Boosting Volatile fatty acids (VFAs) production in fermentation microorganisms through genes expression control: Unraveling the role of iron homeostasis transcription factors.

Iron (Fe0, Fe (II), and Fe (III)) has been previously documented to upregulate the expression of key genes, enhancing the production of volatile fatty acids (VFAs) to achieve waste/wastewater resource recovery. However, the precise mechanism by why iron influences gene expression remains unclear. This study applied iron-assisted fermentation systems to explore the behind enhancing mechanism by constructing regulon networks among genes, microbes, and transcription factors. In iron-conditioned systems, a significant enhancement in VFAs production and upregulation of genes expression (1.19-3.92 folds) related to organic conversion and the electron transfer chain was observed. Besides, gene co-expression network and Procrustes analysis identified ten hub transcription factors (e.g., arsR, crp, iscR, perR) and their major contributors (genus) (e.g., Paludibacter, Acinetobacter, Tolumonas). Further analysis suggested that most of hub transcription factors were implicated in iron homeostasis regulation, which speculated that the induced iron homeostasis transcription factors probably effectively regulated the expression of genes encoding enzymes involving in VFAs production and electron transfer of functional microbes, in the case of Paludibacter, Acinetobacter, and Tolumonas while regulating the iron homeostasis, resulting in the efficient production of VFAs in iron-conditioned systems. This study might contribute to an enhanced understanding of the underlying genetic mechanisms by why iron influences gene expression regulation of microbes, which also provides a genetic theoretical basis for improving system VFAs production and resource recovery.

Establishment of acquired tracheoesophageal fistula using a modified magnetic compression technique in rabbits and its postmodeling evaluation.

BACKGROUND: Previous studies have validated the efficacy of both magnetic compression and surgical techniques in creating rabbit tracheoesophageal fistula (TEF) models. Magnetic compression achieves a 100% success rate but requires more time, while surgery, though less frequently successful, offers rapid model establishment and technical maturity in larger animal models. AIM: To determine the optimal approach for rabbit disease modeling and refine the process. METHODS: TEF models were created in 12 rabbits using both the modified magnetic compression technique and surgery. Comparisons of the time to model establishment, success rate, food and water intake, weight changes, activity levels, bronchoscopy findings, white blood cell counts, and biopsies were performed. In response to the failures encountered during modified magnetic compression modeling, we increased the sample size to 15 rabbit models and assessed the repeatability and stability of the models, comparing them with the original magnetic compression technique. RESULTS: The modified magnetic compression technique achieved a 66.7% success rate, whereas the success rate of the surgery technique was 33.3%. Surviving surgical rabbits might not meet subsequent experimental requirements due to TEF-related inflammation. In the modified magnetic compression group, one rabbit died, possibly due to magnet corrosion, and another died from tracheal magnet obstruction. Similar events occurred during the second round of modified magnetic compression modeling, with one rabbit possibly succumbing to aggravated lung infection. The operation time of the first round of modified magnetic compression was 3.2 ± 0.6 min, which was significantly reduced to 2.1 ± 0.4 min in the second round, compared to both the first round and that of the original technique. CONCLUSION: The modified magnetic compression technique exhibits lower stress responses, a simple procedure, a high success rate, and lower modeling costs, making it a more appropriate choice for constructing TEF models in rabbits.

Accessible Autonomous Transportation and Services: Design Considerations From the Perspective of Consumers and Providers.

OBJECTIVE: To understand the priorities and preferences of people with disabilities (PwDs) and older adults regarding accessible autonomous vehicles (AVs) to address existing transportation barriers. DESIGN: Two national surveys, Voice of the Consumer and Voice of the Provider, were conducted to gather feedback from accessible AV consumers and providers, respectively, in the United States. SETTING: This U.S.-based study focused on PwDs and older adults who may face transportation challenges and those who provide or design AV solutions. PARTICIPANTS: The 922 consumers and 45 providers in the surveys encompassed a diverse range of disability types, caregiver roles, and age groups (N = 967). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The main outcomes were consumer usage needs and provider preferences for features in accessible autonomous transportation. Patterns in usage needs and feature preferences through 2-step clustering algorithm were applied subsequent to the descriptive analysis of participant demographics and their responses. RESULTS: Participants strongly preferred AV features enhancing personal transportation, especially for rural medical appointments. Most sought comprehensive AV automated features. Wheelchair users emphasized accessible entrances, particularly for lower-income brackets ($25,000-$49,000). Provider priorities closely aligned with consumer preferences, reinforcing content validity. CONCLUSIONS: The study highlights the importance of prioritizing wheelchair accessibility in AVs and improving access to medical appointments, especially in rural and low-income communities. Implications include developing inclusive AV services for PwDs and underserved populations. The research establishes a foundation for a more equitable and accessible transportation landscape through AV technology integration.

