A ZTF-7/RPS-2 complex mediates the cold-warm response in C. elegans.

Temperature greatly affects numerous biological processes in all organisms. How multicellular organisms respond to and are impacted by hypothermic stress remains elusive. Here, we found that cold-warm stimuli induced depletion of the RNA exosome complex in the nucleoli but enriched it in the nucleoplasm. To further understand the function and mechanism of cold-warm stimuli, we conducted forward genetic screening and identified ZTF-7, which is required for RNA exosome depletion from nucleoli upon transient cold-warm exposure in C. elegans. ZTF-7 is a putative ortholog of human ZNF277 that may contribute to language impairments. Immunoprecipitation followed by mass spectrometry (IP-MS) found that ZTF-7 interacted with RPS-2, which is a ribosomal protein of the small subunit and participates in pre-rRNA processing. A partial depletion of RPS-2 and other proteins of the small ribosomal subunit blocked the cold-warm stimuli-induced reduction of exosome subunits from the nucleoli. These results established a novel mechanism by which C. elegans responds to environmental cold-warm exposure.

Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development.

Aminoacyl-tRNA synthetases (aaRSs) are essential components for mRNA translation. Two sets of aaRSs are required for cytoplasmic and mitochondrial translation in vertebrates. Interestingly, TARSL2 is a recently evolved duplicated gene of TARS1 (encoding cytoplasmic threonyl-tRNA synthetase) and represents the only duplicated aaRS gene in vertebrates. Although TARSL2 retains the canonical aminoacylation and editing activities in vitro, whether it is a true tRNA synthetase for mRNA translation in vivo is unclear. In this study, we showed that Tars1 is an essential gene since homozygous Tars1 KO mice were lethal. In contrast, when Tarsl2 was deleted in mice and zebrafish, neither the abundance nor the charging levels of tRNAThrs were changed, indicating that cells relied on Tars1 but not on Tarsl2 for mRNA translation. Furthermore, Tarsl2 deletion did not influence the integrity of the multiple tRNA synthetase complex, suggesting that Tarsl2 is a peripheral member of the multiple tRNA synthetase complex. Finally, we observed that Tarsl2-deleted mice exhibited severe developmental retardation, elevated metabolic capacity, and abnormal bone and muscle development after 3 weeks. Collectively, these data suggest that, despite its intrinsic activity, loss of Tarsl2 has little influence on protein synthesis but does affect mouse development.

Comparative efficacy and safety of extended adjuvant endocrine therapy for hormone receptor-positive early breast cancer: a Bayesian network meta-analysis.

PURPOSE: Optimal extended adjuvant endocrine therapy (ET) duration and strategy for hormone receptor-positive (HR +) early breast cancer remain unclear. In this network meta-analysis (NMA), the efficacy and safety of all available extended adjuvant ETs were compared and ranked. METHODS: PubMed, Embase, and Cochrane Library and abstracts presented at ASCO, SABCS, and ESMO were searched on March 5, 2022. Fourteen randomized controlled trials (RCTs) comprising eight extended adjuvant ETs for HR + breast cancer and 38,070 patients were analyzed. Main outcomes were disease-free survival (DFS), overall survival (OS), grade ≥ 3 adverse events (AEs), and contralateral breast cancer (CBC). Direct and indirect comparisons were integrated via Bayesian NMA. Hierarchical cluster analysis was performed to jointly rank efficacy and safety outcomes. RESULTS: Compared with that of 5 year ET, extended 10 year aromatase inhibitor (AI) treatment provided the greatest DFS benefit (HR = 0.45, 95%CrI 0.23-0.83), whereas no strategy differed significantly in terms of the other main outcomes. Extended 10 year AI treatment was the preferred strategy for DFS improvement and CBC prevention (surface under the cumulative ranking curve: 93.51% and 91.29% probability, respectively). All strategies had comparable safeties (grade ≥ 3 AEs). Compared with that of 5 year ET, 10 year extended AI significantly increased arthralgia (OR = 1.65, 95%CrI 1.02-2.93) and osteoporosis (OR = 3.33, 95%CrI 1.19-9.68). CONCLUSION: Extended 10 year AI therapy may be optimal for HR + early breast cancer given its relatively high efficacy and safety.

Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) has been a leading cause of cancer-related mortality worldwide. Early intervention can significantly improve prognosis. DNA methylation could occur in the early stage of tumor. Comprehensive understanding the epigenetic landscape of early-stage LUAD is crucial in understanding tumorigenesis. METHODS: Enzymatic methyl sequencing (EM-seq) was performed on 23 tumors and paired normal tissue to reveal distinct epigenetic landscape, for compared with The Cancer Genome Atlas (TCGA) 450K methylation microarray data. Then, an integrative analysis was performed combined with TCGA LUAD RNA-seq data to identify significant differential methylated and expressed genes. Subsequently, the prognostic risk model was constructed and cellular composition was analyzed. RESULTS: Methylome analysis of EM-seq comparing tumor and normal tissues identified 25 million cytosine-phosphate-guanine (CpG) sites and 30,187 differentially methylated regions (DMR) with a greater number of untraditional types. EM-seq identified a significantly higher number of CpG sites and DMRs compared to the 450K microarray. By integrating the differentially methylated genes (DMGs) with LUAD-related differentially expressed genes (DEGs) from the TCGA database, we constructed prognostic model based on six differentially methylated-expressed genes (MEGs) and verified our prognostic model in GSE13213 and GSE42127 dataset. Finally, cell deconvolution based on the in-house EM-seq methylation profile was used to estimate cellular composition of early-stage LUAD. CONCLUSIONS: This study firstly delves into novel pattern of epigenomic DNA methylation and provides a multidimensional analysis of the role of DNA methylation revealed by EM-seq in early-stage LUAD, providing distinctive insights into its potential epigenetic mechanisms.

Photo-protection and photo-inhibition during light induction in Barbula indica and Conocephalum conicum under different light gradients.

The objectives of this study were to measure the chlorophyll fluorescence (ChlF) parameters of Barbula indica (Hook.) Spreng and Conocephalum conicum (L.) Dumort subjected to various light intensities (LI) as a reflection of their adaptability to their habitats. The electron transport rate (ETR) of all plants under 500 µmol m-2 s-1 photosynthetic photon flux density (PPFD) was significantly higher than other LI treatments, implying that these plants could be grown under a specific and optimal light intensity adapted to 500 PPFD conditions. As LI increased from 50 to 2,000 PPFD, we observed in all plants increased non-photochemical quenching (NPQ) and photo-inhibitory quenching (qI) and decreased photosystem II efficiency (ΦPSII), potential quantum efficiency of PSII (Fv/Fm), actual PSII efficiency (ΔF/Fm'%), and Fv/Fm%. In addition, energy-dependent quenching (qE), the light protection system (qE + qZ + qT), and qI increased as ΦPSII decreased and photo-inhibition% increased under 1000, 1500, and 2000 PPFD conditions, suggesting that these plants had higher photo-protective ability under high LI treatments to maintain higher photosynthetic system performance. B. indica plants remained photochemically active and maintained higher qE under 300, 500, and 1000 PPFD, whereas C. conicum qZ + qT exhibited higher photo-protection under 500, 1000, and 1500 PPFD conditions. These ChlF indices can be used for predicting photosynthetic responses to light induction in different bryophytes and provide a theoretical basis for ecological monitoring.

Tanshinone IIA modulates cancer cell morphology and movement via Rho GTPases-mediated actin cytoskeleton remodeling.

Actin filaments form unique structures with robust actin bundles and cytoskeletal networks affixed to the extracellular matrix and interact with neighboring cells, which are crucial structures for cancer cells to acquire a motile phenotype. This study aims to investigate a novel antitumor mechanism by which Tanshinone IIA (Tan IIA) modulates the morphology and migration of liver cancer cells via actin cytoskeleton regulation. 97H and Huh7 exhibited numerous tentacle-like protrusions that interacted with neighboring cells. Following treatment with Tan IIA, 97H and Huh7 showed a complete absence of cytoplasmic protrusion and adherens junctions, thereby effectively impeding their migration capability. The fluorescence staining of F-actin and microtubules indicated that these tentacle-like protrusions and cell-cell networks were actin-based structures that led to morphological changes after Tan IIA treatment by retracting and reorganizing beneath the membrane. Tan IIA can reverse the actin depolymerization and cell morphology alterations induced by latrunculin A. Tan IIA down-regulated actin and Rho GTPases expression significantly, as opposed to inducing Rho signaling activation. Preventing the activity of proteasomes and lysosomes had no discernible impact on the modifications in cellular structure and protein expression induced by Tan IIA. However, as demonstrated by the puromycin labeling technique, the newly synthesized proteins were significantly inhibited by Tan IIA. In conclusion, Tan IIA can induce dramatic actin cytoskeleton remodeling by inhibiting the protein synthesis of actin and Rho GTPases, resulting in the suppression of tumor growth and migration. Targeting the actin cytoskeleton of Tan IIA is a promising strategy for HCC treatment.

