Efficient biosynthesis of D/L-alanine in the recombinant Escherichia coli BL21(DE3) by biobrick approach.

Alanine is the most abundant chiral amino acid that exists into the D-alanine or L-alanine forms with diverse applications in the biomedical, pharmaceutical, plastics, and food industries. D/L-alanine production can be carried out through chemical, microbial fermentation, and biocatalytic methods and not much effective due to complicated processes or purification issues and is still challenging to achieve a higher yield. In the present study, biobrick method was utilized for efficient production of D/L-alanine in the recombinant Escherichia coli BL21(DE3) with tandem three-gene co-expression plasmid. Firstly, the co-expression plasmid pET-22bNS-DadX-Ald-Gdh containing three genes, alanine dehydrogenase (ald), alanine racemase (dadX), and glucose dehydrogenase (gdh) from Bacillus pseudofirmus OF4 were successfully constructed and introduced into the E. coli BL21(DE3) strain. Then, under optimized conditions in the whole-cell biocatalytic reaction [20 mM Na2CO3-NaHCO3 (pH 10.1), 200 mM D-glucose, 200 mM sodium pyruvate, and 200 mM ammonium chloride], the concentration of D-alanine and L-alanine reached the maximum value (6.48 g/L and 7.05 g/L) after 3.0 h reaction time at 37°C under 180 rpm rotation. Meanwhile, promoter replacement experiments and Western blot analysis revealed that the expression level of protein OF4Ald had a significant effect on the production of D/L-alanine, indicating that alanine dehydrogenase might be the rate-limiting enzyme for D/L-alanine synthesis. This study provides a simple, feasible, and efficient biosynthesis process of D/L-alanine, which could explore emerging applications for large-scale production of industrial bioproducts.

Association of dietary flavonoid intake with the prevalence and all-cause mortality of depressive symptoms: Findings from analysis of NHANES.

BACKGROUND: This study aimed to explore the relationship between flavonoids intake and the prevalence and all-cause mortality of depressive symptoms in American adults. METHODS: Analyzing 2007-2008, 2009-2010, and 2017-2018 NHANES data, we examined the association between dietary flavonoid and depressive symptoms, including specific subclasses assessment and mortality outcomes tracking until December 31, 2019. Our methodology included weighted multivariate logistic regression, weighted cox proportional hazards regression and restricted cubic spline (RCS) models, supported by stratified and sensitivity analyses. RESULTS: Among the 12,340 participants in total, 1129 exhibited depressive symptoms. The multiple logistic regression analysis showed a significant reduction in total flavonoid and subclass intake in individuals with current depressive symptoms. Adjusted odds ratios (ORs) for the highest quartiles were 0.69 for anthocyanidins and 0.63 for flavones. Interaction effects emerged in non-hypertensive, higher-income, and normal-weight groups for flavones intake. The RCS model indicated an L-shaped association between depressive symptoms and total flavonoid intake, with inflection points at 346 mg/day. During a median follow-up of 119 months, 148 deaths occurred among patients with depressive symptoms. Hazard ratios (HRs) for all-cause mortality showed a significant positive correlation between total flavonoid intake and survival in model 1 (HR = 0.56), with an optimal intake range of 45.2-948.3 mg/day according to the RCS model. LIMITATIONS: The study relied on U.S. population survey data, potentially limiting generalizability. Unmeasured confounding factors may exist, and genetic factors were not considered. CONCLUSIONS: Adequate intake of flavonoids, especially anthocyanidins and flavones, is associated with reduced odds of depressive symptoms. Additionally, optimal intake ranges of flavonoid intake for mental health benefits were observed for all-cause mortality in population with depressive symptoms.

Additive-Assisted Forming High-Quality Thin Films of Sn-Oxo Cluster for Nanopatterning.

