Metabolic profiling of peri-implant crevicular fluid in peri-implantitis.

OBJECTS: This study aims to explore the etiology of peri-implantitis by comparing the metabolic profiles in peri-implant crevicular fluid (PICF) from patients with healthy implants (PH) and those with peri-implantitis (PI). MATERIALS AND METHODS: Fifty-six patients were enrolled in this cross-sectional study. PICF samples were collected and analyzed using both non-targeted and targeted metabolomics approaches. The relationship between metabolites and clinical indices including probing depth (PD), bleeding on probing (BOP), and marginal bone loss (MBL) was examined. Additionally, submucosal microbiota was collected and analyzed using 16S rRNA gene sequencing to elucidate the association between the metabolites and microbial communities. RESULTS: Significant differences in metabolic profiles were observed between the PH and PI groups, with 179 distinct metabolites identified. In the PI group, specific amino acids and fatty acids were significantly elevated compared to the PH group. Organic acids including succinic acid, fructose-6-phosphate, and glucose-6-phosphate were markedly higher in the PI group, showing positive correlations with mean PD, BOP, and MBL. Metabolites that increased in the PI group positively correlated with the presence of Porphyromonas and Treponema and negatively with Streptococcus and Haemophilus. CONCLUSIONS: This study establishes a clear association between metabolic compositions and peri-implant condition, highlighting enhanced metabolite activity in peri-implantitis. These findings open avenues for further research into metabolic mechanisms of peri-implantitis and their potential therapeutic implications.

Small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells inhibit cell apoptosis and alveolar bone loss in periodontitis.

OBJECTIVE: This study aimed to explore the effects of small extracellular vesicles derived from lipopolysaccharide-preconditioned dental follicle cells (L-D-sEV) on periodontal ligament cells from periodontitis affected teeth (p-PDLCs) in vitro and experimental periodontitis in mice. DESIGN: In vitro, the biological function of p-PDLCs and the underlying molecular mechanism were investigated by flow cytometry, Western blot, and quantitative real-time PCR (qRT-PCR) analysis. Eighteen-eight-week-old male C57BL/6 mice were randomly divided into three groups: control (Con), periodontitis (Peri), and L-D-sEV groups. Mice periodontitis model was induced by placing the 5-0 silk thread (around the maxillary second molar) and P.gingivalis (1 ×107 CFUs per mouse). In vivo, the alveolar bone loss, osteoclast activity, and macrophage polarization were measured by micro-computed tomography and histological analysis. RESULTS: In vitro, the RANKL/OPG ratio and phosphorylation of JNK and P38 protein levels of p-PDLCs were significantly decreased after L-D-sEV administration. Besides, flow cytometry and qRT-PCR analysis showed that L-D-sEV reduced apoptosis of p-PDLCs, down-regulated apoptosis-related genes Caspase-3 and BCL-2-Associated X expression, and up-regulated B-cell lymphoma-2 gene levels. In vivo, L-D-sEV administration significantly reduced alveolar bone loss, inhibited osteoclast activity, and induced M2 polarization. The histological analysis showed that iNOS/CD206, RANKL/OPG, p-JNK/JNK, and p-P38/P38 ratios were significantly lower in the L-D-sEV group than in the Peri group. CONCLUSIONS: L-D-sEV administration alleviated alveolar bone loss by mediating RANKL/OPG-related osteoclast activity and M2 macrophage polarization, alleviating p-PDLCs apoptosis and proliferation via the JNK and P38 pathways.

Preparation of an injectable and photocurable carboxymethyl cellulose/hydroxyapatite composite and its application in cranial regeneration.

Limited bone regeneration, uncontrollable degradation rate, mismatched defect zone and poor operability have plagued the reconstruction of irregular bone defect by tissue-engineered materials. A combination of biomimetic scaffolds with hydroxyapatite has gained great popularity in promoting bone regeneration. Therefore, we designed an injectable, photocurable and in-situ curing hydrogel by methacrylic anhydride -modified carboxymethyl cellulose (CMC-MA) loading with spherical hydroxyapatite (HA) to highly simulate the natural bony matrix and match any shape of damaged tissue. The prepared carboxymethyl cellulose-methacrylate/ hydroxyapatite(CMC-MA/HA) composite presented good rheological behavior, swelling ratio and mechanical property under light illumination. Meanwhile, this composite hydrogel promoted effectively proliferation, supported adhesion and upregulated the osteogenic-related genes expression of MC3T3-E1 cells in vitro, as well as the activity of the osteogenic critical protein, Integrin α1, ß1, Myosin 9, Myosin 10, BMP-2 and Smad 1 in Integrin/BMP-2 signal pathway. Together, the composite hydrogels realized promotion of bone regeneration, deformity improvement, and the enhanced new bone strength in skull defect. It also displayed a good histocompatibility and stability of subcutaneous implantation in vivo. Overall, this study laid the groundwork for future research into developing a novel biomaterial and a minimally invasive therapeutic strategies for reconstructing bone defects and contour deficiencies.

