Exploring the key deteriorative microorganisms on ancient ivories unearthed from the Sanxingdui Ruins site during temporary cold storage.

Introduction: The ancient ivories unearthed from the Sanxingdui Ruins site are valuable cultural relics, however, the microbial biodeterioration on ivories during temporary cold storage poses a great threat to their later long-term preservation. Methods: Here, the combination of high-throughput sequencing and biochemical assays was applied for the in-depth investigation of the key deteriorative microorganisms colonizing on the ivories and the tracing of their origin, as well as the assessment of the ethanol disinfection impact on the microbial communities on ivories. Results: It was observed that the surfaces of ivories were scattered by the fungal patches of white, dark grey, and hedge green colors during cold storage. The high-throughput sequencing results showed that the genera Mortierella (38.51%), Ilyonectria (14.43%), Penicillium (1.15%), and Aspergillus (1.09%) were the dominant fungi, while Pseudomonas (22.63%), Sphingopyxis (3.06%), and Perlucidibaca (2.92%) were the dominant bacteria on ivories. The isolated Aspergillus A-2 resulted in the highest amount of calcium releasing from the degradation of hydroxyapatite (HAP), the main component of ivory, by the organic acids produced, including oxalic acid and citric acid. The fast expectation-maximization for microbial source tracking (FEAST) analysis revealed that the majority of the fungi (57.45%) and bacteria (71.84%) colonizing on the ivories were derived from the soils surrounding ivories in the sacrifice pits, indicating soils as the primary source for the spoilage microbes growing on ivories. The dominant strains could degrade cellulose, the key components of wet cotton towels commonly applied on ivories for moisture maintenance, aiding the spoilage microbes colonizing on ivories. Notably, the ivory disinfection with 75% ethanol during the cleansing significantly decreased the relative abundance of the dominant genera of Ilyonectria, Aspergillus, and Pseudomonas, with Mortierella becoming the dominant one on ivories. Discussion: Together, the fungi, particularly Aspergillus and Penicillium, played a significant role in the microbial biodeterioration of unearthed ancient ivories by producing the organic acids. These results may improve the control of the microbial biodeterioration and develop more efficient strategies for the long-time conservation of unearthed ancient ivories and other cultural relics.

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation.

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L-1 (NCI-H1299), 3.16 ± 0.11 µmol L-1 (A549), and 1.83 ± 0.13 µmol L-1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L-1 (NCI-H1299), 3.86 ± 0.38 µmol L-1 (A549), and 1.69 ± 0.25 µmol L-1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Isolation and Identification of Chicken-Derived Lactic Acid Bacteria: In Vitro Probiotic Properties and Antagonistic Effects against Salmonella pullorum, Staphylococcus aureus, and Escherichia coli.

The development of probiotics capable of quickly colonizing the intestines of animals is important in promoting the healthy growth of livestock. The aim of this study was to screen lactic acid bacteria (LAB) from the intestinal microbiota of chickens with potential applications, and to evaluate their probiotic properties and antagonistic abilities against Salmonella pullorum, Staphylococcus aureus, and Escherichia coli. The results showed that a total of 79 strains with the characteristics of LAB were isolated from the chicken cecum microbiota, of which 7 strains exhibited strong inhibitory activity against S. pullorum, S. aureus, and E. coli. Performing 16s rDNA sequencing revealed that these seven strains were Lactiplantibacillus pentosus (n = 1), Lactiplantibacillus plantarum (n = 3), Lactiplantibacillus paraplantarum (n = 1), Lactiplantibacillus argentoratensis (n = 1), and Lactiplantibacillus fabifermentans (n = 1). Among them, L. pentosus R26 and L. plantarum R32 exhibited superior antibacterial activity. These two strains demonstrated high lactic acid production ability, with survival rates of 86.29% and 87.99% after 3 h of treatment at pH 1.5, 86.66% and 85.52% after 3 h of treatment with 0.5% bile salts, 90.03% and 88.16% after 2 h of treatment with simulated gastric fluid, and 98.92% and 98.22% after 2 h of treatment with simulated intestinal fluid, respectively. Co-cultivation with L. pentosus R26 for 24 h resulted in 50% of the pathogens being antagonized, while almost complete inhibition was observed following 72 h of co-cultivation. In conclusion, L. pentosus R26 and L. plantarum R32 exhibited high antibacterial activity and acid production capability, while also demonstrating satisfactory tolerance to low pH values and high concentrations of bile salts and digestive fluid. The probiotic characteristics and stress resistance of L. pentosus R26 were slightly superior to those of L. plantarum R32, indicating its potential for development as a probiotic.

