Achieving Tunable Mechanoluminescence in CaZnOS:Tb3+, Sm3+ for Multicolor Stress Sensing.

Mechanoluminescent (ML) materials can exhibit visible-to-near-infrared mechanoluminescence when responding to the fracture or deformation of a solid under mechanical stimulation. Transforming mechanical energy into light demonstrates promising applications in terms of visual mechanical sensing. In this work, we synthesized the phosphor CaZnOS:Tb3+, Sm3+, which exhibited intense and tunable multicolor mechanoluminescence without pre-irradiation. Intense green ML materials were obtained by doping Tb3+ with different concentrations. Tunable multicolor mechanoluminescence (such as green, yellow-green, and orange-red) could be realized by combining green emission (about 542 nm), attributed to Tb3+, and red emission (about 600 nm) generated from the Sm3+ in the CaZnOS substrate. The tunable multicolor ML materials CaZnOS:Tb3+, Sm3+ exhibited intense luminance and recoverable mechanoluminescence when responding to mechanical stimulation. Benefiting from the excellent ML performance and multicolor tunability in CaZnOS:Tb3+, Sm3+, we mixed the phosphor with PDMS and a curing agent to explore its practical application. An application for visual mechanical sensing was designed for handwriting identification. By taking a time-lapsed shot while writing, we easily obtained images of the writer's handwriting. The images of the ML intensity were acquired by using specific software to transform the shooting data. We could easily distinguish people's handwriting through analyzing the different ML performances.

Recombinant hirudin and PAR-1 regulate macrophage polarisation status in diffuse large B-cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a malignant tumour. Although some standard therapies have been established to improve the cure rate, they remain ineffective for specific individuals. Therefore, it is meaningful to find more novel therapeutic approaches. Macrophage polarisation is extensively involved in the process of tumour development. Recombinant hirudin (rH) affects macrophages and has been researched frequently in clinical trials lately. Our article validated the regulatory role of rH in macrophage polarisation and the mechanism of PAR-1 by collecting clinical samples and subsequently establishing a cellular model to provide a scientifically supported perspective for discovering new therapeutic approaches. METHOD: We assessed the expression of macrophage polarisation markers, cytokines and PAR-1 in clinical samples. We established a cell model by co-culture with THP-1 and OCI-Ly10 cell. We determined the degree of cell polarisation and expression of validation cytokines by flow cytometry, ELISA, and RT-qPCR to confirm the success of the cell model. Subsequently, different doses of rH were added to discover the function of rH on cell polarisation. We confirmed the mechanism of PAR-1 in macrophage polarisation by transfecting si-PAR-1 and pcDNA3.1-PAR-1. RESULTS: We found higher expression of M2 macrophage markers (CD163 + CMAF+) and PAR-1 in 32 DLBCL samples. After inducing monocyte differentiation into M0 macrophages and co-culturing with OCI-Ly10 lymphoma cells, we found a trend of these expressions in the cell model consistent with the clinical samples. Subsequently, we discovered that rH promotes the polarisation of M1 macrophages but inhibits the polarisation of M2 macrophages. We also found that PAR-1 regulates macrophage polarisation, inhibiting cell proliferation, migration, invasion and angiogenic capacity. CONCLUSION: rH inhibits macrophage polarisation towards the M2 type and PAR-1 regulates polarisation, proliferation, migration, invasion, and angiogenesis of DLBCL-associated macrophages.

Trap Depth Engineering from Persistent Luminescence Phosphors Mg2-xZnxSnO4 for Dynamic Optical Information Encryption Application.

Traditional information encryption materials that rely on fluorescent/phosphorescent molecules are facing an increasing risk of counterfeiting or tampering due to their static reading mode and advances in counterfeiting technology. In this study, a series of Mg2-xZnxSnO4 (x = 0.55, 0.6, 0.65, 0.7 0.75, 0.8) that realizes the writing, reading, and erasing of dynamic information is developed. When heated to 90 °C, the materials exhibit a variety of dynamic emission changes with the concentration of Zn2+ ions. As the doping concentration increased, the ratio of the shallow trap to deep trap changed from 7.77 to 20.86. When x = 0.55, the proportion of deep traps is relatively large, resulting in a higher temperature and longer time required to read the information. When x = 0.80, the proportion of shallow traps is larger and the encrypted information is easier to read. Based on the above features, encryption binary codes device was designed, displaying dynamic writing, reading, and erasing of information under daylight and heating conditions. Accordingly, this work provides reliable guidance on advanced dynamic information encryption.