Concept and Development of Algebraic Topological Framework Nucleic Acids.

Nucleic acids are considered as promising materials for developing exquisite nanostructures from one to three dimensions. The advances of DNA nanotechnology facilitate ingenious design of DNA nanostructures with diverse shapes and sizes. Especially, the algebraic topological framework nucleic acids (ATFNAs) are functional DNA nanostructures that engineer guest molecules (e. g., nucleic acids, proteins, small molecules, and nanoparticles) stoichiometrically and spatially. The intrinsic precise properties and tailorable functionalities of ATFNAs hold great promise for biological applications, such as cell recognition and immunotherapy. This Perspective highlights the concept and development of precisely assembled ATFNAs, and outlines the new frontiers and opportunities for exploiting the structural advantages of ATFNAs for biological applications.

Impulse control behaviors and apathy commonly co-occur in de novo Parkinson's disease and predict the incidence of levodopa-induced dyskinesia.

OBJECTIVE: Impulse control behaviors (ICBs) and apathy are believed to represent opposite motivational expressions of the same behavioral spectrum involving hypo- and hyperdopaminergic status, but this has been recently debated. Our study aims to estimate the co-occurrence of ICBs and apathy in early Parkinson's disease (PD) and to determine whether this complex neuropsychiatric condition is an important marker of PD prognoses. METHODS: Neuropsychiatric symptoms, clinical data, neuroimaging results, and demographic data from de novo PD patients were obtained from the Parkinson's Progression Markers Initiative, a prospective, multicenter, observational cohort. The clinical characteristics of ICBs co-occurring with apathy and their prevalence were analyzed. We compared the prognoses of the different groups during the 8-year follow-up. Multivariate Cox regression analysis was conducted to predict the development of levodopa-induced dyskinesia (LID) using baseline neuropsychiatric symptoms. RESULTS: A total of 422 PD patients and 195 healthy controls (HCs) were included. In brief, 87 (20.6 %) de novo PD patients and 37 (19.0 %) HCs had ICBs at baseline. Among them, 23 (26.4 %) de novo PD patients and 3 (8.1 %) HCs had clinical symptoms of both ICBs and apathy. The ICBs and apathy group had more severe non-motor symptoms than the isolated ICBs group. Cox regression analysis demonstrated that the co-occurrence of ICBs and apathy was a risk factor for LID development (HR 2.229, 95 % CI 1.209 to 4.110, p = 0.010). CONCLUSIONS: Co-occurrence of ICBs and apathy is common in patients with early PD and may help to identify the risk of LID development.

Mapping gender networks of music self-concept and music emotions: A network analysis study of music majors in China.

BACKGROUND: Students' music self-concept and music emotions are becoming prominent topics within the area of music education. AIMS, SAMPLES AND METHODS: The majority of previous research on self-concept and music emotions has examined the two constructs independently and focused on gender differences in externalizing behaviours in music learning, but has neglected the internal interactions between individual music self-concept and music emotions. Network analysis is a promising method for visually examining music self-concept and music emotions as part of a network of interactions to identify core features and interrelationships among nodes in the network. In this study, 515 students majoring in music from a Chinese university were recruited. RESULTS: The results showed that high music self-concept and boredom were the common features at the core of the network for both men and women college students. The boredom exhibited by women differed from that of men in that men's boredom was directed at the entire music course, while boredom in women manifested as daydreaming and boredom with learning materials. CONCLUSIONS: This study is the first to explore gender differences in the music self-concept and music emotions from a holistic perspective. The findings could help music teachers gain insight into the complex system of music self-concept and music emotions. Music teachers could capture the respective features of men and women to design individualized teaching strategies.

Liposomes Enhance the Immunological Activity of Polygonatum Cyrtonema Hua Polysaccharides.

