Unraveling Shared Diagnostic Biomarkers of Fibromyalgia in Ankylosing Spondylitis: Evidence from Comprehensive Bioinformatic Analysis and Experimental Validation.

Background: Fibromyalgia (FM) is a commonly encountered disease featuring chronic generalized pain, sleep disorder, and physical fatigue. Ankylosing spondylitis (AS) causes chronic lumbodorsalgia involving the sacroiliac joint, often clinically complicated with FM. Nevertheless, the pathophysiology of FM secondary to AS is still lacking. Methods: Gene expression data of the whole blood in FM and AS patients were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were evaluated employing the "limma" package. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to explore common pathways. Weighted gene correlation network analysis (WGCNA) was adopted to screen key gene modules. Three machine learning algorithms were performed to refine the intersected genes. Single sample gene set enrichment analysis (ssGSEA) was applied to explore the relationships between hub genes and immune cells. The dependability of hub gene expressions in clinical blood specimens was verified by RT-PCR. Molecular docking was conducted to predict small molecular compounds targeting hub genes. Results: DEG analysis screened 419 shared up-regulated and 179 shared down-regulated genes in FM and AS. A total of 143 common genes in positive modules of AS and FM were identified via WGCNA. Six key genes (CETN3, CACNA1E, OGT, QRFPR, SCOC, DIAPH1) were obtained by intersecting the WGCNA-derived shared genes and up-regulated DEGs. CETN3 and CACNA1E were refined as hub genes via three machine-learning algorithms and they showed excellent diagnostic value for FM and AS. However, ssGSEA exhibited different immune cell infiltration patterns in FM and AS. Gabapentin enacarbil was recognized as a potential therapeutic drug for AS-FM patients. Conclusion: This study reveals the shared hub genes in AS and FM. Meanwhile, these results were confirmed in clinical samples. CETN3 and CACNA1E may become potential diagnostic biomarkers and therapeutic targets for patients with AS complicated by FM.

Returned samples indicate volcanism on the Moon 120 million years ago.

There is extensive geologic evidence of ancient volcanic activity on the Moon, but it is unclear how long that volcanism persisted. Magma fountains produce volcanic glasses, which have previously been found in samples of the Moon's surface. We investigated ~3000 glass beads in lunar soil samples collected by the Chang'e-5 mission and identified three as having a volcanic origin on the basis of their textures, chemical compositions, and sulfur isotopes. Uranium-lead dating of the three volcanic glass beads shows that they formed 123 ± 15 million years ago. We measured high abundances of rare earth elements and thorium in these volcanic glass beads, which could indicate that such recent volcanism was related to local enrichment of heat-generating elements in the mantle sources of the magma.

A comprehensive single-cell RNA transcriptomic analysis identifies a unique SPP1+ macrophages subgroup in aging skeletal muscle.

Senescence of skeletal muscle (SkM) has been a primary contributor to senior weakness and disability in recent years. The gradually declining SkM function associated with senescence has recently been connected to an imbalance between damage and repair. Macrophages (Mac) are involved in SkM aging, and different macrophage subgroups hold different biological functions. Through comprehensive single-cell transcriptomic analysis, we first compared the metabolic pathways and biological functions of different types of cells in young (Y) and old (O) mice SkM. Strikingly, the Mac population in mice SkM was also explored, and we identified a unique Mac subgroup in O SkM characterized by highly expressed SPP1 with strong senescence and adipogenesis features. Further work was carried out on the metabolic and biological processes for these Mac subgroups. Besides, we verified that the proportion of the SPP1+ Mac was increased significantly in the quadriceps tissues of O mice, and the senotherapeutic drug combination dasatinib + quercetin (D + Q) could dramatically reduce its proportion. Our study provides novel insight into the potential role of SPP1+ Mac in SkM, which may serve as a senotherapeutic target in SkM aging.

Facile synthesis of N-doped graphene quantum dots as a fluorescent sensor for Cr(vi) and folic acid detection.

