RPL22 is a tumor suppressor in MSI-high cancers and a splicing regulator of MDM4.

Microsatellite instability-high (MSI-H) tumors are malignant tumors that, despite harboring a high mutational burden, often have intact TP53. One of the most frequent mutations in MSI-H tumors is a frameshift mutation in RPL22, a ribosomal protein. Here, we identified RPL22 as a modulator of MDM4 splicing through an alternative splicing switch in exon 6. RPL22 loss increases MDM4 exon 6 inclusion and cell proliferation and augments resistance to the MDM inhibitor Nutlin-3a. RPL22 represses the expression of its paralog, RPL22L1, by mediating the splicing of a cryptic exon corresponding to a truncated transcript. Therefore, damaging mutations in RPL22 drive oncogenic MDM4 induction and reveal a common splicing circuit in MSI-H tumors that may inform therapeutic targeting of the MDM4-p53 axis and oncogenic RPL22L1 induction.

Distribution characteristics and risk assessment of fluoride in surface water of urban typical rivers.

Recent research on fluoride in water primarily focuses on groundwater; however, the potential environmental risks of fluoride in urban rivers should not be overlooked. In 2023, this study collected 135 surface water samples from the Ershibu River in Hefei, China, during various flood periods. Through descriptive statistical analysis, correlation analysis, principal component analysis-multiple linear regression (PCA-MLR) modeling, hazard quotient (HQ) assessment, and Monte Carlo simulation analysis, the spatial and temporal distribution, potential sources, and health risks of fluoride were investigated. The results showed that fluoride concentrations in the Ershibu River ranged from 0 to 1.38 mg/L. According to the PCA-MLR calculations, industrial pollution (73.92 %) was identified as the main source, followed by hydrogeochemical evolution (16.10 %) and agricultural activities (9.98 %). The HQ analysis revealed that the average exceedance rates of HQ for the five exposed populations were as follows: infants (64.45 %) > young children (2.22 %) = adults (2.22 %) > children (0) = teenagers (0). Therefore, relevant authorities should improve defluoridation facilities to reduce fluoride levels in industrial and agricultural wastewater and implement measures to protect public health. Future research should investigate the migration processes and toxicity mechanisms of fluoride more thoroughly.

Synthesis and antitumor activity of copper(II) complexes of imidazole derivatives.

Complexes [Cu(PI)2(H2O)](NO3)2 (1), [Cu(PBI)2(NO3)]NO3 (2), [Cu(TBI)2(NO3)]NO3 (3), [Cu(BBIP)2](ClO4)2 (4) and [Cu(BBIP)(CH3OH)(ClO4)2] (5) were synthesized from the reactions of Cu(II) salts with 2-(2'-pyridyl)imidazole (PI), (2-(2'-pyridyl)benzimidazole (PBI), 2-(4'-thiazolyl)-benzimidazole (TBI), 2,6-bis(benzimidazol-2-yl)-pyridine (BBIP), respectively. Their compositions and crystal structures were determined. Their in-vitro antitumor activities were screened on four cancer cell lines and one normal cell line (HL-7702) using cisplatin as the positive control. Complexes 2 and 4 show higher cytotoxicity than the other three complexes. The cytotoxicity of complex 2 are comparable to those for cisplatin, and the cytotoxicity for 4 are much higher than those for cisplatin. From a viewpoint of antitumor, 2 might be a nice choice on the tumor cell line of T24 because its IC50 values on T24 and HL-7702 are 15.03 ± 1.10 and 21.34 ± 0.35, respectively. Thus, a mechanistic study for complexes 2 and 4 on T24 cells was conducted. It revealed that they can reduce mitochondrial membrane potential and increase mitochondrial membrane permeability, resulting in increased intracellular ROS levels, Ca2+ inward flow, dysfunctional mitochondria and the eventual cell apoptosis. In conclusion, they can induce cell apoptosis through mitochondrial dysfunction. These findings could be useful in the development of new antitumor agents.

Unlocking potential of oxytocin: improving intracranial lymphatic drainage for Alzheimer's disease treatment.

Background: The impediment to ß-amyloid (Aß) clearance caused by the invalid intracranial lymphatic drainage in Alzheimer's disease is pivotal to its pathogenesis, and finding reliable clinical available solutions to address this challenge remains elusive. Methods: The potential role and underlying mechanisms of intranasal oxytocin administration, an approved clinical intervention, in improving intracranial lymphatic drainage in middle-old-aged APP/PS1 mice were investigated by live mouse imaging, ASL/CEST-MRI scanning, in vivo two-photon imaging, immunofluorescence staining, ELISA, RT-qPCR, Western blotting, RNA-seq analysis, and cognitive behavioral tests. Results: Benefiting from multifaceted modulation of cerebral hemodynamics, aquaporin-4 polarization, meningeal lymphangiogenesis and transcriptional profiles, oxytocin administration normalized the structure and function of both the glymphatic and meningeal lymphatic systems severely impaired in middle-old-aged APP/PS1 mice. Consequently, this intervention facilitated the efficient drainage of Aß from the brain parenchyma to the cerebrospinal fluid and then to the deep cervical lymph nodes for efficient clearance, as well as improvements in cognitive deficits. Conclusion: This work broadens the underlying neuroprotective mechanisms and clinical applications of oxytocin medication, showcasing its promising therapeutic prospects in central nervous system diseases with intracranial lymphatic dysfunction.

Human milk oligosaccharides in preventing food allergy: A review through gut microbiota and immune regulation.

Food allergy (FA) has increasingly attracted global attention in past decades. However, the mechanism and effect of FA are complex and varied, rendering it hard to prevention and management. Most of the allergens identified so far are macromolecular proteins in food and may have potential cross-reactions. Human milk oligosaccharides (HMOs) have been regarded as an ideal nutrient component for infants, as they can enhance the immunomodulatory capacity to inhibit the progress of FA. HMOs may intervene in the development of allergies by modifying gut microbiota and increasing specific short-chain fatty acids levels. Additionally, HMOs could improve the intestinal permeability and directly or indirectly regulate the balance of T helper cells and regulatory T cells by enhancing the inflammatory signaling pathways to combat FA. This review will discuss the influence factors of FA, key species of gut microbiota involved in FA, types of FA, and profiles of HMOs and provide evidence for future research trends to advance HMOs as potential therapeutic aids in preventing the progress of FA.

A rapid approach with machine learning for quantifying the relative burden of antimicrobial resistance in natural aquatic environments.

The massive use and discharge of antibiotics have led to increasing concerns about antimicrobial resistance (AMR) in natural aquatic environments. Since the dose-response mechanisms of pathogens with AMR have not yet been fully understood, and the antibiotic resistance genes and bacteria-related data collection via field sampling and laboratory testing is time-consuming and expensive, designing a rapid approach to quantify the burden of AMR in the natural aquatic environment has become a challenge. To cope with such a challenge, a new approach involving an integrated machine-learning framework was developed by investigating the associations between the relative burden of AMR and easily accessible variables (i.e., relevant environmental variables and adjacent land-use patterns). The results, based on a real-world case analysis, demonstrate that the quantification speed has been reduced from 3-7 days, which is typical for traditional measurement procedures with field sampling and laboratory testing, to approximately 0.5 hours using the new approach. Moreover, all five metrics for AMR relative burden quantification exceed the threshold level of 85%, with F1-score surpassing 0.92. Compared to logistic regression, decision trees, and basic random forest, the adaptive random forest model within the framework significantly improves quantification accuracy without sacrificing model interpretability. Two environmental variables, dissolved oxygen and resistivity, along with the proportion of green areas were identified as three key feature variables for the rapid quantification. This study contributes to the enrichment of burden analyses and management practices for rapid quantification of the relative burden of AMR without dose-response information.

Nuclear accumulation of rice UV-B photoreceptors is UV-B- and OsCOP1-independent for UV-B responses.

In plants, the conserved plant-specific photoreceptor UV RESISTANCE LOCUS 8 (UVR8) perceives ultraviolet-B (UV-B) light and mediates UV-B-induced photomorphogenesis and stress acclimation. In this study, we reveal that UV-B light treatment shortens seedlings, increases stem thickness, and enhances UV-B stress tolerance in rice (Oryza sativa) via its two UV-B photoreceptors OsUVR8a and OsUVR8b. Although the rice and Arabidopsis (Arabidopsis thaliana) UVR8 (AtUVR8) photoreceptors all form monomers in response to UV-B light, OsUVR8a, and OsUVR8b function is only partially conserved with respect to AtUVR8 in UV-B-induced photomorphogenesis and stress acclimation. UV-B light and CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) promote the nuclear accumulation of AtUVR8; by contrast, OsUVR8a and OsUVR8b constitutively localize to the nucleus via their own nuclear localization signals, independently of UV-B light and the RING-finger mutation of OsCOP1. We show that OsCOP1 negatively regulates UV-B responses, and shows weak interaction with OsUVR8s, which is ascribed to the N terminus of OsCOP1, which is conserved in several monocots. Furthermore, transcriptome analysis demonstrates that UV-B-responsive gene expression differs globally between Arabidopsis and rice, illuminating the evolutionary divergence of UV-B light signaling pathways between monocot and dicot plants.

Anti-inflammation mechanisms of a homogeneous polysaccharide from Phyllanthus emblica L. on DSS induced colitis mice via the gut microbiota and metabolites alteration.

Phyllanthus emblica L. offers promising therapeutic potential for inflammatory diseases. This study revealed the molecular structure of a homogeneous polysaccharide purified from Phyllanthus emblica L. (PEP-1) and evaluated its anti-inflammatory effects on ulcerative colitis (UC) in mice. In the in vivo experiment, administered in varying dosages to dextran sulfate sodium (DSS)-induced UC models, PEP-1 significantly alleviated colonic symptoms, histological damages and reshaped the gut microbiota. Notably, it adjusted the Firmicutes/Bacteroidetes ratio and reduced pro-inflammatory species, closely aligning with shifts in the fecal metabolites and metabolic pathways such as the metabolism of pyrimidine, beta-alanine, and purine. These findings underscore the potential of PEP-1 as a therapeutic agent for UC, providing insights into the mechanisms through gut microbiota and metabolic modulation.

Application of visual intelligent labels in the assessment of meat freshness.

With the increasing demand for meat products, the evaluation and real-time monitoring of its freshness has become one of the focuses of related industry research. Conventional freshness detection methods, including sensory evaluation, microbial experiments, and determination of physicochemical indicators, are time-consuming, low sensitivity, and destructive, so there is an urgent need to develop a convenient, intuitive, and inexpensive detection method. As a representative of smart packaging, visual intelligent labels can realize real-time perception and monitoring of meat freshness by measuring the temperature, pH value or other indicators of meat and converting them into visual signals. This paper first summarizes the common types, basic principles and research progress of visual intelligent labels, then introduces its application in livestock, poultry and seafood freshness monitoring, finally looks forward to the development prospect of visual smart labels.

Superimposed Electric Field Enhanced Electrospray for High-Throughput and Consistent Cell Encapsulation.

Cell encapsulation technology, crucial for advanced biomedical applications, faces challenges in existing microfluidic and electrospray methods. Microfluidic techniques, while precise, can damage vulnerable cells, and conventional electrospray methods often encounter instability and capsule breakage during high-throughput encapsulation. Inspired by the transformation of the working state from unstable dripping to stable jetting triggered by local electric potential, this study introduces a superimposed electric field (SEF)-enhanced electrospray method for cell encapsulation, with improved stability and biocompatibility. Utilizing stiffness theory, the stability of the electrospray, whose stiffness is five times stronger under conical confinement, is quantitatively analyzed. The SEF technique enables rapid, continuous production of ≈300 core-shell capsules per second in an aqueous environment, significantly improving cell encapsulation efficiency. This method demonstrates remarkable potential as exemplified in two key applications: (1) a 92-fold increase in human-derived induced pluripotent stem cells (iPSCs) expansion over 10 d, outperforming traditional 2D cultures in both growth rate and pluripotency maintenance, and (2) the development of liver capsules for steatosis modeling, exhibiting normal function and biomimetic lipid accumulation. The SEF-enhanced electrospray method presents a significant advancement in cell encapsulation technology. It offers a more efficient, stable, and biocompatible approach for clinical transplantation, drug screening, and cell therapy.

A GABAergic system in atrioventricular node pacemaker cells controls electrical conduction between the atria and ventricles.

Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAA receptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN's protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.

Combinatorial Optimization Strategies for 3-Fucosyllactose Hyperproduction in Escherichia coli.

3-Fucosyllactose (3-FL), an important fucosylated human milk oligosaccharide in breast milk, offers numerous health benefits to infants. Previously, we metabolically engineered Escherichia coli BL21(DE3) for the in vivo biosynthesis of 3-FL. In this study, we initially optimized culture conditions to double 3-FL production. Competing pathway genes involved in in vivo guanosine 5'-diphosphate-fucose biosynthesis were subsequently inactivated to redirect fluxes toward 3-FL biosynthesis. Next, three promising transporters were evaluated using plasmid-based or chromosomally integrated expression to maximize extracellular 3-FL production. Additionally, through analysis of α1,3-fucosyltransferase (FutM2) structure, we identified Q126 residues as a highly mutable residue in the active site. After site-saturation mutation, the best-performing mutant, FutM2-Q126A, was obtained. Structural analysis and molecular dynamics simulations revealed that small residue replacement positively influenced helical structure generation. Finally, the best strain BD3-A produced 6.91 and 52.1 g/L of 3-FL in a shake-flask and fed-batch cultivations, respectively, highlighting its potential for large-scale industrial applications.

Evaluating the efficacy of vatiquinone in preclinical models of mitochondrial disease.

Background: Genetic mitochondrial diseases are a major challenge in modern medicine, impacting around 1:4,000 individuals. Leigh syndrome is the most common pediatric presentation of mitochondrial disease. There are currently no effective clinical treatments for mitochondrial disease. In humans, patients are often treated with antioxidants, vitamins, and strategies targeting energetics. The vitamin-E related compound vatiquinone (EPI-743, α-tocotrienol quinone) has been the subject of at least 19 clinical trials in the US since 2012, but the effects of vatiquinone on an animal model of mitochondrial disease have not yet been reported. Here, assessed the impact of vatiquinone on disease progression and in two animal models of mitochondrial disease. Methods: The efficacy of vatiquinone in vitro was assessed using human fibroblasts treated with the general mitochondrial oxidative stress inducer paraquat, the GPX4 inhibitor RSL3, or the glutathione synthase inhibitor BSO in combination with excess iron. The therapeutic potential of vatiquinone in vivo was assessed using tamoxifen-induced mouse model for GPX4 deficiency and the Ndufs4 knockout mouse model of Leigh syndrome. In both models, animals were treated daily with vatiquinone or vehicle and relevant disease endpoints were assessed. Results: Vatiquinone robustly prevented death in cultured cells induced by RSL3 or BSO/iron, but had no effect on paraquat induced cell death. Vatiquinone had no impact on disease onset, progression, or survival in either the tamoxifen-inducible GPX4 deficient model or the Ndufs4(-/-) mouse model, though the drug may have reduced seizure risk. Conclusions: Vatiquinone provided no benefit to survival in two mouse models of disease, but may prevent seizures in the Ndufs4(-/-) model. Our findings are consistent with recent press statements regarding clinical trial results and have implications for drug trial design and reporting in patients with rare diseases.

Genetic and phenotypic associations of frailty with cardiovascular indicators and behavioral characteristics.

INTRODUCTION: Frailty Index (FI) is a common measure of frailty, which has been advocated as a routine clinical test by many guidelines. The genetic and phenotypic relationships of FI with cardiovascular indicators (CIs) and behavioral characteristics (BCs) are unclear, which has hampered ability to monitor FI using easily collected data. OBJECTIVES: This study is designed to investigate the genetic and phenotypic associations of frailty with CIs and BCs, and further to construct a model to predict FI. METHOD: Genetic relationships of FI with 288 CIs and 90 BCs were assessed by the cross-trait LD score regression (LDSC) and Mendelian randomization (MR). The phenotypic data of these CIs and BCs were integrated with a machine-learning model to predict FI of individuals in UK-biobank. The relationships of the predicted FI with risks of type 2 diabetes (T2D) and neurodegenerative diseases were tested by the Kaplan-Meier estimator and Cox proportional hazards model. RESULTS: MR revealed putative causal effects of seven CIs and eight BCs on FI. These CIs and BCs were integrated to establish a model for predicting FI. The predicted FI is significantly correlated with the observed FI (Pearson correlation coefficient = 0.660, P-value = 4.96 × 10-62). The prediction model indicated "usual walking pace" contributes the most to prediction. Patients who were predicted with high FI are in significantly higher risk of T2D (HR = 2.635, P < 2 × 10-16) and neurodegenerative diseases (HR = 2.307, P = 1.62 × 10-3) than other patients. CONCLUSION: This study supports associations of FI with CIs and BCs from genetic and phenotypic perspectives. The model that is developed by integrating easily collected CIs and BCs data in predicting FI has the potential to monitor disease risk.

Mechanism-Guided Computational Design Drives meso-Diaminopimelate Dehydrogenase to Efficient Synthesis of Aromatic d-amino Acids.

Aromatic d-amino acids (d-AAs) play a pivotal role as important chiral building blocks and key intermediates in fine chemical and drug synthesis. Meso-diaminopimelate dehydrogenase (DAPDH) serves as an excellent biocatalyst in the synthesis of d-AAs and their derivatives. However, its strict substrate specificity and the lack of efficient engineering methods have hindered its widespread application. Therefore, this study aims to elucidate the catalytic mechanism underlying DAPDH from Proteus vulgaris (PvDAPDH) through the examination of its crystallographic structure, computational simulations of potential energies and molecular dynamics simulations, and site-directed mutagenesis. Mechanism-guided computational design showed that the optimal mutant PvDAPDH-M3 increased specific activity and catalytic efficiency (kcat/Km) for aromatic keto acids up to 124-fold and 92.4-fold, respectively, compared to that of the wild type. Additionally, it expanded the substrate scope to 10 aromatic keto acid substrates. Finally, six high-value-added aromatic d-AAs and their derivatives were synthesized using a one-pot three-enzyme cascade reaction, exhibiting a good conversion rate ranging from 32 to 84% and excellent stereoselectivity (enantiomeric excess >99%). These findings provide a potential synthetic pathway for the green industrial production of aromatic d-AAs.

The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development.

The Iroquois (Iro/Irx) homeobox genes encode transcription factors with fundamental roles in animal development. Despite their link to various congenital conditions in humans, our understanding of Iro/Irx gene expression, function, and regulation remains incomplete. Here, we conducted a systematic expression analysis of all six mouse Irx genes in the embryonic spinal cord. We found five Irx genes (Irx1, Irx2, Irx3, Irx5, and Irx6) to be confined mostly to ventral spinal domains, offering new molecular markers for specific groups of post-mitotic motor neurons (MNs). Further, we engineered Irx2, Irx5, and Irx6 mouse mutants and uncovered essential but distinct roles for Irx2 and Irx6 in MN development. Last, we found that the highly conserved regulators of MN development across species, the HOX proteins, directly control Irx gene expression both in mouse and C. elegans MNs, critically expanding the repertoire of HOX target genes in the developing nervous system. Altogether, our study provides important insights into Iro/Irx expression and function in the developing spinal cord, and uncovers an ancient gene regulatory relationship between HOX and Iro/Irx genes.

Mini Endoscopic Septoplasty for High Localized Nasal Septum Deviation: Surgical Technique, Outcomes, and Comparison With Regular Septoplasty.

OBJECTIVES: This prospective cohort study aimed to describe the technique of mini endoscopic septoplasty for patients with a high localized nasal septum deviation in front of the middle turbinate and chronic sinusitis or nasal sinus fungus ball. Our primary objective was to investigate the indications and outcomes of this procedure, and the secondary objective was to compare it with regular endoscopic septoplasty. METHODS: Patients with chronic sinusitis or nasal sinus fungus ball and high localized nasal septum deviation underwent mini endoscopic septoplasty, while those with a broad deviation of the nasal septum underwent regular endoscopic septoplasty. The study evaluated the procedure duration, blood loss, and complications associated with both methods. All patients were followed up for 3 months. RESULTS: Thirty patients underwent mini endoscopic septoplasty; another 30 underwent regular endoscopic septoplasty. Mini endoscopic septoplasty demonstrated a significantly shorter procedure duration and lower blood loss than regular endoscopic septoplasty. Neither group experienced operative complications, such as nasal septum perforation or hematoma. CONCLUSION: Mini endoscopic septoplasty is a safe, time-efficient, and effective technique indicated for highly localized nasal septum deviations in patients with chronic sinusitis or nasal sinus fungus ball. This procedure offers advantages in terms of the surgical approach and postoperative debridement. Future research could explore the broader clinical implications of these findings.

Particulate and water-mobilizable phosphorus from a watershed with a plain river network contributes equal amounts of algal available phosphorus to its downstream lake.

This research was designed to estimate the contributions of phosphorus (P) in different factions from an upstream plain river network to algal growth in a downstream shallow eutrophic lake, Taihu Lake, in China. During three flow regimes, the P fractions in multiple phases (particulate, colloidal and dissolved phases) and their algal availabilities were assessed via bioassays with Dolichospermum flos-aquae as the test organism. The P partitioning patterns among multiple phases were strongly affected by the concentration of total suspended solids (TSS) that changed with the river flow regime, with stronger disturbance of sediments at lower water levels (low flow) and weaker disturbance of sediments at higher water levels (high flow) in the plain river network. The median TSS concentration across the river network decreased from 157.4 mg/L during low flow to 31.8 mg/L during high flow, and the median particulate P concentration decreased from 0.132 mg/L to 0.093 mg/L. The particulate P contributed equally to the amount of algal available P (AAP) as did the water-mobilizable P (colloidal plus dissolved phase) in the rivers flowing into Taihu Lake. The annual average concentrations of particulate algal available P (P-AAP), colloidal algal available P (C-AAP) and dissolved algal available P (D-AAP) were estimated to be 0.032 mg/L, 0.012 mg/L and 0.019 mg/L, respectively, during 2012-2018, accounting for 50.8 %, 19.0 % and 30.2 %, respectively, of the total AAP. At the watershed scale, controlling P drainage from downstream urbanized areas should be emphasized. Additionally, controlling sediment resuspension or reducing the TSS concentration in the inflowing rivers is important for decreasing the particulate P flux to downstream lakes.

De Novo Biosynthesis of Difucosyllactose by Artificial Pathway Construction and α1,3/4-Fucosyltransferase Rational Design in Escherichia coli.

Difucosyllactose (DFL) is a significant and plentiful oligosaccharide found in human breast milk. In this study, an artificial metabolic pathway of DFL was designed, focusing on the de novo biosynthesis of GDP-fucose from only glycerol. This was achieved by engineering Escherichia coli to endogenously overexpress genes manB, manC, gmd, and wcaG and heterologously overexpress a pair of fucosyltransferases to produce DFL from lactose. The introduction of α-1,2-fucosyltransferase from Helicobacter pylori (FucT2) along with α-1,3/4-fucosyltransferase (HP3/4FT) addressed rate-limiting challenges in enzymatic catalysis and allowed for highly efficient conversion of lactose into DFL. Based on these results, molecular modification of HP3/4FT was performed based on computer-assisted screening and structure-based rational design. The best-performing mutant, MH5, containing a combination of five mutated sites (F49K/Y131D/Y197N/E338D/R369A) of HP3/4FT was obtained. The best strain BLC09-58 harboring MH5 yielded 45.81 g/L of extracellular DFL in 5-L fed-batch cultures, which was the highest titer reported to date.

Recent Progress in Human Milk Oligosaccharides and Its Antiviral Efficacy.

Gastrointestinal (GI)-associated viruses, including rotavirus (RV), norovirus (NV), and enterovirus, usually invade host cells, transmit, and mutate their genetic information, resulting in influenza-like symptoms, acute gastroenteritis, encephalitis, or even death. The unique structures of human milk oligosaccharides (HMOs) enable them to shape the gut microbial diversity and endogenous immune system of human infants. Growing evidence suggests that HMOs can enhance host resistance to GI-associated viruses but without a systematic summary to review the mechanism. The present review examines the lactose- and neutral-core HMOs and their antiviral effects in the host. The potential negative impacts of enterovirus 71 (EV-A71) and other GI viruses on children are extensive and include neurological sequelae, neurodevelopmental retardation, and cognitive decline. However, the differences in the binding affinity of HMOs for GI viruses are vast. Hence, elucidating the mechanisms and positive effects of HMOs against different viruses may facilitate the development of novel HMO derived oligosaccharides.