Exogenous strigolactone enhanced the drought tolerance of pepper (Capsicum chinense) by mitigating oxidative damage and altering the antioxidant mechanism.

KEY MESSAGE: Exogenous SL positively regulates pepper DS by altering the root morphology, photosynthetic character, antioxidant enzyme activity, stomatal behavior, and SL-related gene expression. Drought stress (DS) has always been a problem for the growth and development of crops, causing significant negative impacts on crop productivity. Strigolactone (SL) is a newly discovered class of plant hormones that are involved in plants' growth and development and environmental stresses. However, the role of SL in response to DS in pepper remains unknown. DS considerably hindered photosynthetic pigments content, damaged root architecture system, and altered antioxidant machinery. In contrast, SL application significantly restored pigment concentration modified root architecture system, and increased relative chlorophyll content (SPAD). Additionally, SL treatment reduced oxidative damage by reducing hydrogen peroxide (H2O2) (24-57%) and malondialdehyde (MDA) (79-89%) accumulation in pepper seedlings. SL-pretreated pepper seedlings showed significant improvement in antioxidant enzyme activity, proline accumulation, and soluble sugar content. Furthermore, SL-related genes (CcSMAX2, CcSMXL6, and CcSMXL3) were down-regulated under DS. These findings suggest that the foliar application of SL can alleviate the adverse effects of drought tolerance by up-regulating chlorophyll content and activating antioxidant defense mechanisms.

Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a prevalent neurodegenerative disease that has become one of the main factors affecting human health. It has serious impacts on individuals, families, and society. With the development of population aging, the incidence of AD will further increase worldwide. Emerging evidence suggests that many physiological metabolic processes, such as lipid metabolism, are implicated in the pathogenesis of AD. Bile acids, as the main undertakers of lipid metabolism, play an important role in the occurrence and development of Alzheimer's disease. Tauroursodeoxycholic acid, an endogenous bile acid, has been proven to possess therapeutic effects in different neurodegenerative diseases, including Alzheimer's disease. This review tries to find the relationship between bile acid metabolism and AD, as well as explore the therapeutic potential of bile acid taurocursodeoxycholic acid for this disease. The potential mechanisms of taurocursodeoxycholic acid may include reducing the deposition of Amyloid-ß protein, regulating apoptotic pathways, preventing tau hyperphosphorylation and aggregation, protecting neuronal synapses, exhibiting anti-inflammatory properties, and improving metabolic disorders. The objective of this study is to shed light on the use of tauroursodeoxycholic acid preparations in the prevention and treatment of AD, with the aim of identifying effective treatment targets and clarifying various treatment mechanisms involved in this disease.

Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives.

In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, 4b and 4c showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC50) values of 4b were 4.42 ± 0.24 µM (NCI-H1299), 3.94 ± 0.01 µM (A549) and 1.56 ± 0.06 µM (NCI-1437). The IC50 values of 4c were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 µM (A549) and 3.51 ± 0.05 µM (NCI-H1437). Furthermore, our results showed that 4b and 4c could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, 4b and 4c exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that 4b and 4c be developed as potential new drugs for lung cancer treatment.

N6-Methyladenosine Regulator-Mediated Methylation Modification Patterns with Distinct Prognosis, Oxidative Stress, and Tumor Microenvironment in Renal Cell Carcinoma.

OBJECTIVE: Emerging evidence suggests the biological implications of N6-methyladenosine (m6A) in carcinogenesis. Herein, we systematically analyzed the role of m6A modification in renal cell carcinoma (RCC) progression. METHODS: Based on 23 m6A regulators, unsupervised clustering analyses were conducted to determine m6A modification subtypes across 893 RCC specimens in the Cancer Genome Atlas (TCGA) cohort. By performing principal component analysis (PCA) analysis, m6A scoring system was developed for evaluating m6A modification patterns of individual RCC patients. The activity of signaling pathways was assessed by gene-set variation analysis (GSVA) algorithm. The single-sample gene set enrichment analysis (ssGSEA) algorithm was applied for quantifying the infiltration levels of immune cells and the activity of cancer immunity cycle. Drug responses were estimated by genomics of drug sensitivity in cancer (GDSC), the Cancer Therapeutics Response Portal (CTRP) and Preservice Research Institute for Science and Mathematics (PRISM) database. RESULTS: Five m6A modification subtypes were characterized by different survival outcomes, oxidative stress, cancer stemness, infiltrations of immune cells, activity of cancer immunity cycle, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression and microsatellite instability (MSI) levels. According to m6A score, RCC patients were categorized into high and low m6A score groups. Patients with high m6A score displayed a prominent survival advantage, and the prognostic value of m6A score was confirmed in two anti-PD-1/PD-L1 immunotherapy cohorts. m6A score was significantly linked to oxidative stress-related genes, and high m6A score indicated the higher sensitivity to axitinib, pazopanib and sorafenib and the lower sensitivity to sunitinib. CONCLUSION: This study analyzed the extensive regulatory mechanisms of m6A modification on oxidative stress, the tumor microenvironment, and immunity. Quantifying m6A scores may enhance immunotherapeutic effects and assist in developing more effective agents.

