LINC00998 Modulating M2 Macrophage Activation in Allergic Rhinitis by Stabilizing BOB.1 mRNA.

Background: Allergic rhinitis (AR) is globally recognized as a considerable threat to human health with a rising prevalence and a substantial medical and socioeconomic burden. Numerous studies have emphasized the significance of long noncoding RNAs (lncRNAs) in allergic responses. Hence, this research dealt with exploring the involvement of the lncRNA LINC00998 in the mechanism of AR. Methods: LINC00998 expression was assessed by qRT-PCR in peripheral blood mononuclear cells acquired from individuals with AR. Additionally, the potential relationship between LINC00998 and macrophage polarization was observed in vitro. Then we constructed AR mice model and macrophage polarization models using THP-1 cells as well as primary human macrophages to verify the M2 shift in AR and the low expression level of LINC00998 in M2 macrophages. We used gain- and loss-of-function experiments to explore the modification of LINC00998 in macrophage polarization. Furthermore, we explored the underlying mechanism of LINC00998 mediates through qRT-PCR, flow cytometry, and Western blot. Results: The analysis revealed a significant decrease in LINC00998 expression in the samples obtained from patients with AR. LINC00998 is markedly increased in M1 macrophages whereas decreased in M2 macrophages in vitro. Furthermore, suppression of LINC00998 caused a remarkable enhancement in M2 polarization, whereas its overexpression led to its attenuation. Knockdown of LINC00998 led to a remarkable downregulation of BOB.1 mRNA and protein, while overexpression of LINC00998 upregulated their expression. Moreover, it was found that BOB.1 modulated macrophage polarization through the PU.1/IL-1ß axis. Meanwhile, the modulation of LINC00098 overexpression on macrophage polarization and PU.1/ IL-1ß can be reversed by BOB.1 siRNA. Conclusion: This research revealed the lncRNA LINC00998 altered M2 macrophage polarization by regulating the BOB.1/PU.1/IL-1ß axis, which open up new avenues for studying the pathogenesis of AR.

Fluorescent bacterial cellulose@Zr-MOF via in-situ synthesis for efficient enrichment and sensitive detection of Cr(VI).

In this study, for the first time, a new Zr-metal-organic framework (MOF) with strong aggregation-induced emission was successfully grown on bacterial cellulose (BC) using an in situ synthesis method, yielding the fluorescent composite nanofiber BC@Zr-MOF. The BC with abundant hydroxyl groups, which can be uniformly wrapped in the interior of the MOF layer to form BC@Zr-MOF, was used as the growth template. The resulting composite nanofibers had a higher specific surface area (1, 116 m2/g), stronger fluorescence emission and better pH stability than MOF particles. In addition, BC@Zr-MOF exhibited selective recognition and enrichment of Cr2O72- in the aqueous phase and a high adsorption capacity of 90 mg/g. Moreover, because of the high aspect ratio and good tensile strength (6.73 N/mm2), BC@Zr-MOF nanofibers could be readily made into freestanding nanopapers via vacuum filtration, thus solving the molding and recycling problems of MOFs. The facilely prepared test paper could rapidly, sensitively and selectively detect Cr2O72- with the limit of detection (LOD) of 41.8 nM, which is nearly 500 times lower than that of the national drinking water standard. Moreover, the LOD of BC@Zr-MOF nanopapers, when used in combination with circulating filtration, decreases to 6.9 nM owing to the adsorption-enrichment effect.

Fluorescent Eu-MOF@nanocellulose-based nanopaper for rapid and sensitive detection of uranium (â ¥).