The development of stable fluorescent sensors for toxic pollutants and drugs is meaningful to the environment and public health. In this work, nitrogen-doped graphene quantum dots (N-GQDs) were facially synthesized by a one-step hydrothermal method using soluble starch and l-arginine as carbon and nitrogen sources in pure water at 190 °C for 4 h. The as-synthesized N-GQDs were well characterized and displayed blue fluorescence emission at 445 nm with excellent pH stability, salt tolerance, thermostability, photobleaching resistance and reproducibility. Moreover, N-GQDs could serve as an "on-off" sensor for selective detection of Cr(vi) and folic acid with low detection limit (0.80 and 2.1 µM), good linear correlation over wide linear range (0-50 µM and 0-200 µM) as well as short response time (<10 s). The practical applications of N-GQDs for Cr(vi) and folic acid detection in actual samples were further investigated and showed acceptable recoveries (92-105%) with relative standard deviations less than 5%. These results indicated that this N-GQDs-based sensor could be a potential alternative for Cr(vi) and folic acid detection in the fields of environmental monitoring and drug analysis.

Identification and validation of CCL5 as a key gene in HIV infection and pulmonary arterial hypertension.

Background: The relationship between human immunodeficiency virus (HIV) infection and pulmonary arterial hypertension (PAH) has garnered significant scrutiny. Individuals with HIV infection have a higher risk of developing PAH. However, the specific mechanism of HIV-associated PAH remains unclear. Our study aims at investigating the shared biomarkers in HIV infection and PAH and predicting the potential therapeutic target for HIV-associated PAH. Methods: Data for HIV infection and PAH were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis was performed to detect shared genes in HIV infection and PAH. Enrichment analysis was conducted to identify the function of common DEGs. Protein-protein interaction (PPI) analysis was used to detect key genes. These crucial genes were subsequently verified by RT-qPCR. Finally, candidate drugs were identified by using the Drug Signatures Database (DSigDB). Results: Nineteen common DEGs were identified in HIV infection and PAH. Enrichment analysis exhibited that the functions of these genes were mainly enriched in inflammatory responses, mainly including cellular immunity and interaction between viral proteins and cytokines. By constructing PPI networks, we identified the key gene CC-type chemokine ligand 5 (CCL5), and we verified that CCL5 was highly expressed in hypoxia induced human pulmonary artery endothelial cells (hPAECs) and human pulmonary artery smooth muscle cells (hPASMCs). In addition, we predicted 10 potential drugs targeting CCL5 by Autodock Vina. Conclusion: This study revealed that CCL5 might be a common biomarker of HIV infection and PAH and provided a new therapeutic target for HIV-associated PAH. However, further clinical validation is still indispensable.

[A comparative study of four combined methods for planning access to the anterior acetabular column for nail placement].

OBJECTIVE: To investigate global optimisation of anterior acetabular column pinning channels can be achieved based on large density point cloud data. METHODS: Data were collected on the CT scans of the normal pelvis in 40 adults from January 2022 to January 2023, including 22 males and 18 females, aged 20 to 54 years old. Medical imaging data from three of the samples were selected for experimental study. In planning access for anterior acetabular column pinning, to address the issue of whether the current CAD planning methods were advanced or not, four combinations of the same point cloud acquisition channels, different directional line creation software, and the same 3D design and virtual experiment software were proposed: Mimics+Imageware+UG, Mimics+3DReshaper+UG, Mimics+ZEISS Quality Suite+UG and Mimics+Design X+UG, and directional lines created based on the centroid point set and solid point cloud of the secondary pruning model, respectively, and it applied to the planning of the left anterior column pinning channel of the three acetabular samples. The maximum internally connected cylinder without acetabular socket and pubic bone penetration was used as a safe passage for nailing of the anterior acetabular column to evaluate the advancement of each method. RESULTS: The fitting effect of the directional line was better than that of the unnoised solid point cloud when the central point set with obvious relevant features was selected as the sample points;and the combination of Mimics+Imageware+UG and Mimics+3DReshaper+UG could efficiently and stably obtain the desirable planning results when planning with the central point set, respectively, in the three acetabular samples 1, 2, 3. The maximum internal joint circle diameters obtained in samples 1, 2, and 3 were 10.35 mm, 9.62 mm, and 9.24 mm;and when the directional lines were based on the solid point cloud the combined methods of Mimics+ZEISS Quality Suite+UG and Mimics+Design X+UG were not applicable;whereas the Mimics+3DReshaper+UG the solid point cloud denoising planning method could stably obtain the maximum value of the safe channel for nail placement, and the maximum internal joint circle diameters obtained in acetabular samples 1, 2, and 3 are 10.66 mm, 10.96 mm, and 9.48 mm, respectively. CONCLUSION: It is recommended that the nail placement channel planners use robust Mimics+Imageware+UG or Mimics+3DReshaper+UG centre point set planning method, and if there is enough time, it is recommended to use the solid point cloud denoising planning method of Mimics+3DReshaper+UG in order to obtain the maximum value of safe channels for nail placement.