Recently, metal-oxo clusters (MOCs) have attracted significant interest in fabricating nanoscale patterns in semiconductors via lithography. However, many MOCs are highly crystalline, making it difficult for them to form films and hindering subsequent nanopatterning processes. In this study, we developed a novel and simple method to enhance the film-forming ability of aromatic tetranuclear Sn-oxo clusters by adding additives. Theoretical calculations and Fourier-transform infrared (FTIR) analysis revealed the formation of intermolecular hydrogen bonds between the Sn-oxo clusters and additives, which induced a crystal-gel phase transition at -20 °C, thereby inhibiting the easy crystallization of the Sn-oxo clusters. High-quality and uniform thin films with surface roughness below 0.3 nm were prepared via spin coating. The obtained thin films exhibited good lithographic performance under deep ultraviolet (DUV), electron beam, and extreme-ultraviolet irradiation without a photo acid generator/photoinitiator, and 13- and 21 nm-wide line patterns were obtained on the films via electron-beam and extreme-ultraviolet lithographies. This study will pave the way for the further investigation of novel MOCs for advanced lithography and other thin-film applications.

Anthropogenic warming is a key climate indicator of rising urban fire activity in China.

China, one of the most populous countries in the world, has suffered the highest number of natural disaster-related deaths from fire. On local scales, the main causes of urban fires are anthropogenic in nature. Yet, on regional to national scales, little is known about the indicators of large-scale co-varying urban fire activity in China. Here, we present the China Fire History Atlas (CFHA), which is based on 19 947 documentary records and represents fires in urban areas of China over the twentieth century (1901-1994). We found that temperature variability is a key indicator of urban fire activity in China, with warmer temperatures being correlated with more urban fires, and that this fire-temperature relationship is seasonally and regionally explicit. In the early twentieth century, however, the fire-temperature relationship was overruled by war-related fires in large urban areas. We further used the fire-temperature relationship and multiple emissions scenarios to project fire activity across China into the twenty-first century. Our projections show a distinct increase in future urban fire activity and fire-related economic loss. Our findings provide insights into fire-climate relationships in China for densely-populated areas and on policy-relevant time scales and they contribute spatial coverage to efforts to improve global fire models.

Nrf2 pathway activation promotes the expression of genes related to glutathione metabolism in alcohol-exposed astrocytes.

Introduction: Oxidative and antioxidant pathways play essential roles in the development of alcohol-induced brain injury. The Nrf2 pathway is an endogenous antioxidant response pathway, but there has been little research on the role of Nrf2 in alcohol-related diseases. Thus, we examined the effects of alcohol and an Nrf2 agonist (TBHQ) on astrocyte function, mRNA expression, and metabolite content to further explore the protective mechanisms of Nrf2 agonists in astrocytes following alcohol exposure. Methods: CTX TNA2 astrocytes were cultured with alcohol and TBHQ and then subjected to transcriptome sequencing, LC-MS/MS analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and malondialdehyde (MDA) and superoxide dismutase (SOD) activity assays. Results: Alcohol exposure significantly increased malondialdehyde (MDA) levels while decreasing superoxide dismutase (SOD) levels in astrocytes. Treatment with TBHQ effectively reversed these effects, demonstrating its protective role against oxidative stress induced by alcohol. Transcriptome sequencing and qRT-PCR analysis revealed that TBHQ specifically upregulates genes involved in glutathione metabolism, including a notable increase in the expression of the glutathione S-transferase A5 (GSTA5) gene, which was suppressed by alcohol exposure. Additionally, metabolomic analysis showed that TBHQ regulates key components of ether lipid metabolism in alcohol-exposed astrocytes, with significant reductions in the levels of lysophosphatidylcholine (18:0) (LysoPC (18:0)) and 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine, both of which are critical markers in the ether lipid metabolic pathway. Discussion: The findings underscore the role of TBHQ as an Nrf2 agonist in mitigating alcohol-induced oxidative damage in astrocytes by modulating glutathione metabolism and ether lipid metabolism. The regulation of GSTA5 gene expression emerges as a key mechanism through which Nrf2 agonists confer neuroprotection against oxidative stress and lipid oxidation. These insights pave the way for potential therapeutic strategies targeting the Nrf2 pathway to protect astrocytes from alcohol-induced damage.

Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORγt.