AAV-Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness.

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.

Effects of a lower limb walking exoskeleton on quality of life and activities of daily living in patients with complete spinal cord injury: A randomized controlled trial.

BACKGROUND: In recent years, lower limb walking exoskeletons have been widely used in the study of spinal cord injury (SCI). OBJECTIVE: To explore the effect of a lower limb walking exoskeleton on quality of life and functional independence in patients with motor complete SCI. METHODS: This was a multi-center, single blind, randomized controlled trial. A total of 16 SCI patients were randomly assigned to either the exoskeleton-assisted walking (EAW) group (n= 8) or the conventional group (n= 8). Both groups received conventional rehabilitation training, including aerobic exercise and strength training. The EAW group additionally conducted the exoskeleton-assisted walking training using an AIDER powered robotic exoskeleton for 40-50 minutes, 5 times/week for 8 weeks. World Health Organization quality of life-BREF (WHOQOL-BREF) and the Spinal Cord Independence Measure III (SCIM-III) were used for assessment before and after training. RESULTS: There was an increasing tendency of scores in the psychological health, physical health, and social relationships domain of WHOQOL-BREF in the EAW group after the intervention compared with the pre-intervention period, but there was no significant difference (P> 0.05). SCIM-III scores increased in both groups compared to pre-training, with only the conventional group showing a significant difference after 8 weeks of training (P< 0.05). CONCLUSION: A lower limb walking exoskeleton may have potential benefits for quality of life and activities of daily living in patients with motor complete SCI.

Preclinical Efficacy And Safety Evaluation of AAV-OTOF in DFNB9 Mouse Model And Nonhuman Primate.

OTOF mutations are the principal causes of auditory neuropathy. There are reports on Otof-related gene therapy in mice, but there is no preclinical research on the drug evaluations. Here, Anc80L65 and the mouse hair cell-specific Myo15 promoter (mMyo15) are used to selectively and effectively deliver human OTOF to hair cells in mice and nonhuman primates to evaluate the efficacy and safety of OTOF gene therapy drugs. A new dual-AAV-OTOF-hybrid strategy to transfer full-length OTOF is generated, which can stably restore hearing in adult OTOFp.Q939*/Q939* mice with profound deafness, with the longest duration being at least 150 days, and the best therapeutic effect without difference in hearing from wild-type mice. An AAV microinjection method into the cochlea of cynomolgus monkeys without hearing impairment is further established and found the OTOF can be safely and effectively driven by the mMyo15 promoter in hair cells. In addition, the therapeutic dose of AAV drugs has no impact on normal hearing and does not cause significant systemic toxicity both in mouse and nonhuman primates. In summary, this study develops a potential gene therapy strategy for DFNB9 patients in the clinic and provides complete, standardized, and systematic research data for clinical research and application.

Rumen fermentation and microbial diversity of sheep fed a high-concentrate diet supplemented with hydroethanolic extract of walnut green husks.

