Positive feedback regulation between RpoS and BosR in the Lyme disease pathogen.

In Borrelia burgdorferi, the Lyme disease pathogen, differential gene expression is primarily controlled by the alternative sigma factor RpoS (σS). Understanding how RpoS levels are regulated is crucial for elucidating how B. burgdorferi is maintained throughout its enzootic cycle. Our recent studies have shown that a homolog of Fur/PerR repressor/activator, BosR, functions as an RNA-binding protein that controls the rpoS mRNA stability. However, the mechanisms of regulation of BosR, particularly in response to host signals and environmental cues, remain largely unclear. In this study, we revealed a positive feedback loop between RpoS and BosR, where RpoS post-transcriptionally regulates BosR levels. Specifically, mutation or deletion of rpoS significantly reduced BosR levels, while artificial induction of rpoS resulted in a dose-dependent increase in BosR levels. Notably, RpoS does not affect bosR mRNA levels but instead modulates the turnover rate of the BosR protein. Furthermore, we demonstrated that environmental cues do not directly influence bosR expression but instead induce rpoS transcription and RpoS production, thereby enhancing BosR protein levels. This discovery adds a new layer of complexity to the RpoN-RpoS pathway and suggests the need to re-evaluate the factors and signals previously believed to regulate RpoS levels through BosR.

[A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children].

Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Isolator-free 60†W diamond Raman laser at 607†nm.

We report an intra-cavity frequency doubled diamond Raman laser operating at 607 nm. A z-fold cavity design was configured to prevent back reflections into the fiber amplifier, which avoided the use of isolators in the pump beam path. A maximum output power of 60 W was generated in two output beams at an optical conversion efficiency of 28% from the 1045 nm pump. A maximum single-beam output power of 40 W was obtained using a highly reflecting end mirror for the visible. Output power and single frequency stability are negatively impacted by an increasing role of stimulated Brillouin scattering at output powers above 10 W.

An IL-23-STAT4 pathway is required for the proinflammatory function of classical dendritic cells during CNS inflammation.

Although many cytokine pathways are important for dendritic cell (DC) development, it is less clear what cytokine signals promote the function of mature dendritic cells. The signal transducer and activator of transcription 4 (STAT4) promotes protective immunity and autoimmunity downstream of proinflammatory cytokines including IL-12 and IL-23. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), Stat4-/- mice are resistant to the development of inflammation and paralysis. To define whether STAT4 is required for intrinsic signaling in mature DC function, we used conditional mutant mice in the EAE model. Deficiency of STAT4 in CD11c-expressing cells resulted in decreased T cell priming and inflammation in the central nervous system. EAE susceptibility was recovered following adoptive transfer of wild-type bone marrow-derived DCs to mice with STAT4-deficient DCs, but not adoptive transfer of STAT4- or IL-23R-deficient DCs. Single-cell RNA-sequencing (RNA-seq) identified STAT4-dependent genes in DC subsets that paralleled a signature in MS patient DCs. Together, these data define an IL-23-STAT4 pathway in DCs that is key to DC function during inflammatory disease.

Effect of temperature on the rheological, textural, and sensory properties of butters from New Zealand market.

Texture and sensory studies at various temperatures are important in evaluating and improving the functionality of butter. While literature is scarce, we evaluated and compared the effect of temperature (5-25°C) on the texture, rheological and sensory properties of commercial butter samples (salted, unsalted, cultured, and spreadable) from the New Zealand market. In addition, the instrumental analyses were compared with the sensory evaluation, to understand the possibility of using instrumental analysis to evaluate consumer liking for different butters. Butter type, temperature, and their type-temperature interaction exhibited significant differences for all instrumental textural parameters. As expected, higher temperature produced softer butter that was more spreadable, liquid-like, less adhesive, less cohesive, had lower storage modulus (G') and lower loss modulus (G″) with the melting of milk fat crystals; however, the rate of change varied for the different butter samples. We have established meltability as the parameter for evaluating butter selection for different applications. The spreadable butter sample exhibited the lowest hardness and G', and highest spreadability (p < .05) at all temperatures, owing to its low solid fat content and the abundance of low-melting triglycerides. The cultured butter sample had the highest melting point, owing to compositional differences. The instrumental and sensory texture analyses were highly correlated, indicating the comparative effectiveness of both approaches for studying the effects of different temperatures on butter textural properties. Overall, our findings provide detailed reference to the dairy industry for butter manufacture, considering variation in fatty acid composition, texture analysis, rheology, and sensory analysis, over the range of storage/usage temperatures.