Chirality-Driven Orbital Angular Momentum and Circular Dichroism in CoSi.

Chiral crystals and molecules were recently predicted to form an intriguing platform for unconventional orbital physics. Here, we report the observation of chirality-driven orbital textures in the bulk electronic structure of CoSi, a prototype member of the cubic B20 family of chiral crystals. Using circular dichroism in soft x-ray angle-resolved photoemission, we demonstrate the formation of a bulk orbital-angular-momentum texture and monopolelike orbital-momentum locking that depends on crystal handedness. We introduce the intrinsic chiral circular dichroism, icCD, as a differential photoemission observable and a natural probe of chiral electron states. Our findings render chiral crystals promising for spin-orbitronics applications.

Light-Assisted Fabrication of Hierarchical Azopolymer Structures Using the Breath Figure Method and AAO Templates.

Hierarchical polymer structures have garnered widespread application across various fields owing to their distinct surface properties and expansive surface areas. Conventional hierarchical polymer structures, however, often lack postfabrication scalability and spatial selectivity. In this study, we propose a novel strategy to prepare light-assisted hierarchical polymer structures using azopolymers (PAzo), the breath figure method, and anodic aluminum oxide (AAO) templates. Initially, the breath figure PAzo films are prepared by dripping a PAzo chloroform solution onto glass substrates in a high-humidity environment. The AAO templates are then placed on the breath figure PAzo film. Upon ultraviolet (UV) light exposure, the azobenzene groups in the azopolymers undergo trans-cis photoisomerization. This process causes the glass transition temperature (Tg) of the PAzo to become lower than room temperature, allowing the azopolymer to enter the nanopores of the AAO templates. The hierarchical azopolymer structures are then formed by using a sodium hydroxide solution to remove the templates. Furthermore, exploring the effects of PAzo concentration and UV light exposure duration on the film morphology reveals optimized conditions for hierarchical structure formation. Additionally, the water contact angles of these polymer structures are measured. The hierarchical PAzo structures exhibit higher hydrophobicity compared with the flat PAzo films and the PAzo breath figure films. Finally, patterned breath figure films can be prepared using designed photomasks, demonstrating the method's capability for spatial selectivity.

Hollow Hafnium Oxide (HfO2) Fibers: Using an Effective Combination of Sol-Gel, Electrospinning, and Thermal Degradation Pathway.

In recent years, hafnium oxide (HfO2) has gained increasing interest because of its high dielectric constant, excellent thermal stability, and high band gap. Although HfO2 bulk and film materials have been prepared and well-studied, HfO2 fibers, especially hollow fibers, have been less investigated. In this study, we present a facile preparation method for HfO2 hollow fibers through a unique integration of the sol-gel process and electrospinning technique. Initially, polystyrene (PS) fibers are fabricated by using electrospinning, followed by dipping in a HfO2 precursor solution, resulting in HfO2-coated PS fibers. Subsequent thermal treatment at 800 °C ensures the selective pyrolysis of the PS fibers and complete condensation of the HfO2 precursors, forming HfO2 hollow fibers. Scanning electron microscopy (SEM) characterizations reveal HfO2 hollow fibers with rough surfaces and diminished diameters, a transformation attributed to the removal of the PS fibers and the condensation of the HfO2 precursors. Our study also delves into the influence of precursor solution molar ratios, showcasing the ability to achieve smaller HfO2 fiber diameters with reduced precursor quantities. Validation of the material composition is achieved through thermogravimetric analysis (TGA) and energy-dispersive spectroscopy (EDS) mapping. Additionally, X-ray diffraction (XRD) analysis provides insights into the crystallinity of the HfO2 hollow fibers, highlighting a higher crystallinity in fibers annealed at 800 °C compared with those treated at 400 °C. Notably, the HfO2 hollow fibers demonstrate a water contact angle (WCA) of 38.70 ± 5.24°, underscoring the transformation from hydrophobic to hydrophilic properties after the removal of the PS fibers. Looking forward, this work paves the way for extensive research on the surface properties and potential applications of HfO2 hollow fibers in areas such as filtration, energy storage, and memory devices.