Transcriptomic and proteomic investigations identify PI3K-akt pathway targets for hyperthyroidism management in rats via polar iridoids from radix Scrophularia.

High-polarity iridoids from Radix Scrophulariae (R. Scrophulariae) offer a range of benefits, including anti-inflammatory, antioxidant, antitumour, antibacterial, antiviral, and antiallergic effects. Although previous studies have indicated the potential of R. Scrophulariae for hyperthyroidism prevention and treatment, the specific active compounds involved and their mechanisms of action are not fully understood. This study explored the effects of high-polarity iridoid glycosides from R. Scrophulariae on hyperthyroidism induced in rats by levothyroxine sodium. The experimental design included a control group, a hyperthyroidism model group, and a group treated with iridoid glycosides. Serum triiodothyronine (T3) and thyroxine (T4) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Transcriptomic and proteomic analyses were applied to liver samples to identify differentially expressed genes and proteins. These analyses were complemented by trend analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The effectiveness of key factors was further examined through molecular biology techniques. ELISA results indicated a notable increase in T3 and T4 in the hyperthyroid rats, which was significantly mitigated by treatment with iridoid glycosides. Transcriptomic analysis revealed 6 upregulated and 6 downregulated genes in the model group, showing marked improvement following treatment. Proteomic analysis revealed changes in 30 upregulated and 50 downregulated proteins, with improvements observed upon treatment. The PI3K-Akt signalling pathway was investigated through KEGG enrichment analysis. Molecular biology methods verified the upregulation of Spp1, Thbs1, PI3K, and Akt in the model group, which was reversed in the treatment group. This study revealed that highly polar iridoids from R. Scrophulariae can modulate the Spp1 gene and Thbs1 protein via the PI3K-Akt signalling pathway, suggesting a therapeutic benefit for hyperthyroidism and providing a basis for drug development targeting this condition.

Individualized lipid profile in urine-derived extracellular vesicles from clinical patients with Mycobacterium tuberculosis infections.

Background: Lipids are a key nutrient source for the growth and reproduction of Mycobacterium tuberculosis (Mtb). Urine-derived extracellular vesicles (EVs), because of its non-invasive sampling, lipid enrichment, and specific sorting character, have been recognized as a promising research target for biomarker discovery and pathogenesis elucidation in tuberculosis (TB). We aim to profile lipidome of Mtb-infected individuals, offer novel lipid signatures for the development of urine-based TB testing, and provide new insights into the lipid metabolism after Mtb infection. Methods: Urine-derived extracellular vesicles from 41 participants (including healthy, pulmonary tuberculosis, latent tuberculosis patients, and other lung disease groups) were isolated and individually detected using targeted lipidomics and proteomics technology platforms. Biomarkers were screened by multivariate and univariate statistical analysis and evaluated by SPSS software. Correlation analyses were performed on lipids and proteins using the R Hmisc package. Results: Overall, we identified 226 lipids belonging to 14 classes. Of these, 7 potential lipid biomarkers for TB and 6 for latent TB infection (LTBI) were identified, all of which were classified into diacylglycerol (DAG), monoacylglycerol (MAG), free fatty acid (FFA), and cholesteryl ester (CE). Among them, FFA (20:1) was the most promising biomarker target in diagnosing TB/LTBI from other compared groups and also have great diagnostic performance in distinguishing TB from LTBI with AUC of 0.952. In addition, enhanced lipolysis happened as early as individuals got latent Mtb infection, and ratio of raft lipids was gradually elevated along TB progression. Conclusion: This study demonstrated individualized lipid profile of urinary EVs in patients with Mtb infection, revealed novel potential lipid biomarkers for TB/LTBI diagnosis, and explored mechanisms by which EV lipid raft-dependent bio-processes might affect pathogenesis. It lays a solid foundation for the subsequent diagnosis and therapeutic intervention of TB.

Quantitative analysis of the lysine acetylome reveals the role of SIRT3-mediated HSP60 deacetylation in suppressing intracellular Mycobacterium tuberculosis survival.

