls. Klebsiella is closely associated with the severity of the disease, which may be due to enhanced ß-glucuronidase activity.

Enhancing lactose recognition of a key enzyme in 2'-fucosyllactose synthesis: α-1,2-fucosyltransferase.

BACKGROUND: 2'-Fucosyllactose, a representative oligosaccharide in human milk, is an emerging and promising food and pharmaceutical ingredient due to its powerful health benefits, such as participating in immune regulation, regulation of intestinal flora, etc. To enable economically viable production of 2'-fucosyllactose, different biosynthesis strategies using precursors and pathway enzymes have been developed. The α-1,2-fucosyltransferases are an essential part involved in these strategies, but their strict substrate selectivity and unsatisfactory substrate tolerance are one of the key roadblocks limiting biosynthesis. RESULTS: To tackle this issue, a semi-rational manipulation combining computer-aided designing and screening with biochemical experiments were adopted. The mutant had a 100-fold increase in catalytic efficiency compared to the wild-type. The highest 2'-fucosyllactose yield was up to 0.65 mol mol-1 lactose with a productivity of 2.56 g mL-1  h-1 performed by enzymatic catalysis in vitro. Further analysis revealed that the interactions between the mutant and substrates were reduced. The crucial contributions of wild-type and mutant to substrate recognition ability were closely related to their distinct phylotypes in terms of amino acid preference. CONCLUSION: It is envisioned that the engineered α-1,2-fucosyltransferase could be harnessed to relieve constraints imposed on the bioproduction of 2'-fucosyllactose and lay a theoretical foundation for elucidating the substrate recognition mechanisms of fucosyltransferases. © 2022 Society of Chemical Industry.

Development of a Novel Nomogram Incorporating Red Blood Cell Distribution Width-Albumin Ratio for the Prediction of 30-day Mortality in Acute Pancreatitis Patients.

Purpose: The available nomograms used to predict acute pancreatitis (AP) are not comprehensive. We sought to investigate the effect of red blood cell distribution width (RDW)-albumin ratio (RA) on prognosis of patients with AP and develop a new nomogram to identify AP patients at high risk for mortality. Methods: We used data from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0). A total of 487 patients with acute pancreatitis were included. Patients enrolled in the study were randomly assigned to the training set and validation set at a 7 : 3 ratio. According to the 30-day mortality rate, the data were divided into a survival group and a death group. Multivariate logistic regression was used to establish a prognostic nomogram for predicting the 30-day mortality in AP patients. The area under the receiver operating characteristic curve (AUC), calibration curve, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA) are used to verify the overall performance of the model. Results: Among 487 patients, 54 patients died (11.1%). 338 patients were assigned to the training cohort and 149 were assigned to the validation cohort. The multivariate analysis results showed that RA, age, heart rate, temperature, AST/ALT, BUN, hemoglobin, potassium, and bilirubin were independent risk factors. The prediction performance of the newly established nomogram was better than those of other common scoring systems (including SOFA, OASIS, and APSIII). The nomogram suggests that RA (OR = 1.706, 95% CI: 1.367-2.185) is the most significant laboratory test indicator influencing prognosis. Conclusion: The new nomogram incorporating RA performed well in predicting AP short-term mortality. A prospective study with a larger sample is needed to validate our findings.