Unravelling cancer subtype-specific driver genes in single-cell transcriptomics data with CSDGI.

Cancer is known as a heterogeneous disease. Cancer driver genes (CDGs) need to be inferred for understanding tumor heterogeneity in cancer. However, the existing computational methods have identified many common CDGs. A key challenge exploring cancer progression is to infer cancer subtype-specific driver genes (CSDGs), which provides guidane for the diagnosis, treatment and prognosis of cancer. The significant advancements in single-cell RNA-sequencing (scRNA-seq) technologies have opened up new possibilities for studying human cancers at the individual cell level. In this study, we develop a novel unsupervised method, CSDGI (Cancer Subtype-specific Driver Gene Inference), which applies Encoder-Decoder-Framework consisting of low-rank residual neural networks to inferring driver genes corresponding to potential cancer subtypes at the single-cell level. To infer CSDGs, we apply CSDGI to the tumor single-cell transcriptomics data. To filter the redundant genes before driver gene inference, we perform the differential expression genes (DEGs). The experimental results demonstrate CSDGI is effective to infer driver genes that are cancer subtype-specific. Functional and disease enrichment analysis shows these inferred CSDGs indicate the key biological processes and disease pathways. CSDGI is the first method to explore cancer driver genes at the cancer subtype level. We believe that it can be a useful method to understand the mechanisms of cell transformation driving tumours.

Spontaneous development of an autoimmune hepatitis - primary biliary cholangitis overlap syndrome in dnTGFßRII Aire-/- mice.

Autoimmune regulator (Aire) and TGF-ß signaling play important roles in central tolerance and peripheral tolerance, respectively, by eliminating or suppressing the activity of autoreactive T cells. We previously demonstrated that dnTGFßRII mice develop a defect in peripheral tolerance and a primary biliary cholangitis (PBC)-like disease. We hypothesized that by introducing the Aire gene to this model, we would observe a more severe PBC phenotype. Interestingly, however, we demonstrated that, while dnTGFßRII Aire-/- mice do manifest key histological and serological features of autoimmune cholangitis, they also develop mild to moderate interface hepatitis and show high levels of alanine transaminase (ALT) and antinuclear antibodies (ANA), characteristics of autoimmune hepatitis (AIH). To further understand this unique phenotype, we performed RNA sequencing (RNA-seq) and flow cytometry to explore the functional pathways and immune cell pathways in the liver of dnTGFßRII Aire-/- mice. Our data revealed enrichments of programmed cell death pathways and predominant CD8+ T cell infiltrates. Depleting CD8+ T cells using an anti-CD8α antibody significantly alleviated hepatic inflammation and prolonged the life span of these mice. Finally, RNA-seq data indicated the clonal expansion of hepatic CD8+ T cells. In conclusion, these mice developed an autoreactive CD8+ T-cell-mediated autoimmune cholangitis with concurrent hepatitis that exhibited key histological and serological features of the AIH-PBC overlap syndrome, representing a novel model for the study of tolerance and autoimmune liver disease. © 2023 The Pathological Society of Great Britain and Ireland.

Thalassospira aquimaris sp. nov. and Winogradskyella marincola sp. nov. two marine bacteria isolated from an agar-degrading co-culture.