Protein acetylation and deacetylation are key epigenetic modifications that regulate the initiation and development of several diseases. In the context of infection with Mycobacterium tuberculosis (M. tb), these processes are essential for host-pathogen interactions and immune responses. However, the specific effects of acetylation and deacetylation on cellular functions during M. tb infection are not fully understood. This study employed Tandem Mass Tag (TMT) labeling for quantitative proteomic profiling to examine the acetylproteome (acetylome) profiles of noninfected and M. tb-infected macrophages. We identified 715 acetylated peptides from 1,072 proteins and quantified 544 lysine acetylation sites (Kac) in 402 proteins in noninfected and M. tb-infected macrophages. Our research revealed a link between acetylation events and metabolic changes during M. tb infection. Notably, the deacetylation of heat shock protein 60 (HSP60), a key chaperone protein, was significantly associated with this process. Specifically, the deacetylation of HSP60 at K96 by sirtuin3 (SIRT3) enhances macrophage apoptosis, leading to the elimination of intracellular M. tb. These findings underscore the pivotal role of the SIRT3-HSP60 axis in the host immune response to M. tb. This study offers a new perspective on host protein acetylation and suggests that targeting host-directed therapies could be a promising approach for tuberculosis immunotherapy. IMPORTANCE: Protein acetylation is crucial for the onset, development, and outcome of tuberculosis (TB). Our study comprehensively investigated the dynamics of lysine acetylation during M. tb infection, shedding light on the intricate host-pathogen interactions that underlie the pathogenesis of tuberculosis. Using an advanced quantitative lysine proteomics approach, different profiles of acetylation sites and proteins in macrophages infected with M. tb were identified. Functional enrichment and protein-protein network analyses revealed significant associations between acetylated proteins and key cellular pathways, highlighting their critical role in the host response to M. tb infection. Furthermore, the deacetylation of HSP60 and its influence on macrophage-mediated clearance of M. tb underscore the functional significance of acetylation in tuberculosis pathogenesis. In conclusion, this study provides valuable insights into the regulatory mechanisms governing host immune responses to M. tb infection and offers promising avenues for developing novel therapeutic interventions against TB.

Comparative analysis of genomic characteristics and immune response between Mycobacterium tuberculosis strains cultured continuously for 25 years and H37Rv.

Tuberculosis (TB) continues to pose a significant global health challenge, emphasizing the critical need for effective preventive measures. Although many studies have tried to develop new attenuated vaccines, there is no effective TB vaccine. In this study, we report a novel attenuated Mycobacterium tuberculosis (M. tb) strain, CHVAC-25, cultured continuously for 25 years in the laboratory. CHVAC-25 exhibited significantly reduced virulence compared to both the virulent H37Rv strain in C57BL/6J and severe combined immunodeficiency disease mice. The comparative genomic analysis identified 93 potential absent genomic segments and 65 single nucleotide polymorphic sites across 47 coding genes. Notably, the deletion mutation of ppsC (Rv2933) involved in phthiocerol dimycocerosate synthesis likely contributes to CHVAC-25 virulence attenuation. Furthermore, the comparative analysis of immune responses between H37Rv- and CHVAC-25-infected macrophages showed that CHVAC-25 triggered a robust upregulation of 173 genes, particularly cytokines crucial for combating M. tb infection. Additionally, the survival of CHVAC-25 was significantly reduced compared to H37Rv in macrophages. These findings reiterate the possibility of obtaining attenuated M. tb strains through prolonged laboratory cultivation, echoing the initial conception of H37Ra nearly a century ago. Additionally, the similarity of CHVAC-25 to genotypes associated with attenuated M. tb vaccine positions it as a promising candidate for TB vaccine development.

Hydrogen Bond and Dipole-Dipole Interaction Enabling Ultrastable, Quick Responding, and Self-Healing Proton Exchange Membranes for Fuel Cells.

