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Abstract Objective To investigate the differential expression genes (DEGs) in spinal tuberculosis using transcriptomics, with the aim of identifying novel therapeutic targets and prognostic indicators for the clinical management of spinal tuberculosis. Methods Patients who visited the Department of Orthopedics at the Second Hospital, Lanzhou University from January 2021 to May 2023 were enrolled. Based on the inclusion and exclusion criteria, there were 5 patients in the test group and 5 patients in the control group. Total RNA was extracted and paired-end sequencing was conducted on the sequencing platform. After processing the sequencing data with clean reads and annotating the reference genome, FPKM normalization and differential expression analysis were performed. The DEGs and long non-coding RNAs (LncRNAs) were analyzed for Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment. The cis-regulation of differentially expressed mRNAs (DE mRNAs) by LncRNAs was predicted and analyzed to establish a co-expression network. Results This study identified 2366 DEGs, with 974 genes significantly upregulated and 1392 genes significantly downregulated. The upregulated genes are associated with cytokine-cytokine receptor interactions, tuberculosis, and TNF-α signaling pathways, primarily enriched in biological processes such as immunity and inflammation. The downregulated genes are related to muscle development, contraction, fungal defense response, and collagen metabolism processes. Analysis of LncRNAs from bone tuberculosis RNA-seq data detected a total of 3652 LncRNAs, with 356 significantly upregulated and 184 significantly downregulated. Further analysis identified 311 significantly different LncRNAs that could cis-regulate 777 target genes, enriched in pathways such as muscle contraction, inflammatory response, and immune response, closely related to bone tuberculosis. There are 51 genes enriched in the immune response pathway regulated by cis-acting LncRNAs. LncRNAs that regulate immune response-related genes, such as upregulated RP11-451G4.2, RP11-701P16.5, AC079767.4, AC017002.1, LINC01094, CTA-384D8.35, and AC092484.1, as well as downregulated RP11-2C24.7, may serve as potential prognostic and therapeutic targets. Conclusion The DE mRNAs and LncRNAs in spinal tuberculosis are both associated with immune regulatory pathways. These pathways promote or inhibit the tuberculosis infection and development at the mechanistic level and play an important role in the process of tuberculosis transferring to bone tissue.

Abstract Background Evidences of comparison of sex difference in Chinese irritable bowel syndrome (IBS) patients were few. We aim to compare gender difference in the biopsychosocial characteristics of Chinese patients of IBS predominant with diarrhea (IBS-D). Methods IBS-D patients meeting Rome III criteria were enrolled. We administered IBS symptom questionnaires, evaluation of psychological status (HAMD and HAMA scales) and IBS quality of life (IBS-QOL), dietary habits, healthcare seeking behaviors, and compared biopsychosocial characteristics between male and female patients. Results Four hundred and ninety patients were enrolled including 299 males and 191 females. More female patients reported abdominal pain associated with defecation (84.3% vs. 74.9%, P = 0.014) while males reported more abdominal discomfort (39.8% vs. 26.7%, P = 0.003). Females had higher IBS symptom score (9.7 ± 1.7 vs. 9.4 ± 1.4, P = 0.025) and more of females had severe abdominal pain/discomfort (17.8% vs. 12.4%, P = 0.013) while there were no significant differences of other bowel symptoms. Females reported higher incidence of comorbid anxiety state (64.9% vs. 52.8%, P = 0.008) and depression state (35.6% vs. 19.7%, P

Irritable bowel syndrome (IBS) is a chronic, recurrent disorder that is characterized by abdominal pain associated with defecation. IBS was previously considered to manifest without any structural alterations until the discovery of post-infection IBS. An increasing body of published evidence indicates that immune activation plays an important role in the development of IBS. Nevertheless, the pathophysiology of IBS, including mainly visceral hypersensitivity and gastrointestinal dysmotility, has not yet been explicitly elucidated. The observation of potential inflammatory degenerative neuropathy, including neuronal degeneration, spearheaded research on autoimmune responses targeting the enteric nervous system. Subsequently, several autoantibodies were detected in the sera of IBS patients, among which some were presumed to exert a pathogenic influence or be associated with the etiology of gastrointestinal dysmotility in IBS. Moreover, certain specific autoantibodies evidently served as biomarkers to facilitate the differentiation between IBS and other related diseases. Therefore, we aimed to present an overview of autoantibodies reported in the sera of IBS patients and highlight their significance in diagnosing and comprehending the pathophysiology of IBS. Consequently, we propose a therapeutic strategy from an autoimmune perspective.