OBJECTIVE: This study aimed to assess the impact of a hydroethanolic extract of walnut green husks (WGH) on rumen fermentation and the diversity of bacteria, methanogenic archaea, and fungi in sheep fed a high-concentrate diet. METHODS: Five healthy small-tailed Han ewes with permanent rumen fistula were selected and housed in individual pens. This study adopted a self-controlled and crossover design with a control period and an experimental period. During the control period, the animals were fed a basal diet (with a ratio of concentrate to roughage of 65:35), while during the treatment period, the animals were fed the basal diet supplemented with 0.5% hydroethanolic extract of WGH. Fermentation parameters, digestive enzyme activities, and microbial diversity in rumen fluid were analyzed. RESULTS: Supplementation of hydroethanolic extract of WGH had no significant effect on feed intake, concentrations of total volatile fatty acids, isovalerate, ammonia nitrogen, and microbial protein (p>0.05). However, the ruminal pH, concentrations of acetate, butyrate and isobutyrate, the ratio of acetate to propionate, protozoa count, and the activities of filter paper cellulase and cellobiase were significantly increased (p<0.05), while concentrations of propionate and valerate were significantly decreased (p<0.05). Moreover, 16S rRNA gene sequencing revealed that the relative abundance of rumen bacteria Christensenellaceae R7 group, Saccharofermentans, and Ruminococcaceae NK4A214 group were significantly increased, while Ruminococcus gauvreauii group, Prevotella 7 were significantly decreased (p<0.05). The relative abundance of the fungus Pseudomonas significantly increased, while Basidiomycota, Fusarium, and Alternaria significantly decreased (p<0.05). However, there was no significant change in the community structure of methanogenic archaea. CONCLUSION: Supplementation of hydroethanolic extract of WGH to a high-concentrate diet improved the ruminal fermentation, altered the structure of ruminal bacterial and fungal communities, and exhibited beneficial effects in alleviating subacute rumen acidosis of sheep.

Antimicrobial Activity and Mechanisms of Walnut Green Husk Extract.

Walnut green husks (WGHs), by-products of walnut production, are believed to possess antimicrobial properties, making them a potential alternative to antibiotics. In this study, the antibacterial activities of three extracts, derived from WGH, against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli were investigated, and the antibacterial mechanisms of an anhydrous ethanol extract of WGH (WGHa) were examined. The results showed that WGHa exhibited inhibitory effects on all tested bacteria. The ultrahigh-performance liquid chromatography-tandem mass spectrometry analysis revealed that the major active compounds present in WGHa were terpenoids, phenols, and flavonoids. Treatment with WGHa resulted in the leakage of intracellular ions and alkaline phosphatase; a reduction in intracellular ATP content, ATPase activity, and nucleic acid content; as well as cellular metabolic viability. The transmission electron microscopy images showed varying degrees of cell deformation and membrane damage following WGHa treatment. The transcriptome sequencing and differentially expressed gene enrichment analyses revealed an up-regulation in pathways associated with RNA degradation, translation, protein export, and oxidative phosphorylation. Conversely, pathways involved in cell movement and localization, as well as cell wall organization and carbohydrate transport, were found to be down-regulated. These findings suggest that WGHa alters cell membrane permeability and causes damage to the cell wall. Additionally, WGHa interferes with cellular energy metabolism, compromises RNA integrity, and induces DNA replication stress, consequently inhibiting the normal growth and proliferation of bacteria. These findings unveiled the antimicrobial mechanisms of WGHa, highlighting its potential application as an antibiotic alternative.

Preshaped 4D Photocurable Ultratough Organogel Microcoils for Personalized Endovascular Embolization.

Endovascular embolization using microcoils can be an effective technique to treat artery aneurysms. However, microcoils with fixed designs are difficult to adapt to all aneurysm types. In this paper, a photocurable ultratough shape memory organogel with a curing time of only 2 s and megapascal-level mechanical properties is proposed. Then, it is used to manufacture the personalized 4D microcoil with a wire diameter of only 0.3 mm. The improved mechanical modulus (511.63 MPa) can reduce the possibility of microcoils' fracture during embolization. Besides, the fast body-temperature-triggering shape memory ability makes the 4D microcoil applicable in vivo. These 4D microcoils are finally delivered into the rabbit, and successfully blocked the blood flow inside different aneurysms, with neoendothelial cells and collagen fibers growing on the microcoil surface snugly, indicating full aneurysm recovery. This 4D organogel microcoil can potentially be used in personalized clinical translation on human beings.

A review of novel research technology to explore the mystery of traditional Chinese medicine: Terahertz.

During the 2022 Annual National Terahertz Biophysics Conference, the hypothesis was proposed that bio frequency electromagnetic fields sensitive points, akin to acupuncture points, exist in the human body. This development has prompted numerous researchers to apply terahertz technology to the field of traditional Chinese medicine (TCM). In recent years, terahertz technology has achieved notable progress in the field of TCM, particularly concerning the meridian-collateral system. This review systematically presents the advancements in terahertz technology and its implications on TCM theory from a biophysical perspective. Additionally, it summarizes the utilization of terahertz waves in elucidating aspects of TCM, particularly focusing on the scientific connotation of Qi, the theoretical foundation of the meridian-collateral system, and moxibustion in diagnosing and treating diseases. We aimed to explore the innovative applications and distinct advantages of terahertz technology in TCM and its feasibility as a pioneering technological tool for the modernization of TCM.