Two novel Gram-stain-negative, aerobic, and non-motile strains, designated FZY0004T and YYF002T, were isolated from an agar-degrading co-culture, which was obtained from seawater of the intertidal zone of Yancheng City, the Yellow Sea of China. Strain FZY0004T optimally grew at 28 °C, pH 7.0, and 2-6% NaCl, while strain YYF002T optimally grew at 28 °C, pH 7.5, and 2-4% NaCl. Strain FZY0004T possessed Q-9 as the major respiratory quinone, and its major fatty acids (> 10%) were summed feature 8 (C18:1 ω7c), C16:0, and summed feature 3 (C16:1 ω7c/C16:1 ω6c). The polar lipids identified in strain FZY0004T were phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and several unidentified phospholipids (PL) and lipids (L). On the other hand, strain YYF002T had MK-6 as the predominant respiratory quinone and its major fatty acids consisted of iso-C15:0, iso-C15:1 G, and iso-C15:0 3-OH. The polar lipids identified in strain YYF002T were aminolipid (AL), PE, and several unidentified lipids. Strain FZY0004T shared 99.5% 16S rRNA gene sequence similarity and 90.1% average nucleotide identity (ANI) with T. povalilytica Zumi 95T, and strain YYF002T shared 99.2% 16S rRNA gene sequence similarity and 88.2% ANI with W. poriferorum JCM 12885T. The genomic DNA G + C contents of strains FZY0004T and YYF002T were 54.5% and 33.5%, respectively. The phylogenetic, phenotypic, and physiological characteristics permitted the distinction of the two strains from their neighbors, and we thus propose the names Thalassospira aquimaris sp. nov. (type strain FZY0004T = JCM 35895T = MCCC 1K08380T) and Winogradskyella marincola sp. nov. (type strain YYF002T = JCM 35950T = MCCC 1K08382T).

Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury.

Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to the myocardium. This phenomenon is known as myocardial ischemia-reperfusion injury (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) is known to play a significant role in regulating the immune response and inflammation, and has been studied for its potential impact on the improvement of heart function after myocardial injury. However, the delivery of miR-146a to the heart in a specific and efficient manner remains a challenge as extracellular RNAs are unstable and rapidly degraded. Milk exosomes (MEs) have been proposed as ideal delivery platform for miRNA-based therapy as they can protect miRNAs from RNase degradation. In this study, the effects of miR-146a containing MEs (MEs-miR-146a) on improvement of cardiac function were examined in a rat model of MIRI. To enhance the targeting delivery of MEs-miR-146a to the site of myocardial injury, the ischemic myocardium-targeted peptide IMTP was modified onto the surfaces, and whether the modified MEs-miR-146a could exert a better therapeutic role was examined by echocardiography, myocardial injury indicators and the levels of inflammatory factors. Furthermore, the expressions of miR-146a mediated NF-κB signaling pathway-related proteins were detected by western blotting and qRT-PCR to further elucidate its mechanisms. MiR-146 mimics were successfully loaded into the MEs by electroporation at a square wave 1000 V voltage and 0.1 ms pulse duration. MEs-miR-146a can be up-taken by cardiomyocytes and protected the cells from oxygen glucose deprivation/reperfusion induced damage in vitro. Oral administration of MEs-miR-146a decreased myocardial tissue apoptosis and the expression of inflammatory factors and improved cardiac function after MIRI. The miR-146a level in myocardium tissues was significantly increased after the administration IMTP modified MEs-miR-146a, which was higher than that of the MEs-miR-146a group. In addition, intravenous injection of IMTP modified MEs-miR-146a enhanced the targeting to heart, improved cardiac function, reduced myocardial tissue apoptosis and suppressed inflammation after MIRI, which was more effective than the MEs-miR-146a treatment. Moreover, IMTP modified MEs-miR-146a reduced the protein levels of IRAK1, TRAF6 and p-p65. Therefore, IMTP modified MEs-miR-146a exerted their anti-inflammatory effect by inhibiting the IRAK1/TRAF6/NF-κB signaling pathway. Taken together, our findings suggested miR-146a containing MEs may be a promising strategy for the treatment of MIRI with better outcome after modification with ischemic myocardium-targeted peptide, which was expected to be applied in clinical practice in future.

Gene variants and clinical characteristics of children with sitosterolemia.