Fluorescent probe for imaging intercellular tension: molecular force approach.

Cellular mechanical force plays a crucial role in numerous biological processes, including wound healing, cell development, and metastasis. To enable imaging of intercellular tension, molecular tension probes were designed, which offer a simple and efficient method for preparing Au-DNA intercellular tension probes with universal applicability. The proposed approach utilizes gold nanoparticles linked to DNA hairpins, enabling sensitive visualization of cellular force in vitro. Specifically, the designed Au-DNA intercellular tension probe includes a molecular spring flanked by a fluorophore-quencher pair, which is anchored between cells. As intercellular forces open the hairpin, the fluorophore is de-quenched, allowing for visualization of cellular force. The effectiveness of this approach was demonstrated by imaging the cellular force in living cells using the designed Au-DNA intercellular tension probe.

A Spectroscopic Method for Distinguishing Two Novel Sandwich-Type Tungsten Oxide Cluster Compounds.

This study introduces two novel sandwich-type tungsten-oxygen cluster compounds synthesized by hydrothermal methods, H4(C6H12N2H2)3{Na(H2O)2[Mn2(H2O)(GeW9O34)]}2 (Compound 1) and H2(C6H12N2H2)3.5{Na3(H2O)4[Co2(H2O)(GeW9O34)]2}·17H2O (Compound 2). The two compounds comprise cluster anions [GeW9O34]10- coordinated with transition metal atoms, either Mn or Co, and are stabilized by organic ligands. These compounds are crystallized in the hexagonal crystal system and P63/m space group. The two compounds were characterized through various techniques. Fourier transform infrared (IR) spectroscopy showed absorption peaks of anionic backbone vibrations of the Keggin cluster at 500-1000 cm-1, IR spectral peaks of δ(N-H) and νas(C-N) of the ligand triethylenediamine at 1000-2000 cm-1, and IR spectral peaks of the ligand νas(N-H) and νas(O-H) of water at 3000-3500 cm-1. Despite similar one-dimensional (1D) IR spectra due to the same cluster anions and similar molecular structures, the two compounds exhibited distinct responses in two-dimensional correlation spectroscopy with IR under magnetic and thermal perturbations. Under magnetic perturbation, Compound 1 showed a strong response peak for νas(W-Ob-W), while Compound 2 exhibited a strong response peak for νas(W=Od), possibly linked to differing magnetic particles. Similarly, Compound 1 displayed a strong response peak under thermal perturbation for νas(W-Oc-W). In contrast, Compound 2 showed a strong response peak for νas(W=Od); these results may be attributed to the different hydrogen bonding connections between the two compounds, which affect the groups in distinct ways through vibration and transmit these vibrations to the W-O bonds. The research presented in this paper expands the theoretical and experimental data of 2D correlation IR spectroscopy.

EGR3 Polymorphism Is a Potential Susceptibility Factor of Schizophrenia Risk in a Chinese Population.