Gender differences in the association between sensory function and CIND among Chinese elderly: Based on CLHLS.

OBJECTIVE: To explore the gender differences of the association between sensory impairment (SI) and the risk of cognitive decline and possible cognitive impairment, no dementia (CIND). METHOD: Data were drawn from three waves of the nationally representative survey of China Longitudinal Healthy Longevity Survey (CLHLS) between 2011/12-2018 surveys, involving 6138 participants aged 65 or older who had no CIND at the baseline. Multivariate linear or logistic regression models were employed to examine the effect of SI on cognitive decline and CIND risk by gender stratification, respectively. RESULTS: Hearing impairment and visual impairment were associated with lower MMSE scores, and the strength of the association was stronger in men than in women. Hearing impairment was related to an elevated risk of CIND both in men and women (Men: OR=2.46; 95% CI=1.81, 3.35; Women: OR=1.43; 95% CI=1.09, 1.88). However, the effect of visual impairment on CIND was statistically significant only in men (OR=1.43; 95% CI=1.09, 1.88). The risk of cognitive decline and CIND were significantly higher with single and dual SI than those without SI, except for women with single visual impairment. CONCLUSION: SI is independently associated with cognitive decline and CIND risk, and the association differed by gender. Further researches should clarify the mechanism between SI and cognitive function among older adults, especially for gender differences.

Effects of bioactive peptides derived from cottonseed meal solid-state fermentation on the growth, metabolism, and immunity of yellow-feathered broilers.

This study investigated the effects of bioactive peptides derived from solid-state fermentation of cottonseed meal on the growth performance, apparent dietary digestibility, serum biochemical parameters, protein metabolism, antioxidant activity, and immunity in yellow-feathered broilers. A total of two hundred forty 21-days-old male broilers were randomly divided into four groups with six replicates per group. The control group received a basal diet and three experimental groups were fed diets with 1%, 2%, and 3% cottonseed meal bioactive peptides (CSBP) replacing equivalent protein of cottonseed meal in basic diet. Dietary supplementation of 2% and 3% CSBP increased the average daily weight gain, crude protein digestibility, total serum protein, and immunoglobulin (Ig) G contents in serum (P < 0.05). The 3% CSBP increased albumin, total antioxidant capacity, spleen weight/bodyweight, interleukin-6, and IgM, while reducing the feed to gain ratio, total cholesterol, urea nitrogen, total superoxide dismutase, glutathione peroxidase, and malondialdehyde contents in serum (P < 0.05). The 2% CSBP diet increased PepT1 expression in duodenum, jejunum, and ileum (P < 0.05). The 1%, 2%, and 3% CSBP diets increased S6kinase-polypeptide-1 and inositol-3-hydroxylase expression in chest and leg muscles (P < 0.05). The CSBP addition in diets can improve growth performance, nutrient digestibility, protein metabolism, antioxidant, and immune capabilities of yellow-feathered broilers.

Relationship between gut microbiota and lymphocyte subsets in Chinese Han patients with spinal cord injury.

This study is to investigate the changes of lymphocyte subsets and the gut microbiota in Chinese Han patients with spinal cord injury (SCI). We enrolled 23 patients with SCI and 21 healthy controls. Blood and fecal samples were collected. The proportion of lymphocyte subsets was detected by flow cytometry. 16S rDNA sequencing of the V4 region was used to analyze the gut microbiota. The changes of the gut microbiota were analyzed by bioinformatics. Correlation analysis between gut microbiota and lymphocyte subsets was performed. CD4 + cells, CD4 + /CD8 + ratio and CD4 + CD8 + cells in peripheral blood of SCI patients were significantly lower than those of the control group (P < 0.05). There was no significant difference in B cells and CIK cells between the SCI group and the control group. The gut microbiota community diversity index of SCI patients was significantly higher than that of healthy controls. In SCI patients, the relative abundance of Lachnospiraceae (related to lymphocyte subset regulation), Ruminococcaceae (closely related to central nervous system diseases), and Escherichia-Shigella (closely related to intestinal infections) increased significantly, while the butyrate producing bacteria (Fusobacterium) that were beneficial to the gut were dramatically decreased. Correlation analysis showed that the five bacterial genera of SCI patients, including Lachnospiraceae UCG-008, Lachnoclostridium 12, Tyzzerella 3, Eubacterium eligens group, and Rumencocciucg-002, were correlated with T lymphocyte subsets and NK cells. In the SCI group, the flora Prevotella 9, Lachnospiraceae NC2004 group, Veillonella, and Sutterella were positively correlated with B cells. However, Fusobacterium and Akkermansia were negatively correlated with B cells. Moreover, Roseburia and Ruminococcaceae UCG-003 were positively correlated with CIK cells. Our results suggest that the gut microbiota of patients with SCI is associated with lymphocyte subsets. Therefore, it is possible to improve immune dysregulation in SCI patients by modulating gut microbiota, which may serve as a new therapeutic method for SCI.

