Mechanisms of Puerariae Lobatae Radix in regulating sebaceous gland secretion: insights from network pharmacology and experimental validation.

Objective: This research aims to explore how Puerariae Lobatae Radix regulates sebaceous gland secretion using network pharmacology, and validate its effects on important targets through animal studies. Methods: This study utilized UPLC-EQ-MS to analyze Puerariae Lobatae Radix extract and identify potential bioactive compounds. Predicted targets of these compounds were obtained from the Swiss Target Prediction database, while targets associated with sebaceous gland secretion were obtained from the GeneCards database. Common targets between the databases were identified and a protein-protein interaction (PPI) network was established using the STRING platform. The PPI network was further analyzed using Cytoscape software. Pathway enrichment analysis was performed using Reactome, and molecular docking experiments targeted pivotal pathway proteins. Animal experiments were then conducted to validate the regulatory effects of the primary active compounds of Puerariae Lobatae Radix on key pathway proteins. Results: This research identified 17 active compounds in Puerariae Lobatae Radix and 163 potential targets associated with the regulation of sebum secretion. Pathway enrichment analysis indicates that these targets may modulate lipid metabolism pathways through involvement in peroxisome proliferator-activated receptor α, SREB, steroid metabolism, and arachidonic acid metabolism pathways. Molecular docking analysis demonstrates that puerarin and daidzein show favorable binding interactions with key targets in these pathways. Animal experiments demonstrated that the administration of Puerariae Lobatae Radix resulted in a significant reduction in the area of sebaceous gland patches compared to the control group. Histological analysis revealed notable alterations in the structure of sebaceous glands, including reductions in size, thickness, and density. Furthermore, the expression levels of TG, DHT, and IL-6 were significantly decreased in the Puerariae Lobatae Radix group (p < 0.05), and immunoblotting indicated a significant decrease in the expression of PPARG and ACC1 (p < 0.05). Conclusion: This study demonstrates that Puerariae Lobatae Radix can regulate skin lipid metabolism by targeting multiple pathways. The primary mechanism involves inhibiting sebaceous gland growth and reducing TG secretion by modulating the expression of PPARG and ACC1. Puerarin and Daidzein are identified as key bioactive compounds responsible for this regulatory effect. These findings highlight the therapeutic potential of Puerariae Lobatae Radix in addressing sebaceous gland-related conditions.

Research on Foot Contact State Detection Technology of Wheel-Legged Robot.

The accurate perception of external environment information through the robot foot is crucial for the mobile robot to evaluate its ability to traverse terrain. Adequate foot-end contact signals can provide robust support for robot motion control and decision-making processes. The shape and uncertain rotation of the wheel-legged robot foot end represent a significant challenge to sensing the robot foot-end contact state, which current foot-end sensing schemes cannot solve. This paper presents a sensing method for the tire stress field of wheel-legged robots. A finite element analysis was conducted to study the deformation characteristics of the foot-end tire under force. Based on this analysis, a heuristic contact position estimator was designed that utilizes symmetrical deformation characteristics. Strain sensors, arranged in an array, extract the deformation information on the inner surface of the tire at a frequency of 200 Hz. The contact position estimator reduces the dimensionality of the data and fits the eigenvalues to the estimated contact position. Using support vector regression, the force estimator utilizes the estimated contact position and sensor signal to estimate the normal reaction force, designated as FZ. The sensing system is capable of detecting the contact position on the wheel circumference (with a root mean square error of 1.150°), as well as the normal force of 160 N on the Z axis (with a root mean square error of 6.04%). To validate the efficacy of the sensor detection method, a series of randomized and repeated experiments were conducted on a self-constructed test platform. This novel approach offers a promising avenue for perceiving contact states in wheel-legged robots.

Anatomical studies and early results on endoscopic transoral medial pterygomandibular fold approach to salvage retropharyngeal lymphadenectomy in nasopharyngeal carcinoma.

OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.

The ER-Golgi transport of influenza virus through NS1-Sec13 association during virus replication.

