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A series of five-coordinate mononuclear DyIII SMMs [(TrapenTMS)Dy(LB)] (LB = THF 1, pyridine 2, ONMe3 3) have been successfully constructed. The results indicated that the magnetic property for 1 –3 are differences (in a sequence of 1> 3 > 2).

Psoriasis is an inflammatory skin disease of chronic recurrence mediated by the interaction between IL-17 and keratinocytes, which sustains a vicious circle of inflammation. Safe and effective natural medicine is a potential strategy for the clinical treatment of psoriasis. Given its prominent anti-proliferative and anti-inflammatory properties, we investigated the actions of allicin in improving psoriasis.Pharmacodynamic studies were carried out in mice after topical administration of allicin against psoriasis-like lesions induced by imiquimod. Skin sensitization tests were evaluated on guinea pigs. Toxicological studies and skin irritation tests were assessed by consecutive topical allicin alone on the skin of rabbits. RNA-seq probed transcriptomic changes following allicin. Western blot explored the actions of allicin on the interaction between IL-17A and keratinocytes. Changes in inflammatory factor expression were analysed by qPCR and immunohistochemistry.Allicin significantly improved the epidermal structure by inhibiting the excessive proliferation and reduced apoptosis of keratinocytes. Furthermore, allicin reduced the secretion of inflammatory cytokines (IL-17A/F, IL-22, IL-12, and IL-20), chemokines (CXCL2, CXCL5, and CCL20), and anti-bacterial peptides (S100a8/9). Mechanistically, allicin directly inhibited the IL-17-induced TRAF6/MAPK/NF-κB and STAT3/NF-κB signalling cascades in keratinocytes, thus breaking the positive inflammatory feedback and alleviating imiquimod-induced psoriasis-like dermatitis in mice. Importantly, topical administration of allicin did not cause skin allergy, and the safety and adaptability of long-term application were verified.Interfering with IL-17 signalling in keratinocytes with allicin is a promising strategy for treating psoriasis, given its safety and effectiveness.

Background Resting-state functional magnetic resonance imaging (RS-fMRI) has been proved to be a useful tool to study the brain mechanism in the quest to probe the distinct pattern of inter-region interactions in the brain. As an important application of RS-fMRI, the graph-based approach characterizes the brain as a complex network. However, the network is susceptible to its scale that determines the trade-off between sensitivity and anatomical variability. Objective To balance sensitivity and anatomical variability, a pyramid representation of the functional network is proposed, which is composed of five individual networks reconstructed at multiple scales. Methods The pyramid representation of the functional network was applied to two groups of participants, including patients with Alzheimer's disease (AD) and normal elderly (NC) individuals, as a demonstration. Features were extracted from the multi-scale networks and were evaluated with their inter-group differences between AD and NC, as well as the discriminative power in recognizing AD. Moreover, the proposed method was also validated by another dataset from people with autism. Results The different features reflect the highest sensitivity to distinguish AD at different scales. In addition, the combined features have higher accuracy than any single scale-based feature. These findings highlight the potential use of multi-scale features as markers of the disrupted topological organization in AD networks. Conclusion We believe that multi-scale metrics could provide a more comprehensive characterization of the functional network and thus provide a promising solution for representing the underlying functional mechanism in the human brain on a multi-scale basis.

Humic-like substances (HULIS) are macromolecular complex groups in water-soluble organic compounds (WSOC). pH is a crucial factor that influences the chemical transformations of HULIS in atmospheric particles, but this has been rarely investigated, especially under varying pH conditions. This study attempted to unveil the chemical transformation mechanisms of HULIS under a range of pH conditions using optical methods. The pH-dependent light absorption and fluorescence properties of HULIS were comprehensively analyzed; the acidity coefficient (p

