Advances in gut-brain organ chips.

The brain and gut are sensory organs responsible for sensing, transmitting, integrating, and responding to signals from the internal and external environment. In-depth analysis of brain-gut axis interactions is important for human health and disease prevention. Current research on the brain-gut axis primarily relies on animal models. However, animal models make it difficult to study disease mechanisms due to inherent species differences, and the reproducibility of experiments is poor because of individual animal variations, which leads to a significant limitation of real-time sensory responses. Organ-on-a-chip platforms provide an innovative approach for disease treatment and personalized research by replicating brain and gut ecosystems in vitro. This enables a precise understanding of their biological functions and physiological responses. In this article, we examine the history and most current developments in brain, gut, and gut-brain chips. The importance of these systems for understanding pathophysiology and developing new drugs is emphasized throughout the review. This article also addresses future directions and present issues with the advancement and application of gut-brain-on-a-chip technologies.

Discovering New Metallo-Deubiquitinase CSN5 Inhibitors by a Non-Catalytic Activity Assay Platform.

COP9 signalosome catalytic subunit CSN5 plays a key role in tumorigenesis and tumor immunity, showing potential as an anticancer target. Currently, only a few CSN5 inhibitors have been reported, at least partially, due to the challenges in establishing assays for CSN5 deubiquitinase activity. Here, we present the establishment and validation of a simple and reliable non-catalytic activity assay platform for identifying CSN5 inhibitors utilizing a new fluorescent probe, CFP-1, that exhibits enhanced fluorescence and fluorescence polarization features upon binding to CSN5. By using this platform, we identified 2-aminothiazole-4-carboxylic acids as new CSN5 inhibitors, which inhibited CSN5 but slightly downregulated PD-L1 in cancer cells. Furthermore, through the integration of deep learning-enabled virtual screening, we discovered that shikonins are nanomolar CSN5 inhibitors, which can upregulate PD-L1 in HCT116 cells. The binding modes of these structurally distinct inhibitors with CSN5 were explored by using microsecond-scale molecular dynamics simulations and tryptophan quenching assays.

Establishment and Characterization of a Chicken Myoblast Cell Line.

Skeletal muscle, which is predominantly constituted by multinucleated muscle fibers, plays a pivotal role in sustaining bodily movements and energy metabolism. Myoblasts, which serve as precursor cells for differentiation and fusion into muscle fibers, are of critical importance in the exploration of the functional genes associated with embryonic muscle development. However, the in vitro proliferation of primary myoblasts is inherently constrained. In this study, we achieved a significant breakthrough by successfully establishing a chicken myoblast cell line through the introduction of the exogenous chicken telomerase reverse transcriptase (chTERT) gene, followed by rigorous G418-mediated pressure screening. This newly developed cell line, which was designated as chTERT-myoblasts, closely resembled primary myoblasts in terms of morphology and exhibited remarkable stability in culture for at least 20 generations of population doublings without undergoing malignant transformation. In addition, we conducted an exhaustive analysis that encompassed cellular proliferation, differentiation, and transfection characteristics. Our findings revealed that the chTERT-myoblasts had the ability to proliferate, differentiate, and transfect after multiple rounds of population doublings. This achievement not only furnished a valuable source of homogeneous avian cell material for investigating embryonic muscle development, but also provided valuable insights and methodologies for establishing primary cell lines.

Guidance of development, validation, and evaluation of algorithms for populating health status in observational studies of routinely collected data (DEVELOP-RCD).

