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A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

A new approach for the challenging C–H arylation of simple arenes using synergistic silver and a robust cationic Pd3 cluster catalyst is disclosed. The Pd3 core most likely remains intact with Pd3Ar species as the key intermediate.

We show that a bottlebrush polymer-antisense oligonucleotide conjugate (termed pacDNA) enters cancer cells by scavenger receptor-mediated endocytosis and micropinocytosis, trafficks via the endolysosomal pathway, and functions as a steric blocker.

ACC (Adaptive Cruise Control) is a crucial technology to control the automatic driving of a vehicle, which can automatically adjust the driving status of the vehicle according to the driving status of the vehicle in front so that the vehicle always keeps a safe distance from the vehicle in front, which can primarily relieve the driver's driving pressure and avoid tailgating. The research is of great significance to the realization of intelligent driving of vehicles. In this paper, the fuzzy PID control method is used to study the vehicle ACC system. Firstly, the basic concept and key components of the ACC system are explained, the vehicle longitudinal dynamics model is established, and the primary ranges of , and parameters are determined through simulation; based on this, the fuzzy PID control algorithm of vehicle ACC is designed considering three different driving conditions of fixed speed and following cruise mode. The fuzzy PID control algorithm of the vehicle ACC system is designed and established. The joint simulation model of MATLAB is used to simulate the vehicle ACC system under three different driving conditions. The simulation results show that the vehicle ACC system designed in this paper ensures the safety and stability of following the vehicle while providing the vehicle's ride's comfort.

This study aims to explore the teacher's role in the process of implementing the Independent Curriculum which has been implemented nationally through central government policies. In its implementation, the independent curriculum requires various adjustments to the social system and institutional support. This research uses a qualitative approach with a case study type. The results of the study show that the role of teacher competence is very important in the implementation of the independent curriculum, especially in achieving the expected educational goals and ideals. In addition, teachers as professional educators have a good role to play in guiding, motivating, and teaching students according to the needs and demands of the industrial revolution 4.0.

The pro-inflammatory cytokine interleukin-17A (IL-17A) is a key driver of multiple inflammatory and immune disorders. Therapeutic antibodies targeting IL-17A have been proven effective in treating patients with these diseases; however, large variations in clinical outcomes have been observed with different antibodies. In this study, we developed HB0017, a novel monoclonal antibody that targets human IL-17A. HB0017 specifically and strongly bound to human, cynomolgus monkey, and mouse IL-17A at the physiological interface with the IL-17A receptor. In human and monkey cells, HB0017 potently antagonized the functions of IL-17A through competitive binding. HB0017 functioned equivalently to that of clinically approved antibodies in terms of therapeutic efficacy for inflammatory disorders and psoriasis in a mouse model. The results indicate that HB0017 may be an alternative biological therapy for treating patients with inflammation and autoimmune diseases.

Accomplishing optical activity in

The intermolecular metallophilic interaction has been exploited to orderly aggregate nanocluster compounds into multidimensional assemblies, while the intramolecular metallophilic interaction was rarely reported. Herein, based on an Au

A novel [Pt1Ag37(SAdm)21(Dppp)3Cl6]2+ nanocluster is reported, and the reaction with PPh3 triggers an intercluster transformation into [Pt1Ag28(SAdm)18(PPh3)4]2+. Using chiral Bdpp, the enantiomeric Pt1Ag37(SAdm)21(R/S-Bdpp)3Cl6 can be prepared.

A strategy of “surface environment complication” has been exploited to endow Ag29 nanoclusters with high robustness and a unique packing mode in the supracrystal lattice.

The horizontal expansion of biicosahedral M25 has been accomplished, yielding an [Au19Ag12(S-Adm)6(DPPM)6Cl7]2+ nanocluster that loads bidentate phosphine and bulky thiol ligands.