Maternal folic acid supplementation to prevent preeclampsia: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review was to examine the association between folic acid supplementation during pregnancy and the risk of preeclampsia. METHODS: Relevant studies were included by searching Embase, PubMed, Scope, Web of science, Cochrane Library databases. Studies were reviewed according to prespecified inclusion and exclusion criteria. Study characteristics were summarized, and study quality was assessed. Risk ratios (RR) and 95% confidence intervals (CI) were used as indicators of effect to assess the relationship between folic acid supplementation and risk of preeclampsia. RESULTS: The protocol of this study was prospectively registered with the PROSPERO (registration No. CRD42022380636). A total of nine studies were included, divided into three groups according to the type of study, containing a total of 107 051 and 105 222 women who were supplemented and not supplemented with folic acid during pregnancy. The results showed that folic acid supplementation during pregnancy could not be proven to reduce the risk of preeclampsia. CONCLUSION: The results of the study suggest that folic acid supplementation alone is not associated with a decreased risk of pre-eclampsia,but the inferences are somewhat limited by the low methodological quality of the included literature, and therefore higher quality studies are needed to prove this point.

irGSEA: the integration of single-cell rank-based gene set enrichment analysis.

irGSEA is an R package designed to assess the outcomes of various gene set scoring methods when applied to single-cell RNA sequencing data. This package incorporates six distinct scoring methods that rely on the expression ranks of genes, emphasizing relative expression levels over absolute values. The implemented methods include AUCell, UCell, singscore, ssGSEA, JASMINE and Viper. Previous studies have demonstrated the robustness of these methods to variations in dataset size and composition, generating enrichment scores based solely on the relative gene expression of individual cells. By employing the robust rank aggregation algorithm, irGSEA amalgamates results from all six methods to ascertain the statistical significance of target gene sets across diverse scoring methods. The package prioritizes user-friendliness, allowing direct input of expression matrices or seamless interaction with Seurat objects. Furthermore, it facilitates a comprehensive visualization of results. The irGSEA package and its accompanying documentation are accessible on GitHub (https://github.com/chuiqin/irGSEA).

Sijunzi decoction alleviates inflammation and intestinal epithelial barrier damage and modulates the gut microbiota in ulcerative colitis mice.

Ethnopharmacological relevance: As a representative classical prescription, Sijunzi decoction has powerful therapeutic effects on spleen-stomach qi insufficiency. Ulcerative colitis (UC) is a chronic, diffuse, and non-specifically inflammatory disorder, the etiology of which still remains unclear. In the traditional Chinese medicine (TCM) perspective, splenic asthenia is the primary cause of UC. Based on this, Sijunzi decoction has been extensively used in TCM clinical practice to alleviate UC in recent years. However, the pharmacological mechanism of Sijunzi decoction in modern medicine is still not completely clear, which limits its clinical application. Aim of the study: The purpose of this study was to investigate the Sijunzi decoction's curative effect on acute UC mice and probe into its potential pharmacological mechanism. Materials and methods: The UC mouse model was set up by freely ingesting a 3% dextran sulfate sodium (DSS) solution. The relieving role of Sijunzi decoction on UC in mice was analyzed by evaluating the changes in clinical parameters, colon morphology, histopathology, inflammatory factor content, intestinal epithelial barrier protein expression level, and gut microbiota balance state. Finally, multivariate statistical analysis was conducted to elucidate the relationship between inflammatory factors, intestinal epithelial barrier proteins, and gut microbiota. Results: First, the research findings revealed that Sijunzi decoction could visibly ease the clinical manifestation of UC, lower the DAI score, and attenuate colonic damage. Moreover, Sijunzi decoction could also significantly inhibit IL-6, IL-1ß, and TNF-α while increasing occludin and ZO-1 expression levels. Subsequently, further studies showed that Sijunzi decoction could remodel gut microbiota homeostasis. Sijunzi decoction was beneficial in regulating the levels of Alistipes, Akkermansia, Lachnospiraceae_NK4A136_group, and other bacteria. Finally, multivariate statistical analysis demonstrated that key gut microbes were closely associated with inflammatory factors and intestinal epithelial barrier proteins. Conclusion: Sijunzi decoction can significantly prevent and treat UC. Its mechanism is strongly associated with the improvement of inflammation and intestinal epithelial barrier damage by regulating the gut microbiota.