The 1,4-α-glucan branching enzyme (GBE, EC 2.4.1.18) has garnered considerable attention for its ability to increase the degree of branching of starch and retard starch digestion, which has great industrial applications. Previous studies have reported that the N-terminal domain plays an important role in the expression and stability of GBEs. To further increase the catalytic ability of Gt-GBE, we constructed five mutants in the N-terminal domain: L19R, L19K, L25R, L25K, and L25A. Specific activities of L25R and L25A were increased by 28.46% and 23.46%, respectively, versus the wild-type Gt-GBE. In addition, the α-1,6-glycosidic linkage ratios of maltodextrin samples treated with L25R and L25A increased to 5.71%, which were significantly increased by 19.96% compared with that of the wild-type Gt-GBE. The results of this study suggest that the N-terminal domain selective modification can improve enzyme catalytic activity, thus further increasing the commercial application of enzymes in food and pharmaceutical industries.

Background: The steady-state intestinal perfusion system represents a tool used in measuring intestinal fluid absorption and bicarbonate secretion in vivo; however, detailed procedures and parameters were not elucidated fully.Aim: We focused on the methods of the steady-state intestinal perfusion system comprehensively including the blood pressure, hematocrit, blood gas, and heart rate of mouse.Methods: Anesthetized, tracheally intubated, and artificially ventilated mice were used for this system. The blood pressure, hematocrit, blood gas, heart rate, and rate of fluid absorption and HCO3- secretion of the small intestine and colon at different time points were evaluated.Results: Blood pressure, hematocrit, blood gas, and heart rate became stable at the 30 min time point after completion of surgery and could be maintained for 2 h. Rates of fluid absorption and bicarbonate secretion were also kept stable during the period of steady state of mice. Rates of fluid absorption and bicarbonate secretion were different among the jejunum, ileum, proximal, and mid-distal colon.Conclusion: The steady-state intestinal perfusion system is a reliable system for measuring intestinal fluid absorption and bicarbonate secretion in vivo.

Abstract Background Approximately 8–9% of the world’s population is affected by autoimmune diseases, and yet the mechanism of autoimmunity trigger is largely understudied. Two unique cell death modalities, ferroptosis and pyroptosis, provide a new perspective on the mechanisms leading to autoimmune diseases, and development of new treatment strategies. Methods Using scRNA-seq datasets, the aberrant trend of ferroptosis and pyroptosis-related genes were analyzed in several representative autoimmune diseases (psoriasis, atopic dermatitis, vitiligo, multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and experimental autoimmune orchitis). Cell line models were also assessed using bulk RNA-seq and qPCR. Results A substantial difference was observed between normal and autoimmune disease samples involving ferroptosis and pyroptosis. In the present study, ferroptosis and pyroptosis showed an imbalance in different keratinocyte lineages of psoriatic skinin addition to a unique pyroptosis-sensitive keratinocyte subset in atopic dermatitis (AD) skin. The results also revealed that pyroptosis and ferroptosis are involved in epidermal melanocyte destruction in vitiligo. Aberrant ferroptosis has been detected in multiple sclerosis, systemic sclerosis-associated interstitial lung disease, Crohn’s disease, and autoimmune orchitis. Cell line models adopted in the study also identified pro-inflammatory factors that can drive changes in ferroptosis and pyroptosis. Conclusion These results provide a unique perspective on the involvement of ferroptosis and pyroptosis in the pathological process of autoimmune diseases at the scRNA-seq level. IFN-γ is a critical inducer of pyroptosis sensitivity, and has been identified in two cell line models.