Rationale and Objectives The direct damage caused by ischemic stroke is relatively localized, but structural reorganization of cortical regions could occur across the brain. Changes of large-scale, cortical structural brain networks after basal ganglia stroke are less well reported. We, therefore, aim to explore the abnormalities of cortical morphology and structural network topology in patients with unilateral basal ganglia stroke during the subacute period. Materials and Methods Thirty patients with first-ever basal ganglia stroke and thirty age- and sex-matched healthy controls were recruited for our analysis. Patients underwent structural magnetic resonance imaging examinations and clinical assessment from seven days to three months post-stroke. Alterations in cortical morphology and topological properties of the cortical structural network were measured respectively using the surface-based morphology and graph-theoretical methods. Results We observed focal cortical atrophy, specifically in areas of frontal and temporal cortices. Moreover, the cortical thickness in the contralesional transverse temporal gyrus and superior temporal gyrus was positively correlated with cognitive function scores. Network analysis revealed that patients with basal ganglia stroke showed increased clustering coefficient, increased mean local efficiency as well as a reorganization of degree-based hubs. In addition, these patients also showed reduced robustness under a random attack compared to healthy controls. Conclusion These findings indicated a unique pattern of cortical reorganization and the abnormal topological organization of cortical thickness-based structural covariance networks in patients with basal ganglia stroke, which is beneficial to understand the pathophysiological mechanisms of functional disorders at the cortical structural network level and find potential targets for induced neuromodulation.

No current academic data is available with respect to the optimal timing to initiate antiretroviral therapy (ART) in HIV-positive patients with talaromycosis. Our study aimed to evaluate the optimal timing of ART initiation for patients presenting with AIDS-related talaromycosis.In this prospective, randomized, open-label multicenter trial, 228 patients from 15 hospitals in China were randomly assigned to an early ART group (initiation of ART within 2 weeks after randomization) and a deferred ART group (initiation of ART 2 weeks after randomization). The primary endpoint was all-cause mortality during the 48 weeks after randomization.We observed a significant difference in mortality between the early ART group and the deferred ART group (2.2% vs. 8.9%, 95%CI: -0.15 to 14.05, p = 0.049). The composite outcome of AIDS-defining events or death in the early ART group was found to be lower than that in the deferred ART group (3.3% vs. 14.9%; 95%CI: 2.93 to 19.23, p = 0.008).The prognosis of HIV-infected patients with talaromycosis in the early ART group was more favorable than that of patients in the deferred ART group. These results demonstrate that early ART initiation should be considered in HIV-infected patients with talaromycosis .

Objectives Repetitive transcranial magnetic stimulation (rTMS) is a promising tool to modulate brain plasticity, but the neural basis has been little addressed. The purpose was to investigate the effects of rTMS on resting-state brain activity in patients with Alzheimer’s disease (AD). Methods Seventeen patients with mild or moderate AD were enrolled and randomly divided into one of the two intervention groups: (1) real rTMS combined with cognitive training (real group, n = 9); (2) sham rTMS with cognitive training (sham group, n = 8). 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex and then the left lateral temporal lobe for 20 min each day for 4 weeks. Each patient underwent neuropsychological assessment and resting-state functional magnetic resonance imaging (rsfMRI) before and after treatment. The fractional amplitude of low frequency fluctuation (fALFF) of rsfMRI data in real group were: (1) compared to sham; (2) correlated with rTMS-induced cognitive alterations. Results Significantly increased fALFF in right cerebellum/declive, left lingual/cuneus and left cingulate gyrus, as well as decreased fALFF in left middle frontal gyrus were found after 10 Hz rTMS, but not after sham stimulation. Using these suprathreshold regions, we found that rTMS increased functional connectivity between the right cerebellum/declive and left precentral/postcentral gyrus. The fALFF increase in left lingual/cuneus and right cerebellum/declive was associated with significant improvement in cognitive function. Conclusions rTMS combined with cognitive training induced increased low frequency fluctuation neural oscillations and functional connectivity in brain regions subserving cognition, suggesting a possible neuronal mechanism of the beneficial effects of rTMS.

pH has a significant effect on the architectures of resulting In(iii)-MOFs, one of which exhibits highly selective uptake of CO2 over CH4.