The efficacy of antiviral treatment in chronic hepatitis B patients with hepatic steatosis.

Background & aims: With a drastic increase in the number of chronic hepatitis B (CHB) patients with coexisting nonalcoholic fatty liver disease (NAFLD), there is an urgent need to evaluate antiviral treatment effects in this special population. Methods: CHB patients with hepatic steatosis (CHB + HS) were prospectively recruited with followed-up of 3 years. HS and liver fibrosis were assessed by transient elastography. HS was defined as controlled attenuation parameter (CAP) ≥248 dB/m, and fibrosis progression was defined with ≥1-stage fibrosis increment. Multivariate and propensity score matching (PSM) analysis were used to evaluate antiviral therapy effects on fibrosis progression. Results: In total 212 recruited CHB + HS patients (median age 36 years, median ALT 59 U/L), 49.1% (104/212) received antiviral therapy and 50.9% (108/212) did not. Among patients with antiviral therapy, rates of serum HBV DNA undetectable, HBeAg and HBsAg loss, and ALT normalization at year 3 were 88.5%, 31.0%, 8.7% and 70.2%, respectively. Patients with mild-moderate HS didn't differ patients with severe HS regarding biochemical and virological responses. Antiviral therapy was independently associated with a lower risk of fibrosis progression among the entire cohort (odds ratio 0.473, 95% CI 0.245-0.911, P = 0.025). This finding was further verified by PSM analysis. When stratified by the severity of HS, the antiviral therapy benefits in reducing fibrosis progression were mainly seen in patients with mild-moderate HS. Conclusions: Among CHB + HS patients, long-term antiviral treatment effectively inhibits HBV replication and reduces fibrosis progression. Our findings have implications for the optimal management of this population.

Relationship between blood cadmium levels and bone mineral density in adults: a cross-sectional study.

Introduction: Osteoporosis, a disease of reduced bone mass and microstructural deterioration leading to fragility fractures, is becoming more prevalent as aging progresses, significantly increasing the socioeconomic burden. In past studies, there has been a growing awareness of the harmful effects of heavy metals on bone, with cadmium being a significant exposure factor. The purpose of this study was to look into the association between adult bone mineral density(BMD) and blood cadmium levels. Methods: Based on information from the 2013-2014, 2017-2018 NHANES, weighted multiple regression, generalized weighted modeling, and smoothed curve fitting were utilized to investigate the association between blood cadmium and femur BMD. Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, sex, race, chronic kidney disease, and diabetes. Results: In 2,146 participants, blood cadmium levels and total femur [-0.02 (-0.03, -0.01), 0.0027], femoral neck [-0.01 (-0.02, -0.00), 0.0240], femoral trochanter [-0.01 (-0.02, -0.00), 0.0042], and intertrochanteric femoral trochanter [-0.02 (-0.03, -0.00), 0.0101] BMD were negatively correlated. Subgroup analyses showed that this association was more pronounced in women, non-Hispanic white people and other Hispanics, and those with chronic kidney disease and diabetes. Our results pointed to a negative relationship between femoral BMD and blood cadmium. This negative association varied by age, sex, race, diabetes, and chronic kidney disease. In particular, bone mineral density was more significantly negatively affected by blood cadmium levels in groups with diabetes and chronic kidney disease. Conclusion: Our findings demonstrated a significant negative association between blood cadmium levels and bone mineral density in a population of U.S. adults.

[Retrospective Study of Bronchoscopic Intervention Therapy for Bronchopleural Fistula Induced by Pulmonary Surgery].

BACKGROUND: As a new technique developed in recent years, bronchoscopic intervention therapy has the advantages of minimal invasion, high safety and repeatability. The aim of this study is to investigate the clinical characteristics of bronchopleural fistula (BPF) induced by surgeries for lung malignancies or benign diseases and the effect of bronchoscopic intervention therapy for BPF, so as to provide support for prevention and treatment of BPF. METHODS: Data 64 patients with BPF who were treated by bronchoscopic intervention in Respiratory Disease Center of Dongzhimen Hospital, Beijing University of Chinese Medicine from June 2020 to September 2023 were collected. Patients with fistula diameter ≤5 mm were underwent submucous injection of macrogol, combined with blocking therapy with N-butyl cyanoacrylate, medical bioprotein glue or silicone prosthesis. Patients with fistula diameter >5 mm were implanted with different stents and cardiac occluders. Locations and characteristics of fistulas were summarized, meanwhile, data including Karnofsky performance status (KPS), shortbreath scale (SS), body temperature, pleural drainage volume and white blood cell count before and after operation were observed. RESULTS: For all 64 patients, 96 anatomic lung resections including pneumonectomy, lobectomy and segmentectomy were executed and 74 fistulas occurred in 65 fistula locations. The proportion of fistula in the right lung (63.5%) was significantly higher than that in the left (36.5%). Besides, the right inferior lobar bronchial fistula was the most common (40.5%). After operation, KPS was significantly increased, while SS, body temperature, pleural drainage volume and white blood cell count were significantly decreased compared to the preoperative values (P<0.05). By telephone follow-up or readmission during 1 month to 38 months after treament, median survival time was 21 months. 33 patients (51.6%) showed complete response, 7 patients (10.9%) showed complete clinical response, 18 patients (28.1%) showed partial response, and 6 patients (9.4%) showed no response. As a whole, the total effective rate of bronchoscopic intervention for BPF was 90.6%. CONCLUSIONS: BPF induced by pulmonary surgery can lead to severe symptoms and it is usually life-threating. Bronchoscopic intervention therapy is one of the fast and effective therapeutic methods for BPF.

GAA/(Au-Au/IrO2)@Cu(PABA) reactor with cascade catalytic activity for α-glucosidase inhibitor screening.

BACKGROUND: In vitro screening strategies based on the inhibition of α-glucosidase (GAA) activity have been widely used for the discovery of potential antidiabetic drugs, but they still face some challenges, such as poor enzyme stability, non-reusability and narrow range of applicability. To overcome these limitations, an in vitro screening method based on GAA@GOx@Cu-MOF reactor was developed in our previous study. However, the method was still not satisfactory enough in terms of construction cost, pH stability, organic solvent resistance and reusability. Thence, there is still a great need for the development of in vitro screening methods with lower cost and wider applicability. RESULTS: A colorimetric sensing strategy based on GAA/(Au-Au/IrO2)@Cu(PABA) cascade catalytic reactor, which constructed through simultaneous encapsulating Au-Au/IrO2 nanozyme with glucose oxidase-mimicking and peroxidase-mimicking activities and GAA in Cu(PABA) carrier with peroxidase-mimicking activity, was innovatively developed for in vitro screening of GAA inhibitors in this work. It was found that the reactor not only exhibited excellent thermal stability, pH stability, organic solvent resistance, room temperature storage stability, and reusability, but also possessed cascade catalytic performance, with approximately 12.36-fold increased catalytic activity compared to the free system (GAA + Au-Au/IrO2). Moreover, the in vitro GAA inhibitors screening method based on this reactor demonstrated considerable anti-interference performance and detection sensitivity, with a detection limit of 4.79 nM for acarbose. Meanwhile, the method owned good reliability and accuracy, and has been successfully applied to the in vitro screening of oleanolic acid derivatives as potential GAA inhibitors. SIGNIFICANCE: This method not only more effectively solved the shortcomings of poor stability, narrow scope of application, and non-reusability of natural enzymes in the classical method compared with our previous work, but also broaden the application scope of Au-Au/IrO2 nanozyme with glucose oxidase and peroxidase mimicking activities, and Cu(PABA) carrier with peroxidase mimicking activity, which was expected to be a new generation candidate method for GAA inhibitor screening.