Objective: The purpose of this study was to evaluate the association between the single nucleotide polymorphisms (SNPs) (EGR3 rs1996147; EGR4 rs3813226, rs6747506; ERBB3 rs2292238; and ERBB4 rs707284, rs7560730) and the risk of schizophrenia (SZ) in a Chinese population. Materials and Methods: We conducted a case-control study, including 248 patients with SZ and 236 healthy controls matched for age and sex. The Mass-array platform was used to detect all the genotypes of the SNPs. Results: The results revealed that the EGR3 rs1996147 AA genotype was associated with borderline decreased SZ risk (AA vs. GG: adjusted OR = 0.43, 95% CI: 0.18-1.02, p = 0.06). However, no significant correlation was found between the other SNPs and overall SZ risk. Subgroup analysis also failed to show any significant association between all SNPs and the risk of SZ. Conclusion: In summary, this study revealed that the EGR3 rs1996147 AA genotype was associated with a borderline risk for SZ.

A novel mutation in hERG gene associated with azithromycin-induced acquired long QT syndrome.

BACKGROUND: Mutations in human ether-à-go-go-related gene (hERG) potassium channels are closely associated with long QT syndrome (LQTS). Previous studies have demonstrated that macrolide antibiotics increase the risk of cardiovascular diseases. To date, the mechanisms underlying acquired LQTS remain elusive. METHODS: A novel hERG mutation I1025N was identified in an azithromycin-treated patient with acquired long QT syndrome via Sanger sequencing. The mutant I1025N plasmid was transfected into HEK-293 cells, which were subsequently incubated with azithromycin. The effect of azithromycin and mutant I1025N on the hERG channel was evaluated via western blot, immunofluorescence, and electrophysiology techniques. RESULTS: The protein expression of the mature hERG protein was down-regulated, whereas that of the immature hERG protein was up-regulated in mutant I1025N HEK-293 cells. Azithromycin administration resulted in a negative effect on the maturation of the hERG protein. Additionally, the I1025N mutation exerted an inhibitory effect on hERG channel current. Moreover, azithromycin inhibited hERG channel current in a concentration-dependent manner. The I1025N mutation and azithromycin synergistically decreased hERG channel expression and hERG current. However, the I1025N mutation and azithromycin did not alter channel gating dynamics. CONCLUSIONS: These findings suggest that hERG gene mutations might be involved in the genetic susceptibility mechanism underlying acquired LQTS induced by azithromycin.

Gut microbiota and risk of endocarditis: a bidirectional Mendelian randomization study.

Background: The associations between gut microbiota and cardiovascular disease have been reported in previous studies. However, the relationship between gut microbiota and endocarditis remains unclear. Methods: A bidirectional Mendelian randomization (MR) study was performed to detect the association between gut microbiota and endocarditis. Inverse variance weighted (IVW) method was considered the main result. Simultaneously, heterogeneity and pleiotropy tests were conducted. Results: Our study suggests that family Victivallaceae (p = 0.020), genus Eubacterium fissicatena group (p = 0.047), genus Escherichia Shigella (p = 0.024), genus Peptococcus (p = 0.028) and genus Sellimonas (p = 0.005) play protective roles in endocarditis. Two microbial taxa, including genus Blautia (p = 0.006) and genus Ruminococcus2 (p = 0.024) increase the risk of endocarditis. At the same time, endocarditis has a negative effect on genus Eubacterium fissicatena group (p = 0.048). Besides, no heterogeneity or pleiotropy was found in this study. Conclusion: Our study emphasized the certain role of specific gut microbiota in patients with endocarditis and clarified the negative effect of endocarditis on gut microbiota.

Excavatolide C/cisplatin combination induces antiproliferation and drives apoptosis and DNA damage in bladder cancer cells.

