Global research status and trends of enteric glia: a bibliometric analysis.

Background: Enteric glia are essential components of the enteric nervous system. Previously believed to have a passive structural function, mounting evidence now suggests that these cells are indispensable for maintaining gastrointestinal homeostasis and exert pivotal influences on both wellbeing and pathological conditions. This study aimed to investigate the global status, research hotspots, and future directions of enteric glia. Methods: The literature on enteric glia research was acquired from the Web of Science Core Collection. VOSviewer software (v1.6.19) was employed to visually represent co-operation networks among countries, institutions, and authors. The co-occurrence analysis of keywords and co-citation analysis of references were conducted using CiteSpace (v6.1.R6). Simultaneously, cluster analysis and burst detection of keywords and references were performed. Results: A total of 514 publications from 36 countries were reviewed. The United States was identified as the most influential country. The top-ranked institutions were University of Nantes and Michigan State University. Michel Neunlist was the most cited author. "Purinergic signaling" was the largest co-cited reference cluster, while "enteric glial cells (EGCs)" was the cluster with the highest number of co-occurring keywords. As the keyword with the highest burst strength, Crohns disease was a hot topic in the early research on enteric glia. The burst detection of keywords revealed that inflammation, intestinal motility, and gut microbiota may be the research frontiers. Conclusion: This study provides a comprehensive bibliometric analysis of enteric glia research. EGCs have emerged as a crucial link between neurons and immune cells, attracting significant research attention in neurogastroenterology. Their fundamental and translational studies on inflammation, intestinal motility, and gut microbiota may promote the treatment of some gastrointestinal and parenteral disorders.

Enhanced Iturin A Production of Engineered Bacillus amyloliquefaciens by Knockout of Endogenous Plasmid and Rap Phosphatase Genes.

Iturin A biosynthesis has garnered considerable interest, yet bottlenecks persist in its low productivity in wild strains and the ability to engineer Bacillus amyloliquefaciens producers. This study reveals that deleting the endogenous plasmid, plas1, from the wild-type B. amyloliquefaciens HM618 notably enhances iturin A synthesis, likely related to the effect of the Rap phosphatase gene within plas1. Furthermore, inactivating Rap phosphatase-related genes (rapC, rapF, and rapH) in the genome of the strain also improved the iturin A level and specific productivity while reducing cell growth. Strategic rap genes and plasmid elimination achieved a synergistic balance between cell growth and iturin A production. Engineered strain HM-DR13 exhibited an increase in iturin A level to 849.9 mg/L within 48 h, significantly shortening the production period. These insights underscore the critical roles of endogenous plasmids and Rap phosphatases in iturin A biosynthesis, presenting a novel engineering strategy to optimize iturin A production in B. amyloliquefaciens.

Integrated Biofilm Modification and Transcriptional Analysis for Improving Fengycin Production in Bacillus amyloliquefaciens.

Although fengycin exhibits broad-spectrum antifungal properties, its application is hindered due to its low biosynthesis level and the co-existence of iturin A and surfactin in Bacillus amyloliquefaciens HM618, a probiotic strain. In this study, transcriptome analysis and gene editing were used to explore the potential mechanisms regulating fengycin production in B. amyloliquefaciens. The fengycin level of B. amyloliquefacien HM-3 (∆itu-ΔsrfAA) was 88.41 mg/L after simultaneously inhibiting the biosyntheses of iturin A and surfactin. The knockout of gene eps associated with biofilm formation significantly increased the fengycin level of the strain HM618, whereas the fengycin level decreased 32.05% after knocking out sinI, a regulator of biofilm formation. Transcriptome analysis revealed that the differentially expressed genes, involved in pathways of amino acid and fatty acid syntheses, were significantly down-regulated in the recombinant strains, which is likely associated with a decrease of fengycin production. The knockout of gene comQXPA and subsequent transcriptome analysis revealed that the ComQXPA quorum sensing system played a positive regulatory role in fengycin production. Through targeted genetic modifications and fermentation optimization, the fengycin production of the engineered strain HM-12 (∆itu-ΔsrfAA-ΔyvbJ) in a 5-L fermenter reached 1.172 g/L, a 12.26-fold increase compared to the fengycin level in the strain HM-3 (∆itu-ΔsrfAA) in the Erlenmeyer flask. Taken together, these results reveal the underlying metabolic mechanisms associated with fengycin synthesis and provide a potential strategy for improving fengycin production in B. amyloliquefaciens.