[A Case of Multidomain Integrated Treatment Strategy 
for Complex Primary Pulmonary Sarcomatoid Carcinoma].

Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant tumor, which includes the following five pathologic types: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. The onset of PSC is occult with non-specific clinical symptoms and signs. The clinical manifestations include irritating cough, bloody sputum, dyspnea, chest pain and so on, which are closely related to the growth and invasion site of the tumor. PSC tends to metastasize early, so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit. A patient with primary PSC which led to 90% stenosis in central airway was treated by combined method of vascular and tracheoscopic intervention in our respiratory center. This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery. Herein we report the case for clinical reference.
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Case report: Bronchoscopic intervention for rare benign airway tumors: a report of 4 cases and literature review.

Due to their unique location, airway tumors have a significant impact on patient quality of life and survival. Current research has focused extensively on malignant airway tumors; however, benign airway tumors, especially rare ones, are less understood due to their low incidence. These tumors are often misdiagnosed and mistreated due to diagnostic challenges. Therefore, there is still a lack of consensus on the treatment of some rare benign airway tumors. Our center summarizes the diagnosis and treatment of four rare cases of benign airway stenosis in recent years, highlighting the bronchoscopic manifestations and therapeutic approaches to improve the understanding of these diseases.

Sweet triterpenoid glycoside from Cyclocarya paliurus ameliorates obesity-induced insulin resistance through inhibiting the TLR4/NF-κB/NLRP3 inflammatory pathway.

Our prophase studies have manifested that the sweet triterpenoid glycoside from the leaves of Cyclocarya paliurus (CPST) effectively improved the disorders of glucolipid metabolism in vitro and in patients. The current purpose was to further detect its mechanisms involved. The results demonstrated that CPST could ameliorate high-fat diet (HFD)-induced insulin resistance (IR), which was linked to reducing HFD-induced mice's body weight, serum glucose (GLUO), triglyceride (TG), total cholesterol (T-CHO) and low-density lipoprotein cholesterol (LDL-C), lowering the area under the oral glucose tolerance curve and insulin tolerance, elevating the percentage of brown adipose, high-density lipoprotein cholesterol (HDL-C), reducing fat droplets of adipocytes in interscapular brown adipose tissue (iBAT) and cross-sectional area of adipocytes. Further studies manifested that CPST obviously downregulated TLR4, MyD88, NLRP3, ASC, caspase-1, cleased-caspase-1, IL-18, IL-1ß, TXNIP, and GSDMD protein expressions and p-NF-кB/NF-кB ratio in iBAT. These aforementioned findings demonstrated that CPST ameliorated HFD induced IR by regulating TLR4/NF-κB/NLRP3 signaling pathway, which in turn enhancing insulin sensitivity and glucose metabolism.

Analysis of airway structural parameters in Han Chinese adults: a prospective cross-sectional study.

INTRODUCTION: Establishing reference ranges for central airway parameters and exploring their influencing factors in Han Chinese non-smoking adults. METHODS: This prospective cross-sectional study was conducted on Han Chinese non-smoking adults who underwent chest CT scans at the Tongzhou Campus of Dongzhimen Hospital Affiliated with the Beijing University of Chinese Medicine between September 2022 and November 2022. The SYNAPSE 3D image analysis software was utilized, enabling the extraction of critical parameters such as central airway length, airway wall thickness (AWT), airway lumen area (ALA), and subcarinal angle (SCA). Pearson's correlation coefficient analysis and multiple linear regression analysis methods were employed to evaluate the relationship between central airway parameters and age, sex, weight, and height. RESULTS: The study encompassed 888 Han Chinese non-smoking adults, comprising 456 females and 432 males. Significant sex differences were noted in central airway length, AWT, and ALA, with measurements in males exceeding those in females (p < 0.01) with no significant difference in SCA. Correlation analyses unveiled relationships between central airway parameters and age, sex, weight, and height. During multiple linear regression analyses, no conclusive evidence emerged to demonstrate the independent or combined explanatory or predictive capacity of the aforementioned variables for central airway length and SCA. Although sex has a significant impact on AWT and ALA, its capability in explanation or prediction remains limited. The conclusions drawn from the primary analysis receive reinforcement from the outcomes of sensitivity analyses. CONCLUSION: Establishing the distribution range of central airway parameters in non-smoking Han Chinese adults. It observed significant sex differences in these parameters, except for the SCA. However, the study found that the predictive or explanatory power of age, sex, weight, and height for central airway parameters was either limited or non-significant.