Poor stability and difficult uptake of natural polysaccharides have been the main problems in their application. The purpose of this study was to optimize the preparation conditions of Polygonatum cyrtonema Hua polysaccharides liposomes (PCPL) and to investigate the immune enhancement activity of PCPL in vitro and in vivo, with a view to discovering new ways of natural polysaccharide application. The optimal preparation conditions of PCPL were as follows: the adding amount of Tween 80 of 0.5 %, the ultrasound time of 2 min and the ultrasound times of once. Under these conditions, the entrapment efficiency, drug loading rate and particle size of PCPL were 38.033 %±0.050, 2.172 %±0.003 and 146 nm, which indicated that PCPL with small particle size could be prepared by the reverse-phase evaporation method. Furthermore, PCPL promoted proliferation, phagocytosis, and secretion of nitric oxide and related cytokines in RAW264.7 cells. Moreover, PCPL improved spleen and thymus indices, increased the number or proportion of red blood cells, platelets, and lymphocytes in the blood, and ameliorated spleen and thymus atrophy in immunosuppressed mice. This study provides a new idea for applying Polygonatum cyrtonema Hua polysaccharides (PCP) and references for studying other polysaccharides.

Combination of fractional carbon dioxide laser with recombinant human collagen in periocular skin rejuvenation.

BACKGROUND: The most visible sign of facial aging is often seen in the periocular area. However, periocular rejuvenation remains challenging due to the particularity of periocular anatomic locations. AIMS: We aimed to evaluate the efficacy and safety of the fractional-ablative CO2 laser-facilitated recombinant human collagen permeation in periocular rejuvenation. PATIENTS/METHODS: This 3-month prospective single-blinded and self-controlled trial enrolled 26 patients with periocular aging who underwent the treatments of fractional-ablative CO2 laser along with laser-facilitated recombinant human collagen permeation. Following the treatments, the patients were quantitatively assessed by various periocular skin aging indices before and after the treatment and monitored for any related adverse events. RESULTS: The patients showed significant improvements with the periocular skin aging indices 3 months after the treatments, which were detailed with a 47.3% decrease in lower eyelid skin rhytids, a 41.4% decrease in the lower eyelid skin texture, a 35.0% decrease in the static crow's feet, a 29.3% decrease in the amount of upper eyelid laxity, and a 20.2% increase in the MRD1 as compared with baseline (p < 0.05). Moreover, total skin thickness under ultrasound was increased in both upper and lower eyelids (5.6% and 3.3%, p < 0.05, respectively). Moreover, six patients (23.1%, 6/26) had erythema for 2 weeks, and two (2/26, 7.7%) had mild hyperpigmentation for 3 months. CONCLUSIONS: Fractional-ablative CO2 laser combined with laser-facilitated recombinant human collagen permeation can be a safe and effective treatment for periocular rejuvenation.

Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease.

Deep brain stimulation (DBS) is a well-established and effective treatment for patients with advanced Parkinson's disease (PD), yet its underlying mechanisms remain enigmatic. Optogenetics, primarily conducted in animal models, provides a unique approach that allows cell type- and projection-specific modulation that mirrors the frequency-dependent stimulus effects of DBS. Opto-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD treatment. DBS-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs, frequency-dependent synaptic depression, and the intrinsic excitability of postsynaptic neurons. This orchestration leads to conversion of firing patterns, enabling both antidromic and orthodromic modulation of neural circuits. Understanding these mechanisms is vital for decoding position- and programming-dependent effects of DBS. Furthermore, patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic benefits. Research on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation patterns. Advanced technologies, such as adaptive DBS or directional electrodes, can also be integrated for circuit-specific neuromodulation. These insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.

Integration of FUNDC1-associated mitochondrial protein import and mitochondrial quality control contributes to TDP-43 degradation.

Though TDP-43 protein can be translocated into mitochondria and causes mitochondrial damage in TDP-43 proteinopathy, little is known about how TDP-43 is imported into mitochondria. In addition, whether mitochondrial damage is caused by mitochondrial mislocalization of TDP-43 or a side effect of mitochondria-mediated TDP-43 degradation remains to be investigated. Here, our bioinformatical analyses reveal that mitophagy receptor gene FUNDC1 is co-expressed with TDP-43, and both TDP-43 and FUNDC1 expression is correlated with genes associated with mitochondrial protein import pathway in brain samples of patients diagnosed with TDP-43 proteinopathy. FUNDC1 promotes mitochondrial translocation of TDP-43 possibly by promoting TDP-43-TOM70 and DNAJA2-TOM70 interactions, which is independent of the LC3 interacting region of FUNDC1 in cellular experiments. In the transgenic fly model of TDP-43 proteinopathy, overexpressing FUNDC1 enhances TDP-43 induced mitochondrial damage, whereas down-regulating FUNDC1 reverses TDP-43 induced mitochondrial damage. FUNDC1 regulates mitochondria-mediated TDP-43 degradation not only by regulating mitochondrial TDP-43 import, but also by increasing LONP1 level and by activating mitophagy, which plays important roles in cytosolic TDP-43 clearance. Together, this study not only uncovers the mechanism of mitochondrial TDP-43 import, but also unravels the active role played by mitochondria in regulating TDP-43 homeostasis.