Inverse Spin Hall Effect Dominated Spin-Charge Conversion in (101) and (110)-Oriented RuO_{2} Films.

Utilizing spin pumping, we present a comparative study of the spin-charge conversion in RuO_{2}(101) and RuO_{2}(110) films. RuO_{2}(101) shows a robust in-plane crystal-axis dependence, whereas RuO_{2}(110) exhibits an isotropic but stronger one. Symmetry-based analysis and first-principles calculations reveal that the spin-charge conversion in RuO_{2}(110) originates from the inverse spin Hall effect (ISHE) due to nodal lines splitting. In RuO_{2}(101), the ISHE also dominates although the inverse spin splitting effect (ISSE) may coexist. These findings, in sharp contrast to previously attributed ISSE, are further corroborated by the reciprocal relation between the spin pumping and the spin-torque ferromagnetic resonance measurements.

Borrelia burgdorferi Secretes c-di-AMP as an Extracellular Pathogen-Associated Molecular Pattern to Elicit Type I Interferon Responses in Mammalian Hosts.

Borrelia burgdorferi (B. burgdorferi), an extracellular spirochetal pathogen, elicits a type-I interferon (IFN-I) response that contributes to the pathology of Lyme disease, including the development and severity of Lyme arthritis. However, the specific Pathogen-Associated Molecular Patterns (PAMPs) of B. burgdorferi responsible for triggering the IFN-I response are not well understood. Previous studies have identified an unknown, nuclease-resistant component in B. burgdorferi culture supernatants that significantly stimulates the IFN-I response, but its identity remains unknown. In this study, we reveal that B. burgdorferi secretes cyclic-di-adenosine monophosphate (c-di-AMP) as a key extracellular PAMP, inducing the host IFN-I response in macrophages. Using genetically manipulated B. burgdorferi strains, we demonstrate a requirement of c-di-AMP for stimulating IFN-I response by macrophages ex vivo. Additionally, infecting mice with B. burgdorferi alongside exogenous c-di-AMP resulted in a markedly increased IFN-I response in mouse tissues. Furthermore, inactivation or inhibition of the host STING signaling pathway significantly reduced the IFN-I response, indicating that c-di-AMP-induced IFN-I production is STING-dependent. Our findings identify c-di-AMP as a crucial PAMP secreted by B. burgdorferi to elicit the host IFN-I response via activation of STING signaling pathway, suggesting that targeting c-di-AMP production could represent a novel therapeutic strategy against Lyme arthritis.

A bright burst from FRB 20200120E in a globular cluster of the nearby galaxy M81.

Fast radio bursts (FRBs) are immensely energetic millisecond-duration radio pulses. Observations indicate that nearby FRBs can be produced by old stellar populations, as suggested by the localization of the repeating source FRB 20200120E in a globular cluster of M81. Nevertheless, the burst energies of FRB 20200120E are significantly smaller than those of other cosmological FRBs. Here, we report the detection of a bright burst from FRB 20200120E in 1.1 - 1.7 GHz, with a fluence of approximately 30 Jy ms, which is more than 42 times larger than the previously detected bursts near 1.4 GHz frequency. It reaches one-third of the energy of the weakest burst from FRB 20121102A and is detectable at a distance exceeding 200 Mpc. Our finding bridges the gap between nearby and cosmological FRBs and indicates that FRBs hosted in globular clusters can be bright enough to be observable at cosmological distances.