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 microRNA (Mirlet7 miRNA) family is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the Mirlet7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here, we show that overall expression of the Mirlet7 clusters, Mirlet7b/Mirlet7c2 and Mirlet7a1/Mirlet7f1/Mirlet7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the Mirlet7b/Mirlet7c2 cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the Mirlet7b/Mirlet7c2 cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing Mirlet7g in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of Mirlet7 in T cells. Overall, our findings shed light on the Mirlet7/RORγt axis with Mirlet7 acting as a molecular brake in the generation of Tc17 cells and suggest a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

Effect of overweight/obesity on relationship between fractional exhaled nitric oxide and airway hyperresponsiveness in Chinese elderly patients with asthma.

Purpose: This retrospective study investigates the influence of overweight and obesity status on pulmonary function, airway inflammatory markers, and airway responsiveness in elderly asthma patients. Methods: Patients with asthma older than 65 years old who completed a bronchial provocation test (BPT) or bronchial dilation test (BDT) and a fractional exhaled nitric oxide (FeNO) test between December 2015 and June 2020 were identified retrospectively for this study. All of the patients were categorized into overweight/obesity and non-obesity groups based on their BMI. Pulmonary function test (PFT) and FeNO measurements were accomplished according to the 2014 recommendations of the Chinese National Guidelines of Pulmonary Function Test and American Thoracic Society/European Respiratory Society recommendations, respectively. Results: A total of 136 patients with an average age of 71.2 ± 5.40 years were identified. The average BMI was 23.8 ± 3.63, while the value of FeNO was 42.3 ± 38.4 parts per billion (ppb). In contrast to the non-obesity group, which had a value of 48.8 ± 43.1 ppb for FeNO, the overweight/obesity group had a significant lower value of 35.4 ± 31.4 ppb. There was no significant difference in the proportion of individuals with high airway hyperresponsiveness between the overweight/obesity and non-obesity groups (96 patients in total). Multiple linear regression analysis established an inverse correlation between FeNO and Provocation concentration causing a 20% fall in FEV1(PC20) but excluded significant relationships with age and BMI. The model's R is 0.289, and its p value is 0.045. Conclusion: The elderly Chinese Han asthmatics with overweight/obesity had lower FeNO levels than those with non-obese according to our findings. In addition, the FeNO level was inversely correlated between FeNO levels and PC20 in elderly asthmatics.

In Situ Hydrogel Modulates cDC1-Based Antigen Presentation and Cancer Stemness to Enhance Cancer Vaccine Efficiency.

Effective presentation of antigens by dendritic cells (DC) is essential for achieving a robust cytotoxic T lymphocytes (CTLs) response, in which cDC1 is the key DC subtype for high-performance activation of CTLs. However, low cDC1 proportion, complex process, and high cost severely hindered cDC1 generation and application. Herein, the study proposes an in situ cDC1 recruitment and activation strategy with simultaneous inhibiting cancer stemness for inducing robust CTL responses and enhancing the anti-tumor effect. Fms-like tyrosine kinase 3 ligand (FLT3L), Poly I:C, and Nap-CUM (NCUM), playing the role of cDC1 recruitment, cDC1 activation, inducing antigen release and decreasing tumor cell stemness, respectively, are co-encapsulated in an in situ hydrogel vaccine (FP/NCUM-Gel). FP/NCUM-Gel is gelated in situ after intra-tumoral injection. With the near-infrared irradiation, tumor cell immunogenic cell death occurred, tumor antigens and immunogenic signals are released in situ. cDC1 is recruited to tumor tissue and activated for antigen cross-presentation, followed by migrating to lymph nodes and activating CTLs. Furthermore, tumor cell stemness are inhibited by napabucasin, which can help CTLs to achieve comprehensive tumor killing. Collectively, the proposed strategy of cDC1 in situ recruitment and activation combined with stemness inhibition provides great immune response and anti-tumor potential, providing new ideas for clinical tumor vaccine design.

Prediction of the Labrum Shape in Patients With Developmental Dysplasia of the Hip Based on Pelvic Radiography.