IMPORTANCE: Influenza A virus is a respiratory virus that can cause complications such as acute bronchitis and secondary bacterial pneumonia. Drug therapies and vaccines are available against influenza, albeit limited by drug resistance and the non-universal vaccine administration. Hence there is a need for host-targeted therapies against influenza to provide an effective alternative therapeutic target. Sec13 was identified as a novel host interactor of influenza. Endoplasmic reticulum-to-Golgi transport is an important pathway of influenza virus replication and viral export. Specifically, Sec13 has a functional role in influenza replication and virulence.

Effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome based on 16S rDNA technique. / 基于16S rDNAæŠ€æœ¯æŽ¢è®¨é’ˆç¸å¯¹è ¹æ³»åž‹è‚ æ˜“æ¿€ç»¼åˆå¾æ¨¡åž‹å¤§é¼ è‚ é“èŒç¾¤çš„å½±å“.

OBJECTIVES: To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique. METHODS: Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected. RESULTS: After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group. CONCLUSIONS: Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.

List Equivalency and Critical Differences of a Mandarin Bamford-Kowal-Bench Sentence in Babble Noise Test for Adults and Preschool Children With Normal Hearing.

PURPOSE: The purpose of this study was to determine the speech recognition equivalence of Mandarin Bamford-Kowal-Bench (BKB) sentence lists with adults and children with normal hearing. METHOD: A total of 32 lists, each of nine sentences, were compiled from a corpus of BKB-like sentences with paired babble in Mandarin. Interlist equivalence, critical differences, and sensitivity of performance to signal-to-noise ratio (SNR) were examined. Experiment 1 included 64 native Mandarin-speaking adults with normal hearing. Experiment 2 included 54 native Mandarin-speaking children with normal hearing aged 4-6 years. RESULTS: Among the 32 sentence lists, 28 lists were confirmed to be equivalent in adults, with a mean SNR required for 50% correct (SNR50) of -5.9 ± 0.1 dB, a mean slope of 22.3%/dB ± 1.5%/dB, and a grand 95% critical difference subsequently calculated as 27.2% for score. From the 28 equivalent lists, 27 lists were selected and observed to be equivalent in children, with a mean SNR50 threshold of -2.0 ± 0.2 dB, a mean slope of 15.8%/dB ± 1.1%/dB, and a grand 95% critical difference of 24.6% for score. CONCLUSIONS: The Mandarin BKB sentences in babble noise test offers an opportunity for clinicians and researchers to assess speech understanding in adults and preschool children in an efficient manner. For comparisons of performance in different test conditions, 28 equivalent lists are available for adults and 27 equivalent lists for preschool children. The 95% critical difference values can be used for total percentage correct or SNR for 50% performance. Future work will examine the clinical utility for school-age children and children who are deaf and hard of hearing. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24400066.

Macrophage IL-1ß contributes to tumorigenesis through paracrine AIM2 inflammasome activation in the tumor microenvironment.

Intracellular recognition of self and non-self -nucleic acids can result in the initiation of effective pro-inflammatory and anti-tumorigenic responses. We hypothesized that macrophages can be activated by tumor-derived nucleic acids to induce inflammasome activation in the tumor microenvironment. We show that tumor conditioned media (CM) can induce IL-1ß production, indicative of inflammasome activation in primed macrophages. This could be partially dependent on caspase 1/11, AIM2 and NLRP3. IL-1ß enhances tumor cell proliferation, migration and invasion while coculture of tumor cells with macrophages enhances the proliferation of tumor cells, which is AIM2 and caspase 1/11 dependent. Furthermore, we have identified that DNA-RNA hybrids could be the nucleic acid form which activates AIM2 inflammasome at a higher sensitivity as compared to dsDNA. Taken together, the tumor-secretome stimulates an innate immune pathway in macrophages which promotes paracrine cancer growth and may be a key tumorigenic pathway in cancer. Broader understanding on the mechanisms of nucleic acid recognition and interaction with innate immune signaling pathway will help us to better appreciate its potential application in diagnostic and therapeutic benefit in cancer.