This work provides a reliable view that the chelator content severely affects the valence state of the V element, the bonding state of the F element, and the particle size, crystal structure and sodium storage performance of NVPF samples.

Single-crystal to single-crystal transformation triggered by a lattice solvent leads to reversible on–off switching of single-molecule magnet (SMM) behaviour in pentagonal-bipyramidal Dy(iii) complexes.

This work provides a reliable view for understanding the phase and composition of as-prepared Na3V2(PO4)2F3, showing that the proper introduction of oxygen substitution for fluorine is beneficial to the electrochemical performance.

Reaction of Dy(iii) ion with tridentate acylhydrazone ligand leads to a field-induced Dy(iii) SIM, of which the magneto-structural correlation is elucidated by the magnetic and theoretical studies.

A timely and reliable inventory is essential for landslide hazard assessment and risk management. In this study, we use images from PlanetScope, which provides global 3 m daily Earth observations, for rapid mapping of landslide inventory. We propose a semi-automated method that combines change detection and region-based level set evolution (RLSE) to improve the landslide mapping efficiency. In particular, our approach uses the change detection methods of independent component analysis (ICA), principal component analysis (PCA) and change vector analysis (CVA) for automated generation of landslide zero-level curves (ZLCs), and then incorporates the RLSE method to refine the landslide mapping results. To corroborate the applicability of the proposed method, we test the landslide mapping performance on the Kodagu event (India, 2018) using ICA-, PCA- and CVA-based RLSE. The results show that ICA-based RLSE can achieve better landslide mapping accuracy in terms of completeness, correctness, and the Kappa coefficient. This study demonstrates the suitability and potential of low-orbit miniature satellites such as PlanetScope for landslide mapping. To the best of our knowledge, it is the first attempt to incorporate PlanetScope images and the change detection-based RLSE method for landslide mapping.

Thermally activated delayed fluorescence (TADF)-sensitized fluorescence is a promising strategy to maintain the advantage of TADF materials and fluorescent materials. Nevertheless, the delayed lifetime of the TADF sensitizer is still relatively long, which causes heavy efficiency roll-off. Here we reported a valid tactic to construct fluorescent devices with low-efficiency roll-off by utilizing the TADF sensitizer with a reduced delayed lifetime. By the construction of the sensitization system, the energy transfer efficiency can reach up to 90%. The high-energy transfer efficiency and the TADFʼs short delayed lifetime result in high sensitization over 95% and the maximum external quantum efficiency of 16.2%. Meanwhile, the TADF-sensitized fluorescent devices exhibit reduced efficiency roll-off with an “onset” current density of 23 mA · cm−2. Our results provide an effective strategy to reduce the efficiency roll-off of the TADF sensitization system.

BACKGROUND AND AIMS Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. APPROACH AND RESULTS In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. CONCLUSIONS Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.

In this paper, APTES was used as the functional monomer, reamed MCM-41 was used as the carrier, and epichlorohydrin was used as the crosslinking agent to prepare the Lanthanide ion-imprinted polymer, La-IIP. The effects of pH, time, temperature, and initial concentration on La-IIP adsorption were investigated, and the adsorption mechanism was discussed by fitting the adsorption data to various kinetic and thermodynamic models. The results showed that La-IIP reached adsorption equilibrium in 20 min at 338 K and pH = 5, and the maximum adsorption capacity was 272.2 mg/g. The La-IIP adsorption process conformed to the Langmuir adsorption model, and La-IIP showed strong selectivity for La(III) in the presence of interfering ions with similarproperties. 2 M hydrochloric acid solution was used to eluate La-IIP and re-adsorb lanthanum ion solution. After elution of La-IIP for five times, the adsorption remained at the initial value of 81%. It shows that La-IIP has stability and reusability.