Proton exchange membranes (PEMs) are subject to mechanical degradation, such as microcracks and pinhole formation, under real-world fuel cell operating conditions, which leads to great issues in terms of device death and safety concerns. Therefore, PEMs with self-healing features are imperative but have rarely been used for proton exchange membrane fuel cells (PEMFCs). Here, a dimensionally stable and self-healing PEM is developed by tuning the hydrogen bond and dipole-dipole interactions between the mature perfluorinated sulfonic acid (PFSA) and a self-healing copolymer, which is specifically synthesized with hexafluorobutyl acrylate (HFBA) and acrylic acid (AA). This hexafluorobutyl acrylate-acrylic acid copolymer (HFBA-co-AA) is suggested as the key to improving the self-healing efficiency of the blended PFSA/HFBA-co-AA membrane. This PFSA/HFBA-co-AA membrane can recover 43.6% of the original tensile strength within only 20 min at 80 °C. This study may pave an avenue toward the development of reliable and durable PEM for fuel cells.

Potential mitigation of titanium dioxide nanoparticles against 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis through inhibiting the canonical NF-κB pathway.

Titanium dioxide nanoparticles (TiO2 NPs) have been widely employed in various industry fields, which makes consumers concerned about their health impact. Our previous work displayed that TiO2 NPs participated in the mitigation of TNBS-induced colitis, but the mechanism is still unknown. This work aimed to explore the role of oxidative stress and NF-κB pathway in the effect of TiO2 NPs on TNBS-induced colitis. The results showed that TiO2 NPs administration reduced the DAI score of colitis mice after TNBS enema. TiO2 NPs did not alter oxidative stress status (GSH/GSSG), but repaired the gut dysbacteriosis and inhibited the canonical NF-κB pathway activation in TNBS-induced colitis mice, manifested as a decrease in pathogenic bacteria and an increase in beneficial bacteria, as well as down-regulation of toll-like receptors (TLRs), IKKα, IKKß, p65 and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and IFN-γ) in mRNA level, and the increased transcription of anti-inflammatory cytokines (IL-10, TGF-ß, and IL-12), along with the declined protein level of TNF-α in TiO2 NPs treated colitis mice. The present study suggested that oral TiO2 NPs administration inhibited the canonical NF-κB pathway activation by repairing gut dysbacteriosis, which made a predominant role in alleviating colitis. These findings provided a new perspective for exploring the safety of TiO2 NPs.

Toxic mechanisms of the antiviral drug arbidol on microalgae in algal bloom water at transcriptomic level.

Increasing antivirals in surface water caused by their excessive consumption pose serious threats to aquatic organisms. Our recent research found that the input of antiviral drug arbidol to algal bloom water can induce acute toxicity to the growth and metabolism of Microcystis aeruginosa, resulting in growth inhibition, as well as decrease in chlorophyll and ATP contents. However, the toxic mechanisms involved remained obscure, which were further investigated through transcriptomic analysis in this study. The results indicated that 885-1248 genes in algae were differentially expressed after exposure to 0.01-10.0 mg/L of arbidol, with the majority being down-regulated. Analysis of commonly down-regulated genes found that the cellular response to oxidative stress and damaged DNA bonding were affected, implying that the stress defense system and DNA repair function of algae might be damaged. The down-regulation of genes in porphyrin metabolism, photosynthesis, carbon fixation, glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation might inhibit chlorophyll synthesis, photosynthesis, and ATP supply, thereby hindering the growth and metabolism of algae. Moreover, the down-regulation of genes related to nucleotide metabolism and DNA replication might influence the reproduction of algae. These findings provided effective strategies to elucidate toxic mechanisms of contaminants on algae in algal bloom water.

Early life stage exposure to fenbuconazole causes multigenerational cardiac developmental defects in zebrafish and potential reasons.

With the increasing use of triazole fungicides in agriculture, triazole pesticides have aroused great concern about their toxicity and ecological risk. The current study investigated the impairments of embryonic exposure to fenbuconazole (FBZ) on cardiac transgenerational toxicity and related mechanisms. The fertilized eggs were exposed to 5, 50 and 500 ng/L FBZ for 72 h, and the larvae were then raised to adulthood in clean water. The adult fish were mated with unexposed fish to produce maternal and paternal F1 and F2 embryos, respectively. The results showed that increased arrhythmia were observed in F0, F1 and F2 larvae. Transcriptome sequencing indicated that the pathway of adrenergic signaling in cardiomyocytes was enriched in F0 and F2 larvae. In both F0 and F1 adult zebrafish hearts, ADRB2 protein expression decreased, and transcription of genes related to cardiac development and Ca2+ homeostasis was downregulated. These alterations might cause cardiac developmental defects. Significantly decreased protein levels of H3K9Ac and H3K14Ac might be linked with the downregulation in transcription of cardiac development genes. Protein‒protein interaction analysis exhibited that the pathway affecting the heart was well inherited in the paternal line. These results provide new ideas for the analysis and prevention of congenital heart disease.