Experimental Study on Laminar Burning Characteristics of Premixed 2,5-Dimethylfuran/Air Mixtures at Elevated Pressures and Temperatures.

Experimental studies of laminar burning velocity and flame instabilities of 2,5-dimethylfuran (DMF) were conducted at different equivalence ratios (from 0.9 to 1.3), initial pressures (from 0.1 to 0.8 MPa), and initial temperatures (from 393 to 493 K) by the method of the schlieren and high-speed photography system in the constant-volume combustion bomb. The results showed that the laminar burning velocity of the DMF/air flame decreased with increasing initial pressure and increased with increasing initial temperature. The maximum laminar burning velocity occurred at φ = 1.1, regardless of the initial pressure and temperature conditions. The power law fitting of baric coefficients, thermal coefficients, and laminar burning velocity was obtained, and the laminar burning velocity of DMF/air flame can be predicted well in the study range. The diffusive-thermal instability of the DMF/air flame was more pronounced during rich combustion. Increasing the initial pressure increased both the diffusive-thermal instability and the hydrodynamic instability of the flame, while increasing the initial temperature increased the diffusive-thermal instability of the flame, which was mainly responsible for flame propagation. In addition, the Markstein length, density ratio, flame thickness, critical radius, acceleration index, and classification excess of the DMF/air flame were investigated. The results of this paper provide a theoretical support for the application of DMF in engineering.

CoVnita, an end-to-end privacy-preserving framework for SARS-CoV-2 classification.

Classification of viral strains is essential in monitoring and managing the COVID-19 pandemic, but patient privacy and data security concerns often limit the extent of the open sharing of full viral genome sequencing data. We propose a framework called CoVnita, that supports private training of a classification model and secure inference with the same model. Using genomic sequences from eight common SARS-CoV-2 strains, we simulated scenarios where the data was distributed across multiple data providers. Our framework produces a private federated model, over 8 parties, with a classification AUROC of 0.99, given a privacy budget of [Formula: see text]. The roundtrip time, from encryption to decryption, took a total of 0.298 s, with an amortized time of 74.5 ms per sample.

Fabrication of a novel antioxidant emulsifier through tuning the molecular interaction between soy protein isolates and young apple polyphenols.

Soy protein isolates (SPI) exhibit weaker emulsifying properties than those of animal proteins, thereby limiting their wide applicability. In this study, a novel plant-based antioxidant emulsifier was developed using SPI and young apple polyphenols (YAP), and its underlying interaction mechanisms were discovered using multispectral technology and molecular docking. YAP physically bound to SPI through hydrogen bonds and hydrophobic interactions, which significantly enhanced the free radicals scavenging, reducing, and metal ion chelating abilities of SPI by introducing free hydroxyl groups. Moreover, SPI modified by YAP exerted better emulsifying performance owing to a looser protein structure, reflected by a higher random coil and a lower α-helix content. In addition, YAP may bridge adjacent SPI molecules, promoting the adsorption and anchoring of SPI at the oil-water interface. SPI-YAP complexes are promising antioxidant emulsifiers that can be used to nano-deliver functional oils and nutrients, thereby broadening SPI and YAP applications in the food industry.

Clinical characteristics, susceptibility profiles, and treatment of nocardiosis: a multicenter retrospective study in 2015-2021.