Excavatolide C (EXCC), a marine coral-derived compound, exhibits an antiproliferation effect on bladder cancer cells. The present study evaluated the improvement in the antiproliferation ability of EXCC by co-treatment with cisplatin in bladder cancer cells. EXCC/cisplatin (12.5 and 1 µg/mL) showed higher antiproliferation effects on bladder cancer cells than single treatments (EXCC or cisplatin alone) in the 48 h ATP assay. EXCC/cisplatin also enhanced the increase in subG1, annexin V-mediated apoptosis, and activation of poly (ADP-ribose) polymerase (PARP) and several caspases (caspases 3, 8, and 9) compared to the single treatments. Cellular and mitochondrial oxidative stress was enhanced with EXCC/cisplatin compared to the single treatments according to analyses of reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial membrane potential; in addition, cellular antioxidants, such as glutathione (GSH), and the mRNA expressions of antioxidant signaling genes (catalase and NFE2-like bZIP transcription factor 2) were downregulated. EXCC/cisplatin treatment produced more DNA damage than the single treatments, as indicated by γH2AX and 8-hydroxy-2'-deoxyguanosine levels. Moreover, several DNA repair genes for homologous recombination (HR) and non-homologous end joining (NHEJ) were downregulated in EXCC/cisplatin compared to others. The addition of the GSH precursor N-acetylcysteine, which has ROS scavenging activity, attenuated all EXCC/cisplatin-induced changes. Notably, EXCC/cisplatin showed lower antiproliferation, apoptosis, ROS induction, GSH depletion, and γH2AX DNA damage in normal cells than in bladder cancer cells. Therefore, the co-treatment of EXCC/cisplatin reduces the proliferation of bladder cancer cells via oxidative stress-mediated mechanisms with normal cell safety.

Taxonomic studies on the genera Echinovelleda Breuning, 1936 and Propedicellus Huang, Huang & Liu, 2020 (Coleoptera, Cerambycidae, Lamiinae, Lamiini).

The genera Echinovelleda Breuning, 1936 and Propedicellus Huang, Huang & Liu, 2020 are revised. The latterisconsideredto be ajunior synonym of theformer based on a comprehensive morphological investigation, especially on the characteristics of male endophallus. Two new species are described from China, viz. Echinovelleda mumuae Bi & Mu sp. nov. from Yunnan and Guangxi, and E. protochinensis Bi & Lin sp. nov. from Yunnan and Sichuan. New records are reported for previously described taxa including one new country record of a morphologically similar genus, Hechinoschema Thomson, 1857 from China. Illustrations of habitus, endophallic structure, major diagnostic features for all studied taxa, as well as a distributional map are provided.

The effects of gonadotropin-releasing hormone agonist on final adult height among girls with early and fast puberty.

Introduction: This study aimed to explore the impact of gonadotropin-releasing hormone agonists (GnRHa) on final adult height (FAH) in girls with early and fast puberty. Methods: A retrospective study was conducted by reviewing data from the medical records of the Pediatric Endocrinology Clinics between January 1, 2010, and December 31, 2020, at MacKay Children's Hospital. The treatment group included 109 patients who received 3.75 mg monthly for at least 1 year, whereas the control group consisted of 95 girls who received no treatment. Results: The treatment group was significantly older at the time of inclusion(chronological age (CA1), treatment vs. control, 8.7 vs. 8.4 years, p < 0.001), had a more advanced bone age (BA) (BA1, 11.5 vs. 10.8 years, p < 0.001), BA1-CA1 (2.7 vs. 2.2 years, p < 0.001), and shorter predicted adult height (PAH1) (153.3 vs. 157.1 cm, p = 0.005) that was significantly lower than their target height (Tht)(PAH1-Tht, -3.9 vs. -1.3 cm, p = 0.039). The FAHs of the GnRHa and the control group were similar (157.0 vs. 156.7 cm, p = 0.357) and were not significantly different from their Tht (FAH vs. Tht in the GnRHa group, 157.0 vs. 157.0 cm; control group, 156.7 vs. 157.0 cm). In the subgroup analysis, FAH was significantly higher after GnRHa treatment in those with PAH1 less than 153 cm and Tht (154.0 vs. 152.0 cm, p = 0.041), and those whose CA1 was between 8 and 9 years (158.0 vs. 155.4 cm, p = 0.004). We defined satisfactory FAH outcome as FAH-PAH1≥5 cm and significant factors were GnRHa therapy, PAH1 shorter than their Tht, age younger than 9 years, and faster growth velocity during the first year. Discussion: GnRHa is effective in restoring the Tht in some early and fast pubertal girls, especially in those with poorly PAH (PAH lower than 153 cm and shorter than their target height). A younger age at initiation of treatment and a faster growth velocity during treatment are associated with a better height gain.

Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.

Highly sensitive and selective detection of triphosgene with a 2-(2'-hydroxyphenyl)benzimidazole derived fluorescent probe.

In this work, a 2-(2'-hydroxyphenyl)benzimidazole derived fluorescent probe, 2-(2'-hydroxy-4'-aminophenyl)benzimidazole (4-AHBI), was synthesized and its fluorescent behavior toward triphosgene were evaluated. The results showed that 4-AHBI exhibited high sensitivity (limit of detection, 0.08 nM) and excellent selectivity for triphosgene over other acyl chlorides including phosgene in CH2Cl2 solution. Moreover, 4-AHBI loaded test strips were prepared for the practical sensing of triphosgene.

[Synthesis of porous organic framework materials based on deep eutectic solvents and their application in solid-phase extraction].

This paper reviews the application of deep eutectic solvents (DESs) in the synthesis of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs) as well as their prospects in the field of solid-phase extraction (SPE). Porous organic frameworks (POFs) have unique properties such as a large specific surface area, high porosity, and easy modification. Thus, these materials are widely applied in the fields of catalysis, adsorption, drug delivery, gas storage, and separation. POFs include MOFs, COFs, conjugated microporous polymers (CMPs), porous aromatic frameworks (PAFs), and covalent triazine frameworks (CTFs). MOFs are constructed from metal ions/clusters and organic ligands through coordination bonds and can be extended in two or three dimensions by repeated coordination with potential voids. COFs are formed from two monomers containing light elements (such as carbon, hydrogen, oxygen, nitrogen, boron, and other elements) via coordination bonds and have large two- or three-dimensional structures. However, conventional POF synthesis methods generally suffer from disadvantages such as long synthesis times, high temperature and pressure requirements, and the use of toxic and hazardous reaction solvents. DES consists of a hydrogen bond acceptor (HBA) and a hydrogen bond donor (HBD) bound by hydrogen-bonding interactions. It is a promising green solvent for material synthesis owing to its low vapor pressure, high stability, and ease of preparation. DES can be used to prepare MOFs and COFs and, in specific cases, acts as a structure-directing agent, which has an important impact on the structure and properties of the resulting frameworks. Using appropriate DES formulations, researchers can modulate the crystal structures, pore sizes, and surface properties of MOFs and COFs, resulting in materials with excellent characteristics. SPE is an analytical technique in which a sample solution is added to an SPE column; the sample solution is forced through the stationary phase, and the target compounds are collected for analysis by elution with an organic solvent. Therefore, suitable stationary-phase materials are critical for SPE. Owing to their large specific surface areas and abundant active sites, MOFs and COFs exhibit outstanding adsorption capacity and selectivity in SPE and can effectively enrich target analytes from complex samples. DES-based MOFs and COFs have shown potential use in a wide range of applications, such as in environmental analysis, food testing, and biological sample analysis. Although DES-based MOFs and COFs for SPE are still in the early stages of development, their properties such as efficient enrichment and high selectivity offer good prospects for practical applications. Future research should continue to explore DES-based synthesis methods in depth to prepare other MOFs and COFs with the desired properties and investigate their potential applications in various fields. These efforts are expected to apply these novel materials in commercialized solid-phase extraction methods, bringing new development opportunities in the field of analytical chemistry.

Design and synthesis of photoaffinity-based probes for labeling ß-glucuronidase.

ß-Glucuronidase (GUSB) plays an important role in human physiological and pathological activities. The activity level of GUSB is closely related to human health and diseases. It is imperative to detect the activity of GUSB for related disease diagnosis and treatment. However, exactly evaluating the activity of GUSB in complicated biological system remains a challenge. In this study, we developed photoaffinity-based probes (AfBPs) equipped with photosensitive benzophenone group for labeling active GUSB. Through molecule docking, we predicted the binding model of the AfBPs and GUSB, and the obtained results suggested thermodynamically favorable binding. The AfBPs indicated high efficiency and showed dose-/time-dependent labeling of Escherichia coli (E. coli) GUSB. The application of AfBPs toward GUSB provides a powerful tool to study the activity of target enzymes and contributes to huge potential of enzyme inhibitor discovery and biomedical diagnostics.