Radioactive uranium leaks into natural water bodies mainly in the form of uranyl ions (UO22+), posing ecological and human health risks. Fluorescent europium-based metal-organic frameworks (Eu-MOFs) have been demonstrated to be effective fluorescent sensors for UO22+, but the large size, powder state and poor dispersity limit their further application. In this work, fluorescent Eu-MOFs were in-situ grown on TEMPO-oxidized cellulose nanofibers (TOCNFs), which is the first time that spherical Eu-MOF crystals with sizes below 10 nm were prepared. Fluorescence spectral analysis revealed a nine-fold increase in the fluorescence intensity of TOCNF@Eu-MOF compared to Eu-MOF. The nanocomposites achieved rapid and sensitive fluorescence quenching to UO22+ through the "antenna effect" and unsaturated Lewis basic sites on the ligands binding with UO22+. Moreover, TOCNF@Eu-MOF demonstrated excellent selectivity and anti-interference for UO22+ detection. For the nanopaper-based sensor made from TOCNF@Eu-MOF, the Stern-Volmer quenching constant (KSV) was calculated as 8.21 × 104 M-1, and the lowest limit of detection (LOD) was 6.6 × 10-7 M, significantly lower than the 1.32 × 10-6 M of Eu-MOFs. In addition, the nanopaper exhibited good fluorescence stability and cyclic detection performance, enabling the rapid and convenient detection of UO22+ in the aqueous phase within 30 s by simple dipping.

Facile and scalable synthesis of Ni3S2/Fe3O4 nanoblocks as an efficient and stable electrocatalyst for oxygen evolution reaction.

This study employed a one-step hydrothermal process to synthesize Ni3S2/Fe3O4 nanoblocks in situ on nickel foam (NF). The resulting Ni3S2/Fe3O4/NF catalyst demonstrates exceptional electrocatalytic activity for the oxygen evolution reaction (OER) and robust long-term stability. It achieves a low overpotential of only 220 mV for a current density of 10 mA cm-2 with a Tafel slope of 54.1 mV dec-1 and remains stable in 1.0 M KOH for 66 h. The binder-free self-supported three-dimensional nanoblocks enhance the reaction region and long-term stability. Electronic interactions between Fe3O4 and Ni3S2, coupled with heterogeneous interfaces, optimize the electronic structure, fostering the formation of highly reactive species. Density-functional theory (DFT) calculations confirm that Ni3S2/Fe3O4, with a heterogeneous interfacial structure, modulates the chemisorption of reaction intermediates on the catalyst surface, optimizing the Gibbs free energies (ΔG) of oxygen-containing intermediates. The synergistic effect between the two active materials within the heterogeneous structure enhances OER catalytic performance. This finding offers a valuable approach to designing efficient and stable OER electrocatalysts.

Causal effects of gut microbiota in the development of lung cancer and its histological subtypes: A Mendelian randomization study.

BACKGROUND: Numerous studies have characterized the gut microbiome (GM) in lung cancer (LC). Yet, the causality between GM and LC and its subtypes remain uncharacterized. METHODS: Two-sample Mendelian randomization (MR) was designed to investigate the causal relationship between the GM and LC and its subtypes, using publicly available summary data of genome-wide association studies. The researchers ran two groups of MR analyses, including the genome-wide statistical significance threshold (5 × 10-8 ) and the locus-wide significance level (1 × 10-5 ). RESULTS: Using MR analysis, we ascertained 42 groups of GM that are intimately linked to LC and its subtypes at the locus-wide significance level. Of the 42 groups, 12 were in LC, nine in non-small cell lung cancer (NSCLC), six in small cell lung cancer (SCLC), two in lung adenocarcinomas, and 13 in lung squamous carcinomas. After false discovery rate correction, we still found a remarkable causal interaction between the Eubacterium ruminantium group and SCLC. Moreover, five groups of GM closely linked to LC and its subtypes were recognised at the genome-wide statistical significance threshold. This finding included one group each in LC, NSCLC and SCLC, two groups in lung adenocarcinoma and none in lung squamous carcinoma. None of the foregoing findings were heterogeneous or horizontal pleiotropy. Reverse MR revealed that genetic susceptibility to LC and its subtypes caused significant changes in three groups of GM. CONCLUSION: Our findings substantiate the causality between GM and LC and its subtypes. This study offers fresh insights into the function of GM in mediating the progression of LC.

α-mangostin derivatives ameliorated mouse DSS-induced chronic colitis via regulating Th17/Treg balance.