[Current situation of surgical treatment of gallbladder polyps and some problems that should be paid attention to].

Gallbladder polyp is a common disease of gallbladder, the incidence of gallbladder polyp in China is about 5%~10%, and the trend is increasing year by year. The patients with gallbladder polyps had no obvious clinical symptoms, which was more than that found by ultrasonography during physical examination. At present, the diameter of gallbladder polyps>10 mm is still used by clinicians as the main surgical indication for cholecystectomy. According to the data, about 80% to 90% of gallbladder polyps are cholesterol type polyps and benign gallbladder polyps. For these patients whose gallbladder is removed due to benign gallbladder polyps, we consider that we can continue to observe or retain the gallbladder, without having to bear the adverse consequences that may be caused by gallbladder removal. Based on the literature analysis at home and abroad, this paper discusses the surgical treatment of gallbladder polyps and the results of postoperative pathological diagnosis, and reminds the majority of clinicians to be careful when removing gallbladder polyps.

[Recombinant Schistosoma japonicum cystatin alleviates acute liver injury in mice by inhibiting endoplasmic reticulum stress, inflammation and hepatocyte apoptosis].

OBJECTIVE: To investigate the protective effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) against acute liver injury induced by lipopolysaccharide (LPS) and D-GalN in mice. METHODS: Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling (n=18), and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling. The survival of the remaining 10 mice in each group within 24 h was observed. Serum levels of ALT, AST, TNF-α and IL-6 of the mice were measured, and liver pathologies was observed with HE staining. The hepatic expressions of macrophage marker CD68, Bax, Bcl-2 and endoplasmic reticulum stress (ERS)-related proteins were detected using immunohistochemistry or immunoblotting, and TUNEL staining was used to detect hepatocyte apoptosis. RESULTS: The survival rates of PBS- and rSj-Cys-treated mouse models of acute liver injury were 30% and 80% at 12 h and were 10% and 60% at 24 h after modeling, respectively; no death occurred in the two control groups within 24 h. The mouse models showed significantly increased serum levels of AST, ALT, IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax, lowered expression of Bcl-2, increased hepatocyte apoptosis, and up-regulated expressions of ERS-related signaling pathway proteins GRP78, CHOP and NF-κB p-p65. Treatment of the mouse models significantly lowered the levels of AST, ALT, IL-6 and TNF-α, alleviated liver pathologies, reduced hepatic expressions of CD68, Bax, GRP78, CHOP and NF-κB p-p65, and enhanced the expression of Bcl-2. In the normal control mice, rSj-Cys injection did not produce any significant changes in these parameters compared with PBS. CONCLUSION: rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS, attenuating inflammation and inhibiting hepatocyte apoptosis.

A nomogram for predicting low cardiac output syndrome in older patients undergoing acute type A aortic dissection surgery.

OBJECTIVE: Low cardiac output syndrome (LCOS) is a dangerous postoperative complication in patients with acute type A aortic dissection (ATAAD). This study aims to develop and evaluate a nomogram model that can reliably identify risk variables for postoperative LCOS in elderly patients suffering from ATAAD. PATIENTS AND METHODS: In this retrospective study, a total of 310 elderly patients with ATAAD admitted to Fujian Medical University Union Hospital were included and categorized into the LCOS and non-LCOS groups. Stepwise logistic regression was used to analyze independent predictors of LCOS, and a nomogram was constructed. The best clinical decision points were found using decision analysis and a clinical impact curve. RESULTS: Postoperative LCOS occurred in 22 (7.1%) of elderly patients with ATAAD. Independent risk factors for postoperative LCOS were age, smoking history, aortic cross-clamp (ACC), coronary heart disease (CHD), and preoperative shock. The nomogram constructed based on the identified risk factors showed good performance. CONCLUSIONS: Our results suggest that preventive treatment can be administered when needed when the risk of LCOS in older patients with ATAAD after surgery is >60%. This study contributes to developing a methodology that may improve therapeutic decision-making in older patients and provides insights for assessing the risk of LCOS.