Abstract Anemia is a significant complication of chronic inflammation and may be related to dysregulated activities among erythroblastic island (EBI) macrophages. GM-CSF was reported to be upregulated and attracted as a therapeutic target in many inflammatory diseases. Among EBIs, we found that the GM-CSF receptor is preferentially and highly expressed among EBI macrophages but not among erythroblasts. GM-CSF treatment significantly decreases human EBI formation in vitro by decreasing the adhesion molecule expression of CD163. RNA-sequence analysis suggests that GM-CSF treatment impairs the supporting function of human EBI macrophages during erythropoiesis. GM-CSF treatment also polarizes human EBI macrophages from M2-like type to M1-like type. In addition, GM-CSF decreases mouse bone marrow (BM) erythroblasts as well as EBI macrophages, leading to a reduction in EBI numbers. In defining the molecular mechanism at work, we found that GM-CSF treatment significantly decreases the adhesion molecule expression of CD163 and Vcam1 in vivo. Importantly, GM-CSF treatment also decreases the phagocytosis rate of EBI macrophages in mouse BM as well as decreases the expression of the engulfment-related molecules Mertk, Axl, and Timd4. In addition, GM-CSF treatment polarizes mouse BM EBI macrophages from M2-like type to M1-like type. Thus, we document that GM-CSF impairs EBI formation in mice and humans. Our findings support that targeting GM-CSF or reprogramming EBI macrophages might be a novel strategy to treat anemia resulting from inflammatory diseases.

Immune activation and several autoantibodies might be involved in the pathophysiology of irritable bowel syndrome (IBS). We aimed to identify serum biomarkers for IBS by HuProt™ microarray. IBS patients met Rome III criteria were enrolled. Control groups included healthy controls (HCs) and disease controls (DCs). In stage I, we profiled sera from IBS and control groups with HuProt™ microarrays. Based on significant different proteins in stage I, IBS focused microarrays were constructed and validated in a larger cohort in stage II, then decision tree models were generated to establish a combination of biomarkers. In stage III, 4 purified proteins were verified by ELISA. Finally, we analyzed the correlation of autoantibodies with symptoms. In stage I, we identified 47 significant different proteins including 8 autoantibodies of IgG, 2 of IgA between IBS and HCs; 13 autoantibodies of IgG, 13 of IgA between IBS and DCs. In stage II, we found the positive rates of 14 IgG and IgA autoantibodies in IBS were significantly higher than HCs. Five autoantibodies of IgG and 7 IgA were comprehensively involved in differentiating IBS and HCs with the sensitivity and specificity to diagnose IBS as 40%–46.7% and 79.4%–86.3%. The median optical density value of ELAVL4 (IgG) and PIGP (IgA) were significantly higher in IBS than HCs. Parts of autoantibodies above were related to IBS symptoms. We found a combination of autoantibodies to differentiate IBS with HCs, but no specific autoantibodies could serve as serum biomarkers for IBS.

Abstract Background Long noncoding RNAs (lncRNAs) have been shown to play important roles in the regulation of plant growth and development. Recent transcriptomic analyses have revealed the gene expression profiling in wheat spike development, however, the possible regulatory roles of lncRNAs in wheat spike morphogenesis remain largely unclear. Results Here, we analyzed the genome-wide profiling of lncRNAs during wheat spike development at six stages, and identified a total of 8,889 expressed lncRNAs, among which 2,753 were differentially expressed lncRNAs (DE lncRNAs) at various developmental stages. Three hundred fifteen differentially expressed cis- and trans-regulatory lncRNA-mRNA pairs comprised of 205 lncRNAs and 279 genes were predicted, which were found to be mainly involved in the stress responses, transcriptional and enzymatic regulations. Moreover, the 145 DE lncRNAs were predicted as putative precursors or target mimics of miRNAs. Finally, we identified the important lncRNAs that participate in spike development by potentially targeting stress response genes, TF genes or miRNAs. Conclusions This study outlines an overall view of lncRNAs and their possible regulatory networks during wheat spike development, which also provides an alternative resource for genetic manipulation of wheat spike architecture and thus yield.