This paper studies the effect of wheel polygonalization and material properties on the fatigue failure of fastener clips in high-speed railway lines and puts forward the corresponding inhibition measures. Vibration frequencies excited by 24th-order wheel out-of-roundness (OOR) were analysed by on-site tests of the axle box vertical vibration acceleration. A finite element modelling method of polygon-shaped wheels was proposed, which was verified by comparing the field measurement with the dynamic simulation. The dynamic response of the fastener clip was simulated by using a rigid–flexible coupled model of the wheelset-track system. The effect of amplitudes as well as typical wavelengths of wheel OOR on the fracture of the clip was analysed based on the Miner fatigue damage accumulation ruler. The results show that when the wheelset ran at 237 km/h on the track, the 24th-order wheel OOR had no obvious effect on the Mises equivalent stress of the clip. When the amplitude of the 24th-order wheel OOR reached 0.225 mm and above, excited vibrations of about 1172 Hz were transmitted from the wheelset-rail system to the fastener systems, thus reducing the safe operating life of the clips. This phenomenon can be inhibited by setting a reasonable amplitude threshold for wheel re-profiling. Wheel eccentric wear (first-order OOR) and 12th-order OOR had lesser effects on the fatigue failure of the clip. The decrease of Poisson’s ratio or the increase of Young’s modulus of the material could cause the maximum Mises equivalent stress at the clip to increase, which might induce cracks, thus leading to the fracture of the clip. Therefore, during the production process, the Poisson’s ratio and Young’s modulus of fastener clips should be strictly controlled to ensure that they are within the permitted range.

The construction of helical nanosized superstructures has long been a challenging pursuit, and little has been achieved in terms of atomic-level manipulation. Herein, intercluster hierarchical triple-helical structures were presented from all-thiol-stabilized Au

The population of satellite galaxies in a host galaxy is a combination of the cumulative accretion of subhaloes and their associated star formation efficiencies, therefore, the luminosity distribution of satellites provides valuable information of both dark matter properties and star formation physics. Recently, the luminosity function of satellites in nearby Milky Way-mass galaxies has been well measured to satellites as faint as Leo I with $M_{V} \sim -8$. In addition to the finding of the diversity in the satellite luminosity functions, it has been noticed that there is a big gap among the magnitude of satellites in some host galaxies, such as M101, where the gap is around 5 in magnitude, noticeably larger than the prediction from the halo abundance matching method. The reason of this gap is still unknown. In this paper, we use a semi-analytical model of galaxy formation, combined with high-resolution N-body simulation, to investigate the probability and origin of such big gap in M101-alike galaxies. We found that, although M101 analogues are very rare with probability of \sim 0.1%-0.2% in the local universe, their formation is a natural outcome of the CDM model. The gap in magnitude is mainly due to the mass of the accreted subhaloes, not from the stochastic star formation in them. We also found that the gap is correlated with the total satellite mass and host halo mass. By tracing the formation history of M101 type galaxies, we find that they likely formed after $z \sim 1$ due to the newly accreted bright satellites. The gap is not in a stable state, and it will disappear in ~7 Gyr due to mergers of bright satellites with the central galaxy., Comment: 8 pages, 11 figures, accepted by MNRAS

Cl atoms can serve as the innermost core, the peripheral ligand, or the counterions of metal nanoclusters. Herein, we report the structural determination a Cl-enriched [Ag52(SAdm)31Cl13]2+. The ratio of Cl to AdmSH is quite high compared to those of other nanoclusters. Structurally, nine Cl atoms, existing at the interlayer of the inner kernel and the surface motif, serve as the bridging ligands to sustain the robustness of the whole structure. Interestingly, four Cl atoms on the motif structure can be substituted by Br. This work allows us to clear the regulation of Cl ligands in the structural construction of metal nanoclusters.

It remains challenging to control the single-, two-, and three-photon excited fluorescence of metal nanoclusters. In this work, the control over the non-linear optics of metal nanoclusters as single-, two-, and three-photon excited fluorescence has been accomplished via exploiting the solvent effect. An emissive nanocluster, Au