OBJECTIVE: To enhance the detection, management and monitoring of Chinese children afflicted with sitosterolemia by examining the physical characteristics and genetic makeup of pediatric patients. METHODS: In this group, 26 children were diagnosed with sitosterolemia, 24 of whom underwent genetic analysis. Patient family medical history, physical symptoms, tests for liver function, lipid levels, standard blood tests, phytosterol levels, cardiac/carotid artery ultrasounds, fundus examinations, and treatment were collected. RESULTS: The majority (19, 73.1%) of the 26 patients exhibited xanthomas as the most prevalent manifestation. The second most common symptoms were joint pain (7, 26.9%) and stunted growth (4, 15.4%). Among the 24 (92.3%) patients whose genetics were analyzed, 16 (66.7%) harbored ABCG5 variants (type 2 sitosterolemia), and nearly one-third (8, 33.3%) harbored ABCG8 variants (type 1 sitosterolemia). Additionally, the most common pathogenic ABCG5 variant was c.1166G > A (p.Arg389His), which was found in 10 patients (66.7%). Further analysis did not indicate any significant differences in pathological traits among those carrying ABCG5 and ABCG8 variations (P > 0.05). Interestingly, there was a greater abundance of nonsense variations in ABCG5 than in ABCG8 (P = 0.09), and a greater frequency of splicing variations in ABCG8 than ABCG5 (P = 0.01). Following a change in diet or a combination of ezetimibe, the levels of cholesterol and low-density lipoprotein were markedly decreased compared to the levels reported before treatment. CONCLUSION: Sitosterolemia should be considered for individuals presenting with xanthomas and increased cholesterol levels. Phytosterol testing and genetic analysis are important for early detection. Managing one's diet and taking ezetimibe can well control blood lipids.

Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8.

METTL8 has recently been identified as the methyltransferase catalyzing 3-methylcytidine biogenesis at position 32 (m3C32) of mitochondrial tRNAs. METTL8 also potentially participates in mRNA methylation and R-loop biogenesis. How METTL8 plays multiple roles in distinct cell compartments and catalyzes mitochondrial tRNA m3C formation remain unclear. Here, we discovered that alternative mRNA splicing generated several isoforms of METTL8. One isoform (METTL8-Iso1) was targeted to mitochondria via an N-terminal pre-sequence, while another one (METTL8-Iso4) mainly localized to the nucleolus. METTL8-Iso1-mediated m3C32 modification of human mitochondrial tRNAThr (hmtRNAThr) was not reliant on t6A modification at A37 (t6A37), while that of hmtRNASer(UCN) critically depended on i6A modification at A37 (i6A37). We clarified the hmtRNAThr substrate recognition mechanism, which was obviously different from that of hmtRNASer(UCN), in terms of requiring a G35 determinant. Moreover, SARS2 (mitochondrial seryl-tRNA synthetase) interacted with METTL8-Iso1 in an RNA-independent manner and modestly accelerated m3C modification activity. We further elucidated how nonsubstrate tRNAs in human mitochondria were efficiently discriminated by METTL8-Iso1. In summary, our results established the expression pattern of METTL8, clarified the molecular basis for m3C32 modification by METTL8-Iso1 and provided the rationale for the involvement of METTL8 in tRNA modification, mRNA methylation or R-loop biogenesis.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

Contribution of the Musculoskeletal Ultrasound in the Diagnosis of Seronegative Rheumatoid Arthritis.

OBJECTIVE: This is a study to investigate the value of musculoskeletal ultrasound for the early diagnosis of seronegative rheumatoid arthritis (SNRA); and to study the relationship between anti-cyclic citrullinated peptide antibody (anti-CCP) and the occurrence of bone erosion in rheumatoid arthritis (RA) detected by ultrasound. METHODS: A total of 101 patients with RA or osteoarthritis (OA) admitted to the First Affiliated Hospital of Anhui Medical University from July 2022 to December 2023 were selected and divided into the SNRA group, the SPRA group, and the OA group. The patients' metacarpophalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, and wrist joints of both hands were ultrasonically examined separately, and the extensor tendon, flexor tendon, synovium, joint surface, joint cavity, and bone surface were observed. RESULTS: The differences in the detection of joint effusion, bone erosion, and joint space narrowing were not statistically significant between SNRA group and OA group (P > .05), the differences in the detection of synovitis and tenosynovitis were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and OA group were significantly different (P < .05). The differences in synovitis, tenosynovitis, joint effusion, and joint space narrowing were not statistically significant between SNRA and SPRA groups (P > .05), and the differences in bone erosion were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and SPRA group were significantly different (P < .05). Logistic regression analysis showed that anti-CCP antibody was an influential factor for bone erosion in RA patients (P < .05). The ROC curve was plotted, and the optimal cut-off value of anti-CCP antibody was 356.5 U/mL, at which time the AUC was 0.716, the sensitivity of diagnosing bone erosion was 0.714, the specificity was 0.694, and the Yoden index was 0.408. CONCLUSION: In summary, ultrasound is helpful for the early diagnosis of SNRA by evaluating the condition of joints, synovium, and tendon sheath, and when anti-CCP antibodies are positive, ultrasound is more likely to detect bone erosion. Ultrasound examination combined with anti-CCP antibody can further observe the joint lesions.