OBJECTIVES: This study aimed to investigate the microbiological characteristics, antimicrobial resistance profiles, antibiotic choice, and outcomes of Nocardia infection in various centers over a 7-year period (from 2015 to 2021). METHODS: We retrospectively analyzed the medical records of all hospitalized patients diagnosed with Nocardia between 2015 and 2021. The isolates were identified to the species level through the sequencing of 16S ribosomal RNA or secA1 or ropB genes. The susceptibility profiles were determined using the broth microdilution method. RESULTS: Of the 130 nocardiosis cases, 99 (76.2%) were established as pulmonary infection, of which the most common underlying disease was chronic lung disease (40.4%, 40/99), including bronchiectasis, chronic obstructive pulmonary disease, and chronic bronchitis. Among 130 isolates, 12 species were identified, with the most common species being Nocardia cyriacigeorgica (37.7%) and Nocardia farcinica (20.8%). All Nocardia strains were susceptible to linezolid and amikacin, and the susceptibility rate of trimethoprim-sulfamethoxazole (TMP-SMX) was 97.7%. Of the 130 patients, 86 (66.2%) received TMP-SMX monotherapy or multidrug regimen. Furthermore, 92.3% patients who were treated achieved clinical improvement. CONCLUSION: TMP-SMX was the treatment of choice for nocardiosis, and other combination drugs with TMP-SMX therapy yielded even better results.

Transoral robotic resection of advanced recurrent nasopharyngeal carcinoma involving the internal carotid artery.

BACKGROUND: Transoral robotic surgery (TORS) is a reliable, minimally invasive approach for treating recurrent nasopharyngeal carcinoma (rNPC). However, tumours involving the internal carotid artery (ICA) are considered to be unsuitable for TORS. This paper presents the first case of transoral robotic resection of advanced rNPC involving the ICA. MATERIALS AND METHODS: This case is a 55 year-old male patient who received radiotherapy 27 years ago. This patient underwent a standard TORS resection 2 weeks after ipsilateral ICA embolization. RESULTS: Postoperative Magnetic resonance imaging and biopsy results indicated total resection. During the 2 month follow-up, no severe complications were found, and the primary site was tumour-free. CONCLUSION: This study preliminarily presents the feasibility and efficiency of advanced rNPC resection with TORS. TORS can potentially provide better quality of life for patients as a less invasive approach than current endoscopic surgery. Even so, the surgical approach should be selected strictly according to the tumour's location.

Clinical and immunological features of primary Sjögren's syndrome patients with positive anti-centromere protein B antibody / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical and immunological features of primary Sjögren's syndrome (pSS) patients with positive anti-centromere protein B (CENP-B) antibody.@*METHODS@#In this cross-sectional study, the general clinical data, radiographic examination and labial salivary gland biopsy data, and serum immunological and biochemical data of patients diagnosed with pSS from January 2016 to August 2022 were evaluated. The included patients were divided into the anti-CENP-B antibody positive and negative groups. Intergroup differences were analyzed with SPSS 23.0 software. Subgroup analysis was further performed by dividing the anti-CENP-B antibody positive group into the single anti-CENP-B antibody positive and with other auto-antibodies positive groups to determine the characters related to anti-CENP-B antibody.@*RESULTS@#In this study, 288 patients with pSS were evaluated, including 75 patients with anti-CENP-B antibody positive and 213 with anti-CENP-B antibody negative. Univariate analysis showed that compared with the anti-CENP-B antibody negative group, the patients of the anti-CENP-B antibody positive group were older, had lower proportion of the patients with salivary gland enlargement and higher proportion of autoimmune liver disease. As for immunological indicators, the positive proportions of anti-SSA/Ro60, anti-Ro52, and anti-SSB antibodies were significantly lower. Moreover, the immunoglobulin (Ig) G and rheumatoid factor levels were significantly lower, while the IgM level was significantly higher in the patients of the anti-CENP-B antibody positive group. As for serum biochemical indicators, for the patients of the anti-CENP-B antibody positive group, the level of total protein (TP) was lower, the albumin/globulin ratio was higher, and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) were higher. Subgroup analysis showed that the levels of TP and IgA in the patients of the single anti-CENP-B antibody positive group were significantly lower than those of the patients with other autoantibodies positive group.@*CONCLUSION@#The pSS patients with anti-CENP-B antibody positive have unique clinical and immunological features of lower disease activity, less likely to involve salivary gland, higher risk for autoimmune liver disease, and higher levels of liver function indicators. Anti-CENP-B antibody may be a marker for a distinct subset of polyautoimmunity in Sjögren's syndrome.

Endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.

Role of probiotics in the treatment of acne / 中华皮肤科杂志

Recent studies have shown that changes in the gut and skin microbiome can directly affect the occurrence of acne. Regulating the skin and gut microbiome has brought new directions for the treatment of acne, and the most direct way to achieve this goal is to restore the balance of the microbiome through the use of probiotics. This review summarizes the relationship between acne and microbiome, and research progress in probiotics for the treatment of acne.

Effects of the combination of acupuncture and medication on orthostatic hypotension after incomplete cervical spinal cord injury / 针灸推拿医学（英文版）

Objective: To observe the effect of the combination of acupuncture and medication on orthostatic hypotension after incomplete cervical spinal cord injury. Methods: Ninety-two patients with orthostatic hypotension after incomplete cervical spinal cord injury were divided into two groups according to the random number table method, with 46 cases in each group. The control group was treated with oral midodrine hydrochloride on the basis of conventional treatment, and the observation group was treated with acupuncture in addition to the intervention used in the control group. Both groups were treated for 4 weeks. The changes in supine and orthostatic blood pressures, motor and sensory scores, quadriplegic function index score, clinical efficacy, and safety evaluation were observed. Results: During the treatment, 2 cases dropped out in the observation group, and 3 cases dropped out in the control group. After 4 weeks of treatment, the clinical efficacy of the observation group was better than that of the control group (P<0.05). After treatment, the supine systolic blood pressure and diastolic blood pressure in the two groups had no significant changes (P>0.05), while the orthostatic systolic blood pressure and diastolic blood pressure, the motor and sensory scores, and the quadriplegic function index score were significantly higher than those before treatment (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). Adverse reactions were mild in both groups. Conclusion: The combination of acupuncture and medication can significantly improve the orthostatic blood pressure, motor and sensory function and daily living ability of patients with orthostatic hypotension after incomplete cervical spinal cord injury, and it is safe and reliable.

Review of the pharmacological effects of astragaloside IV and its autophagic mechanism in association with inflammation.

Astragalus membranaceus Bunge, known as Huangqi, has been used to treat various diseases for a long time. Astragaloside IV (AS-IV) is one of the primary active ingredients of the aqueous Huangqi extract. Many experimental models have shown that AS-IV exerts broad beneficial effects on cardiovascular disease, nervous system diseases, lung disease, diabetes, organ injury, kidney disease, and gynaecological diseases. This review demonstrates and summarizes the structure, solubility, pharmacokinetics, toxicity, pharmacological effects, and autophagic mechanism of AS-IV. The autophagic effects are associated with multiple signalling pathways in experimental models, including the PI3KI/Akt/mTOR, PI3K III/Beclin-1/Bcl-2, PI3K/Akt, AMPK/mTOR, PI3K/Akt/mTOR, SIRT1-NF-κB, PI3K/AKT/AS160, and TGF-ß/Smad signalling pathways. Based on this evidence, AS-IV could be used as a replacement therapy for treating the multiple diseases referenced above.

Enzyme-free and isothermal discrimination of microRNA point mutations using a DNA split proximity circuit with turn-on fluorescence readout.

MicroRNAs (miRNAs) hold immense potential as disease biomarkers, yet their short lengths and high sequence homology pose unique challenges in detection. Conventional methods such as the gold standard qRT-PCR and other isothermal amplification methods require sophisticated primer designs and use of enzymes which add uncertainties to the assay robustness. In this work, we demonstrate the use of a plug-and-play molecular detection platform, termed split proximity circuit (SPC), to achieve a selectivity comparable to qRT-PCR in differentiating point mutations using several miRNAs as proof-of-concept models. The analytical sensitivity of SPC has been improved by a hundred-fold over our previous work and matches/outperforms the enzyme-free assays reported in the literature by evolving the core signal-generating domains. Key design changes include improved hybridization chain reaction (HCR) hairpin sequences and the incorporation of a turn-on fluorescence signal based on fluorophore-quencher format. The core domains were then kept constant while redesigning the target recognition region to be complementary to various target sequences, all of which yield similar analytical performance. Notably, SPC maintained robust signal recovery with low variance even in complex biological matrices. With its enzyme-free and single room temperature operation, SPC presents a promising platform for quick and easy miRNA quantification.

