FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Caloric restriction leading to attenuation of experimental Alzheimer's disease results from alterations in gut microbiome.

BACKGROUND: Caloric restriction (CR) might be effective for alleviating/preventing Alzheimer's disease (AD), but the biological mechanisms remain unclear. In the current study, we explored whether CR caused an alteration of gut microbiome and resulted in the attenuation of cognitive impairment of AD animal model. METHODS: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks. RESULTS: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aß40, Aß42, IL-1ß, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet. CONCLUSIONS: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy.

Colloidal Synthesis of Cu3N Nanorods and Construction of Cu3N-Cu2O Heteronanostructures via Epitaxial Growth.

The synthesis of transition metal nitrides nanocrystals (TMNs NCs) has posed a significant challenge due to the limited reactivity of nitrogen sources at lower temperatures and the scarcity of available synthesis methods. In this study, we present a novel colloidal synthesis strategy for the fabrication of Cu3N nanorods (NRs). It is found that the trace oxygen (O2) plays an important role in the synthesis process. And a new mechanism for the formation of Cu3N is proposed. Subsequently, by employing secondary lateral epitaxial growth, the Cu3N-Cu2O heteronanostructures (HNs) can be prepared. The Cu3N NRs and Cu3N-Cu2O HNs were evaluated as precursor electrocatalysts for the CO2 reduction reaction (CO2RR). The Cu3N-Cu2O HNs demonstrate remarkable selectivity and stability with ethylene (C2H4) Faradaic efficiency (FE) up to 55.3%, surpassing that of Cu3N NRs. This study provides innovative insights into the reaction mechanism of colloidal synthesis of TMNs NCs and presents alternative options for designing cost-effective electrocatalysts to achieve carbon neutrality.

Co-immobilization of whole cells and enzymes by covalent organic framework for biocatalysis process intensification.

Co-immobilization of cells and enzymes is often essential for the cascade biocatalytic processes of industrial-scale feasibility but remains a vast challenge. Herein, we create a facile co-immobilization platform integrating enzymes and cells in covalent organic frameworks (COFs) to realize the highly efficient cascade of inulinase and E. coli for bioconversion of natural products. Enzymes can be uniformly immobilized in the COF armor, which coats on the cell surface to produce cascade biocatalysts with high efficiency, stability and recyclability. Furthermore, this one-pot in situ synthesis process facilitates a gram-scale fabrication of enzyme-cell biocatalysts, which can generate a continuous-flow device conversing inulin to D-allulose, achieving space-time yield of 161.28 g L-1 d-1 and high stability (remaining >90% initial catalytic efficiency after 7 days of continuous reaction). The created platform is applied for various cells (e.g., E. coli, Yeast) and enzymes, demonstrating excellent universality. This study paves a pathway to break the bottleneck of extra- and intracellular catalysis, creates a high-performance and customizable platform for enzyme-cell cascade biomanufacturing, and expands the scope of biocatalysis process intensification.

Application of Fusobacterium nucleatum as a biomarker in gastrointestinal malignancies.

The morbidity and mortality of gastrointestinal (GI) malignancies are among the highest in the world, posing a serious threat to human health. Because of the insidious onset of the cancer, it is difficult for patients to be diagnosed at an early stage, and it rapidly progresses to an advanced stage, resulting in poor treatment and prognosis. Fusobacterium nucleatum (F. nucleatum) is a gram-negative, spore-free anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal, esophageal, gastric, and pancreatic cancers via various intricate mechanisms. Recent development in novel research suggests that F. nucleatum may function as a biomarker in GI malignancies. Detecting the abundance of F. nucleatum in stool, saliva, and serum samples of patients may aid in the diagnosis, risk assessment, and prognosis monitoring of GI malignancies. This editorial systematically describes the biological roles and mechanisms of F. nucleatum in GI malignancies focusing on the application of F. nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F. nucleatum and GI tumors-related research.