Recombinant hirudin suppresses angiogenesis of diffuse large B-cell lymphoma through regulation of the PAR-1-VEGF.

Hirudin is one of the specific inhibitors of thrombin, which has been confirmed to have strong bioactivities, including inhibiting tumors. However, the function and mechanism of hirudin and protease-activated receptor 1 (PAR-1) in diffuse large B-cell lymphoma (DLBCL) have not been clear. Detecting the expression PAR-1 in DLBCL tissues and cells by RT-qPCR and IHC. Transfected sh-NC, sh-PAR-1, or pcDNA3.1-PAR-1 in DLBCL cells or processed DLBCL cells through added thrombin, Vorapaxar, Recombinant hirudin (RH), or Na2S2O4 and co-culture with EA.hy926. And built DLBCL mice observed tumor growth. Detecting the expression of related genes by RT-qPCR, Western blot, IHC, and immunofluorescence, measured the cellular hypoxia with Hypoxyprobe-1 Kit, and estimated the cell inflammatory factors, proliferation, migration, invasion, and apoptosis by ELISA, CCK-8, flow cytometry, wound-healing and Transwell. Co-immunoprecipitation and pull-down measurement were used to verify the relationship. PAR-1 was highly expressed in DLBCL tissues and cells, especially in SUDHL2. Na2S2O4 induced SUDHL2 hypoxia, and PAR-1 did not influence thrombin-activated hypoxia. PAR-1 could promote SUDHL2 proliferation, migration, and invasion, and it was unrelated to cellular hypoxia. PAR-1 promoted proliferation, migration, and angiogenesis of EA.hy926 or SUDHL2 through up-regulation vascular endothelial growth factor (VEGF). RH inhibited tumor growth, cell proliferation, and migration, promoted apoptosis of DLBCL, and inhibited angiogenesis by down-regulating PAR-1-VEGF. RH inhibits proliferation, migration, and angiogenesis of DLBCL cells by down-regulating PAR-1-VEGF.

11-Plex DiLeu Isobaric Labeling Enables Quantitative Assessment of Brain Region Protein Association Networks Impacted by the Gut Microbiome.

Gut microbiota can regulate host brain functions and influence various physiological and pathological processes through the brain-gut axis. To systematically elucidate the intervention of different gut environments on different brain regions, we implemented an integrated approach that combines 11-plex DiLeu isobaric tags with a "BRIDGE" normalization strategy to comparatively analyze the proteome of six brain regions in germ-free (GF)- and conventionally raised (ConvR)-mice. A total of 5945 proteins were identified and 5656 were quantifiable, while 1906 of them were significantly changed between GF- and ConvR-mice; 281 proteins were filtered with FC greater than 1.2 in at least one brain region, of which heatmap analysis showed clear protein profile disparities, both between brain regions and gut microbiome conditions. Gut microbiome impact is most overt in the hypothalamus and the least in the thalamus region. Collectively, this approach allows an in-depth investigation of the induced protein changes by multiple gut microbiome environments in a brain region-specific manner. This comprehensive proteomic work improves the understanding of the brain region protein association networks impacted by the gut microbiome and highlights the critical roles of the brain-gut axis.

The environmental risks of antiviral drug arbidol in eutrophic lake: Interactions with Microcystis aeruginosa.