Th17 cell, an important subpopulation of helper T cell, plays an important role in the development of inflammatory bowel disease (IBD) and is thought to be a potential target for the treatment of IBD. In our previous study, we demonstrated that α-mangostin could relieve lupus nephritis via inhibiting Th17 cell function. In our preliminary study, we obtained four derivatives by adding chemical modification of α-mangostin which could also inhibit Th17 cell differentiation in vitro. In this study, we constructed a chronic IBD mouse model and demonstrated the therapeutic effects of α-mangostin and its derivatives as therapeutic agents for IBD. In compounds treating groups, intestinal inflammation showed significant improvement in symptoms which included weight loss, high disease activity index, colon length shorten and the change of intestinal flora. We also found that compounds could effectively either suppress the number of Th17 cell or increase the number of Treg cell detected by flow cytometry, thus reducing the Th17/Treg ratio and suppressing the level of intestinal inflammation. Notably, IL17-F levels, rather than IL17-A, were reduced in the colon of mice of compounds treating groups. Thus, α-mangostin and its derivatives ameliorate DSS-induced chronic colitis in mice by regulating Th17/Treg balance to alleviate intestinal inflammation and can modulate the intestinal microbial community. These results suggest that α-mangostin and its derivatives may be the new therapeutic option for chronic colitis.

Study on the reversal of epileptic drug resistance by tetramethylpyrazine in combination with carbamazepine through modulation of P-Glycoprotein expression in rat brain microvessel endothelial cell.

The purpose of this study was to detect the changes of P-Glycoprotein (P-GP) expression in rat brain microvessel endothelial cell line RBE4 after the action of Tetramethylpyrazine (TMP) on Carbamazepine (CBZ), so as to clarify the potential mechanism of TMP combined with CBZ against intractable epilepsy drug resistance. The RBE4 cell line was utilized for in vitro analysis. Cells were divided into control, CBZ, and CBZ-TMP group. The expression of P-GP was assessed using Western blot and reverse transcription polymerase chain reaction (RT-PCR). Intracellular concentration of CBZ was measured through high-performance liquid chromatography (HPLC). The differential expression of mRNA was evaluated by RNA sequencing. The intracellular concentration of CBZ in the CBZ-TMP group was significantly higher than that in other groups. The expression of P-GP in the CBZ group was significantly higher than that in the control group, while in the CBZ&TMP group, it was significantly lower than that in the other groups. Comparative analysis also revealed some differentially expressed genes. Compared with the CBZ group, FAM106A, SLC3A2, TENM2, etc. were upregulated most significantly in the CBZ&TMP group. ZBTB10, WDR7, STARD13, etc. were downregulated most significantly. Results suggest that TMP increases the intracellular concentration of CBZ, downregulates the expression of P-GP increased by CBZ, and modulates related cellular metabolism and signaling pathways, thus reversing the drug resistance mechanism of intractable epilepsy, providing a theoretical basis for the combination of traditional Chinese medicine and antiepileptic drugs.

Krukenberg Tumor of Gastric Origin in Pregnant Women with Preeclampsia.

Krukenberg tumor refers to a malignancy in the ovary that metastasizes from a primary site, classically the gastrointestinal tract. Pregnancy complicated with a Krukenberg tumor is very rare. In this report, we present two unusual cases of pregnant women with Krukenberg tumors of gastric origin. One case was a full-term pregnant woman with preeclampsia (PE) who underwent a caesarean section when bilateral enlarged ovaries were incidentally identified. Histopathology of the wedge resection biopsy showed single-ring cell carcinoma; this was followed by gastroscopy, which indicated a gastric origin. The woman received chemotherapy but died 6 months later. Another case was a pregnant woman at 30 gestational weeks with abdominal pain complicated with early-onset PE. Ultrasonography and magnetic resonance imaging showed bilateral enlarged ovaries and elevated tumor markers. Gastroscopy indicated linitis plastica. After an emergency caesarean section, adnexectomy was performed, and postoperative histopathology confirmed a Krukenberg tumor. The woman died 2 months after delivery. Gastrointestinal symptoms during pregnancy may indicate a malignancy of rare gastrointestinal origin. PE complicated with Krukenberg tumors in pregnancy should be considered in future studies.