Assessing impulse control behaviors in early Parkinson's disease: a longitudinal study.

Objective: Impulse control behaviors (ICBs) frequently coexist with Parkinson's disease (PD). However, the predictors of ICBs in PD remain unclear, and there is limited data on the biological correlates of ICBs in PD. In this study, we examined clinical, imaging, and biological variables to identify factors associated with longitudinal changes in ICBs in early-stage PD. Methods: The data for this study were obtained from the Parkinson's Progression Markers Initiative, an international prospective cohort study that evaluates markers of disease progression in PD. We examined clinical, imaging, and biological variables to determine their associations with ICBs over a period of up to 5 years. Cox regression models were employed to investigate the predictors of ICBs in early-stage, untreated PD. Results: The study enrolled 401 individuals with PD and 185 healthy controls (HC). At baseline, 83 PD subjects (20.7%) and 36 HC (19.5%) exhibited ICBs. Over the course of 5 years, the prevalence of ICBs increased in PD (from 20.7% to 27.3%, p < 0.001), while it decreased in HC (from 19.5% to 15.2%, p < 0.001). Longitudinally, the presence of ICBs in PD was associated with depression, anxiety, autonomic dysfunction, and excessive daytime sleepiness (EDS). However, there was no significant association observed with cognitive dysfunction or motor severity. Treatment with dopamine agonists was linked to ICBs at years 3 and 4. Conversely, there was no association found between ICBs and presynaptic dopaminergic dysfunction. Additionally, biofluid markers in baseline and the first year did not show a significant association with ICBs. A predictive index for ICBs was generated, incorporating three baseline characteristics: anxiety, rapid eye movement sleep behavior disorder (RBD), and p-tau levels in cerebrospinal fluid (CSF). Conclusion: During the early stages of PD, there is a notable increase in ICBs over time. These ICBs are associated with depression, anxiety, autonomic dysfunction, EDS, and the use of dopaminergic medications, particularly dopamine agonists. Anxiety, RBD, and p-tau levels in CSF are identified as predictors for the incident development of ICBs in early PD. Further longitudinal analyses will provide a more comprehensive understanding of the associations between ICBs and imaging findings, as well as biomarkers. These analyses will help to better characterize the relationships and implications of these factors in the context of ICBs in early PD.

ROBO1 deficiency impairs HSPC homeostasis and erythropoiesis via CDC42 and predicts poor prognosis in MDS.

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.

Electrochemical Fe-catalysed radical cyclization for the synthesis of oxindoles.

We report an efficient and sustainable electrocatalytic approach for the synthesis of 3,3-disubstituted 2-oxindoles bearing ester groups from readily accessible N-arylacrylamides and carbazates. The reaction proceeds through an electrochemical iron-catalyzed radical addition/cyclization sequence with a commercially available iron catalyst and carbazates as alkoxycarbonyl radical precursors. This mild and operationally simple method transforms a wide range of structurally diverse N-arylacrylamides into oxindole derivatives in good yields and can be smoothly scaled up for the preparation of synthetically valuable oxindoles that are key intermediates for the synthesis of natural products.