[Genotype and phenotype of WWOX gene related developmental and epileptic encephalopathy].

Objective: To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE). Methods: Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children's Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children's characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed. Results: Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

[Clinical features and outcomes of digestive tract perforation in pediatric mature B-cell non-Hodgkin lymphoma].

To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage Ⅲ to Ⅳ. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.

[Research progress on the characteristics of gut microbiome in early life and its influence on atopic march].

Allergic diseases are affected by both genetic background and environmental factors.In recent years, many studies have shown that allergic diseases are closely related to the gut microbiome.This article will elaborate on the composition of gut microbiome in early life and its relationship with allergies, the mechanism of action, and the influence of gut microbiome colonization on the atopic march, in order to improve the understanding of the relationship between allergy prevention or treatment and gut microbiome in children, and provide new ideas for the early prevention of allergic diseases and the early intervention of allergic processes.

[Analysis of allergen-specific IgE in children with atopic dermatitis from 2021 to 2023 in a hospital of pediatric in Tianjin City].

Objective: To explore the distribution of allergen-specific IgE (sIgE) for children with atopic dermatitis in Tianjin City and provide the evidences of clinical diagnosis and treatment. Methods: A retrospective cross-sectional study was conducted to analyze the children who were suspected of atopic dermatitis and tested for serum sIgE in the Tianjin Children's Hospital from March 2021 to February 2023. Using first detection results only, a total of 1 841 serum samples were tested for twenty common allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children's characteristics and factors such as different sexes, ages and seasons by the mass data. Results: Among the 1 841 cases, the results showed that 1 247 (67.73%) were sensitized to at least 1 allergen-sIgE, comprising to 49.86% (918/1 841) to food allergen-sIgE and 47.96% (883/1 841) to aeroallergen-sIgE. The top three food allergens-sIgE were egg 32.10% (591/1 841), milk 25.91% (477/1 841) and wheat flour 14.61% (269/1 841); the top three positive rates of aeroallergens-sIgE were house dust 24.33% (448/1 841), alternaria 20.59% (379/1 841) and dermatophagoides farinae 14.83% (273/1 841). The positive rates of food allergens-sIgE were the highest in the 1-3 years old group (64.11%, 434/677) (χ2=122.854, P<0.001), while the positive rates of aeroallergens-sIgE were higher in the 11-14 years old group (71.26%, 62/87) (χ2=134.968, P<0.001). No seasonal difference was revealed in the overall positive rate of food allergen-sIgE and aeroallergen-sIgE (χ2=4.047, P=0.256; χ2=7.549, P=0.056). The positive rates of soybean-sIgE and milk-sIgE were the highest in summer (χ2=11.329, P=0.010; χ2=28.720, P<0.001), whereas alternaria-sIgE and mugwort-sIgE were the highest in summer and autumn, respectively (χ2=8.462, P=0.037; χ2=10.641, P=0.014). Among the 1 841 cases, 32.21% were sensitized to three or more allergens-sIgE. The sIgE concentration levels of egg, milk and house dust were mainly level 1 to 2, and the proportions of level 3 and above were all under 15%; although the positive rates of crab, shrimp, and peanut were low, the proportions of grade 3 and above were all beyond 30%. Children sensitized to alternaria, dermatophagoides farinae, mugwort, and cat dander had higher sIgE concentration levels, which were 68.07%, 49.45%, 56.57% and 47.83% respectively. Conclusions: This study can reflect the epidemic characteristics of allergen-sIgE in children with atopic dermatitis in Tianjin region to a certain extent. Allergen-sIgE positivity in patients differed by age, and there were seasonal differences and grade distribution differences in the positive rates of some allergens-sIgE. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of atopic dermatitis.

[Research progress on the effects of exposure to major persistent organic pollutants during pregnancy on the functional development of nervous system in children].

Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.