An Engineered Microbial Consortium Provides Precursors for Fengycin Production by Bacillus subtilis.

Fengycin has great potential for applications in biological control because of its biosafety and degradability. In this study, the addition of exogenous precursors increased fengycin production by Bacillus subtilis. Corynebacterium glutamicum was engineered to produce high levels of precursors (Thr, Pro, Val, and Ile) to promote the biosynthesis of fengycin. Furthermore, recombinant C. glutamicum and Yarrowia lipolytica providing amino acid and fatty acid precursors were co-cultured to improve fengycin production by B. subtilis in a three-strain artificial consortium, in which fengycin production was 2100 mg·L-1. In addition, fengycin production by the consortium in a 5 L bioreactor reached 3290 mg·L-1. Fengycin had a significant antifungal effect on Rhizoctonia solani, which illustrates its potential as a food preservative. Taken together, this work provides a new strategy for improving fengycin production by a microbial consortium and metabolic engineering.

An evaluation of cervical maturity for Chinese women with labor induction by machine learning and ultrasound images.

BACKGROUND: To evaluate the improvement of evaluation accuracy of cervical maturity for Chinese women with labor induction by adding objective ultrasound data and machine learning models to the existing traditional Bishop method. METHODS: The machine learning model was trained and tested using 101 sets of data from pregnant women who were examined and had their delivery in Peking University Third Hospital in between December 2019 and January 2021. The inputs of the model included cervical length, Bishop score, angle, age, induced labor time, measurement time (MT), measurement time to induced labor time (MTILT), method of induced labor, and primiparity/multiparity. The output of the model is the predicted time from induced labor to labor. Our experiments analyzed the effectiveness of three machine learning models: XGBoost, CatBoost and RF(Random forest). we consider the root-mean-squared error (RMSE) and the mean absolute error (MAE) as the criterion to evaluate the accuracy of the model. Difference was compared using t-test on RMSE between the machine learning model and the traditional Bishop score. RESULTS: The mean absolute error of the prediction result of Bishop scoring method was 19.45 h, and the RMSE was 24.56 h. The prediction error of machine learning model was lower than the Bishop score method. Among the three machine learning models, the MAE of the model with the best prediction effect was 13.49 h and the RMSE was 16.98 h. After selection of feature the prediction accuracy of the XGBoost and RF was slightly improved. After feature selection and artificially removing the Bishop score, the prediction accuracy of the three models decreased slightly. The best model was XGBoost (p = 0.0017). The p-value of the other two models was < 0.01. CONCLUSION: In the evaluation of cervical maturity, the results of machine learning method are more objective and significantly accurate compared with the traditional Bishop scoring method. The machine learning method is a better predictor of cervical maturity than the traditional Bishop method.

[Effect of Coconut Fiber Biochar and Its Nitrate Modification on Pb Passivation in Paddy Soils].

