Ubiquitination of hnRNPA1 by TRAF6 links chronic innate immune signaling with myelodysplasia.

Toll-like receptor (TLR) activation contributes to premalignant hematologic conditions, such as myelodysplastic syndromes (MDS). TRAF6, a TLR effector with ubiquitin (Ub) ligase activity, is overexpressed in MDS hematopoietic stem/progenitor cells (HSPCs). We found that TRAF6 overexpression in mouse HSPC results in impaired hematopoiesis and bone marrow failure. Using a global Ub screen, we identified hnRNPA1, an RNA-binding protein and auxiliary splicing factor, as a substrate of TRAF6. TRAF6 ubiquitination of hnRNPA1 regulated alternative splicing of Arhgap1, which resulted in activation of the GTP-binding Rho family protein Cdc42 and accounted for hematopoietic defects in TRAF6-expressing HSPCs. These results implicate Ub signaling in coordinating RNA processing by TLR pathways during an immune response and in premalignant hematologic diseases, such as MDS.

DRMref: comprehensive reference map of drug resistance mechanisms in human cancer.

Drug resistance poses a significant challenge in cancer treatment. Despite the initial effectiveness of therapies such as chemotherapy, targeted therapy and immunotherapy, many patients eventually develop resistance. To gain deep insights into the underlying mechanisms, single-cell profiling has been performed to interrogate drug resistance at cell level. Herein, we have built the DRMref database (https://ccsm.uth.edu/DRMref/) to provide comprehensive characterization of drug resistance using single-cell data from drug treatment settings. The current version of DRMref includes 42 single-cell datasets from 30 studies, covering 382 samples, 13 major cancer types, 26 cancer subtypes, 35 treatment regimens and 42 drugs. All datasets in DRMref are browsable and searchable, with detailed annotations provided. Meanwhile, DRMref includes analyses of cellular composition, intratumoral heterogeneity, epithelial-mesenchymal transition, cell-cell interaction and differentially expressed genes in resistant cells. Notably, DRMref investigates the drug resistance mechanisms (e.g. Aberration of Drug's Therapeutic Target, Drug Inactivation by Structure Modification, etc.) in resistant cells. Additional enrichment analysis of hallmark/KEGG (Kyoto Encyclopedia of Genes and Genomes)/GO (Gene Ontology) pathways, as well as the identification of microRNA, motif and transcription factors involved in resistant cells, is provided in DRMref for user's exploration. Overall, DRMref serves as a unique single-cell-based resource for studying drug resistance, drug combination therapy and discovering novel drug targets.

Revolutionizing the structural design and determination of covalent-organic frameworks: principles, methods, and techniques.

Covalent organic frameworks (COFs) represent an important class of crystalline porous materials with designable structures and functions. The interconnected organic monomers, featuring pre-designed symmetries and connectivities, dictate the structures of COFs, endowing them with high thermal and chemical stability, large surface area, and tunable micropores. Furthermore, by utilizing pre-functionalization or post-synthetic functionalization strategies, COFs can acquire multifunctionalities, leading to their versatile applications in gas separation/storage, catalysis, and optoelectronic devices. Our review provides a comprehensive account of the latest advancements in the principles, methods, and techniques for structural design and determination of COFs. These cutting-edge approaches enable the rational design and precise elucidation of COF structures, addressing fundamental physicochemical challenges associated with host-guest interactions, topological transformations, network interpenetration, and defect-mediated catalysis.

Unraveling a Stable 16-Ring Aluminophosphate DNL-11 through Three-Dimensional Electron Diffraction for Atmospheric Water Harvesting.

Sorption-based atmospheric water harvesting (AWH) is a promising solution for addressing water scarcity. Developing cost-effective and stable water adsorbents with high water uptake capacity and a low-temperature regeneration requirement is a crucially important procedure. In this Communication, we present a novel and stable aluminophosphate (AlPO) molecular sieve (MS) named DNL-11 with 16-ring channels synthesized by using an affordable and commercialized organic structure directing agent (OSDA), whose crystallographic structure is elucidated by three-dimensional electron diffraction (3D ED). DNL-11 exhibits a significant water uptake capacity (189 mg/g) at a very low vapor pressure (5% relative humidity at 30 °C). In addition, most of the adsorbed water can be effortlessly removed by purging N2 at 25 °C under ambient pressure conditions. This may expand the possibility of AWH under extreme drought conditions.