The purpose of the study was to explore the relationship between multiple proteins belonging to the LIMK/Cofilin pathway, including LIMK1, LIMK2, Cofilin-1, and p-Cofilin-1 and clinical features of gastric cancer (GC) patients, including overall survival, TNM stages, and pathological subtypes. The expression of LIMK1, LIMK2, Cofilin-1 and p-Cofilin-1 in the GC tissues and adjacent normal stomach tissues from 141 patients were detected using immunohistochemistry (IHC) staining. Wilcoxon rank-sum test and Spearman rank correlation coefficients were used to measure the relationship between different TNM stages, pathological types, and selected parameters. OS was estimated using the Kaplan-Meier method and survival curves were compared using the log-rank test. Our results showed that, compared to those in the adjacent normal stomach tissues, LIMK1, LIMK2 and Cofilin-1 were up-regulated while p-Cofilin-1 was down-regulated in the GC tissues. LIMK1 level was positively correlated to the TNM stages of GC. According to the published dataset, the expression levels of both LIMK1 and LIMK2 were correlated to the overall survival time of GC patients. The level of Cofilin-1 was significantly different between GCs of different TNM stages. Moreover, most importantly, this is the first study to reveal that the level of Cofilin-1 is higher, and the level of p-Cofilin-1 is lower in the diffuse type of GC compared to that in intestinal type. Taken together, our study demonstrated that multiple factors in LIMK/Cofilin pathway including LIMK1, LIMK2, Cofilin-1, and p-Cofilin-1 were associated with the clinical and pathological features of GC, which is potentially helpful for the diagnosis and treatment of GC.

The interactions between SbF

For metal nanoclusters with the "cluster of clusters" intramolecular evolution pattern, most efforts have been made towards the vertical superposition of icosahedral nanobuilding blocks (

Photoluminescence (PL) serves as one of the most attractive chemical-physical properties of metal nanoclusters. However, the control over the PL nature of metal nanoclusters as fluorescence or phosphorescence remains challenging. Basically, the PL nature control concerns the transition regulation of excited electrons in nanoclusters from their excited state to the ground state. Up to the present, some cases have been reported on adjusting the PL nature of emissive nanoclusters via different means, including the composition regulation, the isomerization, the aggregation, and the temperature variation. At the same time, theoretical calculations have been performed to thoroughly understand the PL nature transformation of these emissive nanoclusters in terms of their electronic structures and transition pathways. This Concept highlights and reviews the recent progress in controlling the PL nature of emissive nanoclusters as fluorescence or phosphorescence, which hopefully paves the way for fabricating novel nanoclusters or cluster-based nanomaterials with customized PL properties.

The structural determination of alloy hydride nanoclusters with high nuclearity remains challenging. We herein report the synthetic procedure and the structural elucidation of an Au-Ag alloy nanocluster with 12 hydride ligands-[Au16Ag43H12(SPhCl2)34]5-. The structure of [Au16Ag43H12(SPhCl2)34]5- comprises an Au16Ag3 kernel that is stabilized by 12 hydride ligands, 8 thiol bridges, and 6 Agm(SR)n motif units. The 12 hydride ligands in Au16Ag43 have been confirmed by both 2H NMR and ESI-MS measurements, and their positions have been theoretically evaluated, located at the interlayer between the Au16Ag3 kernel and the Ag-SR shell. The metastable [Au16Ag43H12(SPhCl2)34]5- can convert to [Au12Ag32(SPhCl2)30]4- spontaneously. Structurally, the Au16Ag3 kernel of [Au16Ag43H12(SPhCl2)34]5- could be regarded as the overlapping of two hollow Au8Ag3 cages via sharing an Ag3 line, which is in contrast to the solely icosahedral Au12 kernel of [Au12Ag32(SPhCl2)30]4-. Besides, the overall construction of Au16Ag43 or Au12Ag32 follows a complementing or overlapping assembly mode, respectively. Overall, the structural anatomy of Au16Ag43H12(SPhCl2)34 sheds some new insight into the structural evolution of metal nanoclusters.

Although intermolecular aggregation-induced emission (AIE) has been extensively studied in nanocluster science, it remains challenging to activate AIE via intracluster aggregation (i.e., the aggreg...

Two previously undescribed dibenzocyclooctadiene lignans, named sieverlignans D–E (1–2), as well as eight known ones (3–10), were isolated from the aerial parts of Artemisia sieversiana. Their structures were elucidated from extensive spectroscopic analysis, including HRMS, NMR and electronic circular dichroism (ECD) experiments. This study is the first to report dibenzocyclooctadiene lignans in the genus Artemisia and this plant. All the compounds were evaluated for their anti-neuroinflammatory activities on the lipopolysaccharides (LPS)-induced nitric oxide production in BV-2 murine microglial cells. Compounds 1 and 6 exhibited the moderate activities with their IC50 values of 47.7 and 21.9 μM, compared to a positive control quercetin with the IC50 value of 16.0 μM.