Simple dual-readout immunosensor based on phosphate-triggered and potassium permanganate for visual detection of fenitrothion.

Multicolor-based visual immunosensor is a promising tool for rapid analysis without the use of bulky instruments. Herein, an anti-fenitrothion nanobody-alkaline phosphatase fusion protein (VHHjd8-ALP) was employed to develop a multicolor visual immunosensor (MVIS) and a ratiometric fluorescence MVIS (RFMVIS, respectively). After one-step competitive immunoassay, the VHHjd8-ALP bound to microplate catalyzed phenyl phosphate disodium salt (ArP) into phenol. Under high alkaline condition (pH 12), the phenol reduced KMnO4 to intermediate (K2MnO4) and further to MnO2 in alkaline condition (pH 12), accompanied by a visible color transition of purple-green-yellow, which can be used for semiquantitative visual analysis or qualitative detection by measuring RGB value. RFMVIS was proposed on the basis of MVIS to further improve sensitivity. The CdTe quantum dot and fluorescein were used as signal probes to develop the fluorescent immunosensor. The CdTe dots with red emission (644 nm) was quenched by oxidation of KMnO4, whereas the fluorescein with green emission (520 nm) remained constant, accompanied by a fluorescent color transition of green-yellow-red. By measuring the ratio of the fluorescence intensity (I644/I520), the ratiometric fluorescence immunosensor was developed for qualitative analysis. The two visual immunosensors were sensitive and simple, and they showed good accuracy and practicability in the recovery test, thus are ideal tools for rapid screening.

Disease severity and antiviral response in patients with chronic hepatitis B with non-obese NAFLD.

BACKGROUND: The burden of nonalcoholic fatty liver disease (NAFLD) is growing in patients with chronic hepatitis B (CHB). NAFLD is typically associated with obesity, however, it is increasingly being identified in non-obese patients. This study aimed to investigate disease severity and antiviral response in non-obese patients with CHB with NAFLD (CHB + NAFLD). METHODS: A total of 809 patients with CHB + NAFLD were prospectively recruited and followed up for 3 years. NAFLD was diagnosed by transient elastography and defined as controlled attenuation parameter ≥248 dB/m, in the absence of excessive alcohol intake. Obesity status was defined by the Asian body mass index (BMI) cutoff of 25 kg/m2. Metabolic abnormality was defined by the presence of dyslipidemia, hypertension or diabetes. Fibrosis staging was defined according to the EASL-ALEH guidelines, with fibrosis progression defined as ≥1-stage increment. RESULTS: In the total cohort (median age 40 years, 59.0% antiviral-treated), 33.3% were non-obese. Non-obese patients were less metabolically abnormal than obese patients (60.2% vs 72.0%, P = 0.003). After 3-year follow up, the rate of fibrosis progression was comparable between non-obese and obese patients (17.5% vs 21.9% in the total cohort, P = 0.145; 15.7% vs 14.6% in antiviral-treated cohort with persistent viral suppression, P = 0.795). No significant differences in virological and biochemical responses were observed between non-obese and obese patients (P >0.05 for all). CONCLUSIONS: Approximately one third of CHB + NAFLD patients were non-obese. Non-obese patients, while less metabolically abnormal, had a similar risk for fibrosis progression as obese patients. Obesity status did not impact the efficiency of antiviral therapy.