A comparative study of shockwave intravascular lithotripsy and conventional percutaneous coronary intervention in the treatment of severe coronary artery calcification lesions.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of intravascular lithotripsy (IVL) in the treatment of severe coronary artery calcification (CAC) lesions. METHODS: In this study, we selected patients diagnosed with severe CAC lesions confirmed by coronary angiography (CAG) who were hospitalized in Yulin First People's Hospital between December 2021 and December 2022 and required percutaneous coronary intervention (PCI). Using a random number table, we divided all patients into the IVL group and the PCI group in the order of interventional therapy. We compared both groups in terms of the surgical success rate, intraoperative manipulation characteristics, procedural complication, and cumulative incidence of major adverse cardiovascular events (MACE). RESULTS: (1) There were no differences in the surgical success rate, incidence of MACE, and occurrence of procedural complication between the two groups; (2) Compared with the conventional PCI group, patients in the IVL group used fewer predilatation balloons, and the difference was statistically significant (all P < 0.05); (3) Compared with the conventional PCI group, patients in the IVL group had lesser surgery time and lesser radiation time, with lesser proportion of patients who were assisted with stent implantation using coronary artery rotational atherectomy, and this difference was statistically significant (P < 0.05); (4) The mean stent diameter and length in the IVL group was greater than those in the conventional PCI group but the difference was not statistically significant (P > 0.05). CONCLUSION: In this study, we found that IVL was a highly safe and effective procedure in the treatment of severe CAC lesions that did not increase the surgery and radiation time, and it could also reduce the use of predilatation balloons, thus improving the management of CAC lesions. Thus, IVL can be a novel choice in treating severe CAC lesions.

Metagenomic Next-Generation Sequencing as an Effective Diagnostic Tool for Talaromycosis in HIV-Negative Patients.

The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.

Efficacy and mechanism of action of Yanxiao Di'naer formula for non-alcoholic steatohepatitis treatment based on metabolomics and RNA sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. OBJECTIVE: The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. METHODS: The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro. In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo. Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. RESULTS: This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p-NF-κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. CONCLUSIONS: YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.

Rh(III)-catalyzed atroposelective C-H alkynylation of 1-aryl isoquinolines with hypervalent iodine-alkyne reagents.

An efficient Rh(III)-catalyzed enantioselective C-H alkynylation of isoquinolines is disclosed. The C-H alkynylation of 1-aryl isoquinolines with hypervalent iodine-alkyne reagents proceeded in DMA at room temperature in the presence of 2.5 mol% chiral SCpRh(III) complex along with 20 mol% AgSbF6, providing axially chiral alkynylated 1-aryl isoquinolines in excellent yields (up to 93%) and enantioselectivity (up to 95% ee). The diverse transformations of the product further enhance the potential utility of this reaction.

Diagnostic and Management Value of Multi-Slice Computed Tomography in Esophageal Jujube Pit Impaction.

Objective: The diagnostic value of multi-slice computed tomography (MSCT) in esophageal jujube pit impaction was explored in this study. Methods: A retrospective analysis was performed on MSCT data obtained from a cohort of 40 patients experiencing esophageal jujube pit impaction. The study period encompassed the interval from December 2018 to November 2019. The analysis involved examining the age distribution of the patients, the location of the jujube pit impaction, its connection to the esophagus, associated complications, and the methods used for treatment. All imaging results were compared with the outcomes of surgical or endoscopic interventions. Results: (1) Out of 40 patients, 30 individuals were 58 years old or above, constituting 75% of the study sample. (2) In 80% of the instances (32 cases), the jujube pit was located in the initial segment of the esophagus, exhibiting a spindle shape with varying levels of central low density. (3) We examined the correlation between the angle of the impacted jujube pit and the esophageal longitudinal axis, categorizing 2 cases as longitudinal impaction, 16 as oblique impaction, and 22 as transverse impaction. Among the 40 cases, 28 displayed only slight thickening of the esophageal wall at the impaction site, while 9 cases exhibited heightened periesophageal fat density, and 3 showed small periesophageal air bubbles. (4) Endoscopic evaluation identified damage to the esophageal mucosa in 35 instances and the formation of esophageal perforation in 5 cases. Among patients with perforation, one or both ends of the jujube pit had penetrated the esophageal wall, accompanied by different levels of surrounding inflammatory encapsulation. Conclusion: MSCT is crucial for pinpointing jujube pit impaction and its relation to the esophageal wall and nearby structures, aiding in preoperative and postoperative complications. It is highly feasible for endoscopic cases but limited in complex ones needing thoracoscopy or open-heart surgery.