As a kind of high linear energy transfer (LET) radiation, internal conversion electrons are emitted from some radionuclides, such as 125I, triggering severe DNA damage to tumor cells when transported into the nucleus. Herein, we develop a curcumin-loaded nanomicelle composed of a photosensitizer chlorin e6 (Ce6) and amphiphilic poly(ethylene glycol) (poly(maleic anhydride-alt-1-octadecene)-poly(ethylene glycol) (C18-PMH-PEG)) to deliver 125I into the nucleus under 660 nm laser irradiation, leading to the optimized imaging-guided internal conversion electron therapy of cancer. Ce6-containing nanomicelles (Ce6-C18-PEG) self-assemble with nucleus-targeted curcumin (Cur), obtaining Ce6-C18-PEG/Cur nanoparticles. After labeling Cur with 125I, Ce6-C18-PEG/Cur enables single-photon emission computed tomography and fluorescence imaging of the tumor, serving as a guide for follow-up laser irradiation. Notably, the 660 nm laser-triggered photodynamic reaction of Ce6 optimizes the delivery of Ce6-C18-PEG/125I-Cur at various stages, including tumor accumulation, cellular uptake, and lysosome escape, causing plenty of 125I-Cur to enter the nucleus. By this strategy, Ce6-C18-PEG/125I-Cur showed optimal antitumor efficacy and high biosafety in mice treated with local 660 nm laser irradiation using efficient energy deposition of internally converted electrons over short distances. Therefore, our work provides a novel strategy to optimize 125I delivery for tumor treatment.

Spinal muscular atrophy (SMA), a degenerative motor neuron disease and a leading cause of infant mortality, is caused by loss of functional survival motor neuron (SMN) protein due to SMN1 gene mutation. Here, using mouse and cell models for behavioral and histological studies, we found that SENP2 (SUMO/sentrin-specific protease 2)-deficient mice developed a notable SMA-like pathology phenotype with significantly decreased muscle fibers and motor neurons. At the molecular level, SENP2 deficiency in mice did not affect transcription but decreased SMN protein levels by promoting the SUMOylation of SMN. SMN was modified by SUMO2 with the E3 PIAS2α and deconjugated by SENP2. SUMOylation of SMN accelerated its degradation by the ubiquitin-proteasome degradation pathway with the ubiquitin E1 UBA1 (ubiquitin-like modifier activating enzyme 1) and E3 ITCH. SUMOylation of SMN increased its acetylation to inhibit the formation of Cajal bodies (CBs). These results showed that SENP2 deficiency induced hyper-SUMOylation of the SMN protein, which further affected the stability and functions of the SMN protein, eventually leading to the SMA-like phenotype. Thus, we uncovered the important roles for hyper-SUMOylation of SMN induced by SENP2 deficiency in motor neurons and provided a novel targeted therapeutic strategy for SMA. KEY MESSAGES: SENP2 deficiency enhanced the hyper-SUMOylation of SMN and promoted the degradation of SMN by the ubiquitin-proteasome pathway. SUMOylation increased the acetylation of SMN to inhibit CB formation. SENP2 deficiency caused hyper-SUMOylation of SMN protein, which further affected the stability and functions of SMN protein and eventually led to the occurrence of SMA-like pathology.

Dynamic magnetic behaviours of a series of Co(ii) SIMs with pentagonal-bipyramidal geometry have been modulated by an alteration of the ligand field effect.

Background: This study's objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV patients with talaromycosis. Methods: A total of 170 HIV patients with talaromycosis were enrolled from January 1st, 2019 to September 30th, 2020. Results: Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia and severe thrombocytopenia, respectively. Baseline lower hemoglobin levels, higher serum creatinine levels, higher AST/ALT ratios, lower sodium levels, and higher administered doses of amphotericin B were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis and lower platelet levels at baseline were shown to be independent risk factors associated with the development of severe leukopenia. A lower platelet level at baseline was the independent risk factor found to be associated with the development of severe thrombocytopenia. Conclusion: The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia, which will favor prevention and timely treatment of hematological toxicity, improvement of patient’s outcomes, shorter hospital stays, and a reduction of the requirement for blood transfusion.