The environmental risks resulting from the increasing antivirals in water are largely unknown, especially in eutrophic lakes, where the complex interactions between algae and drugs would alter hazards. Herein, the environmental risks of the antiviral drug arbidol towards the growth and metabolism of Microcystis aeruginosa were comprehensively investigated, as well as its biotransformation mechanism by algae. The results indicated that arbidol was toxic to Microcystis aeruginosa within 48 h, which decreased the cell density, chlorophyll-a, and ATP content. The activation of oxidative stress increased the levels of reactive oxygen species, which caused lipid peroxidation and membrane damage. Additionally, the synthesis and release of microcystins were promoted by arbidol. Fortunately, arbidol can be effectively removed by Microcystis aeruginosa mainly through biodegradation (50.5% at 48 h for 1.0 mg/L arbidol), whereas the roles of bioadsorption and bioaccumulation were limited. The biodegradation of arbidol was dominated by algal intracellular P450 enzymes via loss of thiophenol and oxidation, and a higher arbidol concentration facilitated the degradation rate. Interestingly, the toxicity of arbidol was reduced after algal biodegradation, and most of the degradation products exhibited lower toxicity than arbidol. This study revealed the environmental risks and transformation behavior of arbidol in algal bloom waters.

IL-36 antagonism blunts the proliferation and migration of oral squamous cell carcinoma cells.

IL-36 is known to mediate inflammation and fibrosis. Nevertheless, IL-36 signalling axis has also been implicated in cancer, although understanding of exact contribution of IL-36 to cancer progression is very limited, partly due to existence of multiple IL-36 ligands with agonistic and antagonistic function. Here we explored the role of IL-36 in oral squamous cell carcinoma (OSCC). Firstly, we analyzed expression of IL-36 ligands and receptor and found that the expression of IL-36γ was significantly higher in head and neck cancer (HNSCC) than that of normal tissues, and that the high expression of IL-36γ predicted poor clinical outcomes. Secondly, we investigated the direct effect of IL-36γ on OSCC cells and found that IL-36γ stimulated proliferation of OSCC cells with high expression of IL-36R expression. Interestingly, IL-36γ also promoted migration of OSCC cells with low to high IL-36R expression. Critically, both proliferation and migration of OSCC cells induced by IL-36γ were abrogated by anti-IL-36R mAb. Fittingly, RNA sequence analysis revealed that IL-36γ regulated genes involved in cell cycle and cell division. In summary, our results showed that IL-36γ can be a tumor-promoting factor, and targeting of IL-36R signalling may be a beneficial targeted therapy for patients with abnormal IL-36 signalling.

Identification of important modules and biomarkers in tuberculosis based on WGCNA.

Background: Tuberculosis (TB) is a significant public health concern, particularly in China. Long noncoding RNAs (lncRNAs) can provide abundant pathological information regarding etiology and could include candidate biomarkers for diagnosis of TB. However, data regarding lncRNA expression profiles and specific lncRNAs associated with TB are limited. Methods: We performed ceRNA-microarray analysis to determine the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs). Weighted gene co-expression network analysis (WGCNA) was then conducted to identify the critical module and genes associated with TB. Other bioinformatics analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and co-expression networks, were conducted to explore the function of the critical module. Finally, real-time quantitative polymerase chain reaction (qPCR) was used to validate the candidate biomarkers, and receiver operating characteristic analysis was used to assess the diagnostic performance of the candidate biomarkers. Results: Based on 8 TB patients and 9 healthy controls (HCs), a total of 1,372 differentially expressed lncRNAs were identified, including 738 upregulated lncRNAs and 634 downregulated lncRNAs. Among all lncRNAs and mRNAs in the microarray, the top 25% lncRNAs (3729) and top 25% mRNAs (2824), which exhibited higher median expression values, were incorporated into the WGCNA. The analysis generated 16 co-expression modules, among which the blue module was highly correlated with TB. GO and KEGG analyses showed that the blue module was significantly enriched in infection and immunity. Subsequently, considering module membership values (>0.85), gene significance values (>0.90) and fold-change value (>2 or < 0.5) as selection criteria, the top 10 upregulated lncRNAs and top 10 downregulated lncRNAs in the blue module were considered as potential biomarkers. The candidates were then validated in an independent validation sample set (31 TB patients and 32 HCs). The expression levels of 8 candidates differed significantly between TB patients and HCs. The lncRNAs ABHD17B (area under the curve [AUC] = 1.000) and ENST00000607464.1 (AUC = 1.000) were the best lncRNAs in distinguishing TB patients from HCs. Conclusion: This study characterized the lncRNA profiles of TB patients and identified a significant module associated with TB as well as novel potential biomarkers for TB diagnosis.

The incremental value of Mycobacterium tuberculosis trace nucleic acid detection in CT-guided percutaneous biopsy needle rinse solutions for the diagnosis of tuberculosis.