Annexin-A1 deficiency attenuates stress-induced tumor growth via fatty acid metabolism in mice: an Integrated multiple omics analysis on the stress- microbiome-metabolite-epigenetic-oncology (SMMEO) axis.

Background: High emotional or psychophysical stress levels have been correlated with an increased risk and progression of various diseases. How stress impacts the gut microbiota to influence metabolism and subsequent cancer progression is unclear. Methods: Feces and serum samples from BALB/c ANXA1+/+ and ANXA1-/- mice with or without chronic restraint stress were used for 16S rRNA gene sequencing and GC-MS metabolomics analysis to investigate the effect of stress on microbiome and metabolomics during stress and breast tumorigenesis. Breast tumors samples from stressed and non-stressed mice were used to perform Whole-Genome Bisulfite Sequencing (WGBS) and RNAseq analysis to construct the potential network from candidate hub genes. Finally, machine learning and integrated analysis were used to map the axis from chronic restraint stress to breast cancer development. Results: We report that chronic stress promotes breast tumor growth via a stress-microbiome-metabolite-epigenetic-oncology (SMMEO) axis. Chronic restraint stress in mice alters the microbiome composition and fatty acids metabolism and induces an epigenetic signature in tumors xenografted after stress. Subsequent machine learning and systemic modeling analyses identified a significant correlation among microbiome composition, metabolites, and differentially methylated regions in stressed tumors. Moreover, silencing Annexin-A1 inhibits the changes in the gut microbiome and fatty acid metabolism after stress as well as basal and stress-induced tumor growth. Conclusions: These data support a physiological axis linking the microbiome and metabolites to cancer epigenetics and inflammation. The identification of this axis could propel the next phase of experimental discovery in further understanding the underlying molecular mechanism of tumorigenesis caused by physiological stress.

Elevation of neutrophil carcinoembryonic antigen-related cell adhesion molecule 1 associated with multiple inflammatory mediators was related to different clinical stages in ischemic stroke patients.

BACKGROUND: We aimed to analyze the level of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in neutrophils of ischemic stroke (IS) patients at different stages, together with its roles in neutrophils. PATIENTS AND METHODS: Sixty-seven patients were classified into acute phase group (n = 19), subacute phase group (n = 28), and stable phase group (n = 20), and 20 healthy individuals who had received physical examination at the same time period as healthy control. We then analyzed the expression level of CEACAM1 and cell viability in CEACAM1 positive and CEACAM1 negative neutrophils by flow cytometry and the content of plasma CEACAM1, neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinases-9 (MMP-9) was measured using enzyme-linked immunosorbent assay (ELISA), while that of interleukin-10 (IL-10) and tumor necrosis factor (TNF) was determined using a Human Enhanced Sensitivity Flex set. RESULTS: Compared with healthy control, the percentage of CEACAM1 positive neutrophils in IS patients showed a significant increase, and a significant increase was also noticed in the content of plasma CEACAM1 at the subacute stage. Reduction in cell viability was observed in CEACAM1 positive neutrophils compared with CEACAM1 negative counterparts. There was a positive correlation between CEACAM1 expression rate in neutrophils and plasma CEACAM1 and IL-10 content in the subacute group. Compared with acute group and healthy control group, there was an instinct increase in the level of plasma MMP-9 and NGAL in subacute group. CONCLUSIONS: Our data showed that there was a rapid increase of CEACAM1 in neutrophils at the acute stage of IS. We speculated that CEACAM1 may serve as an inhibitory regulator involving in the progression of IS.