SCARA5 as a downstream factor of PCAT29, inhibits proliferation, migration, and invasion of bladder cancer.

Scavenger receptor class A, member 5 (SCARA5) has been identified a novel tumor suppressor in several cancers. However, the functional and underlying mechanism of SCARA5 in bladder cancer (BC) need investigation. Here, we found SCARA5 expression was downregulated in both BC tissues and cell lines. Low SCARA5 in BC tissues was associated with a shorter overall survival. Moreover, SCARA5 overexpression reduced BC cell viability, colony formation, invasion, and migration. Further investigation demonstrated that the expression of SCARA5 was negatively regulated by miR-141. Furthermore, the long non-coding RNA prostate cancer associated transcript 29 (PCAT29) inhibited the proliferation, invasion, and migration of BC cells by sponging miR-141. Luciferase activity assays revealed that PCAT29 targeted miR-141 and miR-141 targeted SCARA5. In conclusion, SCARA5, as a downstream factor of the PCAT29/miR-141 axis, inhibited the proliferation, migration, and invasion of BC cells. These findings provide novel insights into the detailed molecular mechanisms of BC development.

A simple, organized web-based system improved the transfer efficiency and patient outcomes for endovascular thrombectomy in regional stroke network.

BACKGROUND: Endovascular thrombectomy (EVT) is a time-sensitive treatment for acute ischemic stroke with large vessel occlusion. To optimize transfer efficiency, a web-based platform was introduced in the Tainan Stroke Network (TSN). We assessed its application and effectiveness in regional stroke care. METHOD: This new web-based platform containing a questionnaire-style interface was introduced on October 1, 2021. To assess the transfer efficiency and patient outcomes, acute stroke patients transferred from PSCs to CSC for EVT from April 01, 2020, to December 30, 2022, were enrolled. The patients were classified into the traditional transferal pathway (TTP) group and the new transferal pathway (NTP) group depending on mode of transfer. Patient characteristics, time segments after stroke onset and outcome were compared between groups. RESULT: A total of 104 patients were enrolled, with 77 in the TTP group and 27 in the NTP group. Compared to the TTP group, the NTP group had a significantly shorter onset-to-CSC door time (TTP vs. NTP: 267 vs. 198 min; p = 0.041) and a higher EVT rate (TTP vs. NTP: 18.2% vs. 48.1%, p = 0.002). Among EVT patients, those in the NTP group had a significantly shorter CSC door-to-puncture time (TTP vs. NTP: 131.5 vs. 110 min; p = 0.029). The NTP group had a higher rate of good functional outcomes at 3 months (TTP vs. NTP: 21% vs. 61.5%; p = 0.034). CONCLUSION: This new web-based EVT transfer system provides notable improvements in clinical outcomes, transfer efficiency, and EVT execution for potential EVT candidates without markedly changing the regional stroke care paradigm.

Application of magnetic resonance imaging radiomics in endometrial cancer: a systematic review and meta-analysis.

PURPOSE: We aimed to systematically assess the methodological quality and clinical potential application of published magnetic resonance imaging (MRI)-based radiomics studies about endometrial cancer (EC). METHODS: Studies of EC radiomics analyses published between 1 January 2000 and 19 March 2023 were extracted, and their methodological quality was evaluated using the radiomics quality score (RQS) and Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Pairwise correlation analyses and separate meta-analyses of studies exploring differential diagnoses and risk prediction were also performed. RESULTS: Forty-five studies involving 3 aims were included. The mean RQS was 13.77 (range: 9-22.5); publication bias was observed in the areas of 'index test' and 'flow and timing'. A high RQS was significantly associated with therapy selection-aimed studies, low QUADAS-2 risk, recent publication year, and high-performance metrics. Raw data from 6 differential diagnosis and 34 risk prediction models were subjected to meta-analysis, revealing diagnostic odds ratios of 23.81 (95% confidence interval [CI] 8.48-66.83) and 18.23 (95% CI 13.68-24.29), respectively. CONCLUSION: The methodological quality of radiomics studies involving patients with EC is unsatisfactory. However, MRI-based radiomics analyses showed promising utility in terms of differential diagnosis and risk prediction.