Tailoring Titanium Carbide Clusters for New Materials: from Met-Cars to Carbon-Doped Superatoms.

Tailoring materials with prescribed properties and regular structures is a critical and challenging research topic. Early transition metals were found to form supermagic M8C12 metallocarbohedrenes (Met-Cars); however, stable metal carbides are not limited to this common stoichiometry. Utilizing self-developed deep-ultraviolet laser ionization mass spectrometry, here, we report a strategy to generate new titanium carbides by reacting pure Tin clusters with acetylene. Interestingly, two products corresponding to Ti17C2 and Ti19C10 exhibit superior abundances in addition to the Ti8C12 Met-Cars. Using global-minimum search, the structures of Ti17C2 and Ti19C10 are determined to be an ellipsoidal D4d and a rod-shaped D5h geometry, respectively, both with carbon-capped Ti4C moieties and superatomic features. We illustrate the electronic structures and bonding nature in these carbon-doped superatoms concerning their enhanced stability and local aromaticity, shedding light on a new class of metal-carbide nanomaterials with atomic precision.

The Reactivity of Ptn + Clusters With N2O Facilitated by Dual Lewis-Acid Sites.

The size dependence of metal cluster reactions frequently reveals valuable information on the mechanism of nanometal catalysis. Here, the reactivity of the Ptn + (n = 1-40) clusters with N2O is studied and a significant dependence on the size of these clusters is noticed. Interestingly, the small Ptn + clusters like Pt3 + and Pt4 + are inclined to form N2O complexes; some larger clusters, such as Pt19 +, Pt21 +, and Pt23 +, appear to be unreactive; however, the others such as Pt3 , 9,15 + and Pt18 + are capable of decomposing N2O. While Pt9 + rapidly reacts with N2O to form a stable quasitetrahedron Pt9O+ product, Pt18 + experiences a series of N2O decompositions to produce Pt18O1-7 +. Utilizing high-precision theoretical calculations, it is shown how the atomic structures and active sites of Ptn + clusters play a vital role in determining their reactivity. Cooperative dual Lewis-acid sites (CDLAS) can be achieved on specific metal clusters like Pt18 +, rendering accelerated N2O decomposition via both N- and O-bonding on the neighboring Pt atoms. The influence of CDLAS on the size-dependent reaction of Pt clusters with N2O is illustrated, offering insights into cluster catalysis in reactions that include the donation of electron pairs.

To What Extent Do Iodomethane and Bromomethane Undergo Analogous Reactions?

Iodomethane and bromomethane (CH3I/CH3Br) are common chemicals, but their chemistry on nanometals is not fully understood. Here, we analyze the reactivity of Rhn+ (n = 3-30) clusters with halomethanes and unveil the spin effect and concentration dependence in the C-H and C-X bond activation. It is found that the reactions under halomethane-rich conditions differ from those under metal-rich conditions. Both CH3I and CH3Br undergo similar dehydrogenation on the Rhn+ clusters in the presence of small quantity reactants; however, different reactions are observed in the presence of sufficient CH3I/CH3Br, showing dominant Rh(CH3Br)x+ (x = 1-4) products but a series of RhnCxHyIz+ species (x = 1-4, y = 1-12, and z = 1-5) pertaining to H2, HI, or CH4 removal. Density functional theory calculations reveal that the dehydrogenation and demethanation of CH3Br are relatively less exothermic and will be deactivated by sufficient gas collisions if helium cooling takes away energy immediately; instead, the successive adsorption of CH3Br gives rise to a series of Rh(CH3Br)x+ species with accidental C-Br bond dissociation.

Improved efficacy of linear glutathione-peptide chaperon complexes on melanogenesis inhibition and transdermal delivery.