Kinematic difference and asymmetries during level walking in adolescent patients with different types of mild scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS), three-dimensional spine deformation, affects body motion. Previous research had indicated pathological gait patterns of AIS. However, the impact of the curve number on the walking mechanism has not been established. Therefore, this study aimed to compare the gait symmetry and kinematics in AIS patients with different curve numbers to healthy control. RESULTS: In the spinal region, double curves AIS patients demonstrated a smaller sagittal symmetry angle (SA) and larger sagittal convex ROM of the trunk and lower spine than the control group. In the lower extremities, the single curve patients showed a significantly reduced SA of the knee joint in the frontal plane, while the double curves patients showed a significantly reduced SA of the hip in the transverse plane. CONCLUSION: The curve number indeed affects gait symmetry and kinematics in AIS patients. The double curves patients seemed to adopt a more "careful walking" strategy to compensate for the effect of spinal deformation on sensory integration deficits. This compensation mainly occurred in the sagittal plane. Compared to double curves patients, single curve patients unitized a similar walking strategy with healthy subjects.

Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Clinic Analysis and Effective Improvement Tips for Poor Eyebrow Transplantation.

BACKGROUND: Follicular unit hair transplantation has greatly elevated the results of eyebrow restoration. However, unnatural and unbeautiful-looking results are still often seen after the surgery. OBJECTIVES: This study focused on poor eyebrow transplantation, discussed its possible reasons, and offered refined proposals. METHODS: A retrospective analysis was performed on 100 patients who were dissatisfied with the results of eyebrow grafting and came to our department from 2011 to 2021. Demographic characteristics, primary disease, and clinical data were objectively summarized and analyzed for these patients. RESULTS: The patients' medical charts and photographs were analyzed and summarized into the following outcomes: Thirty-six patients (36%) had sparse eyebrows. Forty-one patients (41%) had eyebrows with inhomogeneous density and disordered growth direction. Eleven patients (11%) did not have single-hair grafting. Seven reconstructed eyebrows (7%) had a poor connection with the remaining eyebrows. Five new eyebrows (5%) had inconsistent hair characteristics with the original eyebrows. Lower hair survival rates, insufficient understanding of naturally beautiful eyebrows, and inadequate communication with patients were the main reasons for poor outcomes. CONCLUSIONS: Good reconstructed eyebrows should have a high hair survival rate, and hair growth direction and characteristics should also be consistent with the natural eyebrow to achieve ideal surgical effects. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Research on leaching behavior of uranium from a uranium tailing and its adsorption behavior in geotechnical media.

The release of uranium from uranium tailings into the aqueous environment is a complex process controlled by a series of interacting geochemical reactions. In this paper, uranium tailings from a uranium tailings pond in southern China were collected at different depths by means of borehole sampling and mixed to analyze the fugacity state of U. Static leaching experiments of U at different pH, oxidant concentration and solid-to-liquid ratios and dynamic leaching experiments of U at different pH were carried out, and the adsorption and desorption behaviour of U in five representative stratigraphic media were investigated. The results show that U is mainly present in the residue state in uranium tailings, that U release is strong in the lower pH range, that the leached U is mainly in the form of U(VI), mainly from the water-soluble, Fe/Mn oxides and exchangeable fraction of uranium tailings, and that the reduction in U leaching at higher pH is mainly due to the combined effect of precipitation formation and larger particle size of platelets in uranium tailings. Experiments with different oxidant concentrations and solid-liquid ratios showed that the oxygen-enriched state and low solid-liquid ratios were favorable for the leaching of U from uranium tailings. Adsorption and desorption experiments show that U is weakly adsorbed in representative strata, reversibly adsorbed, and that U is highly migratory in groundwater. The present research results have important guiding significance for the management of existing uranium tailings ponds and the control of U migration in groundwater, which is conducive to ensuring the long-term safety, stability and sustainability of uranium mining sites.

Drinking brick tea containing high fluoride increases the prevalence of osteoarthritis in Tibetan, China.

The prevalence of osteoarthritis (OA) in Tibetans is higher than that in Han, while Tibetans have a habit of drinking brick tea with high fluoride. A cross-sectional study was conducted to explore the association between fluoride exposure in drinking brick tea and OA. All subjects were divided into four groups by the quartiles (Q) of tea fluoride (TF) and urine fluoride (UF). ROC was plotted and OR were obtained using logistic regression model. The prevalence of OA in the Q3 and Q4 group of TF were 2.2 and 2.7 times higher than in the Q1 group, and the prevalence of OA in the Q2, Q3 and Q4 group of UF were 3.2, 3.5, and 4.1 times higher than in the Q1 group. ROC analysis showed the cutoff values were 4.523 mg/day (TF) and 1.666 mg/L (UF). In conclusion, excessive fluoride in drinking brick tea could be a risk factor for developing OA.