Primary cilia transduce signals via transmembrane and membrane-associated proteins localized to the ciliary membrane in vertebrate cells. In humans, transmembrane protein 67 (TMEM67), a component of the multiprotein complex functioning as a gatekeeper at the transition zone (TZ) of primary cilia, is mutated in patients suffering from cilia-related pleiotropic diseases, collectively referred to as ciliopathies. The requirement of TMEM67 for the gating function of the TZ that delivers membrane proteins into the ciliary compartment has not been determined. In this study, we established hTERT-RPE1 cells with knockout (KO) of TMEM67 and examined whether cilium formation and TZ gating are affected by its ablation. TMEM67-KO cells displayed impaired ciliogenesis, elongated cilia, perturbed ciliary localization of membrane-associated proteins ARL13B and INPP5E but normal recruitment of TZ proteins CEP290, RPGRIP1L and NPHP5. The exogenous expression of ciliopathy-associated TMEM67 mutants restored ciliary localization of ARL13B and INPP5E but failed to attenuate aberrant cilium elongation in TMEM67-KO cells. Furthermore, we found that TMEM67 localization is not confined to the TZ but extends into the cilium. Our findings indicate that TMEM67 is required not only for ciliogenesis and cilium length regulation but also for the gating function of the TZ independently of RPGRIP1L/CEP290/NPHP5 recruitment to this region. They further suggest that aberrant cilium elongation underlies the pathogenesis of TMEM67-linked ciliopathies.

As an important predictor of adulthood psychopathology, self-reported childhood abuse appears heritable and is associated with brain abnormalities. However, the specific genetic mechanisms behind these brain alterations remain largely unknown. This study recruited young adults who reported different degrees of childhood abuse from the community. In order to fully understand the influence of genes on brain changes related to self-reported childhood abuse, various experiments were conducted in this study. Firstly, volume changes of gray matter and white matter related to childhood abuse were investigated by using advanced magnetic resonance imaging techniques. After sequencing the whole exons, we further investigated the relationship between polygenic risk score, brain volume alterations, and childhood abuse score. Furthermore, transcription-neuroimaging association analysis was used to identify risk genes whose expressions were associated with brain volume alterations. The gray matter volumes of left caudate and superior parietal lobule, and white matter volumes of left cerebellum and right temporal lobe-basal ganglia region were significantly correlated with the childhood abuse score. More importantly, brain volume changes mediated the influence of polygenic risk on self-reported childhood abuse. Additionally, transcription-neuroimaging association analysis reported 63 risk genes whose expression levels were significantly associated with childhood abuse-related brain volume changes. These genes are involved in multiple biological processes, such as nerve development, synaptic transmission, and cell construction. Combining data from multiple perspectives, our work provides evidence of brain abnormalities associated with childhood abuse, and further indicates that polygene genetic risk and risk gene expression may affect the occurrence of childhood abuse by brain regulation, which provides insights into the molecularpathology and neuromechanism of childhood adversity. Paying attention to the physical and mental health of high-risk children may be a fundamental way to prevent childhood abuse and promote lifelong mental health.

Neurogenesis plays a critical role in brain physiology and behavioral performance, and defective neurogenesis leads to neurological and psychiatric disorders. Here, we show that PLCβ4 expression is markedly reduced in SENP2-deficient cells and mice, resulting in decreased IP(3) formation and altered intracellular calcium homeostasis. PLCβ4 stability is regulated by the SUMO-dependent ubiquitin-mediated proteolytic pathway, which is catalyzed by PIAS2α and RNF4. SUMOylated PLCβ4 is transported to the nucleus through Nup205- and RanBP2-dependent pathways and regulates nuclear signaling. Furthermore, dysregulated calcium homeostasis induced defects in neurogenesis and neuronal viability in SENP2-deficient mice. Finally, SENP2 and PLCβ4 are stimulated by starvation and oxidative stress, which maintain calcium homeostasis regulated neurogenesis. Our findings provide mechanistic insight into the critical roles of SENP2 in the regulation of PLCβ4 SUMOylation, and the involvement of SENP2-PLCβ4 axis in calcium homeostasis regulated neurogenesis under stress.