Peritoneal metastasis is a common form of metastasis among advanced gastric cancer patients. In this study, we reported the identification of LIM domain kinase 1 (LIMK1) as a promoter of gastric cancer peritoneal metastasis, and its potential to be a therapeutic target of dabrafenib (DAB). Using transcriptomic sequencing of paired gastric cancer peritoneal metastasis, primary tumors, and normal gastric tissues, we first unveiled that LIMK1 is selectively up-regulated in metastatic tumors. Increased LIMK1 in gastric cancer peritoneal metastasis was validated by immunohistochemistry analysis of an independent patient cohort. In vitro functional studies demonstrated that LIMK1 knockout or knockdown significantly inhibited cell migration and invasion of gastric cancer cells. LIMK1 knockout also abrogated peritoneal and liver metastases of gastric cancer cells in nude mice in vivo. Dabrafenib, a small molecule targeting LIMK1, was found to decrease cell migration and invasion of gastric cancer cells in vitro and abolish peritoneal and liver metastasis formation in vivo. Mechanistically, either LIMK1 knockout or Dabrafenib inhibited LIMK1 expression and phosphorylation of its downstream target cofilin. Taken together, our results demonstrated that LIMK1 functions as a metastasis promoter in gastric cancer by inhibiting LIMK1-p-cofilin and that Dabrafenib has the potential to serve as a novel treatment for gastric cancer peritoneal metastasis.

The determination of active sites in metal nanoclusters is of great significance for the in-depth understanding of the structural evolution and the mechanism of physicochemical properties. In this work, the surface active Ag2(SR)3 units of the Ag48Cl14(S-Adm)30 nanocluster are determined, and the active-site tailoring of this nanocluster gives rise to two derivative nanoclusters, i.e., the structure-maintained Ag48Cl14(S-Adm)26(S-c-C6H11)4 and the structure-growth Ag50Cl16(S-Adm)28(DPPP)2. Both Ag48 and Ag50 nanoclusters exhibit almost the same cluster framework, but the Ag2(S-Adm)3 active units are regulated to Ag3(S-Adm)2(DPPP)1Cl1 with the transformation from Ag48 to Ag50. The surface active sites on Ag48 are rationalized by analyzing its crystal structure and the ligand-exchange-induced cluster transformation. This study provides some inspiration toward the active-site tailoring of nanocluster surface structures, which is significant for the preparation of new cluster-based nanomaterials with customized structures and enhanced performance.

We have developed a non-cationic transfection vector in the form of a bottlebrush polymer-antisense oligonucleotide (ASO) conjugate. Termed pacDNA (polymer-assisted compaction of DNA), these agents show improved biopharmaceutical characteristics and antisense potency in vivo while suppressing non-antisense side effects. Nonetheless, there still lacks a mechanistic understanding regarding the cellular uptake, subcellular trafficking, and gene knockdown with pacDNA. Here, we show that the pacDNA enters human non-small cell lung cancer cells (NCI-H358) predominantly by scavenger receptor-mediated endocytosis and macropinocytosis, and trafficks via the endolysosomal pathway within the cell. The pacDNA significantly reduces a target gene expression (KRAS) in the protein level but not in the mRNA level, despite that the transfection of free ASOs causes ribonuclease H1 (RNase H)-dependent degradation of KRAS mRNA. In addition, the antisense activity of pacDNA is independent of ASO chemical modification, suggesting that the pacDNA functions as a steric blocker.TOC

Exploring the structural evolution of clusters with similar sizes and atom numbers induced by the removal or addition of a few atoms contributes to a deep understanding of structure-property relationships. Herein, three well-characterized copper-hydride nanoclusters that provide insight into the surface-vacancy-defect to non-defect structural evolution were reported. A surface-defective copper hydride nanocluster [Cu

Oligonucleotide-based materials such as spherical nucleic acid (SNA) have been reported to exhibit improved penetration through the epidermis and the dermis of the skin upon topical application. Herein, we report a self-assembled, skin-depigmenting SNA structure, which is based upon a bifunctional oligonucleotide amphiphile containing an antisense oligonucleotide and a tyrosinase inhibitor prodrug. The two components work synergistically to increase oligonucleotide cellular uptake, enhance drug solubility, and promote skin penetration. The particles were shown to reduce melanin content in B16F10 melanoma cells and exhibited a potent antimelanogenic effect in an ultraviolet B-induced hyperpigmentation mouse model.