[Anisotropy and viscoelasticity of different corneal regions in rabbit corneal ectasia model].

The mechanical properties of the cornea in corneal ectasia disease undergo a significant reduction, yet the alterations in mechanical properties within distinct corneal regions remain unclear. In this study, we established a rabbit corneal ectasia model by employing collagenase II to degrade the corneal matrix within a central diameter of 6 mm. Optical coherence tomography was employed for the in vivo assessment of corneal morphology (corneal thickness and corneal curvature) one month after operation. Anisotropy and viscoelastic characteristics of corneal tissue were evaluated through biaxial and uniaxial testing, respectively. The results demonstrated a marked decrease in central corneal thickness, with no significant changes observed in corneal curvature. Under different strains, the elastic modulus of the cornea exhibited no significant differences in the up-down and naso-temporal directions between the control and model groups. However, the cornea in the model group displayed a significantly lower elastic modulus compared to the control group. Specifically, the elastic modulus of the central region cornea in the model group was significantly lower than that of the entire cornea within the same group. Moreover, in comparison to the control group, the cornea in the model group exhibited a significant increase in both creep rate and overall deformation rate. The instantaneous modulus and equilibrium modulus were significantly reduced in the model cornea. No significant differences were observed between the entire cornea and the central cornea concerning these parameters. The results indicate that corneal anisotropy remains unchanged in collagenase-induced ectatic cornea. However, a significant reduction in viscoelastic properties is noticed. This study provides valuable insights for investigating changes in corneal mechanical properties within different regions of ectatic corneal disease.

Isolable T-Shaped Planar Silyl Anion.

Silyl anions have garnered significant attention due to their synthetic abilities. However, previously reported silyl anions have been limited to either trigonal-pyramidal or trigonal-planar geometries, which confine them primarily as nucleophiles in substitution reactions. Herein, we report the isolation of the unprecedented T-shaped planar silyl anion salt 2 by employment of a geometrically constrained triamido pincer ligand. Theoretical calculations disclosed that the silicon centre in 2 possesses both a lone pair of electrons and an empty 3pz orbital. In addition to nucleophilic substitution reactions with Ph3PAuCl and W(CO)6, 2 readily undergoes oxidative additions with CO2 and 2,6-dimethylphenylisonitrile at room temperature. Furthermore, under mild conditions, compound 2 cleaves Csp2-H, Csp2-H, and H-H bonds in 1,2,4,5-tetrafluorobenzene, an intramolecular iPr group, and dihydrogen, representing the first examples of C-H and H-H activations mediated by a silyl anion, respectively. This work unveils new reactivity of silyl anions owing to the non-classical geometry and electronic structure.

Fluoride- and Seed-Free Synthesis of Pure-Silica Zeolite Adsorbent and Matrix Using OSDA-Mismatch Approach.

The pure-silica zeolite plays a crucially important role in the gas separation of alkane/alkene, the low-k dielectric material, and the robust matrix for confining metal species during catalysis. However, the environmentally friendly synthesis of pure-silica zeolites is still challenging since (1) the toxic fluoride or dealuminum seeds are inevitably utilized through the hydrothermal synthesis and (2) it will also take a longer crystallization time. Herein, we present an efficient method called the OSDA-mismatch approach for the fluoride- and seed-free synthesis of pure-silica zeolites using Si-SOD (enriched 4-rings) as the sole silica source. This approach allows for the rapid and green synthesis of 15 pure-silica zeolites (CHA, *BEA, EUO, SFF, STF, -SVR, *-SVY, DOH, MTN, NON, *MRE, MEL, MFI, MTW, and *STO). Furthermore, distinct crystallization mechanisms of two significant pure-silica CHA- and *BEA-type zeolites (denoted as Si-CHA and Si-BEA) are investigated in detail by advanced characterization techniques such as FIB, 3D ED, 4D-STEM, HRTEM, Raman, and 29Si MAS NMR. More importantly, Si-CHA displays promising propane/propylene separation performance even better than the one synthesized in the presence of toxic HF. In addition, the incorporation of Zn species within Si-BEA fabricated by this approach also renders superior performance on propane dehydrogenation.