BACKGROUND: The non-invasive characterization of glioma metabolites would greatly assist the management of glioma patients in the clinical setting. This study investigated the applicability of intra-subject inter-metabolite correlation analyses for differentiating glioma malignancy and proliferation. METHODS: A total of 17 negative controls (NCs), 39 low-grade gliomas (LGGs) patients, and 25 high-grade gliomas (HGGs) subjects were included in this retrospective study. Amide proton transfer (APT) and magnetization transfer contrast (MTC) imaging contrasts, as well as total choline/total creatine (tCho/tCr) and total N-acetylaspartate/total creatine (tNAA/tCr) ratios quantified from magnetic resonance spectroscopic imaging (MRSI) were co-registered voxel-wise and used to produce three intra-subject inter-metabolite correlation coefficients (IMCCs), namely, R(APT) (vs)(. MTC), R(APT) (vs)(. tCho/tCr), and R(MTC) (vs)(. tNAA/tCr). The correlation between the IMCCs and tumor grade and Ki-67 labeling index (LI) for tumor proliferation were explored. The differences in the IMCCs between the three groups were compared with one-way analysis of variance (ANOVA). Finally, regression analysis was used to build a combined model with multiple IMCCs to improve the diagnostic performance for tumor grades based on receiver operator characteristic curves. RESULTS: Compared with the NCs, gliomas showed stronger inter-metabolic correlations. R(APT) (vs)(. MTC) was significantly different among the three groups (NC vs. LGGs vs. HGGs: −0.18±0.38 vs. −0.40±0.34 vs. −0.70±0.29, P

Familial chylomicronemia syndrome (FCS) caused by mutations of lipoprotein lipase (LPL) gene and other triglyceride-rich lipoprotein genes related with catabolism is an autosomal recessive rare disease. Herein, we report an infant with FCS and review the relevant literature. The proband is a male infant with FCS for which the whole-exome sequencing (WES), sanger sequencing and copy number variation (CNV) based on WES were performed. Compound heterozygous mutations (LPL gene c.1322+1GC and loss in exons 8 to 10) were found in the LPL gene of the proband, the c.1322+1GC mutation was inherited from his father with the heterozygous mutation, and the deletion of exons 8-10 due to CNVs was inherited from his mother. Carriers of heterozygous mutation or heterozygous deletion in LPL may have normal plasma lipids or develop FCS. Plasma lipids management of FCS in infancy should focus on the diet and adopt an individualized management.

Background HIV self-testing (HIVST) is recommended by the World Health Organization as a valid approach to routine HIV testing services. The scale of HIVST use has gradually been expanded in China over the past 5 years. To take a closer look at the role of HIVST in China, we reviewed the promotion and application of HIVST within China. Objective The main objective of this study was to systematically analyze the proportion of past use and actual uptake of HIVST within China. Moreover, we aimed to quantify the effect of HIVST on HIV prevention and treatment. Methods In all, 5 medical databases and 2 registration systems, including PubMed, Web of Science, MEDLINE, WanFang, China National Knowledge Internet, ClinicalTrials.gov, and the Chinese Clinical Trial Registry were systematically searched for studies reporting the prevalence of HIVST use from January 1, 2010, to December 25, 2021. Meta-analyses of the pooled proportion estimates were carried out by the meta-package in R software (version 4.1.2). Statistical heterogeneity among the studies was estimated using Cochran Q test and the inconsistency index (I2). Results A total of 50 studies were included in our systematic review. The estimated pooled prevalence of HIVST use in China was 29.9% (95% CI 22.5%-37.9%). Among individuals who have ever used HIVST, 47.5% (95% CI 37.2%-57.8%) were tested for HIV for the first time. The pooled reactive rate of HIVST was 4.2% (95% CI 3.1%-5.8%). When HIVST revealed a reactive result, 81.3% (95% CI 70.9%-91.6%) of individuals sought medical care. Conclusions In recent times, HIVST has become a valuable tool for HIV prevention in China. The widespread use of HIVST in non–men who have sex with men populations needs to be endorsed and promoted. The long-term applications of HIVST and the potential consequences of self-financing of HIVST in China have yet to be explored. Trial Registration PROSPERO CRD42022304846; https://tinyurl.com/54d9pxy8