Comprehensive assessment of base excision repair (BER)-related lncRNAs as prognostic and functional biomarkers in lung adenocarcinoma: implications for personalized therapeutics and immunomodulation.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, and comprehending its molecular mechanisms is pivotal for advancing treatment efficacy. This study aims to explore the prognostic and functional significance of base excision repair (BER)-related long non-coding RNAs (BERLncs) in LUAD. METHODS: A risk score model for BERLncs was developed using the least absolute shrinkage and selection operator regression and Cox regression analysis. Model validation and prognostic evaluation were performed using Kaplan-Meier and receiver-operating characteristic curve analyses. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to elucidate the potential biological functions of BERLncs. Comparative analyses were carried out to investigate disparities in tumor mutation burden (TMB), immune infiltration, tumor immune dysfunction and exclusion (TIDE) score, chemosensitivity, and immune checkpoint gene expression between the two risk groups. RESULTS: A predictive risk score model comprising 19 BERLncs was successfully developed. Patients were divided into high-risk and low-risk groups according to the median risk score. The high-risk subgroup exhibited significantly inferior overall survival. Functional enrichment analysis revealed pathways associated with lung cancer development, notably the neuroactive ligand-receptor interaction pathway. High-risk patients demonstrated elevated TMB, diminished TIDE scores, and an immunosuppressive tumor microenvironment, while low-risk patients displayed potential benefits from immunotherapy. Additionally, the risk model identified potential anticancer agents. CONCLUSION: The risk score model based on BERLncs shows promise as a prognostic biomarker for LUAD patients, providing valuable insights for clinical decision-making, therapeutic strategies, and understanding of underlying biological mechanisms.

Recalcitrant nodular scabies showing excellent response to tofacitinib: five case reports.

Scabies is a contagious skin condition caused by Sarcoptes scabiei, and it is always associated with an intense, unbearable, nocturnal deteriorating itch. Its presentations include classic burrows, erythema, pruritic papules, pustules, vesicles, and inflammatory nodules, with diffuse or localized distribution on the finger webs, wrist flexors, elbows, axillae, buttocks, genitalia, and breasts. Nodular scabies is an uncommon clinical variant of scabies. Its management is still challenging for some patients up to date, although topical, intralesional or systemic corticosteroids, topical calcineurin inhibitors, and crotamiton as well as cryotherapy alone or in different combinations are used. We here report five male patients of nodular scabies, aged between 14 and 25 years, who had classical scabies that had been cured by sulfur ointment for at least 4 weeks except for their itching nodules, and their residual pruritic nodules also failed in previous treatments including antihistamines, topical applying and intralesional injection of steroids as well as topical tacrolimus in different combinations before being recruited to this study. The patients were administered tofacitinib 5 mg, twice a day, which led to excellent and rapid improvement for both lesions and symptoms after 1-4 weeks of treatment, respectively, without any associations. During 6 months of follow-up, only one had re-infection of scabies associated with nodules that were cured by sulfur ointment and tofacitinib again. No adverse reaction was observed. The present results suggested that tofacitinib might be a potential agent for nodular scabies with excellent response.

A case of false positive opiate immunoassay results from rifampin (rifampicin) treatment.

The drug screen test on a 12-year-old male patient was positive for opiates by a kinetic interaction of microparticles in solution (KIMS) immunoassay method on the Roche Cobas C502. The positive opiates result was not confirmed by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. A chart review revealed that the patient had tuberculosis and was on rifampin. We spiked rifampin into drug-free urine and tested opiates with the Cobas method. Once again, a positive result was obtained. This case showed that rifampin can still cause false positive opiate results measured with the KIMS method. We want to stress the importance of confirming positive screen results by more specific methods such as LC-MS/MS.

Fatigue reliability analysis of aeroengine blade-disc systems using physics-informed ensemble learning.

For the fatigue reliability analysis of aeroengine blade-disc systems, the traditional direct integral modelling methods or separate independent modelling methods will lead to low computational efficiency or accuracy. In this work, a physics-informed ensemble learning (PIEL) method is proposed, i.e. firstly, based on the physical characteristics of blade-disc systems, the complex multi-component reliability analysis is split into a series of single-component reliability analyses; moreover, the PIEL model is established by introducing the mapping of multiple constitutive responses and the multi-material physical characteristics into the ensemble learning; finally, the PIEL-based system reliability framework is established by quantifying the failure correlation with the Copula function. The reliability analysis of a typical aeroengine high-pressure turbine blade-disc system is regarded as an example to verify the effectiveness of the proposed method. Compared with the direct Monte Carlo, support vector regression, neural network, ensemble learning and physics-informed neural network, the proposed method exhibits the highest computing accuracy and efficiency, and is validated to be an efficient method for the reliability analysis of blade-disc systems. The current work can provide a novel insight for physics-informed modelling and fatigue reliability analyses. This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 1)'.

Unravelling and engineering an operon involved in the side-chain degradation of sterols in Mycolicibacterium neoaurum for the production of steroid synthons.