BACKGROUND: The shape of the labrum is strongly correlated with outcomes of developmental dysplasia of the hip (DDH). Magnetic resonance imaging (MRI) is the generally preferred imaging technique for observing the labrum. PURPOSE: We aimed to find a correlation between the labrum shape and anterior-posterior (AP) pelvic measurements in children with DDH. METHODS: Preoperative AP pelvic x-ray radiographs and MRI of patients with DDH from January 2019 to December 2021 were retrospectively collected and divided into three groups by labrum shape on MRI: everted, partly inverted, and inverted. The acetabular length ratio (RAL) in patients with unilateral DDH and the ratio of acetabular length to interpedicular distance (RALI) in all patients were calculated. T-tests were used to analyze differences between the groups. Receiver operating characteristic curve (ROC) analysis was performed between the everted group and the partly inverted and inverted groups. RESULTS: We found significant differences in RAL between the everted and partly inverted groups, everted and inverted groups, and everted and combined groups. The ROC analysis showed that the best cutoff value for RAL was 0.945 between the everted and combined groups, with an area under the curve (AUC) of 88.4%. The sensitivity at the best RAL value was 0.783, and the specificity was 0.887. Moreover, we observed a significant difference in RALI between the everted, partly inverted, and inverted groups, as well as between the everted and combined groups. The optimal cutoff value for RALI between the everted and combined groups was 0.575, with an AUC of 74.5%. The sensitivity at the best RALI value was 0.765, and the specificity was 0.674. CONCLUSION: The RAL or RALI values on pelvic AP radiographs can be used to predict the shape of the labrum. LEVEL OF EVIDENCE: III.

Nuts and seeds consumption impact on adolescent obesity: sex-specific associations from 2003 to 2018 National Health and Nutrition Examination Survey.

The nutritional benefits and immunological advantages of consuming nuts and seeds are well-established. However, the link between nuts and seeds consumption and the susceptibility of being overweight or obese among adolescents is not clear. This study aims to explore this relationship in adolescents aged 12-19. Using a weighted multiple logistic regression model, we analysed data of the Food Patterns Equivalents Database and the U.S. National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. We found a significant association between nuts and seeds consumption and a reduced odds of being overweight or obese in females. Specifically, females who habitually consumed nuts and seeds had lower odds of being overweight or obese (OR = 0.55, 95% CI: 0.32-0.94). Additionally, we found an L-shaped relationship between nuts and seeds consumption and appropriate waist-to-height ratio in males. The findings suggest that nuts and seeds consumption may contribute to healthier physical development in adolescents.

Downregulation of Let-7 miRNA promotes Tc17 differentiation and emphysema via de-repression of RORγt.

Environmental air irritants including nanosized carbon black (nCB) can drive systemic inflammation, promoting chronic obstructive pulmonary disease (COPD) and emphysema development. The let-7 family of miRNAs is associated with IL-17-driven T cell inflammation, a canonical signature of lung inflammation. Recent evidence suggests the let-7 family is downregulated in patients with COPD, however, whether this repression conveys a functional consequence on emphysema pathology has not been elucidated. Here we show that overall expression of the let-7 miRNA clusters, let-7b/let-7c2 and let-7a1/let-7f1/let-7d, are reduced in the lungs and T cells of smokers with emphysema as well as in mice with cigarette smoke (CS)- or nCB-elicited emphysema. We demonstrate that loss of the let-7b/let-7c2-cluster in T cells predisposed mice to exaggerated CS- or nCB-elicited emphysema. Furthermore, ablation of the let-7b/let-7c2-cluster enhanced CD8+IL17a+ T cells (Tc17) formation in emphysema development in mice. Additionally, transgenic mice overexpressing let-7 in T cells are resistant to Tc17 and CD4+IL17a+ T cells (Th17) development when exposed to nCB. Mechanistically, our findings reveal the master regulator of Tc17/Th17 differentiation, RAR-related orphan receptor gamma t (RORγt), as a direct target of let-7 miRNA in T cells. Overall, our findings shed light on the let-7/RORγt axis with let-7 acting as a molecular brake in the generation of Tc17 cells and suggests a novel therapeutic approach for tempering the augmented IL-17-mediated response in emphysema.

Macrophage-camouflaged epigenetic nanoinducers enhance chemoimmunotherapy in triple negative breast cancer.