Tetraspanin 1 regulates papillary thyroid tumor growth and metastasis through c-Myc-mediated glycolysis.

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer and is characterized by its tendency for lymphatic metastasis, leading to a poor prognosis. Tetraspanin 1 (TSPAN1) is a member of the tetra-transmembrane protein superfamily and has been implicated in tumorigenesis and cancer metastasis in various studies. However, the role of TSPAN1 in PTC tumor development remains unclear. In this study, we aimed to investigate the impact of TSPAN1 on PTC cell behavior. Our results demonstrate that knockdown of TSPAN1 inhibits PTC cell proliferation, migration, and invasion, while overexpression of TSPAN1 has the opposite effect. These findings suggest that TSPAN1 might play a role in the tumorigenesis and invasiveness of PTC. Mechanistically, we found that TSPAN1 activates the ERK pathway by increasing its phosphorylation, subsequently leading to upregulated expression of c-Myc. Additionally, we observed that TSPAN1-ERK-c-Myc axis activation promotes glycolytic activity in PTC cells, as evidenced by the upregulation of glycolytic genes such as LDHA. Taken together, our findings indicate that TSPAN1 acts as an oncogene in PTC by regulating glycolytic metabolism. This discovery highlights the potential of TSPAN1 as a promising therapeutic target for PTC treatment. Further research in this area could provide valuable insights into the development of targeted therapies for PTC patients.

Causal effect of body mass index and physical activity on the risk of joint sports injuries: Mendelian randomization analysis in the European population.

BACKGROUND: Observational studies can suggest potential associations between variables but cannot establish a causal effect on their own. This study explored the causal associations between body mass index (BMI), physical activity (PA), and joint sports injuries. METHODS: We conducted two-sample Mendelian randomization (MR) using publicly accessed genome-wide association studies (GWAS) datasets to investigate the causal effects of BMI and PA on joint sports injury risk. The inverse-variance weighted method was believed to be the primary MR analysis. Subsequently, sensitivity, pleiotropy, and heterogeneity analyses were employed to estimate the reliability of the results of the current research. RESULTS: Genetically predicted increased BMI was causally related to the higher sports injury risk of the ankle-foot (OR 1.23, 95% CI 1.09-1.37, p = 4.20E-04), knee (OR 1.32, 95% CI 1.21-1.43, p = 1.57E-11), and shoulder (OR 1.23, 95% CI 1.08-1.40, p = 1.28E-03). Further, the mentioned effects were validated using another set of GWAS data on BMI. Similar causal linkages were exhibited between increased BMI and the growing risk of sports injuries of the ankle-foot (OR 1.34, 95% CI 1.13-1.60, p = 9.51E-04), knee (OR 1.26, 95% CI 1.09-1.45, p = 1.63E-03), and shoulder (OR 1.35, 95% CI 1.09-1.67, p = 5.66E-03). Additionally, accelerometer-based PA measurement (overall average acceleration) (AccAve) was negatively related to sports injuries of the ankle-foot (OR 0.93, 95% CI 0.87-0.99, p = 0.046) and lumbar spine (OR 0.68, 95% CI 0.51-0.92, p = 0.012). Furthermore, we verified that the effect of AccAve on the risk of injury at the ankle-foot still had statistical significance after adjusting BMI. Results were verified as reliable under all sensitive analyses. CONCLUSIONS: This research determined that a higher BMI could raise the sports injury risk of the ankle-foot, knee, and shoulder, while an overall average acceleration PA could reduce the injury risk of the ankle-foot and lumbar spine. These conclusions contribute to a greater knowledge of the roles of BMI and PA in the mechanism of joint sports injuries and offer several suggestions for patients and clinicians.