BACKGROUND: Harnessing engineered Mycolicibacteria to convert cheap phytosterols into valuable steroid synthons is a basic way in the industry for the production of steroid hormones. Thus, C-19 and C-22 steroids are the two main types of commercial synthons and the products of C17 side chain degradation of phytosterols. During the conversion process of sterols, C-19 and C-22 steroids are often produced together, although one may be the main product and the other a minor byproduct. This is a major drawback of the engineered Mycolicibacteria for industrial application, which could be attributed to the co-existence of androstene-4-ene-3,17-dione (AD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (HBC) sub-pathways in the degradation of the sterol C17 side chain. Since the key mechanism underlying the HBC sub-pathway has not yet been clarified, the above shortcoming has not been resolved so far. RESULTS: The key gene involved in the putative HBC sub-pathway was excavated from the genome of M. neoaurum by comparative genomic analysis. Interestingly, an aldolase- encoding gene, atf1, was identified to be responsible for the first reaction of the HBC sub-pathway, and it exists as a conserved operon along with a DUF35-type gene chsH4, a reductase gene chsE6, and a transcriptional regulation gene kstR3 in the genome. Subsequently, atf1 and chsH4 were identified as the key genes involved in the HBC sub-pathway. Therefore, an updated strategy was proposed to develop engineered C-19 or C-22 steroid-producing strains by simultaneously modifying the AD and HBC sub-pathways. Taking the development of 4-HBC and 9-OHAD-producing strains as examples, the improved 4-HBC-producing strain achieved a 20.7 g/L production titer with a 92.5% molar yield and a 56.4% reduction in byproducts, and the improved 9-OHAD producing strain achieved a 19.87 g/L production titer with a 94.6% molar yield and a 43.7% reduction in byproduct production. CONCLUSIONS: The excellent performances of these strains demonstrated that the primary operon involved in the HBC sub-pathway improves the industrial strains in the conversion of phytosterols to steroid synthons.

Surface Modulation of Co3O4 Yolk-Shell Spheres with Tungsten Doping for Superior Acetone Sensitivity.

This study introduces a promising technique to enhance the sensitivity of p-type semiconductors in gas-sensing applications. By utilizing a glycerate-templated synthesis approach, a unique hierarchical W-doped Co3O4 yolk-shell sphere (YSS)-based sensor was developed, exhibiting exceptional sensitivity toward acetone gas. The synthesized YSSs feature a yolk-shell structure with a diameter of approximately 500 nm and a large surface area of 117.46 m2/g, which allows for efficient gas interaction and high sensitivity toward acetone gas. Furthermore, the incorporation of tungsten (W), a non-noble metal, as a dopant significantly enhances the surface activity of Co3O4, leading to a remarkably high response of 16.5 toward 5 ppm acetone, which is substantially higher than that of the pure Co3O4 YSS (2.9). The W-doped Co3O4 YSS also exhibits excellent selectivity to other interfering gases and the ability to detect ultralow concentrations of acetone as low as 10 ppb. The proposed non-noble metal doping strategy presents a practical solution for enhancing the sensitivity and selectivity of p-type semiconductor-based gas sensors. This approach holds great potential for practical gas-sensing applications due to their affordability and abundance, making them a cost-effective and versatile alternative to noble metal-catalyzed sensors.

Improved cryptic plasmids in probiotic Escherichia coli Nissle 1917 for antibiotic-free pathway engineering.

The engineered probiotic Escherichia coli Nissle 1917 (EcN) is expected to be employed in the diagnosis and treatment of various diseases. However, the introduced plasmids typically require antibiotics to maintain genetic stability, and the cryptic plasmids in EcN are usually eliminated to avoid plasmid incompatibility which may change the inherent probiotic characteristics. Here, we provided a simple design to minimize the genetic change of probiotics by eliminating native plasmids and reintroducing the recombinants carrying functional genes. Specific insertion sites in the vectors showed significant differences in the expression of fluorescence proteins. Selected integration sites were applied in the de novo synthesis of salicylic acid, leading to a titer of 142.0 ± 6.0 mg/L in a shake flask with good production stability. Additionally, the design successfully realized the biosynthesis of ergothioneine (45 mg/L) by one-step construction. This work expands the application scope of native cryptic plasmids to the easy construction of functional pathways. KEY POINTS: • Cryptic plasmids of EcN were designed to express exogenous genes • Insertion sites with different expression intensities in cryptic plasmids were provided • Target products were stably produced by engineering cryptic plasmids.