Burkitt lymphoma (BL) is an aggressive Epstein-Barr virus (EBV)-driven B-cell lymphoma characterized by the translocation and rearrangement of the c-Myc proto-oncogene. High-intensity multidrug chemotherapy regimens have a limited effect on the survival of refractory or relapsed BL patients, mainly owing to the high EBV load and drug resistance. l-asparaginase ( l-Asp) and etoposide (VP-16) play a beneficial role in EBV-related lymphoproliferative diseases; however, their roles and mechanisms in BL remain unclear. In this study, we found that VP-16 inhibited BL cell proliferation and arrested the cell cycle at the G

Bone is the most common late metastasis of breast cancer. Bone metastasis causes not only severe bone pain, but also bone-related diseases such as pathological fractures, which are closely related to osteoclasts. The effects of demethoxycurcumin (DMC) on osteoclast biology has not been investigated. In this study, we explored the effects of DMC on MDA-MB-231 cells, MCF-7 cells, and osteoclasts induced by RANKL in vitro, as well as the protective effect on bone destruction of tumor bone metastasis in vivo. DMC showed inhibitory effect on the migration and promotes the apoptosis of MDA-MB-231 and MCF-7 cells. At the same time, DMC inhibited osteoclast maturation and mature osteoclast bone resorption in a dose-dependent manner, and suppressed the expression of osteoclast marker genes TRAP, CTSK, MMP9, V-ATPase-d2 and DC-STAMP significantly. Biochemical data showed that DMC inhibited tumor cells and osteoclasts by inhibiting the early activation of ERK and JNK MAPK pathway. Consistent with the results in vitro, we confirmed that DMC protects bone destruction caused by tumor metastasis in vivo. In short, our study confirmed that DMC could be used as a potential drug for the treatment of tumor bone destruction.

Despite advancement in the treatment of diffuse large B-cell lymphoma (DLBCL), many patients tend to relapse or become refractory after initial therapy. Therefore, it is essential to identify novel therapeutic targets and drugs, understand the molecular pathogenesis mechanism of DLBCL, and find ways to prevent and treat relapsed or refractory DLBCL. BIX-01294 is a small molecule compound that specifically inhibits EHMT2 activity. In this study, we demonstrate that BIX-01294 triggered the inhibition of human DLBCL cell proliferation, lead to G1 phase arrest via increasing P21 level and reducing cyclin E level. BIX-01294 also induced apoptosis via endogenous and exogenous apoptotic pathways. Moreover, BIX-01294 triggered autophagy and activated ER stress in human DLBCL cells. Furthermore, we showed that both key components of ER stress, ATF3, and ATF4, are required for BIX-01294-induced apoptosis and autophagy. Hence, this study provides new evidence that EHMT2 may be a new therapeutic target, and BIX-01294 may be a potential therapeutic drug for treating DLBCL.