A novel ratiometric electrochemical aptasensor for highly sensitive detection of carcinoembryonic antigen.

A novel ratiometric electrochemical aptasensor was proposed for carcinoembryonic antigen (CEA) detection based on exonuclease III (Exo III)-assisted recycling and rolling circle amplification (RCA) strategies. A thiolated ferrocene-labeled hairpin probe 2 (Fc-HP2) was fixed on the gold nanoparticles (AuNPs)-modified gold electrode (AuE) surface through Au-S bonds. The presence of CEA led to the release of trigger, which hybridized with the 3'-protruding of hairpin probe 1 (HP1) and triggered the Exo III cleavage reaction, accompanied by the releasing of trigger and generation of new DNA fragment which was used for the successive hybridization with Fc-HP2. After the Exo III cleavage process, the remaining Fc-HP2 fragments hybridized as primers with the RCA template to initiate the RCA process, and long single-stranded polynucleotides were produced for methylene blue (MB) binding. Such changes resulted in the signal of Fc (IFc) decreased and that of MB (IMB) increased, achieving a linear relationship between IMB/IFc and logarithm of CEA concentrations ranging from 1.0 pg mL-1 to 100.0 ng mL-1 with a detection limit of 0.59 pg mL-1. Additionally, the developed aptasensor had been successfully applied to detect CEA in human serum samples. Therefore, the proposed strategy might provide a new platform for clinical detections of CEA.

Molecular divergence of mammalian astrocyte progenitor cells at early gliogenesis.

During mammalian brain development, how different astrocytes are specified from progenitor cells is not well understood. In particular, whether astrocyte progenitor cells (APCs) start as a relatively homogenous population or whether there is early heterogeneity remains unclear. Here, we have dissected subpopulations of embryonic mouse forebrain progenitors using single-cell transcriptome analyses. Our sequencing data revealed two molecularly distinct APC subgroups at the start of gliogenesis from both dorsal and ventral forebrains. The two APC subgroups were marked, respectively, by specific expression of Sparc and Sparcl1, which are known to function in mature astrocytes with opposing activities for regulating synapse formation. Expression analyses showed that SPARC and SPARCL1 mark APC subgroups that display distinct temporal and spatial patterns, correlating with major waves of astrogliogenesis during development. Our results uncover an early molecular divergence of APCs in the mammalian brain and provide a useful transcriptome resource for the study of glial cell specification.

Identification of a Novel circ_0010235/miR-1249-3p/HOXA13 Axis in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is an aggressive malignancy with a poor prognosis. In this study, we explored the critical role and mechanism of circ_0010235 in the pathogenesis of LUAD. The expression levels of circ_0010235, microRNA (miR)-1249-3p, and homeobox A13 (HOXA13) were gauged by quantitative real-time PCR (qRT-PCR) and Western blot. Cell proliferation, cycle progression, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-Deoxyuridine (Edu), flow cytometry, and transwell assays, respectively. The direct relationship between miR-1249-3p and circ_0010235 or HOXA13 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. Xenograft experiments were used to examine the role of circ_0010235 in vivo. Circ_0010235 was significantly overexpressed in human LUAD. Silencing of circ_0010235 hindered LUAD cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0010235 targeted and inhibited miR-1249-3p. Moreover, circ_0010235 depletion repressed cell malignant behaviors by upregulating miR-1249-3p. HOXA13 was identified as a direct and functional target of miR-1249-3p. Furthermore, circ_0010235 regulated HOXA13 expression by competing for shared miR-1249-3p. Our findings demonstrate that the circ_0010235/miR-1249-3p/HOXA13 axis is implicated in the pathogenesis of LUAD.