Selective Oxidation of 5-Hydroxymethyl Furfural Coupled with H2 Production over Surface Sulfur Vacancy-Rich Zn3In2S6/Bi2MoO6 Heterojunction Photocatalyst.

The construction of heterojunctions and surface defects is a promising strategy for enhancing photocatalytic activity. A surface sulfur vacancy (VS)-rich Zn3In2S6/Bi2MoO6 heterojunction photocatalyst (ZIS-VS/BMO) was herein developed for the selective oxidation of biomass-derived 5-hydroxymethyl furfural (HMF) to value-added 2,5-diformylfuran (DFF) coupled with H2 production. The ZIS-VS/BMO heterojunction consisted of Bi2MoO6 (BMO) with preferentially exposed high-index (131) facets and VS-rich two-dimensional (2D) Zn3In2S6 (ZIS-VS) nanosheets with preferentially exposed high-index (102) facets. The directional transfer of light-driven electrons from BMO to ZIS-VS occurs in the heterojunction interface, as confirmed by an in situ irradiated XPS (ISI-XPS) measurement, which facilitates the electron-hole separation. The benefits of VS in activating HMF, suppressing overoxidation of DFF, and accelerating electron transport were disclosed by molecular simulation. ZIS-VS/BMO displays outstanding performance with a DFF yield of 74.1% and a DFF selectivity of 90%, as well as a rapid rate of H2 evolution. This research would help design highly efficient photocatalysts and develop a new technology for biomass resource utilization.

Association between arsenic (+3 oxidation state) methyltransferase gene polymorphisms and arsenic methylation capacity in rural residents of northern China: a cross-sectional study.

Arsenic is a toxic metal-like element. The toxic reaction of the body to arsenic is related to the ability of arsenic methylation metabolism. As the rate-limiting enzyme of arsenic methylation metabolism, the genetic single nucleotide polymorphisms (SNPs) of arsenic (+ 3 oxidation state) methyltransferase (AS3MT) gene are related to capacity of arsenic methylation. In this paper, we investigated the association of five SNPs (rs7085104, rs3740390, 3740393, rs10748835, and rs1046778) in AS3MT with arsenic methylation metabolizing using the data and samples from a cross-sectional case-control study of arsenic and Type 2 diabetes mellitus conducted in Shanxi, China. A total of 340 individuals were included in the study. Urinary total arsenic (tAs, µg/L) was detected by liquid chromatography-atomic fluorescence spectrometry (LC-AFS). According to "safety guidance value of urinary arsenic for population" as specified in WS/T665-2019 (China), participants were divided into the control group (tAs ≤ 32 µg/L, n = 172) and arsenic-exposed group (tAs > 32 µg/L, n = 168). iAs%, MMA%, and DMA% are as the indicator of arsenic methylation capacity. The genotypes of AS3MT SNPs were examined by Multiple PCR combined sequencing. Linear regression analysis showed that AG + GG genotype in rs7085104 was associated with decreased iAs% and increased DMA%. Moreover, AG + AA genotype in rs10748835 and TC + CC genotype in rs1046778 were associated with decreased iAs% and MMA% and increased DMA%. The interaction between rs7085104 and arsenic is associated with iAs% and DMA%. The interaction of rs3740390 and rs10748835 with arsenic is associated with iAs%. Haplotype CTAC (rs3740393-rs3740390-rs10748835-rs1046778) was associated with lower iAs% and higher DMA%, but this association disappeared after adjusting for age, gender, drink, smoking, BMI and tAs. Haplotype GCAC was associated with decreased MMA%. Our study provides additional support for revealing the factors influencing the metabolic capacity of arsenic methylation and might be helpful to identify the population susceptible to arsenic exposure through individualized screening in the future.

Comparison of 2 Incisional Methods in Hair Transplantation.

Hair transplantation has been an effective technique for facial contour modification. Hair follicular units (FU) harvested from scalp strip is the gold-standard method for hair transplantation. The difference in obtaining FU from different shapes of scalp strips is not clear yet. Follicular units of 127 patients were harvested from scalp strip through parallelogram incision or fusiform incision from October 2017 to January 2020. The number of FU in 1 cm 2 scalp strip were calculated and paired t test were used to compare the difference in hair follicle acquirement rate between 2 incisions. The number and acquisition rate of FU by parallelogram incision were significantly higher than that by fusiform incision. Therefore, parallelogram incision might be more suitable to harvest FU for hair transplantation surgery.