The effects of coconut fiber biochar (CFB) and nitrate-modified coconut fiber biochar (NCFB) on the passivation of exogenous lead (Pb) in paddy soils and their underlying mechanisms were investigated using soil incubation experiments combined with spectroscopic techniques such as scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), synchrotron radiation X-ray fluorescence (SRXRF), and Fourier transform infrared absorption spectroscopy (FTIR). The effects of NCFB and CFB on the passivation of exogenous lead (Pb) in paddy soils and its underlying mechanisms were investigated. Compared with that of CFB, the inner wall of NCFB honeycomb pores was rougher, and the amount of alcohol-phenol-ether functional groups containing the C-O structure and the amount of carboxyl groups containing the C[FY=,1]O/O[FY=,1]C-O structure on the surface of CFB was significantly decreased after nitric acid modification. Compared with that in the control (without biochar) paddy soil after 150 d of incubation, the EDTA-extracted Pb content in the paddy soil with CFB and NCFB was reduced by 39.7% and 105.4%, respectively. The carbonate-bound and Fe-Mn oxide-bound Pb contents were significantly lower, and the organic-bound and residue Pb contents were significantly higher in the NCFB-added soil. The SRXRF scans showed that the exogenous Pb was enriched in the microregions of CFB particles rich in Ca and Cu elements and relatively less so in the microregions of soil aggregates rich in the Fe, Mn, and Ti elements. In addition, the characteristic peaks of carboxylates (1384 cm-1) in A-CFBPb and A-NCFBPb were significantly enhanced in the incubation experiment in the presence of exogenous Pb compared to A-CFB and A-NCFB in the absence of exogenous Pb. The addition of CFB or NCFB was more effective in passivating exogenous Pb in paddy soils and promoted the gradual transformation of Pb from unstable to more stable forms in paddy soils to achieve the effect of passivating Pb. The greater amount of carboxyl functional groups in NCFB participated in the passivation of exogenous Pb, which made NCFB more effective than CFB in passivating Pb. NCFB was more effective than CFB in passivating exogenous Pb in paddy soils due to its rougher inner walls of honeycomb pores and abundant carboxyl functional groups. In tropical areas such as Hainan, coconut fiber biochar and its modification can be considered as an environmentally friendly candidate method for the remediation of soil Pb contamination.

3D printing of inorganic nanomaterials by photochemically bonding colloidal nanocrystals.

3D printing of inorganic materials with nanoscale resolution offers a different materials processing pathway to explore devices with emergent functionalities. However, existing technologies typically involve photocurable resins that reduce material purity and degrade properties. We develop a general strategy for laser direct printing of inorganic nanomaterials, as exemplified by more than 10 semiconductors, metal oxides, metals, and their mixtures. Colloidal nanocrystals are used as building blocks and photochemically bonded through their native ligands. Without resins, this bonding process produces arbitrary three-dimensional (3D) structures with a large inorganic mass fraction (~90%) and high mechanical strength. The printed materials preserve the intrinsic properties of constituent nanocrystals and create structure-dictated functionalities, such as the broadband chiroptical responses with an anisotropic factor of ~0.24 for semiconducting cadmium chalcogenide nanohelical arrays.

Enhancing Spns2/S1P in macrophages alleviates hyperinflammation and prevents immunosuppression in sepsis.

Sepsis is a leading cause of in-hospital mortality resulting from a dysregulated response to infection. Novel immunomodulatory therapies targeting macrophage metabolism have emerged as an important focus for current sepsis research. However, understanding the mechanisms underlying macrophage metabolic reprogramming and how they impact immune response requires further investigation. Here, we identify macrophage-expressed Spinster homolog 2 (Spns2), a major transporter of sphingosine-1-phosphate (S1P), as a crucial metabolic mediator that regulates inflammation through the lactate-reactive oxygen species (ROS) axis. Spns2 deficiency in macrophages significantly enhances glycolysis, thereby increasing intracellular lactate production. As a key effector, intracellular lactate promotes pro-inflammatory response by increasing ROS generation. The overactivity of the lactate-ROS axis drives lethal hyperinflammation during the early phase of sepsis. Furthermore, diminished Spns2/S1P signaling impairs the ability of macrophages to sustain an antibacterial response, leading to significant innate immunosuppression in the late stage of infection. Notably, reinforcing Spns2/S1P signaling contributes to balancing the immune response during sepsis, preventing both early hyperinflammation and later immunosuppression, making it a promising therapeutic target for sepsis.

Enhancing fengycin production in the co-culture of Bacillus subtilis and Corynebacterium glutamicum by engineering proline transporter.

Fengycin possesses antifungal activity but has limited application due to its low yields. Amino acid precursors play a crucial role in fengycin synthesis. Herein, the overexpression of alanine, isoleucine, and threonine transporter-related genes in Bacillus subtilis increased fengycin production by 34.06%, 46.66%, and 7.83%, respectively. Particularly, fengycin production in B. subtilis reached 871.86 mg/L with the addition of 8.0 g/L exogenous proline after enhancing the expression of the proline transport-related gene opuE. To overcome the metabolic burden caused by excessive enhancement of gene expression for supplying precursors, B. subtilis and Corynebacterium glutamicum which produced proline, were co-cultured, which further improved fengycin production. Fengycin production in the co-culture of B. subtilis and C. glutamicum in shake flasks reached 1554.74 mg/L after optimizing the inoculation time and ratio. The fengycin level in the fed-batch co-culture was 2309.96 mg/L in a 5.0-L bioreactor. These findings provide a new strategy for improving fengycin production.

Phage Display-Derived Peptides and Antibodies for Bacterial Infectious Diseases Therapy and Diagnosis.

The emergence of antibiotic-resistant-bacteria is a serious public health threat, which prompts us to speed up the discovery of novel antibacterial agents. Phage display technology has great potential to screen peptides or antibodies with high binding capacities for a wide range of targets. This property is significant in the rapid search for new antibacterial agents for the control of bacterial resistance. In this paper, we not only summarized the recent progress of phage display for the discovery of novel therapeutic agents, identification of action sites of bacterial target proteins, and rapid detection of different pathogens, but also discussed several problems of this technology that must be solved. Breakthrough in these problems may further promote the development and application of phage display technology in the biomedical field in the future.

Mutualistic microbial community of Bacillus amyloliquefaciens and recombinant Yarrowia lipolytica co-produced lipopeptides and fatty acids from food waste.

Bioconversion is an important method for transforming food waste (FW) into high value-added products, rendering it harmless, and recycling resources. An artificial microbial consortium (AMC) was constructed to produce FW-based lipopeptides in order to investigate the strategy of FW bioconversion into value-added products. Exogenous fatty acids as a precursor significantly improved the lipopeptide production of Bacillus amyloliquefaciens HM618. To enhance fatty acid synthesis and efflux in AMC, the recombinant Yarrowia lipolytica YL21 (strain YL21) was constructed by screening 12 target genes related to fatty acids to replace exogenous fatty acids in order to improve lipopeptide production. The levels of fengycin, surfactin, and iturin A in the AMC of strains HM618 and YL21 reached 76.19, 192.80, and 31.32 mg L-1, increasing 7.24-, 12.13-, and 3.23-fold compared to the results from the pure culture of strain HM618 in flask with Landy medium, respectively. Furthermore, free fatty acids were almost undetectable in the co-culture of strains HM618 and YL21, although its level was around 1.25 g L-1 in the pure culture of strain YL21 with Landy medium. Interestingly, 470.24 mg L-1 of lipopeptides and 18.11 g L-1 of fatty acids were co-produced in this AMC in a bioreactor with FW medium. To our knowledge, it is the first report of FW biotransformation into co-produce of lipopeptides and fatty acids in the AMC of B. amyloliquefaciens and Y. lipolytica. These results provide new insights into the biotransformation potential of FW for value-added co-products by AMC.

Improved Production of Fengycin in Bacillus subtilis by Integrated Strain Engineering Strategy.

Fengycin is a lipopeptide with broad-spectrum antifungal activity. However, its low yield limits its commercial application. Therefore, we iteratively edited multiple target genes associated with fengycin synthesis by combinatorial metabolic engineering. The ability of Bacillus subtilis 168 to manufacture lipopeptides was restored, and the fengycin titer was 1.81 mg/L. Fengycin production was further increased to 174.63 mg/L after knocking out pathways associated with surfactin and bacillaene synthesis and replacing the native promoter (PppsA) with the Pveg promoter. Subsequently, fengycin levels were elevated to 258.52 mg/L by upregulating the expression of relevant genes involved in the fatty acid pathway. After blocking spore and biofilm formation, fengycin production reached 302.51 mg/L. Finally, fengycin production was increased to approximately 885.37 mg/L after adding threonine in the optimized culture medium, which was 488-fold higher compared with that of the initial strain. Integrated strain engineering provides a strategy to construct a system for improving fengycin production.