Introduction: Tuberculosis (TB) diagnosis still faces challenges with high proportion of bacteriologic test negative incidences worldwide. We assessed the diagnostic value of digital PCR (dPCR) analysis of ultramicro Mycobacterium tuberculosis (M.tb) nucleic acid in CT-guided percutaneous biopsy needle rinse solution (BNRS) for TB. Methods: BNRS specimens were consecutively collected and total DNA was purified. The concentrations of M.tb-specific IS6110 and IS1081 were quantified using droplet dPCR. The diagnostic performances of BNRS-dPCR and its sensitivity in comparison with conventional tests were analyzed. Results: A total of 106 patients were enrolled, 63 of whom were TB (48 definite and 15 clinically suspected TB) and 43 were non-TB. The sensitivity of BNRS IS6110 OR IS1081-dPCR for total, confirmed and clinically suspected TB was 66.7%, 68.8% and 60.0%, respectively, with a specificity of 97.7%. Its sensitivity was higher than that of conventional etiological tests, including smear microscopy, mycobacterial culture and Xpert using sputum and BALF samples. The positive detection rate in TB patients increased from 39.3% for biopsy AFB test alone to 73.2% when combined with BNRS-dPCR, and from 71.4% for biopsy M.tb molecular detection alone to 85.7% when combined with BNRS-dPCR. Conclusion: Our results preliminarily indicated that BNRS IS6110 OR IS1081-dPCR is a feasible etiological test, which has the potential to be used as a supplementary method to augment the diagnostic yield of biopsy and improve TB diagnosis.

Effectiveness of Parent-Child Interaction Therapy for Maltreated Families: A Meta-Analysis of Randomized Controlled Trials.

This meta-analysis evaluated the effectiveness of Parent-Child Interaction Therapy (PCIT) for maltreated families and examined potential moderators associated with the intervention. Seven English electronic databases (PubMed, PsycINFO, Web of Science, MEDLINE, Scopus, Cochrane Library, and ProQuest Dissertations and Theses Global) were systematically searched to identify randomized controlled trials (RCTs) published before January 20, 2023. Eleven studies involving 1,069 maltreated or high-risk families were included in the meta-analysis. Our results showed that PCIT significantly reduced child externalizing behaviors, improved parenting skills, and decreased parenting stress and child abuse potential in maltreated families. Additionally, families with confirmed maltreatment history reported larger effect sizes across all outcomes than those at high risk of maltreatment; parenting skills outcomes were more effective in adapted PCIT versions, using per-protocol analysis, and American caregivers, whereas none of the outcomes were related to the number of sessions. These findings provide encouraging evidence for the use of PCIT as an intervention for families with a history of maltreatment, although more high-quality RCTs are required to confirm its effects.

Mass Spectrometry-Based Precise Identification of Citrullinated Histones via Limited Digestion and Biotin Derivative Tag Enrichment.

Histone citrullination is an essential epigenetic post-translational modification (PTM) that affects many important physiological and pathological processes, but effective tools to study histone citrullination are greatly limited due to several challenges, including the small mass shift caused by this PTM and its low abundance in biological systems. Although previous studies have reported frequent occurrences of histone citrullination, these methods failed to provide a high-throughput and site-specific strategy to detect histone citrullination. Recently, we developed a biotin thiol tag that enabled precise identification of protein citrullination coupled with mass spectrometry. However, very few histone citrullination sites were identified, likely due to the highly basic nature of these proteins. In this study, we develop a novel method utilizing limited digestion and biotin derivative tag enrichment to facilitate direct in vivo identification of citrullination sites on histones. We achieve improved coverage of histone identification via partial enzymatic digestion and lysine block by dimethylation. With biotin tag-assisted chemical derivatization and enrichment, we also achieve precise annotation of histone citrullination sites with high confidence. We further compare different fragmentation methods and find that the electron-transfer-dissociation-based approach enables the most in-depth analysis and characterization. In total, we unambiguously identify 18 unique citrullination sites on histones in human astrocytoma U87 cells, including 15 citrullinated sites being detected for the first time. Some of these citrullination sites are observed to exhibit noticeable alterations in response to DNA damage, which demonstrates the superiority of our strategy in understanding the roles of histone citrullination in critical biological processes.