Engineered low-pathogenic Helicobacter pylori as orally tumor immunomodulators for the stimulation of systemic immune response.

Gastric cancer constitutes a malignant neoplasm characterized by heightened invasiveness, posing significant global health threat. Inspired by the analysis that gastric cancer patients with Helicobacter pylori (H. pylori) infection have higher overall survival, whether H. pylori can be used as therapeutics agent and oral drug delivery system for gastric cancer. Hence, we constructed engineered H. pylori for gastric cancer treatment. A type Ⅱ H. pylori with low pathogenicity, were conjugated with photosensitizer to develop the engineered living bacteria NIR-triggered system (Hp-Ce6). Hp-Ce6 could maintain activity in stomach acid, quickly infiltrate through mucus layer and finally migrate to tumor region owing to the cell morphology and urease of H. pylori. H. pylori, accumulated in the tumor site, severed as vaccine to activate cGAS-STING pathway, and synergistically remodel the macrophages phenotype. Upon irradiation within stomach, Hp-Ce6 directly destroyed tumor cells via photodynamic effect inherited by Ce6, companied by inducing immunogenic tumor cell death. Additionally, Hp-Ce6 exhibited excellent biosafety with fecal elimination and minimal blood absorption. This work explores the feasibility and availability of H. pylori-based oral delivery platforms for gastric tumor and further provides enlightening strategy to utilize H. pylori invariably presented in the stomach as in-situ immunomodulator to enhance antitumor efficacy.

IL-6 significantly correlated with the prognosis in low-grade glioma and the mediating effect of immune microenvironment.

To screen immune-related prognostic biomarkers in low-grade glioma (LGG), and reveal the potential regulatory mechanism. The differential expressed genes (DEGs) between alive and dead patients were initially identified, then the key common genes between DEGs and immune-related genes were obtained. Regarding the key DEGs associated with the overall survival (OS), their clinical value was assessed by Kaplan-Meier, RCS, logistic regression, ROC, and decision curve analysis methods. We also assessed the role of immune infiltration on the association between key DEGs and OS. All the analyses were based on the TGCA-LGG data. Finally, we conducted the molecular docking analysis to explore the targeting binding of key DEGs with the therapeutic agents in LGG. Among 146 DEGs, only interleukin-6 (IL-6) was finally screened as an immune-related biomarker. High expression of IL-6 significantly correlated with poor OS time (all P < .05), showing a linear relationship. The combination of IL-6 with IDH1 mutation had the most favorable prediction performance on survival status and they achieved a good clinical net benefit. Next, we found a significant relationship between IL-6 and immune microenvironment score, and the immune microenvironment played a mediating effect on the association of IL-6 with survival (all P < .05). Detailly, IL-6 was positively related to M1 macrophage infiltration abundance and its biomarkers (all P < .05). Finally, we obtained 4 therapeutic agents in LGG targeting IL-6, and their targeting binding relationships were all verified. IL6, as an immune-related biomarker, was associated with the prognosis in LGG, and it can be a therapeutic target in LGG.

Identification and validation of a platelet-related signature for predicting survival and drug sensitivity in multiple myeloma.