Artificial microbial consortium producing oxidases enhanced the biotransformation efficiencies of multi-antibiotics.

Antibiotic mixtures in the environment result in the development of bacterial strains with resistance against multiple antibiotics. Oxidases are versatile that can bio-remove antibiotics. Various laccases (LACs), manganese peroxidases (MNPs), and versatile peroxidase (VP) were reconstructed in Pichia pastoris. For the single antibiotics, over 95.0% sulfamethoxazole within 48 h, tetracycline, oxytetracycline, and norfloxacin within 96 h were bio-removed by recombinant VP with α-signal peptide, respectively. In a mixture of the four antibiotics, 80.2% tetracycline and 95.6% oxytetracycline were bio-removed by recombinant MNP2 with native signal peptide (NSP) within 8 h, whereas < 80.0% sulfamethoxazole was bio-removed within 72 h, indicating that signal peptides significantly impacted removal efficiencies of antibiotic mixtures. Regarding mediators for LACs, 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) resulted in better removal efficiencies of multi-antibiotic mixtures than 1-hydroxybenzotriazole or syringaldehyde. Furthermore, artificial microbial consortia (AMC) producing LAC2 and MNP2 with NSP significantly improved bio-removal efficiency of sulfamethoxazole (95.5%) in four-antibiotic mixtures within 48 h. Tetracycline and oxytetracycline were completely bio-removed by AMC within 48 and 72 h, respectively, indicating that AMC accelerated sulfamethoxazole, tetracycline, and oxytetracycline bio-removals. Additionally, transformation pathways of each antibiotic by recombinant oxidases were proposed. Taken together, this work provides a new strategy to simultaneously remove antibiotic mixtures by AMC.

3D nanoprinting of semiconductor quantum dots by photoexcitation-induced chemical bonding.

Three-dimensional (3D) laser nanoprinting allows maskless manufacturing of diverse nanostructures with nanoscale resolution. However, 3D manufacturing of inorganic nanostructures typically requires nanomaterial-polymer composites and is limited by a photopolymerization mechanism, resulting in a reduction of material purity and degradation of intrinsic properties. We developed a polymerization-independent, laser direct writing technique called photoexcitation-induced chemical bonding. Without any additives, the holes excited inside semiconductor quantum dots are transferred to the nanocrystal surface and improve their chemical reactivity, leading to interparticle chemical bonding. As a proof of concept, we printed arbitrary 3D quantum dot architectures at a resolution beyond the diffraction limit. Our strategy will enable the manufacturing of free-form quantum dot optoelectronic devices such as light-emitting devices or photodetectors.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

Amphipathic dendritic poly-peptides carrier to deliver antisense oligonucleotides against multi-drug resistant bacteria in vitro and in vivo.

BACKGROUND: Outbreaks of infection due to multidrug-resistant (MDR) bacteria, especially Gram-negative bacteria, have become a global health issue in both hospitals and communities. Antisense oligonucleotides (ASOs) based therapeutics hold a great promise for treating infections caused by MDR bacteria. However, ASOs therapeutics are strangled because of its low cell penetration efficiency caused by the high molecular weight and hydrophilicity. RESULTS: Here, we designed a series of dendritic poly-peptides (DPP1 to DPP12) to encapsulate ASOs to form DSPE-mPEG2000 decorated ASOs/DPP nanoparticles (DP-AD1 to DP-AD12) and observed that amphipathic DP-AD2, 3, 7 or 8 with a positive charge ≥ 8 showed great efficiency to deliver ASOs into bacteria, but only the two histidine residues contained DP-AD7 and DP-AD8 significantly inhibited the bacterial growth and the targeted gene expression of tested bacteria in vitro. DP-AD7anti-acpP remarkably increased the survival rate of septic mice infected by ESBLs-E. coli, exhibiting strong antibacterial effects in vivo. CONCLUSIONS: For the first time, we designed DPP as a potent carrier to deliver ASOs for combating MDR bacteria and demonstrated the essential features, namely, amphipathicity, 8-10 positive charges, and 2 histidine residues, that are required for efficient DPP based delivery, and provide a novel approach for the development and research of the antisense antibacterial strategy.