Chemoimmunotherapy has been approved as standard treatment for triple-negative breast cancer (TNBC), but the clinical outcomes remain unsatisfied. Abnormal epigenetic regulation is associated with acquired drug resistance and T cell exhaustion, which is a critical factor for the poor response to chemoimmunotherapy in TNBC. Herein, macrophage-camouflaged nanoinducers co-loaded with paclitaxel (PTX) and decitabine (DAC) (P/D-mMSNs) were prepared in combination with PD-1 blockade therapy, hoping to improve the efficacy of chemoimmunotherapy through the demethylation of tumor tissue. Camouflage of macrophage vesicle confers P/D-mMSNs with tumor-homing properties. First, DAC can achieve demethylation of tumor tissue and enhance the sensitivity of tumor cells to PTX. Subsequently, PTX induces immunogenic death of tumor cells, promotes phagocytosis of dead cells by dendritic cells, and recruits cytotoxic T cells to infiltrate tumors. Finally, DAC reverses T cell depletion and facilitates immune checkpoint blockade therapy. P/D-mMSNs may be a promising candidate for future drug delivery design and cancer combination therapy in TNBC.

Simultaneous evaluation of the fractional exhaled nitric oxide and blood eosinophil count of T2-high endotype in patients with non-cystic fibrosis bronchiectasis.

OBJECTIVE: Recently, a type 2 inflammation (T2) high endotype in bronchiectasis was identified. The fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC) are recognized as representative biomarkers of T2 inflammation. Herein, we investigate the clinical characteristics of T2-high endotype in non-cystic fibrosis bronchiectasis patients classified by FeNO and BEC. METHODS: This retrospective study included 164 bronchiectasis patients treated in the First Affiliated Hospital of Sun Yat-sen University from December 2017 to July 2022. Clinical characteristics were analyzed after classifying patients into four groups according to T2 inflammation biomarkers (FeNO ≥25 ppb; BEC ≥200/µL). RESULTS: Among the 164 bronchiectasis patients, 35.3% (58/164) presented with high FeNO, 30.5% (50/164) presented with high BEC, and 10.4% (17/164) had high FeNO and BEC. Patients with high FeNO and low BEC presented with better lung function, fewer affected lobes, and lower dyspnea prevalence compared with the three other groups. Moreover, decreased FeNO, instead of decreased BEC, is revealed to be an independent predictor for disease severity and airflow obstruction in bronchiectasis. CONCLUSIONS: Simultaneous evaluation of FeNO and BEC proposed different endotypes of bronchiectasis established that patients with low BEC and high FeNO had better lung function, fewer affected lobes, lower dyspnea prevalence, and less disease severity. This result will contribute to a more comprehensive assessment of the disease severity and lead to more precise treatment of T2 inflammation in bronchiectasis patients.

Magnetic resonance-enhanced high-resolution three-dimensional water-selective cartilage sequence visualization of hip vessels in children.

PURPOSE: Hip vessel examination provides key information on many hip-related pediatric diseases, and it has an important role in the evaluation of femoral head (FH) blood supply and diagnosis of avascular necrosis (AVN). The aim of this study was to investigate the feasibility of MR-enhanced high-resolution three-dimensional water-selective cartilage (3D-WATSc) sequence in visualizing the vessels of the hip joint in children. PATIENTS AND METHODS: Children with hip disease were randomly enrolled prospectively at our hospital from January 2021 to August 2022. We performed our institution's hip MRI protocol and enhanced high-resolution 3D-WATSc sequence. The 3D-WATSc images were reconstructed and analyzed, and images of the normal hip were categorized into grades 0-3. The abnormal hip images were compared with those of the normal side using the χ2 test. RESULTS: Twenty-four patients with unilateral hip abnormalities were included in this study. The cartilaginous vascular canal and ossification centre vessels of normal FHs were observed in 18 patients (75%) and met the grade 3 standard. An abnormal cartilaginous canal was observed in 16 patients (67%); meanwhile, 18 patients (75%) had abnormal extrachondral vessels. Comparison of high-resolution 3D-WATSc images with those of the normal side provided effective abnormal vascular information in 95.8% of patients. CONCLUSIONS: Enhanced high-resolution 3D-WATSc can visualize the blood vessels of the hip in children. This may provide a new method for the vascular study of various pediatric hip diseases.

Association between nut consumption and frailty in the elderly: a large sample cross-sectional study.

BACKGROUND: Limited literature has addressed the impact of nut consumption in mitigating frailty. This study aimed to investigate the association between nut consumption and frailty among Americans aged above 60 years, employing two 24-h dietary recalls for analysis. METHODS: The data sets of the National Health and Nutrition Examination Survey (NHANES) (2003-2018) and the Food Patterns Equivalents Database were utilised for a weighted multiple logistic regression model to evaluate the association between nut consumption and frailty in elderly adults. Furthermore, a restricted cubic spline model was employed to investigate the nonlinear relationship between nut intake and frailty. Besides, stratified and interaction analyses were conducted to explore the sensitivity of nut consumption in reducing the risk of frailty in diverse subgroups. RESULTS: The research study comprised 10,033 individuals aged 60 years or above, of whom 3591 were classified as frailty and 5302 consumed nuts. In the multivariate logistic regression analysis that adjusted for covariates, the weighted multivariate adjusted odds ratios demonstrated that the prevalence of frailty was lower in the nut intake group than in nonconsumers. The stratified analysis indicated that nearly all subgroups who consumed nuts had a significantly lower risk of frailty compared to nonconsumers, and an interaction was observed between nut intake and nonhypertensive populations. The optimal threshold for nut intake to decrease the risk of frailty was identified as 1.02 ounces. CONCLUSIONS: The study concluded that nut consumption has a constructive impact on averting frailty in elderly adults, particularly in nonhypertensive individuals. Nut intake of ~1.02 ounces per day is advantageous in improving the quality of life in elderly adults.

Anti-cariogenic Properties of Lactobacillus plantarum in the Utilization of Galacto-Oligosaccharide.

Ecological approaches can help to correct oral microbial dysbiosis and drive the advent and persistence of a symbiotic oral microbiome, which benefits long-term dental caries control. The aim of this study was to investigate the impact of the prebiotic Galacto-oligosaccharide (GOS) on the growth of probiotics L. plantarum 14,917 and its effect on the inhibitory ability of L. plantarum 14,917 against the growth of Streptococcus mutans and Candida albicans in an in vitro model. Single-species growth screenings were conducted in TSBYE broth with 1% glucose and 1-5% GOS. Interaction experiments were performed using duo- and multi-species models with inoculation of 105 CFU/mL S. mutans, 103 CFU/mL C. albicans, and 108 CFU/mL L. plantarum 14,917 under 1%, 5% GOS or 1% glucose. Viable cells and pH changes were measured. Real-time PCR was utilized to assess expression of C. albicans and S. mutans virulence genes. Six replicates were used for each group. Student's t-test, one-way ANOVA, and Kruskal-Wallis were employed to compare the outcomes of different groups. GOS significantly inhibited the growth of C. albicans and S. mutans in terms of growth quantity and speed when the two strains were grown individually. However, GOS did not affect the growth of L. plantarum 14,917. Moreover, 1% and 5% GOS enhanced the anti-fungal performance of L. plantarum 14,917 in comparison to 1% glucose. GOS as the carbon source resulted in a less acidic environment in the C. albicans and S. mutans duo-species model and multispecies model where L. plantarum 14,917 was added. When GOS was utilized as the carbohydrate substrate, S. mutans and C. albicans had a significant reduction in the expression of the HWP1, ECE1, atpD, and eno genes (p < 0.05). To our knowledge, this is the first study that reported the ability of GOS to neutralize S. mutans-C. albicans high caries of medium pH and to disrupt virulence gene expression. Moreover, as a prebiotic, GOS augmented the inhibitory ability of L. plantarum against C. albicans in vitro. The current study revealed the anti-caries potential of prebiotics GOS and shed light on novel caries prevention strategies from the perspective of prebiotics and probiotics. These findings provide a rationale for future biofilm or clinical studies to elucidate the effect of GOS on modulating oral microbiota and caries control.

A Review on Higher Education of Fire Safety in China.

Along with the rapid urbanization and economic growth in China over the last four decades, the higher education in Fire Safety Science and Engineering has been developed and changed significantly. This work systemically reviews the origin and evolution of fire safety higher education history in China, from Fire Protection Technology (before the 1980s) to Fire Safety Science and Engineering (from about 1985 to the 2010s) and to Human-Oriented Public Safety and Smart Firefighting (from the 2010s to today). The scopes of fire safety discipline are discussed by introducing the requirements of firefighters, registered professional fire protection engineers and safety engineers in China. The courses and curriculum in fire safety higher education in representative universities are introduced and compared in detail. By comparing their undergraduate and postgraduate programmes, we explain the context of fire safety education in different universities. From a historical viewpoint, we introduce the unique features and the diversity developed in different institutes, based on the evolution of programme documents and first-hand teaching materials. This review aims to introduce the higher education systems of fire safety in China to the world and encourage more international collaboration with the Chinese fire safety science and engineering communities in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s10694-023-01416-5.

Effect of inactivated COVID-19 vaccine on the negative conversion of nucleic acid in asymptomatic or mild patients with COVID-19.

BACKGROUND: Negative conversion of nucleic acid was a key factor in deciding discharge or the end of isolation of asymptomatic or mild COVID-19 patients. We aimed to explore the effect of vaccination on the time to negative conversion after Omicron infection. METHODS: This retrospective cohort study included asymptomatic or mild patients with COVID-19 admitted to Fangcang shelter Hospital from November 10, 2022 to December 2, 2022. The relationship between vaccination status and the time to negative conversion was analyzed by multiple linear regression. RESULTS: A total of 2,104 asymptomatic or mild COVID-19 patients were included in the analysis, of whom 1,963 were vaccinated. The mean time to negative conversion of no vaccination, one dose, two doses, and three doses were 12.57 (5.05), 12.18 (3.46), 11.67 (4.86) and 11.22 (4.02) days, respectively (p = 0.002). Compared with no vaccination, two doses (ß=-0.88, 95% CI: -1.74, -0.02, p = 0.045), and three doses (ß=-1.51, 95% CI: -2.33, -0.70, p < 0.001) were both associated with shorter time to negative conversion. Comparing with two doses, booster dose was associated significantly with shorter time to negative conversion (ß=-0.63, 95% CI: -1.07, -0.20, p = 0.004). Age was positively correlated with the time to negative conversion (ß = 0.04, 95% CI: 0.02, 0.05, p < 0.001). CONCLUSION: Vaccination with inactivated vaccine and booster dose can shorten the time to negative conversion of asymptomatic or mild COVID-19 patients. The significant prolongation of time to negative conversion with increasing age suggests the promotion of vaccination, especially booster dose, particularly in the elderly.

Transforming Cancer-Associated Fibroblast Barrier into Drug Depots to Boost Chemo-Immunotherapy in "Shooting Fish in a Barrel" Pattern.

The cancer-associated fibroblast (CAF) barrier in pancreatic ductal adenocarcinoma (PDAC) greatly restricts clinical outcomes. Major obstacles to PDAC treatment include restricted immune cell infiltration and drug penetration and the immunosuppressive microenvironment. Here, we reported a "shooting fish in a barrel" strategy by preparing a lipid-polymer hybrid drug delivery system (PI/JGC/L-A) that could overcome the CAF barrier by turning it into a "barrel" with antitumor drug depot properties to alleviate the immunosuppressive microenvironment and increase immune cell infiltration. PI/JGC/L-A is composed of a pIL-12-loaded polymeric core (PI) and a JQ1 and gemcitabine elaidate coloaded liposomal shell (JGC/L-A) that has the ability to stimulate exosome secretion. By normalizing the CAF barrier to create a CAF "barrel" with JQ1, stimulating the secretion of gemcitabine-loaded exosomes from the CAF "barrel" to the deep tumor site, and leveraging the CAF "barrel" to secrete IL-12, PI/JGC/L-A realized effective drug delivery to the deep tumor site, activated antitumor immunity at the tumor site, and produced significant antitumor effects. In summary, our strategy of transforming the CAF barrier into antitumor drug depots represents a promising strategy against PDAC and might benefit the treatment of any tumors facing a drug delivery barrier.