ScSmOP: a universal computational pipeline for single-cell single-molecule multiomics data analysis.

Single-cell multiomics techniques have been widely applied to detect the key signature of cells. These methods have achieved a single-molecule resolution and can even reveal spatial localization. These emerging methods provide insights elucidating the features of genomic, epigenomic and transcriptomic heterogeneity in individual cells. However, they have given rise to new computational challenges in data processing. Here, we describe Single-cell Single-molecule multiple Omics Pipeline (ScSmOP), a universal pipeline for barcode-indexed single-cell single-molecule multiomics data analysis. Essentially, the C language is utilized in ScSmOP to set up spaced-seed hash table-based algorithms for barcode identification according to ligation-based barcoding data and synthesis-based barcoding data, followed by data mapping and deconvolution. We demonstrate high reproducibility of data processing between ScSmOP and published pipelines in comprehensive analyses of single-cell omics data (scRNA-seq, scATAC-seq, scARC-seq), single-molecule chromatin interaction data (ChIA-Drop, SPRITE, RD-SPRITE), single-cell single-molecule chromatin interaction data (scSPRITE) and spatial transcriptomic data from various cell types and species. Additionally, ScSmOP shows more rapid performance and is a versatile, efficient, easy-to-use and robust pipeline for single-cell single-molecule multiomics data analysis.

Diagnosis and treatment of HS after endoscopic thyroid surgery: case report and brief literature review.

Background: Horner's syndrome (HS) is a rare condition due to damage to the 3-neuron sympathetic pathway anywhere between the posterior-lateral nuclei of the hypothalamus and the oculosympathetic fiber, particularly as a post-thyroidectomy symptom. In this case report, we present a case of HS following endoscopic thyroid surgery (ETS) and briefly review the literature. Case report: During a routine physical examination, a 29-year-old female patient was incidentally found to have multiple nodules in the right thyroid. She was subsequently admitted to the Department of General Surgery for further examinations and treatment. A fine-needle aspiration biopsy confirmed malignancy in these nodules. As a result, the patient underwent radical resection of the right thyroid and ipsilateral central lymph node dissection using endoscopy. Pathological diagnosis revealed papillary thyroid carcinoma. Unexpectedly, on the third day after the operation, the patient was diagnosed with Horner's syndrome based on the presence of miosis and ptosis. After 1 week of follow-up, the symptoms related to HS significantly improved. Conclusion: Horner's syndrome is an uncommon complication of thyroidectomy in patients undergoing ETS. Therefore, it is crucial to perform careful operations and minimize iatrogenic surgical damage to reduce the incidence of HS. This case serves as a reminder that making rational judgments and implementing appropriate measures are essential for achieving a favorable prognosis and preserving facial esthetics.

Heterostructural NiSe-CoFe LDH as a highly effective and stable electrocatalyst for the oxygen evolution reaction.

Design and exploration of highly efficient oxygen evolution reaction (OER) electrocatalysts is an urgent task to realize the future ideals of the hydrogen economy. Non-precious metal-based nanomaterials have been widely developed as electrocatalysts to expedite reaction rate and solve the low efficiency problem of the OER. A novel nanocatalyst, NiSe-CoFe LDH, in which lamellar CoFe LDH covered the surface of NiSe, was fabricated through a simple chemical vapor deposition and hydrothermal method. The specific heterogeneous three-dimensional structure of NiSe-CoFe LDH showed impressive electrochemical performance towards the OER. When used as an OER electrocatalyst, the NiSe-CoFe LDH nanomaterial afforded an overpotential of 228 mV to attain 10 mA cm-2. Furthermore, NiSe-CoFe LDH also maintained excellent stability with negligible activity after chronopotentiometry measurement for 60 hours.