Background: Significant progress has been achieved in the management of multiple myeloma (MM) by implementing high-dose therapy and stem cell transplantation. Moreover, the prognosis of patients has been enhanced due to the introduction of novel immunomodulatory drugs and the emergence of new targeted therapies. However, predicting the survival rates of patients with multiple myeloma is still tricky. According to recent researches, platelets have a significant impact in affecting the biological activity of tumors and are essential parts of the tumor microenvironment. Nonetheless, it is still unclear how platelet-related genes (PRGs) connect to the prognosis of multiple myeloma. Methods: We analyzed the expression of platelet-related genes and their prognostic value in multiple myeloma patients in this study. We also created a nomogram combining clinical metrics. Furthermore, we investigated disparities in the biological characteristics, immunological microenvironment, and reaction to immunotherapy, along with analyzing the drug susceptibility within diverse risk groups. Results: By using the platelet-related risk model, we were able to predict patients' prognosis more accurately. Subjects in the high-risk cohort exhibited inferior survival outcomes, both in the training and validation datasets, as compared to those in the low-risk cohort (p < 0.05). Moreover, there were differences in the immunological microenvironments, biological processes, clinical features, and chemotherapeutic drug sensitivity between the groups at high and low risk. Using multivariable Cox regression analyses, platelet-related risk score was shown to be an independent prognostic influence in MM (p < 0.001, hazard ratio (HR) = 2.001%, 95% confidence interval (CI): 1.467-2.730). Furthermore, the capacity to predict survival was further improved when a combined nomogram was utilized. In training cohort, this outperformed the predictive value of International staging system (ISS) alone from a 5-years area under curve (AUC) = 0.668 (95% CI: 0.611-0.725) to an AUC = 0.721 (95% CI: 0.665-0.778). Conclusion: Our study revealed the potential benefits of PRGs in terms of survival prognosis of MM patients. Furthermore, we verified its potential as a drug target for MM patients. These findings open up novel possibilities for prognostic evaluation and treatment choices for MM.

Parametric analysis of craniocerebral injury mechanism in pedestrian traffic accidents based on finite element methods.

PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the total human model for safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities were conducted. Von Mises stress, intracranial pressure, maximum principal strain, cumulative strain damage measure, shear stress, and cranial strain were employed to analyze the injury response of all areas of the brain. To examine the association between injury conditions and injury consequences, correlation analysis, principal component analysis, linear regression, and stepwise linear regression were utilized. RESULTS: There is a significant correlation observed between each criterion of skull and brain injury (p < 0.01 in all Pearson correlation analysis results). A 2-phase increase of cranio-cerebral stress and strain as impact speed increases. In high-speed impact (> 40 km/h), the Von Mises stress on the skull was with a high possibility exceed the threshold for skull fracture (100 MPa). When falling and making temporal and occipital contact with the ground, the opposite side of the impacted area experiences higher frequency stress concentration than contact at other conditions. Run-over injuries tend to have a more comprehensive craniocerebral injury, with greater overall deformation due to more adequate kinetic energy conduction. The mean value of maximum principal strain of brain and Von Mises stress of cranium at run-over condition are 1.39 and 403.8 MPa, while they were 1.31, 94.11 MPa and 0.64, 120.5 MPa for the impact and fall conditions, respectively. The impact velocity also plays a significant role in craniocerebral injury in impact and fall loading conditions (the p of all F-test < 0.05). A regression equation of the craniocerebral injury manners in pedestrian accidents was established. CONCLUSION: The study distinguished the craniocerebral injuries caused in different manners, elucidated the biomechanical mechanisms of craniocerebral injury, and provided a biomechanical foundation for the identification of craniocerebral injury in legal contexts.

Neurosyphilis complicated by anti-γ-aminobutyric acid-B receptor encephalitis: A case report.

BACKGROUND: Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system, causing encephalitis. Few cases of anti-N-methyl-D-aspartate receptor autoimmune encephalitis (AE) secondary to neurosyphilis have been reported. We report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor (GABABR) AE. CASE SUMMARY: A young man in his 30s who presented with acute epileptic status was admitted to a local hospital. He was diagnosed with neurosyphilis, according to serum and cerebrospinal fluid (CSF) tests for syphilis. After 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin, epilepsy was controlled but serious cognitive impairment, behavioral, and serious psychiatric symptoms were observed. He was then transferred to our hospital. The Mini-Mental State Examination (MMSE) crude test results showed only 2 points. Cranial magnetic resonance imaging revealed significant cerebral atrophy and multiple fluid-attenuated inversion recovery high signals in the white matter surrounding both lateral ventricles, left amygdala and bilateral thalami. Anti-GABABR antibodies were discovered in CSF (1:3.2) and serum (1:100). The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE, and received methylprednisolone and penicillin. Following treatment, his mental symptoms were alleviated. Cognitive impairment was significantly improved, with a MMSE of 8 points. Serum anti-GABABR antibody titer decreased to 1:32. The patient received methylprednisolone and penicillin after discharge. Three months later, the patient's condition was stable, but the serum anti-GABABR antibody titer was 1:100. CONCLUSION: This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.

Enhanced magnetic anisotropy of iridium dimers on antisite defects of two-dimensional transition-metal dichalcogenides.

The combination of transition-metal (TM) elements with two-dimensional (2D) transition-metal dichalcogenides (TMDs) provides an effective route to realizing a 2D controllable magnetic order, leading to significant applications in multifunctional nanospintronics. However, in most TM atoms@TMDs nanostructures, it is challenging for the magnetic anisotropy energy (MAE) to exceed 30 meV when affected by the crystal field. Hence, the stronger magnetic anisotropy of TMDs has yet to be developed. Here, utilizing first-principle calculations based on density functional theory (DFT), a feasible method to enhance the MAEs of TMDs via configurating iridium dimers (Ir2) on 2D traditional and Janus TMDs with antisite defects is reported. Calculations revealed that 28 of the 54 configurations considered possessed structure-dependent MAEs of >60 meV per Ir2 in the out-of-plane direction, suggesting the potential for applications at room temperature. We also showed the ability to tune the MAE further massively by applying a biaxial strain as well as the surface asymmetric polarization reversal of Janus-type substrates. This approach led to changes to >80 meV per Ir2. This work provides a novel strategy to achieve tunable large magnetic anisotropy in 2D TMDs. It also extends the functionality of antisite-defective TMDs, thereby providing theoretical support for the development of magnetic nanodevices.

Prognostic significance of ß2-microglobulin decline index in multiple myeloma.

Purpose: To assess the prognostic significance of ß2-microglobulin decline index (ß2M DI) in multiple myeloma (MM). Methods: 150 MM patients diagnosed with MM were enrolled in this study. Cox proportional hazards model was used to analyze the uni- and multivariate prognosis in training cohort (n=105). A new combined prognostic model containing ß2M DI was built up based on the data in training cohort. The validation group was used to verify the model. Results: ß2M DI showed significant correlation with prognosis in both uni- and multivariate analyses and had a good correlation with complete response (CR) rate and deep remission rate. The ROC and calibration curves in validation cohort (n=45) indicated a good predictive performance of the new model. Based on the median risk score of the training group, we classified patients into high- and low- risk groups. In both training and validation groups, patients in the low-risk group had longer overall survival (OS) time than that in the high-risk group (p<0.05). Conclusion: ß2M DI is a good predictive index for predicting treatment response and survival time in MM patients. The prognostic model added with ß2M DI showed a better correlation with OS.

Epidemiological Survey of Congenital Heart Disease Among Children Aged from 2 to 18 in Suo County, Nagqu, Tibet.

Lin, Tian, Huaping Jia, Yunming Li, Yongxing Xu, Bei Zhao, Dong Zheng, Hongfeng Yan, Meihui Zhao, Yanlei Li, Liping Xia, Fengxia Zhou, Cuiping Liu, Ke Ma, Ma Mi, and Jianwen Gu. Epidemiological survey of congenital heart disease among children aged from 2 to 18 in Suo County, Nagqu, Tibet. High Alt Med Biol. 00:000-000, 2024. Background: Studies have reported the prevalence of congenital heart disease (CHD) in parts of Tibet, but relative epidemiological surveys are rare. We aimed to explore the prevalence of CHD in children and its relationship with family history in Suo County, Nagqu, Tibet, an altitude of 3,980 meters. Methods: We recruited 4,002 children aged 2-18 years. Subjects underwent a family history investigation, cardiac auscultation, and clinical manifestation examination and then received echocardiographic screening. Results: The prevalence of CHD among children in Suo County was 0.97% (39 cases), much higher than the prevalence at sea level. The most common subtype was atrial septal defect, accounting for 53.9% of CHD, followed by patent ductus arteriosus (33.3%) and ventricular septal defect (12.8%). We also found that children whose mothers had previously borne children with CHD had a higher risk of CHD than those without (p = 0.002); other factors related to CHD during pregnancy, such as smoking, drinking, drug use, and viral infection, showed no statistical differences between children with and without CHD. Conclusions: The prevalence of CHD in children in Suo County is much higher than at low altitude, consisting mostly of simple forms with left-to-right shunt, with rare complex CHD. These results support implementing diagnostic and treatment plans to prevent CHD in Suo County.

Intestinal epithelial cells of Japanese flounder (Paralichthys olivaceus) as an in vitro model for studying intestine immune function based on transcriptome analysis.

Japanese flounder (Paralichthys olivaceus) is an economically crucial marine species, but diseases like hemorrhagic septicemia caused by Edwardsiella tarda have resulted in significant economic losses. E. tarda infects various hosts, and its pathogenicity in fish is not fully understood. Lipopolysaccharides (LPS) are components of the outer membrane of Gram-negative bacteria and are representative of typical PAMP molecules that cause activation of the immune system. The PoIEC cell line is a newly established intestinal epithelial cell line from P. olivaceus. In order to investigate whether it can be used as an in vitro model for studying the pathogenesis of E. tarda and LPS stimulation, we conducted RNA-seq experiments for the PoIECs model of E. tarda infection and LPS stimulation. In this study, transcriptome sequencing was carried out in the PoIEC cell line after treatment with LPS and E. tarda. A total of 62.52G of high-quality data from transcriptome sequencing results were obtained in nine libraries, of which an average of 87.96% data could be aligned to the P. olivaceus genome. Data analysis showed that 283 and 414 differentially expressed genes (DEGs) in the LPS versus Control (LPS-vs-Con) and E. tarda versus Control groups (Et-vs-Con), respectively, of which 60 DEGs were shared in two comparation groups. The GO terms were predominantly enriched in the extracellular space, inflammatory response, and cytokine activity in the LPS-vs-Con group, whereas GO terms were predominantly enriched in nucleus and positive regulation of transcription by RNA polymerase II in the Et-vs-Con group. KEGG analysis revealed that three immune-related pathways were co-enriched in both comparison groups, including the Toll-like receptor signaling pathway, C-type lectin receptor signaling pathway, and Cytokine-cytokine receptor interaction. Five genes were randomly screened to confirm the validity and accuracy of the transcriptome data. These results suggest that PoIEC cell line can be an ideal in vitro model for studies of marine fish gut immunity and pathogenesis of Edwardsiellosis.

Chemical Interactions between Dissolved Polysulfides and Potential Catalytic Host Materials for Li-S Batteries.

Given that both elemental sulfur (S8) and lithium sulfide (Li2S) exhibit insulating properties, the involvement of conductive host materials becomes crucial for facilitating charge transfer in sulfur cathodes within lithium-sulfur (Li-S) batteries. Furthermore, there has been a recent surge in the exploration of host materials for sulfur cathodes to address the "polysulfide shuttle" effect. This effect arises from the formation of polysulfide species during the charge-discharge cycles of the Li-S batteries and can be mitigated through physical or chemical interactions with specific materials. To qualitatively and accurately assess the interactions between polysulfides and the potential host materials, this study utilized a well-established high-performance liquid chromatography method for polysulfide analysis. The objective was to monitor the changes in polysulfide solutions after contact with 44 different carbon and inorganic materials. Based on both qualitative and quantitative chromatographic results, it was determined that 20 out of the 44 materials exhibit significant interactions with polysulfides. The primary form of interaction observed is the irreversible disproportionation reaction with elemental sulfur being one of the resulting products.