A Synergetic Strategy for Brand Characterization of Colla Corii Asini (Ejiao) by LIBS and NIR Combined with Partial Least Squares Discriminant Analysis.

A synergetic strategy was proposed to address the critical issue in the brand characterization of Colla corii asini (Ejiao, CCA), a precious traditional Chinese medicine (TCM). In all brands of CCA, Dong'e Ejiao (DEEJ) is an intangible cultural heritage resource. Seventy-eight CCA samples (including forty DEEJ samples and thirty-eight samples from other different manufacturers) were detected by laser-induced breakdown spectroscopy (LIBS) and near-infrared spectroscopy (NIR). Partial least squares discriminant analysis (PLS-DA) models were built first considering individual techniques separately, and then fusing LIBS and NIR data at low-level. The statistical parameters including classification accuracy, sensitivity, and specificity were calculated to evaluate the PLS-DA model performance. The results demonstrated that two individual techniques show good classification performance, especially the NIR. The PLS-DA model with single NIR spectra pretreated by the multiplicative scatter correction (MSC) method was preferred as excellent discrimination. Though individual spectroscopic data obtained good classification performance. A data fusion strategy was also attempted to merge atomic and molecular information of CCA. Compared to a single data block, data fusion models with SNV and MSC pretreatment exhibited good predictive power with no misclassification. This study may provide a novel perspective to employ a comprehensive analytical approach to brand discrimination of CCA. The synergetic strategy based on LIBS together with NIR offers atomic and molecular information of CCA, which could be exemplary for future research on the rapid discrimination of TCM.

Fluoride exposure and prevalence of osteochondroma in drinking water Endemic fluorosis areas of Heilongjiang Province, China: a cross-sectional study.

To investigate the relationship between fluoride exposure and Osteochondroma (OC) prevalence, a cross-sectional study was conducted in drinking water endemic fluorosis areas of Heilongjiang Province, China. Our study first reported that the prevalence of OC was 2.3% in drinking water endemic fluorosis areas of Heilongjiang Province, China, and no difference in gender. Logistic regression analysis found that compared to 1st quartile participants, the prevalence of OC was 73% lower in the 2nd quartile participants of WF (Water fluoride), and 3.4 times higher among the 2nd quartile UF (Urinary fluoride) participants. Our study suggests that 0.259-0.420 mg/L of WF may be considered an appropriate level for reducing OC prevalence, while UF (≥0.750 mg/L) could slightly increase the prevalence of OC. In summary, the link between fluoride and OC prevalence is complicated and needs to be further investigated in a cohort population.

Malignant growth of arsenic-transformed cells depends on activated Akt induced by reactive oxygen species.

Arsenic is an identified carcinogen for humans.In this study, chronic exposure of human hepatocyte L-02 to low-doses of inorganic arsenic caused cell malignant proliferation. Meanwhile, compared with normal L-02 cells, arsenic-transformed malignant cells, L-02-As displayed more ROS and significantly higher Cyclin D1 expression as well as aerobic glycolysis. Moreover, Akt activation is followed by the upregulation of Cyclin D1 and HK2 expression in L-02-As cells, since inhibition of Akt activity by Ly294002 attenuated the colony formation in soft agar and decreased the levels of Cyclin D1 and HK2. In addition, scavenging of ROS by NAC resulted in a decreased expression of phospho-Akt, HK2 and Cyclin D1, and attenuates the ability of anchorage-independent growth ofL-02-As cells, suggested that ROS mediated the Akt activation in L-02-As cells. In summary, our results demonstrated that ROS contributes to the malignant phenotype of arsenic-transformed human hepatocyte L-02-As via the activation of Akt pathway.

Development of Conductive Hydrogels for Fabricating Flexible Strain Sensors.

Conductive hydrogels can be prepared by incorporating various conductive materials into polymeric network hydrogels. In recent years, conductive hydrogels have been developed and applied in the field of strain sensors owing to their unique properties, such as electrical conductivity, mechanical properties, self-healing, and anti-freezing properties. These remarkable properties allow conductive hydrogel-based strain sensors to show excellent performance for identifying external stimuli and detecting human body movement, even at subzero temperatures. This review summarizes the properties of conductive hydrogels and their application in the fabrication of strain sensors working in different modes. Finally, a brief prospectus for the development of conductive hydrogels in the future is provided.