Predictive Value of Eosinophil Cationic Protein in Nasal Secretions in Eosinophilic Chronic Rhinosinusitis.

OBJECTIVES: To investigate the value of secretions Eosinophilic cationic protein (ECP) detection in the diagnosis of endotypes of Chronic rhinosinusitis (CRS) and its correlation with clinical symptoms, so as to provide guidance for the clinical application of EOS and ECP detection in secretions. METHODS: Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their EOS% and ECP levels were measured. Correlation analysis was performed for EOS% and ECP levels in secretions and tissues, respectively. The correlation between secretions EOS% and ECP and clinical symptom scores (symptomatic visual analog scale (VAS) scores, Lanza-kennedy scores from nasal endoscopy and Lund-Mackay scores from sinus CT) was further analyzed. Receiver operating characteristic curves were used to assess the predictive potential of EOS% and ECP in nasal secretions. RESULTS: Eosinophilic chronic rhinosinusitis (ECRS) patients had higher concentrations of ECP in nasal secretions than healthy subjects and NECRS (non-eosinophilic CRS) (p < 0.0001;0.0001); EOS% in nasal secretions was higher in ECRS than healthy subjects (p = 0.0055), but the differences between ECRS and NECRS were not statistically significant (p = 0.0999). Correlation analysis showed that tissue EOS% was correlated with ECP concentration and EOS% in nasal secretions (R = 0.5943;0.2815). There was a correlation between EOS% in secretions with a total LM score (R = 0.3131); ECP concentration in secretions with a total LK score (R = 0.3792). To diagnose ECRS, the highest area under the curve (0.8230) was determined for ECP in secretions; the highest area under the curve (0.6635) was determined for EOS% in secretions. CONCLUSION: Measurement of ECP in nasal secretions is useful for non-invasive diagnosis of ECRS. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3304-3312, 2023.

Multiscale stiffness of human emphysematous precision cut lung slices.

Emphysema is a debilitating disease that remodels the lung leading to reduced tissue stiffness. Thus, understanding emphysema progression requires assessing lung stiffness at both the tissue and alveolar scales. Here, we introduce an approach to determine multiscale tissue stiffness and apply it to precision-cut lung slices (PCLS). First, we established a framework for measuring stiffness of thin, disk-like samples. We then designed a device to verify this concept and validated its measuring capabilities using known samples. Next, we compared healthy and emphysematous human PCLS and found that the latter was 50% softer. Through computational network modeling, we discovered that this reduced macroscopic tissue stiffness was due to both microscopic septal wall remodeling and structural deterioration. Lastly, through protein expression profiling, we identified a wide spectrum of enzymes that can drive septal wall remodeling, which, together with mechanical forces, lead to rupture and structural deterioration of the emphysematous lung parenchyma.

Diagnostic value of myeloperoxidase and eosinophil cationic protein in nasal secretions for endotypes of chronic rhinosinusitis.

OBJECTIVES: To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions. METHODS: We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions. RESULTS: Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions. CONCLUSIONS: Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.

Mycobacterium bovis BCG Given at Birth Followed by Inactivated Respiratory Syncytial Virus Vaccine Prevents Vaccine-Enhanced Disease by Promoting Trained Macrophages and Resident Memory T Cells.