Abstract Background Opposing needling has an obvious curative effect in the treatment of post-stroke hemiplegia; however, the mechanism of the opposing needling in the treatment of post-stroke hemiplegia is still not clear. The purpose of this study is to investigate the effect of opposing needling on the excitability of primary motor cortex (M1) of healthy participants and patients with post-stroke hemiplegia, which may provide insight into the mechanisms of opposing needling in treating post-stroke hemiplegia. Methods This will be a single-blind, randomised, sham-controlled trial in which 80 healthy participants and 40 patients with post-stroke hemiplegia will be recruited. Healthy participants will be randomised 1:1:1:1 to the 2-Hz, 50-Hz, 100-Hz, and sham electroacupuncture groups. Patients with post-stroke hemiplegia will be randomised 1:1 to the opposing needling or conventional treatment groups. The M1 will be located in all groups by using neuroimaging-based navigation. The stimulator coil of transcranial magnetic stimulation (TMS) will be moved over the left and right M1 in order to identify the TMS hotspot, followed by a recording of resting motor thresholds (RMTs) and motor-evoked potentials (MEPs) of the thenar muscles induced by TMS before and after the intervention. The primary outcome measure will be the percent change in the RMTs of the thenar muscles at baseline and after the intervention. The secondary outcome measures will be the amplitude (μV) and latency (ms) of the MEPs of the thenar muscles at baseline and after the intervention. Discussion The aim of this trial is to explore the effect of opposing needling on the excitability of M1 of healthy participants and patients with post-stroke hemiplegia. Trial registration Chinese Clinical Trial Registry ChiCTR1900028138 . Registered on 13 December 2019.

We demonstrate amorphous Ge0.92Sn0.08 surface illuminated metal-semiconductor-metal (MSM) photodetectors on flexible substrates for visible wavelength. Photodetection at 633 nm is achieved with an I-V response up to 10-4 A for a 2 V bias voltage. Different evaporation rate effects on the amorphous GeSn MSM photodetector are examined. Bending/strain effects on device performance were studied by evaluating the current density versus voltage characteristics. Amorphous GeSn thin film deposition on polyethylene terephthalate flexible substrate and Ni/Au-GeSn-Ni/Au MSM photodetector finger pattern deposition were performed via thermal evaporation. Photocurrent and dark current densities of amorphous GeSn MSM photodetectors were obtained at 1.36 A/cm2 and 0.24 A/cm2, respectively, where the photocurrent to dark current contrast ratio was found to be equal to 5.6. We also examined the evaporation rate, strain, and bending effect.

Cloud computing technology plays a very important role in many areas, such as in the construction and development of the smart city. Meanwhile, numerous cloud services appear on the cloud-based platform. Therefore how to how to select trustworthy cloud services remains a significant problem in such platforms, and extensively investigated owing to the ever-growing needs of users. However, trust relationship in social network has not been taken into account in existing methods of cloud service selection and recommendation. In this paper, we propose a cloud service selection model based on the trust-enhanced similarity. Firstly, the direct, indirect, and hybrid trust degrees are measured based on the interaction frequencies among users. Secondly, we estimate the overall similarity by combining the experience usability measured based on Jaccard's Coefficient and the numerical distance computed by Pearson Correlation Coefficient. Then through using the trust degree to modify the basic similarity, we obtain a trust-enhanced similarity. Finally, we utilize the trust-enhanced similarity to find similar trusted neighbors and predict the missing QoS values as the basis of cloud service selection and recommendation. The experimental results show that our approach is able to obtain optimal results via adjusting parameters and exhibits high effectiveness. The cloud services ranking by our model also have better QoS properties than other methods in the comparison experiments.

We evaluated the role and mechanism of acteoside in the regulation of memory impairment induced by chronic unpredictable mild stress (CUMS). CUMS was used to induce depression in rats and the successful establishment of CUMS model were verified by forced swimming test and sucrose preference test. The Y-maze test and novel object recognition test assessed memory functions. The structural changes in the cortex and hippocampus were observed by hematoxylin and eosin (HE) staining. Immunofluorescence staining and western blotting determined the protein levels. Y-maze test and novel object recognition test showed that there was memory performance impairment in rats of CUMS group, which was improved by the acteoside treatment. HE staining showed that CUMS exposure damaged the structure in the cortex and hippocampus, while the acteoside treatment alleviated the structural changes. Compared with the control group, the levels of BNDF and CREB in the cortex and hippocampus of the CUMS group were significantly decreased. Acteoside significantly reversed the expressions of these proteins in CUMS rats. Meanwhile, compared with the control group, the levels of p-mTOR and pP70S6K in the cortex and hippocampus of the CUMS group were significantly increased, and these changes were significantly reversed by acteoside. Nevertheless, the effect of acteoside on mTOR signaling was markedly blocked by rapamycin, a specific inhibitor of mTOR signaling. Acteoside can attenuate memory impairment and ameliorate neuronal damage and synaptic plasticity in depression rats probably via inhibiting the mTOR signaling pathway. Acteoside may serve as a novel reagent for the prevention of depression. [ABSTRACT FROM AUTHOR]