BACKGROUND: In recent years, there has been a growing trend in the utilization of observational studies that make use of routinely collected healthcare data (RCD). These studies rely on algorithms to identify specific health conditions (e.g. diabetes or sepsis) for statistical analyses. However, there has been substantial variation in the algorithm development and validation, leading to frequently suboptimal performance and posing a significant threat to the validity of study findings. Unfortunately, these issues are often overlooked. METHODS: We systematically developed guidance for the development, validation, and evaluation of algorithms designed to identify health status (DEVELOP-RCD). Our initial efforts involved conducting both a narrative review and a systematic review of published studies on the concepts and methodological issues related to algorithm development, validation, and evaluation. Subsequently, we conducted an empirical study on an algorithm for identifying sepsis. Based on these findings, we formulated specific workflow and recommendations for algorithm development, validation, and evaluation within the guidance. Finally, the guidance underwent independent review by a panel of 20 external experts who then convened a consensus meeting to finalize it. RESULTS: A standardized workflow for algorithm development, validation, and evaluation was established. Guided by specific health status considerations, the workflow comprises four integrated steps: assessing an existing algorithm's suitability for the target health status; developing a new algorithm using recommended methods; validating the algorithm using prescribed performance measures; and evaluating the impact of the algorithm on study results. Additionally, 13 good practice recommendations were formulated with detailed explanations. Furthermore, a practical study on sepsis identification was included to demonstrate the application of this guidance. CONCLUSIONS: The establishment of guidance is intended to aid researchers and clinicians in the appropriate and accurate development and application of algorithms for identifying health status from RCD. This guidance has the potential to enhance the credibility of findings from observational studies involving RCD.

Establishment of a nomogram model for predicting therapy complications in patients with polycythemia and deep venous thrombosis.

BACKGROUND: Patients with deep venous thrombosis (DVT) residing at high altitudes can only rely on anticoagulation therapy, missing the optimal window for surgery or thrombolysis. Concurrently, under these conditions, patient outcomes can be easily complicated by high-altitude polycythemia (HAPC), which increases the difficulty of treatment and the risk of recurrent thrombosis. To prevent reaching this point, effective screening and targeted interventions are crucial. Thus, this study analyzes and provides a reference for the clinical prediction of thrombosis recurrence in patients with lower-extremity DVT combined with HAPC. AIM: To apply the nomogram model in the evaluation of complications in patients with HAPC and DVT who underwent anticoagulation therapy. METHODS: A total of 123 patients with HAPC complicated by lower-extremity DVT were followed up for 6-12 months and divided into recurrence and non-recurrence groups according to whether they experienced recurrence of lower-extremity DVT. Clinical data and laboratory indices were compared between the groups to determine the influencing factors of thrombosis recurrence in patients with lower-extremity DVT and HAPC. This study aimed to establish and verify the value of a nomogram model for predicting the risk of thrombus recurrence. RESULTS: Logistic regression analysis showed that age, immobilization during follow-up, medication compliance, compliance with wearing elastic stockings, and peripheral blood D-dimer and fibrin degradation product levels were indepen-dent risk factors for thrombosis recurrence in patients with HAPC complicated by DVT. A Hosmer-Lemeshow goodness-of-fit test demonstrated that the nomogram model established based on the results of multivariate logistic regression analysis was effective in predicting the risk of thrombosis recurrence in patients with lower-extremity DVT complicated by HAPC (χ 2 = 0.873; P > 0.05). The consistency index of the model was 0.802 (95%CI: 0.799-0.997), indicating its good accuracy and discrimination. CONCLUSION: The column chart model for the personalized prediction of thrombotic recurrence risk has good application value in predicting thrombotic recurrence in patients with lower-limb DVT combined with HAPC after discharge.

Dynamic development of microglia and macrophages after spinal cord injury.

Secondary injury following spinal cord injury is primarily characterized by a complex inflammatory response, with resident microglia and infiltrating macrophages playing pivotal roles. While previous studies have grouped these two cell types together based on similarities in structure and function, an increasing number of studies have demonstrated that microglia and macrophages exhibit differences in structure and function and have different effects on disease processes. In this study, we used single-cell RNA sequencing and spatial transcriptomics to identify the distinct evolutionary paths of microglia and macrophages following spinal cord injury. Our results showed that microglia were activated to a pro-inflammatory phenotype immediately after spinal cord injury, gradually transforming to an anti-inflammatory steady state phenotype as the disease progressed. Regarding macrophages, our findings highlighted abundant communication with other cells, including fibroblasts and neurons. Both pro-inflammatory and neuroprotective effects of macrophages were also identified; the pro-inflammatory effect may be related to integrin ß2 (Itgb2) and the neuroprotective effect may be related to the oncostatin M pathway. These findings were validated by in vivo experiments. This research underscores differences in the cellular dynamics of microglia and macrophages following spinal cord injury, and may offer new perspectives on inflammatory mechanisms and potential therapeutic targets.