Respiratory syncytial virus (RSV) infects more than 60% of infants in their first year of life. Since an experimental formalin-inactivated (FI) RSV vaccine tested in the 1960s caused enhanced respiratory disease (ERD), few attempts have been made to vaccinate infants. ERD is characterized by Th2-biased responses, lung inflammation, and poor protective immune memory. Innate immune memory displays an increased nonspecific effector function upon restimulation, a process called trained immunity, or a repressed effector function upon restimulation, a process called tolerance, which participates in host defense and inflammatory disease. Mycobacterium bovis bacillus Calmette-Guérin (BCG) given at birth can induce trained immunity as well as heterologous Th1 responses. We speculate that BCG given at birth followed by FI-RSV may alleviate ERD and enhance protection through promoting trained immunity and balanced Th immune memory. Neonatal mice were given BCG at birth and then vaccinated with FI-RSV+Al(OH)3. BCG/FI-RSV+Al(OH)3 induced trained macrophages, tissue-resident memory T cells (TRM), and specific cytotoxic T lymphocytes (CTL) in lungs and inhibited Th2 and Th17 cell immune memory, all of which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH)3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH)3 prevented the innate tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or TRM in lungs but not memory T cells in spleens. Therefore, BCG given at birth to regulate trained immunity and TRM may be a new strategy for developing safe and effective RSV killed vaccines for young infants. IMPORTANCE RSV is the leading cause of severe lower respiratory tract infection of infants. ERD, characterized by Th2-biased responses, inflammation, and poor immune memory, has been an obstacle to the development of safe and effective killed RSV vaccines. Innate immune memory participates in host defense and inflammatory disease. BCG given at birth can induce trained immunity as well as heterologous Th1 responses. Our results showed that BCG/FI-RSV+Al(OH)3 induced trained macrophages, TRM, specific CTL, and balanced Th cell immune memory, which contributed to inhibition of ERD and increased protection. Notably, FI-RSV+Al(OH)3 induced tolerant macrophages, while BCG/FI-RSV+Al(OH)3 prevented tolerance through promoting trained macrophages. Moreover, inhibition of ERD was attributed to trained macrophages or TRM in lungs but not memory T cells in spleens. BCG at birth as an adjuvant to regulate trained immunity and TRM may be a new strategy for developing safe and effective RSV killed vaccines for young infants.

Nitrogen-doped Fe2O3/NiTe2 as an excellent bifunctional electrocatalyst for overall water splitting.

The development of inexpensive, high efficiency electrocatalysts is a major challenge for electrolytic water to hydrogen production. Herein, an efficient porous nanoblock catalyst N-doped Fe2O3/NiTe2 heterojunction for overall water splitting is reported. Notably, the obtained 3D self-supported catalysts exhibit good hydrogen evolution. reaction (HER) activity and oxygen evolution reaction (OER) properties in alkaline solution (only 70 mV and 253 mV of overpotential are needed to provide 10 mA cm-2 current density, respectively). This is mainly due to the N-doped electronic structure optimized, the strong electronic interaction between Fe2O3 and NiTe2 that facilitates rapid electron transfer, the porous structure which allows the catalyst to have large surface area for effective gas release, and their synergistic effect. When used as a dual function catalyst with overall water splitting, it achieved a current density of 10 mA cm-2 under 1.54 V with good durability (at least 42 h). The present work provides a new methodology for the study of high-performance, low-cost, and corrosion-resistant bifunctional electrocatalysts.

Maternal Group B Streptococcal Rectovaginal Colonization after Intrapartum Antibiotic Prophylaxis.

Maternal rectovaginal colonization with Group B Streptococcus (GBS) during labor is a prerequisite for neonatal early-onset GBS disease. Intrapartum antibiotic prophylaxis (IAP) has been proven to prevent GBS perinatal infection, while there are few studies on the evaluation of the effectiveness of different antibiotic prophylaxis regimens. This study aimed to assess the maternal rectovaginal GBS colonization status after IAP, antimicrobial susceptibility and maternal and neonatal outcomes among women administered different antibiotic prophylaxis regimens. A prospective study was conducted between June 2018 and June 2022. GBS carriers identified at 35-37 weeks of gestation were provided IAP (penicillin, cefazolin or clindamycin) at delivery based on the local protocol for GBS prevention. Rectovaginal samples were obtained from participants again after delivery. Antimicrobial susceptibility testing in GBS isolates was performed using the broth microdilution method. A total of 295 cases were included in this study. In the postpartum re-examination for GBS, the overall negative rectovaginal culture rate was 90.8% (268/295). Women who received cefazolin prophylaxis had the highest negative culture rate (95.2%, 197/207), which was followed by those who received penicillin (80.7%, 67/83) and clindamycin (80.0%, 4/5) (p = 0.001). All GBS isolates achieved sensitivity to penicillin and cefazolin, whereas resistance to clindamycin was shown in 21.4% of the strains. There were no significant differences in maternal and neonatal outcomes among the IAP groups. The use of IAP is highly effective in reducing the maternal rectovaginal GBS colonization. Cefazolin may offer equivalent efficacy and safety compared to standard penicillin prophylaxis.