Smart Multifunctional Polymer Systems as Alternatives or Supplements of Antibiotics To Overcome Bacterial Resistance.

In recent years, infectious diseases have again become a critical threat to global public health largely due to the challenges posed by antimicrobial resistance. Conventional antibiotics have played a crucial role in combating bacterial infections; however, their efficacy is significantly impaired by widespread drug resistance. Natural antimicrobial peptides (AMPs) and their polymeric mimics demonstrate great potential for killing bacteria with low propensity of resistance as they target the microbial membrane rather than a specific molecular target, but they are also toxic to the host eukaryotic cells. To minimize antibiotics systemic spread and the required dose that promote resistance and to advocate practical realization of the promising activity of AMPs and polymers, smart systems to target bacteria are highly sought after. This review presents bacterial recognition by various specific targeting molecules and the delivery systems of active components in supramolecules. Bacteria-induced activations of antimicrobial-based nanoformulations are also included. Recent advances in the bacteria targeting and delivery of synthetic antimicrobial agents may assist in developing new classes of highly selective antimicrobial systems which can improve bactericidal efficacy and greatly minimize the spread of bacterial resistance.

Phylotranscriptomic insights into a Mesoproterozoic-Neoproterozoic origin and early radiation of green seaweeds (Ulvophyceae).

The Ulvophyceae, a major group of green algae, is of particular evolutionary interest because of its remarkable morphological and ecological diversity. Its phylogenetic relationships and diversification timeline, however, are still not fully resolved. In this study, using an extensive nuclear gene dataset, we apply coalescent- and concatenation-based approaches to reconstruct the phylogeny of the Ulvophyceae and to explore the sources of conflict in previous phylogenomic studies. The Ulvophyceae is recovered as a paraphyletic group, with the Bryopsidales being a sister group to the Chlorophyceae, and the remaining taxa forming a clade (Ulvophyceae sensu stricto). Molecular clock analyses with different calibration strategies emphasize the large impact of fossil calibrations, and indicate a Meso-Neoproterozoic origin of the Ulvophyceae (sensu stricto), earlier than previous estimates. The results imply that ulvophyceans may have had a profound influence on oceanic redox structures and global biogeochemical cycles at the Mesoproterozoic-Neoproterozoic transition.

Improved the lipopeptide production of Bacillus amyloliquefaciens HM618 under co-culture with the recombinant Corynebacterium glutamicum producing high-level proline.

The application of antibacterial lipopeptides is limited by high cost and low yield. Herein, the exogenous L-proline significantly improved lipopeptide production by Bacillus amyloliquefaciens HM618. A recombinant Corynebacterium glutamicum producing high levels of proline using genetically modifying proB and putA was used to establish consortium, to improve lipopeptide production of strain HM618. Compared to a pure culture, the levels of iturin A, fengycin, and surfactin in consortium reached 67.75, 39.32, and 37.25 mg L-1, respectively, an increase of 3.19-, 2.05-, and 1.63-fold over that produced by co-cultures of B. amyloliquefaciens and recombinant C. glutamicum with normal medium. Commercial amylase and recombinant Pichia pastoris with a heterologous amylase gene were used to hydrolyze kitchen waste. A three-strain consortium with recombinant P. pastoris and C. glutamicum increased the lipopeptide production of strain HM618 in medium containing KW. This work provides new strategies to improve lipopeptide production by B. amyloliquefaciens.