[Research status and reflection of the mechanism of TCM manipulation in the treatment of cervical spondylosis under the background of multi-disciplinary intersection].

The study of TCM manipulation's mechanism is the key scientific issue in the current manipulation research. It is the key and difficult point on the road of modernization and internationalization of Chinese orthopedics and traumatology. Meanwhile, it is also an important way to clarify systematically the scientific connotation of TCM manipulation. At present, our country is in an important period when multi-disciplinary intersection lead knowledge production, scientific innovation, and discipline development. The trend of cross-innovation between Chinese orthopedics and traumatology and other disciplines provides the carrier and method for the study of TCM manipulation's mechanism. Cervical spondylosis is the traditional dominant disease of Chinese orthopedics and traumatology. In recent years, many scholars have applied multi-disciplinary techniques and theories to explore the mechanism of TCM manipulation by focusing on the four dimensions of muscle, bone, blood vessel and nerve. The article takes the treatment of cervical spondylosis by TCM manipulation as the research entry point, and integrates the application status and implementation strategies of various techniques and theories under the background of multi-disciplinary intersection, which is conducive to the better combination, innovation and transformation of Chinese orthopedics and traumatology with other disciplines, and provides ideas and references for systematically clarifying the scientific connotation of TCM manipulation.

Mycenabrunnescens (Basidiomycota, Mycenaceae), a new species of Mycena sect. Pterigenae from China.

Background: Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycenagalericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described. New information: Mycenabrunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M.albiceps and M.flosoides.

Study on the Effects of Pasture Fiber on Thermal Properties of Slag Bricks.

In the context of ecological sustainability, this study focuses on the effect of variables of pasture fibers on the thermal properties of slag bricks made from a green recyclable material. This experiment uses slag as the binder, sand as the aggregate, and pasture fiber as an additive. The experimental variables include the additive content ratio of the pasture fiber, the size of the pasture fiber, and the type of pasture fiber. Significance analysis of the experimental results of the thermal performance tests is carried out using Minitab 18.1.0 software, and the optimal ratios for the thermal performance of the composite samples are derived from the response optimizer and conformity analysis. The results of the experiment's test analysis using Minitab 18 software indicate that, with an increase in pasture fiber content, the thermal performance of the composite samples initially decreases before increasing. Additionally, the lower the thermal conductivity of the composite sample, the lower the apparent density and the higher the porosity. Incorporating pasture fibers into slag bricks, as revealed in this study, reduces the waste of pasture resources in pastoral areas and promotes the development of sustainable building materials with favorable thermal properties.

Four new lycoctonine-type C19-diterpenoid alkaloids from the whole plants of Delphinium kamaonense.

Four new lycoctonine-type C19-diterpenoid alkaloids kamaonensines H-K (1-4) have been isolated from the whole plants of Delphinium kamaonense, together with 12 known compounds (5-16). Interestingly, kamaonensines 1-3 contained a rare nitrone (immine N-oxide) moiety, respectively. Their structures were established by spectroscopic analyses. The active evaluation of compounds (1-16) by LPS induced RAW 264.7 macrophages showed that compounds 4 and 8 displayed strong anti-inflammatory activities. While compounds 11 and 12 also showed strong cytotoxicities by the RAW 264.7 cell viability assay.

Research on online monitoring of aircraft skin laser paint removal thickness using standard curve method and PCA-SVR based on LIBS.

High-frequency pulse lasers, applied in the form of rapid scanning, act upon the surface of aircraft skin paint layers, thereby removing the paint layers, exhibiting characteristics of efficiency and eco-friendliness. Real-time monitoring of the paint removal effect and prevention of substrate damage necessitates the continuous monitoring of paint removal thickness. Combining Laser-Induced Breakdown Spectroscopy (LIBS) online monitoring technology enables laser-controlled paint removal under multiple effects coupling, meeting the requirements of airworthiness maintenance. This paper, based on a high-frequency nanosecond infrared pulse laser paint removal LIBS monitoring platform, conducts research on laser paint removal thickness LIBS online monitoring of aluminum alloy plates coated with dual-layer paint. Spectra corresponding to the removal thickness of each group are collected and, respectively, paint removal thickness monitoring models based on LIBS spectra are established using the standard curve method and Principal Component Analysis-Support Vector Regression (PCA-SVR) algorithm. When monitoring paint removal thickness using the standard curve method, the intensity of five Ti element characteristic spectral lines selected is correlated with the paint removal thickness, and segmented curve fitting according to the paint layer structure satisfies the segmented curve fitting of topcoat and topcoat + primer. Among them, the average coefficient of the curve fitting of the Ti II 589.088 nm characteristic spectral line is 0.89, and the root mean square error (RMSE) is 12.28 µm. Its performance is superior in the five standard curves; thus, its fitting equation is used as the criterion for paint removal thickness monitoring. To further improve monitoring accuracy, research on paint removal thickness monitoring models based on PCA-SVR is conducted. Compared to the traditional univariate standard curve method, the PCA-SVR model does not require segmented monitoring. After parameter optimization, the average fitting coefficient reaches 0.97, and the RMSE is 2.92 µm. The results indicate that the PCA-SVR-based paint removal thickness monitoring model has higher accuracy, thereby forming the basis for paint removal thickness monitoring. Through comparative research on paint removal thickness monitoring models, two types of paint removal thickness monitoring criteria are obtained, providing model solutions for high-precision monitoring and automation of aircraft skin laser paint removal thickness.

Comparative Transcriptome Analysis of Henosepilachna vigintioctomaculata Reveals Critical Pathways during Development.

Henosepilachna vigintioctomaculata is distributed in several Asian countries. The larvae and adults often cause substantial economic losses to Solanaceae crops such as potato, tomato, eggplant, and Chinese boxthorn. Even though a chromosome-level genome has been documented, the expression profiles of genes involved in development are not determined. In this study, we constructed embryonic, larval, pupal, and adult transcriptomes, generated a comprehensive RNA-sequencing dataset including ~52 Gb of clean data, and identified 602,773,686 cleaned reads and 33,269 unigenes. A total of 18,192 unigenes were successfully annotated against NCBI nonredundant protein sequences, Swissprot, Eukaryotic Orthologous Groups, Gene Ontology (GO), or Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. There were 3580, 2040, 5160, 2496, 3008, and 3895 differentially expressed genes (DEGs) between adult/egg, egg/larval, larval/pupal, adult/pupal, egg/pupal, and adult/larval samples, respectively. GO and KEGG analyses of the DEGs highlighted several critical pathways associated with specific developing stages. This is the first comprehensive transcriptomic dataset encompassing all developmental stages in H. vigintioctomaculata. Our data may facilitate the exploitation of gene targets for pest control and can serve as a valuable gene resource for future molecular investigations.

Optimal image quality and radiation doses with optimal tube voltages/currents for pediatric anthropomorphic phantom brains.

OBJECTIVE: Using pediatric anthropomorphic phantoms (APs), we aimed to determine the scanning tube voltage/current combinations that could achieve optimal image quality and avoid excessive radiation exposure in pediatric patients. MATERIALS AND METHODS: A 64-slice scanner was used to scan a standard test phantom to determine the volume CT dose indices (CTDIvol), and three pediatric anthropomorphic phantoms (APs) with highly accurate anatomy and tissue-equivalent materials were studied. These specialized APs represented the average 1-year-old, 5-year-old, and 10-year-old children, respectively. The physical phantoms were constructed with brain tissue-equivalent materials having a density of ρ = 1.07 g/cm3, comprising 22 numbered 2.54-cm-thick sections for the 1-year-old, 26 sections for the 5-year-old, and 32 sections for the 10-year-old. They were scanned to acquire brain CT images and determine the standard deviations (SDs), effective doses (EDs), and contrast-to noise ratios (CNRs). The APs were scanned by 21 combinations of tube voltages/currents (80, 100, or 120 kVp/10, 40, 80, 120, 150, 200, or 250 mA) and rotation time/pitch settings of 1 s/0.984:1. RESULTS: The optimal tube voltage/current combinations yielding optimal image quality were 80 kVp/80 mA for the 1-year-old AP; 80 kVp/120 mA for the 5-year-old AP; and 80 kVp/150 mA for the 10-year-old AP. Because these scanning tube voltages/currents yielded SDs, respectively, of 12.81, 13.09, and 12.26 HU, along with small EDs of 0.31, 0.34, and 0.31 mSv, these parameters and the induced values were expediently defined as optimal. CONCLUSIONS: The optimal tube voltages/currents that yielded optimal brain image quality, SDs, CNRs, and EDs herein are novel and essentially important. Clinical translation of these optimal values may allow CT diagnosis with low radiation doses to children's heads.

Tough Self-Healing Materials via In Situ Growth of Zeolitic Imidazolate Framework-8 Nanocrystals in Polymers.

Construction of self-healing materials with improved mechanical performance is a great challenge. A strong and tough self-healing composite is fabricated via in situ growth of zeolitic imidazole framework-8 (ZIF-8) nanocrystals in imidazole-containing polymer networks. By adjusting the stoichiometric ratio of the zinc salt to 2-methylimidazole, composites with various mechanical performances are obtained. The existence of ZIF-8 nanocrystals via in situ growth in the polymer networks is confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM), and atomic force microscopy (AFM). The zinc-imidazole interactions between the ZIF-8 nanocrystals and the polymer are confirmed by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. The composites can repair themselves under mild conditions owing to dynamic zinc-imidazole interactions. The self-healing efficiency of composites can reach up to 91% under the condition of 60 °C for 48 h. In contrast to the pure zinc cation crosslinking system, the composite containing ZIF-8 nanocrystals prepared via in situ growth exhibited enhanced tensile strength and toughness by 43% and 100%, respectively. This study proves that incorporating the metal-organic frameworks (MOFs) materials into a self-healing system via an in situ growth strategy is highly promising for designing self-healing materials with improved mechanical performance.

Behavioral events and functional analysis of bursicon signal during adult eclosion in the 28-spotted larger potato ladybird.

To accommodate growth, insects must periodically shed their exoskeletons. In Manduca sexta, Drosophila melanogaster and Tribolium castaneum, Bursicon (Burs)/ Partner of bursicon (Pburs)-LGR2 signal is an indispensable component for the proper execution of ecdysis behavior during adult eclosion. Nevertheless, the behavioral events and the roles of bursicon signaling in other insects deserve further exploration. In the current paper, we found that the pupal-adult ecdysis in Henosepilachna vigintioctomaculata could be divided into three distinct stages, preecdysis, ecdysis and postecdysis. Preecdysis behavioral sequences included abdomen twitches, dorsal-ventral contractions and air filling that function to loosen the old cuticle. Ecdysis events began with anterior-posterior contractions that gradually split the old integument along the dorsal body midline, followed by freeing of legs and mouthparts, and culminated in detachment from pupal cuticle. Postecdysis behavioral processes contained three actions: perch selection and stretching of elytra and hindwings. RNA interference for HvBurs, HvPburs or Hvrk (encoding LGR2) strongly impaired wing expansion actions, and slightly influenced preecdysis and ecdysis behaviors. The RNAi beetles failed to extend their elytra and hindwings. In addition, injected with dsrk also caused kinked femurs and tibia. Our findings establish that bursicon pathway is involved in regulation of adult eclosion behavior, especially wing expansion motor programs. Given that wings facilitate food foraging, courtship, predator avoidance, dispersal and migration, our results provide a potential target for controlling H. vigintioctomaculata.

Identification of lncRNA-mRNA network linking ferroptosis and immune infiltration to colon adenocarcinoma suppression.

Background: Colon adenocarcinoma (COAD) is one of the most common malignant tumors. The interplay involving ferroptosis between tumor and immune cells plays a crucial in cancer progression. However, the biological basis of this interplay in COAD development remains elusive. Methods: Transcriptome data of COAD samples were obtained from The Cancer Genome Atlas and National Center for Biotechnology Information databases. Using single-sample gene set enrichment analysis, we calculated the ferroptosis score (FS) and immune cell infiltration levels for each sample, leveraging the expression levels of genes related to ferroptosis and various immune cell types. Samples with FSs greater than the 75th percentile were classified into the high-FS subgroup, while those below the 25th percentile were categorized as the low-FS subgroup. Moreover, tumor tissue samples and adjacent normal tissue samples were collected from twenty colon patients. Using real-time quantitative polymerase chain reaction, we validated the expression of certain genes in these samples. Results: The COAD samples with high FSs experienced favorable survival probability and heightened sensitivity to anticancer drugs, with FSs negatively associated with the pathological stages. Moreover, the up-regulated genes in high-FS subgroup exhibited enrichment in immune-related pathways, suggesting a correlation between immunity and ferroptosis. Importantly, we discovered a key lncRNA-mRNA co-expression network linking tumor cell ferroptosis and immune infiltration (e.g., neutrophil) in the progression and classification of COAD. Further analysis identified several ferroptosis-related lncRNAs (e.g., RP11-399O19.9) within this network, indicating their potential roles in COAD progression and deserving in-depth study. Conclusions: Our findings provide novel insights into the underlying biological basis, particularly involving lncRNAs, at gene expression level associated with ferroptosis in COAD and cancer therapy. Nevertheless, further analysis and validation are required to expand the findings.

Progress in SARS-CoV-2, diagnostic and clinical treatment of COVID-19.

Background: Corona Virus Disease 2019(COVID-19)is a global pandemic novel coronavirus infection disease caused by Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Although rapid, large-scale testing plays an important role in patient management and slowing the spread of the disease. However, there has been no good and widely used drug treatment for infection and transmission of SARS-CoV-2. Key findings: Therefore, this review updates the body of knowledge on viral structure, infection routes, detection methods, and clinical treatment, with the aim of responding to the large-section caused by SARS-CoV-2. This paper focuses on the structure of SARS-CoV-2 viral protease, RNA polymerase, serine protease and main proteinase-like protease as well as targeted antiviral drugs. Conclusion: In vitro or clinical trials have been carried out to provide deeper thinking for the pathogenesis, clinical diagnosis, vaccine development and treatment of SARS-CoV-2.

Boosting electrocatalytic ammonia synthesis from nitrate by asymmetric chemical potential activated interfacial electric fields.

The electrocatalytic nitrate reduction reaction (NO3- RR) has immense potential to alleviate the problem of groundwater pollution and may also become a key route for the environmentally benign production of ammonia (NH3) products. Here, the unique effects of interfacial electric fields arising from asymmetric chemical potentials and local defects were integrated into the binary Bi2S3-Bi2O3 sublattices for enhancing electrocatalytic nitrate reduction reactions. The obtained binary system showed a superior Faraday efficiency (FE) for ammonia production of 94 % and an NH3 yield rate of 89.83 mg gcat-1h-1 at -0.4 V vs. RHE. Systematic experimental and computational results confirmed that the concerted interplay between interfacial electric fields and local defects not only promoted the accumulation and adsorption of NO3-, but also contributed to the destabilization of *NO and the subsequent deoxygenation hydrogenation reaction. This work will stimulate future designs of heterostructured catalysts for efficient electrocatalytic nitrate reduction reactions.

Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence.

BACKGROUND: The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation. RESEARCH DESIGN AND METHODS: Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group. Kaplan-Meier recovery analysis and Cox proportional hazards models were used to evaluate the recovery time and hazard ratios. Additionally, study-level pooled analyses for multiple clinical outcomes were performed. RESULTS: In the 115-patient cohort, UDCA treatment was significantly associated with a reduced recovery time. The subgroup analysis suggests that the 300 mg subgroup had a significant (adjusted hazard ratio: 1.63 [95% CI, 1.01 to 2.60]) benefit with a shorter duration of fever. The results of pooled analyses also show that UDCA treatment can significantly reduce the incidence of severe/critical diseases in COVID-19 (adjusted odds ratio: 0.68 [95% CI, 0.50 to 0.94]). CONCLUSIONS: UDCA treatment notably improves the recovery time following an Omicron strain infection without observed safety concerns. These promising results advocate for UDCA as a viable treatment for COVID-19, paving the way for further large-scale and prospective research to explore the full potential of UDCA.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.