A Mendelian randomization study of the effect of tea intake on breast cancer.

Background: The relationship between tea consumption and the risk of breast cancer is inconsistent in previous observational studies and is still in dispute. We intended to detect the causal association between tea consumption and breast cancer risk using two-sample Mendelian randomization (MR) analysis. Materials and methods: The summary statistics of tea consumption was obtained from the UK Biobank Consortium with 349,376 individuals and breast cancer information was obtained from the Breast Cancer Association Consortium (BCAC) (122,977 cases and 105,974 non-cases). Sensitivity analyses of evaluating the influence of outliers and pleiotropy effects were performed by a variety of MR methods under different model assumptions. Results: After potentially excluding pleiotropic single nucleotide polymorphisms (SNPs) using the MR Pleiotropy RESidual Sum and Outlier method, the odds ratio (OR) for per extra daily cup of tea intake for overall, estrogen receptor (ER)-positive, and ER-negative breast cancer risk was 1.029 [95% confidence interval (CI) = 0.983-1.077, P = 0.2086], 1.050 (95% CI = 0.994-1.109, P = 0.078), and 1.081 (95% CI = 0.990-1.103, P = 0.6513), respectively. The results were consistent with a sensitivity analysis that excluded SNPs associated with other phenotypes, manifesting that the findings were convincing and robust. Moreover, in the multivariable MR analysis, the null associations for breast cancer risk remained after adjusting for smoking and alcohol consumption separately or together. Conclusion: Our MR results based on genetic data did not support a causal relationship between tea consumption and breast cancer risk.

Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood of mice.

Background: Infants with respiratory syncytial virus (RSV)-associated bronchiolitis are at increased risk of childhood asthma. Recent studies demonstrated that certain infections induce innate immune memory (also termed trained immunity), especially in macrophages, to respond more strongly to future stimuli with broad specificity, involving in human inflammatory diseases. Metabolic reprogramming increases the capacity of the innate immune cells to respond to a secondary stimulation, is a crucial step for the induction of trained immunity. We hypothesize that specific metabolic reprogramming of lung trained macrophages induced by neonatal respiratory infection is crucial for childhood allergic asthma. Objective: To address the role of metabolic reprogramming in lung trained macrophages induced by respiratory virus infection in allergic asthma. Methods: Neonatal mice were infected and sensitized by the natural rodent pathogen Pneumonia virus of mice (PVM), a mouse equivalent strain of human RSV, combined with ovalbumin (OVA). Lung CD11b+ macrophages in the memory phase were re-stimulated to investigate trained immunity and metabonomics. Adoptive transfer, metabolic inhibitor and restore experiments were used to explore the role of specific metabolic reprogramming in childhood allergic asthma. Results: PVM infection combined with OVA sensitization in neonatal mice resulted in non-Th2 (Th1/Th17) type allergic asthma following OVA challenge in childhood of mice. Lung CD11b+ macrophages in the memory phage increased, and showed enhanced inflammatory responses following re-stimulation, suggesting trained macrophages. Adoptive transfer of the trained macrophages mediated the allergic asthma in childhood. The trained macrophages showed metabolic reprogramming after re-stimulation. Notably, proline biosynthesis remarkably increased. Inhibition of proline biosynthesis suppressed the development of the trained macrophages as well as the Th1/Th17 type allergic asthma, while supplement of proline recovered the trained macrophages as well as the allergic asthma. Conclusion: Proline metabolism reprogramming of trained macrophages induced by early respiratory infection combined with allergen sensitization contributes to development of allergic asthma in childhood. Proline metabolism could be a well target for prevention of allergic asthma in childhood.