Glutathione (GSH) exhibits considerable potential in the cosmetic industry for reducing intracellular tyrosinase activity and inhibiting melanin synthesis. However, its efficacy is hindered by limited permeability, restricting its ability to reach the basal layer of the skin where melanin production occurs. The transdermal enhancer peptide TD1 has emerged as a promising strategy to facilitate the transdermal transfer of proteins or peptides by creating intercellular gaps in keratinocytes, providing access to the basal layer. The primary objective of this study is to enhance the transdermal absorption capacity of GSH while augmenting its inhibitory effect on melanin. Two coupling structures were designed for investigation: linear (TD1-linker-GSH) and branched (TD1-GSH). The study examined the impact of the peptide skeleton on melanin inhibition ability. Our findings revealed that the linear structure not only inhibited synthetic melanin production in B16F10 cells through a direct pathway but also through a paracrine pathway, demonstrating a significant tyrosinase inhibition of nearly 70 %, attributed to the paracrine effect of human keratinocyte HaCaT. In pigmentation models of guinea pigs and zebrafish, the application of TD1-linker-GSH significantly reduced pigmentation. Notably, electric two-photon microscopy demonstrated that TD1-linker-GSH exhibited significant transdermal ability, penetrating 158.67 ± 9.28 µm into the skin of living guinea pigs. Molecular docking analysis of the binding activity with tyrosinase revealed that both TD1-linker-GSH and TD1-GSH occupy the same active pocket, with TD1-linker-GSH binding more tightly to tyrosinase. These results provide a potential foundation for therapeutic approaches aimed at enriched pigmentation and advance our understanding of the mechanisms underlying melanogenesis inhibition.

Clinical Performance of Immunonephelometric Assay and Chemiluminescent Immunoassay for Detection of IgG Subclasses in Chinese.

BACKGROUND: Detection of IgG subclasses (IgGSc) is vital for the diagnosis and management of disease, especially IgG4-related diseases (IgG4-RD). This study aimed to evaluate the performances of the chemiluminescent immunoassay (CLIA) for detecting IgGSc and diagnosing IgG4-RD by IgGSc. METHODS: A total of 40 individuals with IgG4-RD, 40 with primary Sjogren's syndrome (pSS), and 40 healthy controls (HCs) were enrolled. Serum samples were collected for the simultaneous detection of IgG1, IgG2, IgG3, and IgG4 by the Siemens immunonephelometric assay and the CLIA. The correlation analysis was performed, and diagnostic value was analyzed by the receiver operating characteristic (ROC) curve. RESULTS: Patients with IgG4-RD had higher IgG4 (p < 0.001) and lower IgG1 (p < 0.001) than those with pSS, and HC. The results by the Siemens immunonephelometric assay and the CLIA showed a strong correlation in detecting IgG1, IgG2, IgG3, and IgG4 (r = 0.937, r = 0.847, r = 0.871, r = 0.990, all p < 0.001, respectively). The sum of IgG1, IgG2, IgG3, and IgG4 using two assays strongly correlated with total IgG by the IMMAGE 800 (r = 0.866, r = 0.811, both p < 0.001, respectively). For discriminating IgG4-RD from pSS and HC, no significant differences were observed in CLIA IgG4 and Siemens immunonephelometric assay IgG4 (z = 0.138, p = 0.891), which provided the area under the curves (AUCs) of 0.951 (p < 0.001) and 0.950 (p < 0.001), respectively. The AUCs of CLIA IgG1 and Siemens immunonephelometric assay IgG1 in distinguishing pSS from IgG4-RD and HC were 0.761 (p < 0.001) and 0.765 (p < 0.001), respectively, with no significant differences (z = 0.228, p = 0.820). CONCLUSIONS: The CLIA and the Siemens immunonephelometric assay appeared to have good consistency with comparable diagnostic value in detecting IgGSc, especially IgG4, and IgG1 that can accurately identify IgG4-RD or pSS in clinical practice.

Enhanced Stability of Rhombic Dodecahedron Nb15- with Well-Organized Superatomic States.

Well-resolved Nbn- clusters are produced and reacted with ethene and propene via a downstream flow tube reactor. Interestingly, the Nbn- clusters readily react with ethene and propene to form dehydrogenation products; however, Nb15- shows up in the mass spectra with prominent mass abundance indicating its inertness to react with olefins. For this cluster, we conduct photoelectron velocity map imaging (VMI) experiments and verify the stability of Nb15- within a highly symmetrical rhombic dodecahedron structure. Theoretical studies show that the stability of the Nb15- cluster is correlated with its superatomic nature pertaining to both geometric and electronic shell closures. Notably, the superatomic 1s orbital is dominated by the 5s electron of the central Nb atom, while the other superatomic orbitals are contributed by s-d hybridization, especially a remarkable contribution of s-dz2 hybridization. Apart from the closed shells, the highly symmetric geometry of Nb15- is associated with a regular polyhedral structure directed by all rhombus facets, embodying a magic number for body-centered dodecahedra, indicative of enhanced stability as a double magic cluster free of olefin adsorption.

The influence of media use degree on public depressive symptoms: mediating role of big five personality.

BACKGROUND: Mixed results have been found regarding the relationship between media use degree and depressive symptoms. The purpose of this study is to explore the relationship between media use degree, big five personality and depressive symptoms with a mediation model. METHOD: This was a cross-sectional study. With 9-item Patient Health Questionnaire (PHQ-9), 10-item Big Five Inventory (BFI-10) and self-designed media usage scale, 11,031 participants aged 12 and above in 120 cities in China were collected. Pearson correlation analysis and regression analysis were performed on the data. The Process plug-in was used to construct the mediation model and explore the relationship among media use degree, big five personality and depressive symptoms. The nonparametric percentile Bootstrap method was used to test the mediating effect of personality traits. RESULTS: The degree of media use was positively correlated with depressive symptoms (r = 0.20, P < 0.001), and big five personality played a mediating role between the degree of media use and depressive symptoms. Among five traits, extroversion (r=-0.12, P < 0.001), conscientiousness (r=-0.23, P < 0.001), openness (r=-0.03, P < 0.01) and agreeableness (r=-0.22, P < 0.001) were negatively correlated with depressive symptoms, and neuroticism (r = 0.25, P < 0.001) were positively correlated with depressive symptoms. In addition, extraversion (-0.004, -0.001), conscientiousness (-0.015, -0.008), agreeableness (-0.008, -0.001) and neuroticism (-0.015, -0.007) in big five personality played a mediating role between media use and depressive symptoms. CONCLUSION: The degree of media use positively predicted depressive symptoms, and excessive media use may bring risks to mental health. People with high neuroticism, low agreeableness, low conscientiousness and low extroversion are more likely to suffer from depressive symptoms.

Plasma-Assisted Dinitrogen Activation on Small Cobalt Clusters: Co4 N9 + with Enhanced Stability.

We have performed a study on the accommodation of nitrogen doping toward superatomic states of transition metal clusters. By reacting cobalt clusters with N2 in the presence of plasma radiation, a large number of odd-nitrogen clusters were observed, typically Co3 N2m-1 + (m=1-5) and Co4 N2m-1 + (m=1-6) series, showing N≡N bond cleavage in the mild plasma atmosphere. Interestingly, the Co3 N7 + , Co4 N9 + , and Co5 N9 + clusters exhibit prominent mass abundances. First-principles calculation results elucidate the stability of the diverse cobalt nitride clusters and find unique stability of Co4 N9 + with a swallow-kite structure of which four coordinated N2 molecules causes a significantly enlarged HOMO-LUMO gap, while the single N atom doping gives rise to superatomic states of 1S2 1P3 ||1D0 . We reveal an efficient dinitrogen activation strategy by reacting multiple N2 molecules with cobalt clusters under a plasma atmosphere.

Melatonin Attenuates H2O2-Induced Oxidative Injury by Upregulating LncRNA NEAT1 in HT22 Hippocampal Cells.

More research is required to understand how melatonin protects neurons. The study aimed to find out if and how long non-coding RNA (lncRNA) contributes to melatonin's ability to defend the hippocampus from H2O2-induced oxidative injury. LncRNAs related to oxidative injury were predicted by bioinformatics methods. Mouse hippocampus-derived neuronal HT22 cells were treated with H2O2 with or without melatonin. Viability and apoptosis were detected by Cell Counting Kit-8 and Hoechst33258. RNA and protein levels were measured by quantitative real-time PCR, Western blot, and immunofluorescence. Bioinformatics predicted that 38 lncRNAs were associated with oxidative injury in mouse neurons. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was related to H2O2-induced oxidative injury and up-regulated by melatonin in HT22 cells. The knockdown of NEAT1 exacerbated H2O2-induced oxidative injury, weakened the moderating effect of melatonin, and abolished the increasing effect of melatonin on the mRNA and protein level of Slc38a2. Taken together, melatonin attenuates H2O2-induced oxidative injury by upregulating lncRNA NEAT1, which is essential for melatonin stabilizing the mRNA and protein level of Slc38a2 for the survival of HT22 cells. The research may assist in the treatment of oxidative injury-induced hippocampal degeneration associated with aging using melatonin and its target lncRNA NEAT1.

Gas-phase preparation and the stability of superatomic Nb11O15.

We report a study of the reactions of pure metal clusters Nbn- with dioxygen in the gas phase. It is found that the presence of low-concentration dioxygen reactants results in oxygen-addition products, whereas sufficient high-concentration dioxygen enables oxygen-etching reactions giving rise to molecular niobium oxides. Interestingly, in the presence of a suitable gas flow rate of an intermediate dioxygen concentration, a highly selective product Nb11O15- shows up in the mass spectra. Utilizing density functional theory (DFT) calculations, we have discussed the reactivities of Nbn- (3 ≤ n ≤ 14) clusters with oxygen, and unveiled the reasonable stability of Nb11O15- pertaining to its unique geometric structure with a D5h Nb@Nb10 core fully protected by 15 bridge-oxygen atoms. The oxygen-passivated Nb@Nb10O15- cluster exhibits a large HOMO-LUMO gap (1.46 eV) and effective multicenter bonds with remarkable superatom orbitals for all the 26 valence electrons of the Nb@Nb10 core corresponding to well-staggered energy levels. We illustrate the superatomic features in the Nb@Nb10 metallic core for which the adaptive natural density partitioning (AdNDP) analysis unveils thirteen 11c-2e bonds. Among them, one of the 11c-2e bonds accounts for the superatomic S orbital, three bonds correspond to superatomic P orbitals, another five display vivid D orbital characteristics, and the remaining four 11c-2e bonds are assigned to F orbital features. In addition, the net atomic charge of the center Nb atom is as high as -0.804 |e| rendering core-shell electrostatic interactions and the shielding effect of the Nb10O15 shell.

An oxygen-passivated vanadium cluster [V@V10O15]- with metal-metal coordination produced by reacting Vn- with O2.

Vanadium cluster anions are highly reactive making the preparation of pure Vn- and the observation of their reactivity extremely challenging. Herein, well-resolved anionic Vn- clusters are prepared enabling an in-depth study on their reactions with O2 in the gas phase. While pure metal clusters of a magic number are not identified due to the strong V-O bonding, interestingly an unexpected oxide V11O15- was experimentally observed in surviving O2 etching reactions. First-principles theory calculations indicate that V11O15- possesses a body-centered pentagonal prism structure (D5h, ), with the V@V10 core fully protected by 15 oxygen bridges. Such an oxygen-protected metal cluster [V@V10O15]- exhibits typical superatom orbital features pertaining to the V@V10 core which shows effective metal-metal coordination bonding. Meanwhile, the high stability of [V@V10O15]- is reinforced by the V-O-V conjugation interactions which help to maintain the structural integrity, resulting in 3D inorganic aromaticity. This finding of such an oxygen-passivated superatom cluster sheds light on the bonding nature in ligand-protected metal clusters via wet synthesis.

Reactivity of Cobalt Clusters Con±/0 with Dinitrogen: Superatom Co6+ and Superatomic Complex Co5N6.

We report a joint experimental and theoretical study on the reactions of cobalt clusters (Con±/0) with nitrogen using the customized reflection time-of-flight mass spectrometer combined with a 177.3 nm deep-ultraviolet laser. Comparing to the behaviors of neutral Con (n = 2-30) and anionic Con- clusters (n = 7-53) which are relatively inert in reacting with nitrogen in the fast-flow tube, Con+ clusters readily react with nitrogen resulting in adducts of one or multiple N2 except Co6+ which stands firm in the reaction with nitrogen. Detailed quantum chemistry calculations, including the energetics, electron occupancy, and orbital analysis, well-explained the reasonable reactivity of Con+ clusters with nitrogen and unveiled the open-shell superatomic stability of Co6+ within a highly symmetric (D3d) structure. The D3d Co6+ bears an electron configuration of a half-filled superatomic 1P orbital (i.e., 1S21P3||1D0), a large α-highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gap, symmetric multicenter bonds, and reasonable electron delocalization pertaining to metallic aromaticity. Topology analysis by atom-in-molecule illustrates the interactions between Con+ and N2 corresponding to covalent bonds, but the Co-N interactions in cationic Co2+N2 and Co6+N2 clusters are apparently weaker than those in the other systems. In addition, we identify a superatomic complex Co5N6+ which exhibits similar frontier orbitals as the naked Co5+ cluster, but the alpha HOMO-LUMO gap is nearly double-magnified, which is consistent with the high-abundance peak of Co5N6+ in the experimental observation. The enhanced stability of such a ligand-coordinated superatomic complex Co5N6+, along with the superatom Co6+ with aromaticity, sheds light on special and general superatoms.

Charge-Sensitive Cluster-π Interactions Cause Altered Reactivity of Aln±,0 Clusters with Benzene: Enhanced Stability of Al13+Bz.

Utilizing the homemade reflection time-of-flight mass spectrometer (Re-TOFMS), here we report a comprehensive study of the reactivity of aluminum clusters Aln±,0 with molecular benzene in the gas-phase flow tube reactor. During the reactions with benzene, Aln+ clusters were found to be relatively more reactive than Aln0/-, and interestingly, the Al13+ cluster exhibited more reaction product than its neighboring Aln+ clusters. With an emphasis on Al13±,0 clusters, we have performed an in-depth study utilizing DFT calculations to unravel the diverse reactivity of aluminum clusters with benzene. It is revealed that the Al13+Bz cluster has a short Al-C distance and high binding energy, as well as an enlarged HOMO-LUMO gap in comparison with that of Al13+. This contrasts with Al130/- and Al15+, of which the HOMO-LUMO gaps are reduced when the cluster binds with a benzene molecule. Further, the cluster-π interactions between aluminum clusters and benzene are fully demonstrated via topological analysis, natural bonding orbital (NBO) analysis, and noncovalent interaction plots based on independent gradient model (IGM). The unique gyro-like structure of Al13+ and cluster-π interaction induce uneven redistribution of charges on the 13- atoms of Al13+, enabling a tight Al-C bond with strong electrostatic attraction and orbital interactions, which largely differs from the weak orbital overlap and electrostatic repulsion between benzene molecule and Al130/- clusters.

Reactivity of Cobalt Clusters Con±/0 with Ammonia: Co3+ Cluster Catalysis for NH3 Dehydrogenation.

A customized reflection time-of-flight (Re-TOF) mass spectrometer combined with a 177 nm deep-ultraviolet laser has enabled us to observe well-resolved cobalt clusters Con±/0 and perform a comprehensive study of their reactivity with ammonia (NH3). The anions Con- are found to be inert, the neutrals allow the adsorption of multiple NH3 molecules, while the cationic Con+ clusters readily react with NH3 giving rise to dehydrogenation. However, incidental dehydrogenation of NH3 on Con+ is only observed for n ≥ 3. The dramatic charge- and size-dependent reactivities of Con±/0 clusters with NH3 are studied by the density functional theory (DFT)-calculation results of energetics, density of states, orbital interactions, and reaction dynamics. We illustrate the dehydrogenation from two NH3 molecules, where a significantly reduced transition-state energy barrier is found pertaining to the dimolecular co-catalysis effect. The reactivity of Co3+ with NH3 is illustrated showing effective catalysis for N-H dissociation to produce hydrogen applicable for designing ammonia fuel cells.

Furthering the reaction mechanism of cationic vanadium clusters towards oxygen.

Vanadium is a polyvalent metallic element. The fact that V-O bears a much larger bond energy than the V-V metal bond challenges the preparation of pure vanadium clusters and the observation of their reactions with oxygen-containing chemicals. Utilizing a customized reflection time-of-flight mass spectrometer (Re-TOFMS), here we have prepared well-resolved small and large cationic vanadium clusters Vn+ (n < 30), and we conducted a comprehensive study on their reactivity with oxygen. It is illustrated that cationic Vn+ clusters readily react with oxygen leading to the production of both etched building blocks and oxygen-rich VnOm+ (n < m) species profiting from the ion-molecule attraction and hence increased collisional cross section. Furthermore, DFT-based energy calculations reveal that the oxygen-addition reactions are thermodynamically and kinetically favorable pathways. Also the generalized charge decomposition analysis (GCDA) illustrates that the ion-molecule charge-transfer interactions initiate the incorporation of vanadium oxides. This finding of synchronous channels of both etching and growth of vanadium clusters clarifies the reactivity of Vn+ clusters with oxygen, interprets the readily formed VnOm+ clusters within the classification of the CxAyBz series (A = VO2, B = VO3, C = VO), and enriches the understanding of the industrial chemistry of vanadium.

Al Valence Controls the Coordination and Stability of Cationic Aluminum-Oxygen Clusters in Reactions of Aln+ with Oxygen.

The reactivity of cationic aluminum clusters with oxygen is studied via a customized time-of-flight mass spectrometer. Unlike the etching effect for anionic aluminum clusters exposed to oxygen, here, the cationic Aln+ clusters react and produce a range of small AlnOm+ clusters. Relatively large-mass abundances are found for Al3O4+, Al4O5+, and Al5O7+ at lower O2 reactivity, while at higher O2 concentration, oxygen addition leads to Al2O7+, Al3O6,8-10+, and Al4O7,9+, showing relatively high abundance, and Al5O7+ remains as a stable species dominating the Al5Om+ distribution. To understand these results, we have investigated the structures and stabilities of the AlnOm+ clusters. First-principles theoretical investigations reveal the structures, highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gaps, fragmentation energies, ionization energies, and Hirshfield charge of the AlnOm+ clusters (2 ≤ n ≤ 7; 0 ≤ m ≤ 10). Energetically, Al3O4+, Al4O5+, and Al5O7+ are calculated to be most stable with high fragmentation energies; however, they still allow for the chemisorption of additional O2 with large binding energies leading to clusters with higher O/Al ratios. The stability of the species is consistent with Al possessing three valence electrons, while O typically accepts two, leading to the expectation that Al3O4+, Al5O7+, and Al7O10+ are reasonably stable. In addition to this, Al3O+, Al5O3+, and Al7O5+ are found to exhibit large HOMO-LUMO gaps associated with the different oxidation states of Al. The oxygen-rich species such as Al2O7+, Al3O10+, and Al4O9+ all display superoxide structures providing further insights into the oxidation of aluminum clusters.

Exploration of Risk Factors for Cardiovascular Disease in Patients with Rheumatoid Arthritis: A Retrospective Study.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have increased mortality and morbidity rates owing to cardiovascular diseases (CVD). Timely detection of CVD in RA can greatly improve patient prognosis; however, this technique remains challenging. We aimed to investigate the risk factors for CVD incidence in patients with RA. METHODS: This retrospective study included RA patients without CVD risk factors (n = 402), RA with CVD risk factors (n = 394), and RA with CVD (n = 201). Their data on routine examination indicators, vascular endothelial growth factor (VEGF), and immune cells were obtained from medical records. The characteristic variables between each group were screened using univariate analysis, least absolute shrinkage and selection operator (LASSO), random forest (RF), and logistic regression (LR) models, and individualized nomograms were further established to more conveniently observe the likelihood of CVD in RA. RESULTS: Univariate analysis revealed significantly elevated levels of white blood cells (WBC), blood urea nitrogen (BUN), creatinine, creatine kinase (CK), lactate dehydrogenase (LDH), VEGF, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), apolipoprotein B100 (ApoB100), and apolipoprotein E (ApoE) in RA patients with CVD, whereas apolipoprotein A1 (ApoA1) and high-density lipoprotein/cholesterol (HDL/TC) were decreased. Furthermore, the ratio of regulatory T (Treg) cells exhibiting excellent separation performance in RA patients with CVD was significantly lower than that in other groups, whereas the ratios of Th1/Th2/NK and Treg cells were significantly elevated. The LASSO, RF, and LR models were also used to identify the risk factors for CVD in patients with RA. Through the final selected indicators screened using the three machine learning models and univariate analysis, a convenient nomogram was established to observe the likelihood of CVD in patients with RA. CONCLUSIONS: Serum lipids, lipoproteins, and reduction of Treg cells have been identified as risk factors for CVD in patients with RA. Three nomograms combining various risk factors were constructed to predict CVD occurring in patients with RA (RA with/without CVD risk factors).

NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation.

Nucleophosmin (NPM1) is a nucleolar protein and one of the most frequently mutated genes in acute myeloid leukemia (AML). In addition to the commonly detected frameshift mutations in exon12 (NPM1c), previous studies have identified NPM1 gene rearrangements leading to the expression of NPM1-fusion proteins in pediatric AML. However, whether the NPM1-fusions are indeed oncogenic and how the NPM1-fusions cause AML have been largely unknown. In this study, we investigated the subcellular localization and leukemogenic potential of two rare NPM1-fusion proteins, NPM1::MLF1 and NPM1::CCDC28A. NPM1::MLF1 is present in both the nucleus and cytoplasm and occasionally induces AML in the mouse transplantation assay. NPM1::CCDC28A is more localized to the cytoplasm, immortalizes mouse bone marrow cells in vitro and efficiently induces AML in vivo. Mechanistically, both NPM1-fusions bind to the HOX gene cluster and, like NPM1c, cause aberrant upregulation of HOX genes in cooperation with XPO1. The XPO1 inhibitor selinexor suppressed HOX activation and colony formation driven by the NPM1-fusions. NPM1::CCDC28A cells were also sensitive to menin inhibition. Thus, our study provides experimental evidence that both NPM1::MLF1 and NPM1::CCDC28A are oncogenes with functions similar to NPM1c. Inhibition of XPO1 and menin may be a promising strategy for the NPM1-rearranged AML.

The Impact of Problematic Internet Use on Adolescent Loneliness-Chain Mediation Effects of Social Support and Family Communication.

Purpose: To explore the relationship between adolescents' problematic Internet use and loneliness and the mediating roles of social support and family communication. Methods: A questionnaire survey of 2483 adolescents aged 12-17 years in 148 cities in China was conducted using the Problematic Internet Use Scale, the Collaborative Social Support Scale, the Family Communication Scale, and the Loneliness Scale. The data were statistically analyzed by SPSS 26.0 and validated by AMOS 28.0. Structural equation modelling (SEM) was conducted to test the effects of problematic Internet use on adolescents' loneliness and the mediating effects of perceptions of social support and family communication. Results: There was a significant positive effect of adolescents' problematic Internet use on loneliness (B-0.471, P<0.001), and the mediating effects of perceptual social support (0.003, 0.012) and family communication (0.008, 0.019) were found to play a chain effect between adolescents' problematic Internet use and loneliness, respectively. Use and feelings of loneliness played a chain mediating role (0.002, 0.006). Conclusion: This study identified the effects of adolescent problematic Internet use on loneliness and its mechanism of action, emphasized the importance of social support and family communication, and provided practical insights for improving family parenting styles and preventing and intervening in adolescent loneliness problems.

Predicting the risk of interstitial lung disease in patients with primary Sjögren's syndrome: Novel nomogram and elevated Th2 cells.

OBJECTIVE: Interstitial lung disease (ILD) is one of the most common pulmonary complications in patients with primary Sjögren's syndrome (pSS). This study was performed to identify immunological risk factors of pSS-associated ILD (pSS-ILD) and to further establish and evaluate of nomograms predicting the risk of ILD in patients with pSS. METHODS: A total of 622 patients with pSS (117 with ILD and 505 without lung involvement) and 166 healthy control subjects (HCs) were ultimately recruited to this retrospective study. Routine examination indicators, tumour markers and lymphocyte (LYMP) subpopulations were extracted. Simple and multiple logistic regressions analyses were performed to screen for independent predictors. Restricted cubic splines were used to examine associations of independent predictors with ILD, and a risk assessment model was constructed. A nomogram prediction model was developed, and receiver operating characteristic (ROC) curve analysis was performed to assess its performance. RESULTS: Univariate and multivariate logistic regression analyses showed that the older age, white blood cell (WBC) count, haemoglobin (HB) level, albumin (ALB) level, CA242 level, and the C-reactive protein (CRP)/LYMP ratio (CLR) were independent predictors of pSS-ILD in a linear manner, these factors were integrated and used to construct a nomogram prediction model. The model had clinical predictive value. In addition, the elevated Th2 cells proportion in pSS patients was significantly positively correlated with lung involvement, while it was negatively correlated with HB and ALB levels. Remarkably, the numbers of Th2 cells were correlated with the CLR in both pSS patients and those with pSS-ILD. CONCLUSIONS: Our novel ILD nomogram could be used to assess the risk of ILD in pSS patients with good discrimination ability. As well as, elevated peripheral blood Th2 cell levels may be related to ILD in patients with pSS.