Genetics-associated asthenoteratozoospermia is often seen in patients with multiple morphological abnormalities of the sperm flagella (MMAF). Although 24 causative genes have been identified, these explain only approximately half of patients with MMAF. Since sperm flagella and motile cilia (especially respiratory cilia) have similar axonemal structures, many patients with MMAF also exhibit respiratory symptoms, such as recurrent airway infection, chronic sinusitis, and bronchiectasis, which are frequently associated with primary ciliary dyskinesia (PCD), another recessive disorder. Here, exome sequencing was conducted to evaluate the genetic cause in 53 patients with MMAF and classic PCD/PCD-like symptoms. Two homozygous missense variants and a compound-heterozygous variant in the BRWD1 gene were identified in three unrelated individuals. BRWD1 staining was detected in the whole flagella and respiratory cilia of normal controls but was absent in BRWD1-mutated individuals. Transmission electron microscopy and immunostaining demonstrated that BRWD1 deficiency in human affected respiratory cilia and sperm flagella differently, as the absence of outer and inner dynein arms in sperm flagellum and respiratory cilia, while with a decreased number and outer doublet microtubule defects of respiratory cilia. To our knowledge, this is the first report of a BRWD1-variant-related disease in humans, manifesting as an autosomal recessive form of MMAF and PCD/PCD-like symptoms. Our data provide a basis for further exploring the molecular mechanism of BRWD1 gene during spermatogenesis and ciliogenesis.

Although several approaches have been exploited to trigger the structural transformation of metal nanoclusters, most cases are assigned to the unidirectional conversion, while the reversible conversion of nanoclusters remains challenging. In this work, the reversible conversion between two Au–Ag alloy nanoclusters, Au14Ag8(Dppm)6(CN)4Cl4 and Au14Ag4(Dppm)6Cl4, has been accomplished, which was tracked by UV-vis and ESI-MS spectroscopy. The condition of the nanocluster reversible conversion has been meticulously mapped out. Our results provide some new insights into the cluster transformation, which will benefit the future preparation of metalloid clusters with customized structures and properties.

Research on nanocluster transformation has generally focused on stable nanoclusters, while analysis of the structural evolutions of metastable nanoclusters just began to receive attention recently. Herein, we report the structural determination of a metastable Ag27H11(SPhMe2)12(DPPM)6 nanocluster and its spontaneous transformation into a size-reduction Ag8(SPhMe2)8(DPPM)1 nanocluster as well as ligand-exchange-triggered transformation into a size-growth Ag29(SSR)12(DPPM)4 nanocluster. The new structure of Ag27 and its structural transformations hopefully provide some implication to the in-depth understanding of metastable nanoclusters.

The structural determination of metastable nanoclusters remains challenging, which impedes the in-depth understanding of their structural evolution. Herein, based on a case study of Pd1Au9, we present a "cocrystallization-driven stabilization" approach to stabilize the metastable nanocluster and then determine its atomically precise structure. The [Pd1Au9(TFPP)7Br2]+ nanocluster is unstable in solution and would spontaneously convert to Pd2Au23(TFPP)10Br7. The introduction of Au11(TFPP)7Br3 nanocluster to the crystallization process of [Pd1Au9(TFPP)7Br2]+ gives rise to the cocrystallized Pd1Au9(TFPP)6Br3@Au11(TFPP)7Br3, although the composition of Pd1Au9 changes from [Pd1Au9(TFPP)7Br2]+ to Pd1Au9(TFPP)6Br3 among this cocrystallization. With this approach, the overall structure of the metastable Pd1Au9 has been determined. Owing to the very similar cluster size and surface ligand environment between Au11 and Pd1Au9, the obtained Pd1Au9@Au11 cocrystal exhibits almost the same cell parameters as those of the single crystalized Au11. Overall, the proposed "cocrystallization-driven stabilization" approach hopefully sheds light on the structural determination of more metastable nanoclusters.

Molecular isomerization has been well established in small-sized organic molecules, whereas bulk inorganic solids present the phase transformation. Studies of molecular isomerization and phase tran...