Background and Purpose: Psoriasis is an inflammatory skin disease of chronic recurrence mediated by the interaction between IL-17 and keratinocytes, which sustains a vicious circle of inflammation. Currently, there is no safe and effective natural medicine for the clinical treatment of psoriasis. Given its prominent anti-proliferative and anti-inflammatory properties, we investigated the mechanism of allicin improving psoriasis. Experimental Design: Pharmacodynamics and toxicology experimental studies were estimated after topical administration of allicin on the skin of mice. Changes in inflammatory factors expression were analyzed by qPCR and immunohistochemistry after topical treatment with allicin in mice with psoriasis-like lesions induced by imiquimod. The impacts of allicin on proliferation and apoptosis of keratinocytes were analyzed by CCK8 assay and flow cytometry. The interaction between IL-17A and keratinocytes was studied using HaCaT cells, and the mechanism of action of allicin was explored by Western Blot. Transcriptomic changes following the action of allicin were probed by RNA-seq. Key Results: Our study demonstrated that allicin significantly improved the epidermal structure by inhibiting excessive proliferation and evasion of apoptosis of keratinocytes. Furthermore, allicin reduced the secretion of inflammatory cytokines (IL-17A/F, IL-22, IL-12, IL-20), chemokines (CXCL2, CXCL5, CCL20), and antibacterial peptides (S100A8/9). Mechanistically, allicin directly inhibited the IL-17-induced TRAF6/MAPK/NF-κB and STAT3/NF-κB signaling cascades in keratinocytes, thus breaking the positive inflammation feedback and alleviating imiquimod-induced psoriasis-like dermatitis in mice. Importantly, topical administration of allicin did not cause skin allergy, and the safety and adaptability of long-term application were verified.

Distinct structures and dynamic magnetic behaviours have been observed in two pseudotetrahedral Co(ii) complexes.

While the interest in single-molecule magnets (SMMs) lies in their potential applications in information storage and quantum computing, the switching of their slow magnetic relaxation associated with dynamic crystal-to-crystal transformation is insufficiently exploited. Herein, three pentagonal-bipyramidal (PBP) Dy(III) complexes, [Dy(Bcpen)(Cl)

Current guidelines recommend amphotericin B as the preferred drug for induction therapy; however, amphotericin B is not available in certain settings. Induction therapy with amphotericin B deoxycholate or voriconazole has been shown to be an effective treatment for talaromycosis. However, prospective clinical trials comparing these two antifungal drugs are absent from the literature.In this open-labeled, multicenter, prospective controlled trial, we enrolled patients at 15 hospitals in China from 2019 to 2020. Participants received induction treatment with either amphotericin B deoxycholate intravenously at a dose of 0.5 to 0.7 mg per kilogram per day or voriconazole at a dose of 6 mg/kg intravenously twice daily for the first day, followed by 4 mg/kg intravenously twice daily for 3 days, and then voriconazole was given either intravenously (4 mg/kg intravenously twice daily) or orally (200 mg twice daily) for the remaining 10 days. The primary outcome was all-cause mortality during 48 weeks after baseline. Secondary outcomes were mortality at week 2 or week 24, clinical resolution of talaromycosis, and fungal clearance at week 2. A propensity score (PS) matching analysis was performed to control confounding factors.We observed no difference in the risk of death at week 2, at week 24, or at week 48 in either the unmatched cohort or the matched cohort. Both in the unmatched and the matched cohorts, logistic regression analysis revealed a significantly lower odds ratio of clinical resolution (OR 0.450, 95% CI 0.291-0.696, p 0.001; OR 0.443, 95% CI 0.261-0.752, p = 0.003) and fungal clearance (OR 0.514, 95% CI 0.333-0.793, p = 0.003; OR 0.542, 95% CI 0.318-0.923, p = 0.024) in voriconazole users compared to amphotericin B deoxycholate users over the course of 2 weeks. In the induction therapy without ART subgroup patients in the amphotericin B deoxycholate group showed a significantly higher rate of clinical resolution and fungal clearance than those in the voriconazole group (56.1% vs. 30.4%, 95% CI 13.4-36.5, p = 0.000; 63.8% vs. 40.4%, 95% CI 11.1-34.7, p = 0.000), whereas there was no significant difference in clinical resolution and fungal clearance in the induction therapy combined with ART subgroup.Induction therapy using voriconazole had a similar efficacy, in terms of all-cause mortality rate, to induction therapy using amphotericin B deoxycholate in HIV-infected patients with talaromycosis over a 48-week observation period. Amphotericin B deoxycholate contributed to earlier fungal clearance and earlier clinical resolution of symptoms in the induction therapy without ART subgroup, whereas amphotericin B deoxycholate use did not contribute to a significant difference in clinical resolution and fungal clearance in the induction therapy combination with ART subgroup.ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .