A Novel Method for Remaining Useful Life Prediction of RF Circuits Based on the Gated Recurrent Unit-Convolutional Neural Network Model.

The remaining useful life (RUL) prediction of RF circuits is an important tool for circuit reliability. Data-driven-based approaches do not require knowledge of the failure mechanism and reduce the dependence on knowledge of complex circuits, and thus can effectively realize RUL prediction. This manuscript proposes a novel RUL prediction method based on a gated recurrent unit-convolutional neural network (GRU-CNN). Firstly, the data are normalized to improve the efficiency of the algorithm; secondly, the degradation of the circuit is evaluated using the hybrid health score based on the Euclidean and Manhattan distances; then, the life cycle of the RF circuits is segmented based on the hybrid health scores; and finally, an RUL prediction is carried out for the circuits at each stage using the GRU-CNN model. The results show that the RMSE of the GRU-CNN model in the normal operation stage is only 3/5 of that of the GRU and CNN models, while the prediction uncertainty is minimized.

Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients.

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P = .002) compared with the control group. Additionally, the time duration of CMV reactivation (P = .001) and bacterial infection rate (P = .013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P = .006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.

Coordination recognition of differential template units of lanthanide chiral chain.

Coordination-driven self-assembly processes often produce remarkable structures. In particular, self-assembly processes mediated by chiral template units have provided research ideas for analyzing the formation of chiral macromolecules in living organisms. In this study, by regulating the proportion of reaction raw materials in the "one-pot" synthesis of lanthanide complexes, we constructed chiral template units with different coordination orientations. As a result, lanthanide chiral chains connected to different structures were obtained through the self-assembly process of coordination recognition. In particular, driven by coordination, chiral template units with codirectional coordination points (called cis configuration) coordinate solely with cis template units during the self-assembly process to obtain a one-dimensional (1D) chain R-1/S-1 with an "S"-shaped distribution. Moreover, chiral template units with reversed coordination sites (called trans configuration) and twisted chiral template units are connected solely to templates with the same configuration to form a 1D chain R-2/S-2 with an axial helix. A circular dichroism spectrum shows that R-1/S-1 and R-2/S-2 are two pairs of enantiomers. The controllable construction of these two differential 1D chains is of great significance for studying coordination recognition at the molecular level. To the best of our knowledge, this is the first study to construct a 1D lanthanide chain through the self-assembly process of coordination recognition. The assembly process of nucleotides to form a hierarchical structure is simulated. This work provides a vivid example of the controllable synthesis of lanthanide complexes with precise structures and offers a new perspective on the formation process of chiral macromolecules that simulates natural processes.

Autophagy is essential for human myelopoiesis.

Emergency myelopoiesis (EM) is essential in immune defense against pathogens for rapid replenishing of mature myeloid cells. During the EM process, a rapid cell-cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs) is critical. How the rapid proliferation of MPs during EM is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor, is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB)-mobilized hematopoietic stem/progenitor cells (HSPCs) with ATG7 knockdown or HSPCs derived from ATG7-/- human embryonic stem cells (hESCs) exhibit severe defect in proliferation during fate transition from HSPCs to MPs. Mechanistically, we show that ATG7 deficiency reduces p53 localization in lysosome for a potential autophagy-mediated degradation. Together, we reveal a previously unrecognized role of autophagy to regulate p53 for a rapid proliferation of MPs in human myelopoiesis.

Function analysis and characterisation of a novel chitinase, MdCht9, in Musca domestica.

Insect chitinases have been proposed as potential targets for pest control. In this work, a novel group IV chitinase gene, MdCht9, from Musca domestica was found to have multiple functions in the physiological activity, including chitin regulation, development and antifungal immunity. The MdCht9 gene was cloned and sequenced, its phylogeny was analysed and its expression was determined in normal and 20E treated larvae. Subsequently, RNA interference (RNAi)-mediated MdCht9 knockdown was performed, followed by biochemical assays, morphological observations and transcriptome analysis. Finally, the recombinant protein MdCht9 (rMdCht9) was purified and tested for anti-microbial activity and enzyme characteristics. The results showed that MdCht9 consists of three domains, highly expressed in a larval salivary gland. RNAi silencing of MdCht9 resulted in significant down-regulation of chitin content and expression of 15 chitin-binding protein (CBP) genes, implying a new insight that MdCht9 might regulate chitin content by influencing the expression of CBPs. In addition, more than half of the lethality and partial wing deformity appeared due to the dsMdCht9 treatment. In addition, the rMdCht9 exhibited anti-microbial activity towards Candida albicans (fungus) but not towards Escherichia coli (G-) or Staphylococcus aureus (G+). Our work expands on previous studies of chitinase while providing a potential target for pest management.

[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Generation of an NSD2-deficient human embryonic stem cell line using CRISPR/Cas9 technology.

NSD2 is a histone methyltransferase (HMT) and is involved in the epigenetic regulation of hematopoiesis and hematological cancers. To understand and illustrate the precise roles of NSD2 in hematopoietic development, here we constructed a human embryonic stem cell (hESC) line with knockout of NSD2 using CRISPR/Cas9-mediated gene targeting. The cell line maintained typical stem cell morphology and normal karyotype. Furthermore, the pluripotency of the cell line was evidenced by high expression level of pluripotency genes and differentiation potential into three germ layers. The cell line provides a good model for studying roles of NSD2 in embryonic development, especially hematopoiesis.

Fabrication of ß-Ga2O3 Nanotubes via Sacrificial GaSb-Nanowire Templates.

ß-Ga2O3 nanostructures are attractive wide-band-gap semiconductor materials as they exhibit promising photoelectric properties and potential applications. Despite the extensive efforts on ß-Ga2O3 nanowires, investigations into ß-Ga2O3 nanotubes are rare since the tubular structures are hard to synthesize. In this paper, we report a facile method for fabricating ß-Ga2O3 nanotubes using pre-synthesized GaSb nanowires as sacrificial templates. Through a two-step heating-treatment strategy, the GaSb nanowires are partially oxidized to form ß-Ga2O3 shells, and then, the residual inner parts are removed subsequently in vacuum conditions, yielding delicate hollow ß-Ga2O3 nanotubes. The length, diameter, and thickness of the nanotubes can be customized by using different GaSb nanowires and heating parameters. In situ transmission electron microscopic heating experiments are performed to reveal the transformation dynamics of the ß-Ga2O3 nanotubes, while the Kirkendall effect and the sublimation process are found to be critical. Moreover, photoelectric tests are carried out on the obtained ß-Ga2O3 nanotubes. A photoresponsivity of ~25.9 A/W and a detectivity of ~5.6 × 1011 Jones have been achieved with a single-ß-Ga2O3-nanotube device under an excitation wavelength of 254 nm.

Hydrothermal Synthesis of Te Nanosheets: Growth Mechanism and Electrical Property.

Hydrothermal synthesis is a highly efficient way to yield multiform Te nanosheets. However, the growth mechanisms and property discrepancies between different types of Te nanosheets are still unclear. In this paper, we perform an investigation on this issue by monitoring the hydrothermally synthesized Te nanosheets at different growth stages with transmission electron microscopy and electrical tests. Three main types of Te nanosheets and their variants are revealed including trapezoidal and "V"-shaped configurations. It is found that the different types of Te nanosheets dominate at different reaction stages, indicating a sequential growth scenario. Surfactants and surface energy co-determine the growth kinetics, while the crystallographic attachments lead to specifically included angles of 74° and 41° in the "V"-shaped Te nanosheets. The fractions of the three main types of Te nanosheets as a function of reaction time are statistically tracked, and their crystalline structures, interfaces, and preferential growth orientations are uncovered. Moreover, the electrical properties of the Te nanosheets are tested, and the results show an interface-related feature. These findings provide some new insights into the synthesis and property of low-dimensional Te functional materials.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

Super-enhancer-associated gene CAPG promotes AML progression.

Acute myeloid leukemia is the most common acute leukemia in adults, the barrier of refractory and drug resistance has yet to be conquered in the clinical. Abnormal gene expression and epigenetic changes play an important role in pathogenesis and treatment. A super-enhancer is an epigenetic modifier that promotes pro-tumor genes and drug resistance by activating oncogene transcription. Multi-omics integrative analysis identifies the super-enhancer-associated gene CAPG and its high expression level was correlated with poor prognosis in AML. CAPG is a cytoskeleton protein but has an unclear function in AML. Here we show the molecular function of CAPG in regulating NF-κB signaling pathway by proteomic and epigenomic analysis. Knockdown of Capg in the AML murine model resulted in exhausted AML cells and prolonged survival of AML mice. In conclusion, SEs-associated gene CAPG can contributes to AML progression through NF-κB.

Impact of lane-changing behavior on traffic emissions of road sections in multi-dimensional mixed traffic flow environment.

This study analyzed the effect of lane-changing behavior on traffic flow emissions and energy consumption of road sections in fuel vehicle-battery electric vehicle (FV-BEV) and human-driven vehicle-cooperative adaptive cruise control (HDV-CACC) multi-dimensional mixed traffic flow environments. Based on the traditional energy consumption model, a multi-dimensional mixed traffic flow energy consumption model was established by considering the BEV and CACC penetration rates. The microscopic traffic flow theory approach was used to analyze lane-changing behavior and the influencing mechanism of lane-changing behavior on the energy consumption of multi-dimensional mixed traffic flow, and MATLAB was used for the experimental simulation. The lane-changing behavior of the leading vehicle had a negative impact on the energy consumption of road segment traffic flow. Within the 95% effective impact range, the average energy consumption of traffic flow with respect to lane-changing behavior was 7.8% higher than that of the following traffic flow. The BEV penetration rate was beneficial for reducing the energy consumption of mixed traffic flow. At an economic velocity, the energy consumption of homogeneous BEV traffic flow was only 58.3% of that of homogeneous FV traffic flow. The CACC penetration rate could increase the traffic flow toughness. When the BEV penetration rate was constant, the higher the CACC penetration rate, the smaller the impact of lane-changing behavior on emissions. When traffic flow was completely transformed to homogeneous CACC traffic flow, lane-changing behavior only increased the overall energy consumption of the traffic flow by 4.99%, which was lower than the average level. Consequently, the promotion of BEV and CACC can improve the impact of traffic emissions on air pollution. When CACC penetration is low, reducing unnecessary lane-changing behavior to ensure the stability of traffic flow is also an effective way to reduce emissions.Implications: Multi-dimensional mixed traffic flow energy consumption model is proposed.CACC penetration rate, BEV penetration rate and lane-changing behavior will change traffic energy consumption. In this paper, different influencing factors are analyzed one by one.It provides a theoretical basis for relevant departments of traffic management to optimize vehicle emissions and traffic organization.

Optimization model for bus priority control considering carbon emissions.

To study the impact of bus priority control (BPC) on traffic carbon emissions under the strategies of speed guidance, green extension (GE), and red truncation (RT), with consideration of the main influencing factors such as delay, stopping times, and speed, a combination optimization method was used to develop a bi-level optimization model for BPC. The optimal carbon-emission reductions of buses and social vehicles with different fuel types in the upstream section of the intersection and the intersection control area was the upper-level objective, and the optimal total passenger-delay reduction was the lower-level objective. The Gauss - Seidel iterative algorithm was used to solve the model. Finally, the model was applied to the analysis of calculation cases. The results indicated that after BPC was adopted under the guidance acceleration strategy, the reductions in the carbon emissions and total delay of passenger were optimal when the guidance speed was 38 km/h, i.e. 12.67% and 21.05%, respectively. Under the guidance acceleration and GE strategy, the reductions in the carbon emissions and total delay of passenger were optimal when the guidance speed was 39 km/h and the GE was 6 s, i.e. 27.49% and 38.62%, respectively. Under the guidance deceleration and RT strategy, the reductions in the carbon emissions and total delay of passenger were optimal when the guidance speed was 29 km/h and the RT was 6 s, i.e. 22.18% and 33.52%, respectively. The model reduced the carbon emissions and total delay of passenger in the upstream section of the intersection and the intersection control area to achieve the optimal overall traffic benefit for the intersection.

Two bus signal priority control strategies ­ green extension and red truncation ­ were studied.Carbon emission and delay calculation methods under the bus priority control were developed.Considering carbon-emission reductions of buses and social vehicles with different fuel types under different working conditions.Three control methods were studied: guidance acceleration, guidance acceleration and green extension, and guidance deceleration and red truncation.

Revealing the alloying and dealloying behaviours in AuAg nanorods by thermal stimulus.

Binary metallic nanocrystals are attractive as they offer an extra degree of freedom for structure and phase modulation to generate synergistic effects and extraordinary properties. However, whether the binary structures and phases at the nanoscale still follow the rules established on the bulk counterparts remains unclear. In this work, AuAg nanorods were used as a sample to probe into this issue. An in situ heating method by combining aberration-corrected transmission electron microscopes with a chip-based heating holder was employed to perform the heating experiments. It was found that the AuAg nanorods, which initially possessed heterostructures, can be designed and engineered to be gradient phase alloys with thermal pulses over 350 °C. Atomic diffusion inside the rod structures did not alter the shape of the rods but provided a route to fine-tune their properties. At higher temperatures, the discrepant sublimation behaviours between Au and Ag lead to dealloying of the nanorods. Durative sublimation of the Ag element can continuously tailor the lengths of the nanorods while concentrating the Au composition simultaneously. Especially, nearly pure Au nanocrystals can be obtained with the depletion of Ag by sublimation. These findings give insights into the nanoscale structure and phase behaviours in binary alloys and provide an alternative way to fine-tune their structure, phase, and properties.

The Application and Efficacy of Second Allogeneic Hematopoietic Stem Cell Transplantation in Acute Leukemia.

BACKGROUND: We retrospectively analyzed the application and clinical efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia patients who relapsed or had primary graft failure (PGF) after first transplantation. METHODS: From 2007 to 2021, eight patients with acute leukemia who received second allo-HSCT in our hospital were collected, including 6 relapsed patients and 2 patients with PGF after the first HSCT. RESULTS: All the patients received complete donor implantation after second transplantation. The median time of neutrophils and platelet implantation were 12 days (10 days - 13 days) and 23 days (12 days - 123 days). Two cases (25.0%) developed grade II aGVHD, and 4 cases (50.0%) developed cGVHD. Leukemia-free survival (LFS) and overall survival (OS) at 1 year both were 71.4% and at 3 years both were 28.6%. After a median follow-up of 1,556 days (range, 257 - 5,252 days), 3 of the patients (37.5%) survived and 5 (62.5%) died. One patient with NR before second transplantation, treated with a conditioning regime of CLAG-M bridging BuCy, has survived for more than 5 years (61 months). Relapse was the main death reason. CONCLUSIONS: Second allo-HSCT is an effective means to treat acute leukemia patients with relapsed and PGF after first transplantation.

CMV infection is a risk factor for hemorrhagic cystitis after hematopoietic stem cell transplantation.

Hemorrhagic cystitis (HC) is a common complication after transplantation. The purpose of this study was to examine the incidence and risk factors for HC after hematopoietic stem cell transplantation (HSCT). The records of patients who underwent allogenic HSCT from January 2012 to December 2018 at our institution were retrospectively reviewed. Cox proportional regression and Kaplan-Meier analyses were performed to determine independent risk factors for HC. The statistical analysis was performed in May 2020. A total of 173 patients underwent HSCT, and 53 (30.6%) developed grade 2 or 3 HC cystitis at a median of 37 days (range - 5 to 98 days) after transplantation. Thirty-two patients developed moderate (grade 2) cystitis and 21 severe (grade 3) cystitis. Of the 173 patients, 61 developed acute graft-versus-host disease (GVHD) (median onset day 24) and 79 experienced cytomegalovirus (CMV) reactivation (median onset day 35). The relative risk (RR) of developing a CMV infection for patients with acute GVHD was 2.77 times that of patients without acute GVHD (P < 0.001). CMV infection was the only independent variable significantly associated with HC in both univariate and multivariate analyses. The estimated hazard ratio (HR) of CMV infection for the development of HC was 5.57 (95% confidence interval [CI]: 2.52 to 12.33, P < 0.001). CMV infection is an independent risk factor for the development of HC after HSCT, and acute GVHD is a risk factor for CMV reactivation. Decreasing the frequency of GVHD after HSCT may result in a lower frequency of HC.

Diagnosis and treatment for the early stage of cytomegalovirus infection during hematopoietic stem cell transplantation.

Cytomegalovirus (CMV) infection remains a frequent complication after hematopoietic stem cell transplantation (HSCT) and causes significant morbidity and mortality in transplantation recipients. In this review, we highlight the role of major risk factors that are associated with the incidence of CMV infection. Advances in immunosurveillance may predict CMV infection, allowing early interventions to prevent severe infection. Furthermore, numerous therapeutic strategies against CMV infection after HSCT are summarized. A comprehensive understanding of the current situation of CMV treatment may provide a hint for clinical practice and even promote the development of novel strategies for precision medicine.

Assembly of pinwheel/twist-shaped chiral lanthanide clusters with rotor structures by an annular/linear growth mechanism and their magnetic properties.

Although progress has been made in the design and synthesis of chiral lanthanide clusters with pleasing structural connections and special shapes, assembly rules that guide their directional construction are still lacking. We reacted R/S-mandelic acid hydrazide, 2,3-dihydroxybenzaldehyde and DyCl3·6H2O under solvothermal conditions to obtain two octanuclear chirality clusters R-1 and S-1, which are the enantiomers of each other. R/S-mandelic acid hydrazide and 2,3-dihydroxybenzaldehyde underwent an in situ reaction under "one-pot" conditions to generate a monohydrazone-type organic ligand R/S-mandelic acid hydrazide-2,3-dihydroxybenzaldehyde hydrazone (R/S-H2L). Four R/S-H2L ligands captured eight metal-centered Dy(III) ions and presented an annular arrangement, which assembled to form a pinwheel-shaped chiral cluster R/S-1. The benzene rings at the four vertices of R/S-1 can rotate freely as rotors. This is the first discovery of an annular growth mechanism during the self-assembly of lanthanide clusters. By changing the metal salt to Dy(NO3)3·6H2O, two twist-shaped hexanuclear clusters R-2 and S-2, which are the enantiomers of each other were obtained. Four R/S-H2L and two R/S-H3L ligands captured six metal-centered Dy(III) ions, respectively, and were assembled through a linear growth mechanism to form the twist-shaped chiral clusters R/S-2. This is the first time that a linear growth mechanism has been proposed for the directional construction of lanthanide clusters with specific shapes. Circular dichroism results showed that R/S-1 and R/S-2 were both chiral clusters and enantiomers of each other. Magnetic studies showed that both R/S-1 and R/S-2 exhibit obvious single-molecule magnet (SMM) behaviors under zero-field conditions. This work is the first to propose an annular/linear growth mechanism for the design and synthesis of lanthanide clusters and allows the directional construction of chiral lanthanide clusters with special shapes and structural connections.

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function.

Global burden of fungal infections and related health risk has accelerated at an incredible pace, and multidrug resistance emergency aggravates the need for the development of new effective strategies. Candida albicans is clinically the most ubiquitous pathogenic fungus that leads to high incidence and mortality in immunocompromised patients. Antimicrobial peptides (AMPs), in this context, represent promising alternatives having potential to be exploited for improving human health. In our previous studies, a Cecropin-4-derived peptide named C18 was found to possess a broader antibacterial spectrum after modification and exhibit significant antifungal activity against C. albicans. In this study, C18 shows antifungal activity against C. albicans or non-albicans Candida species with a minimum inhibitory concentration (MIC) at 4∼32 µg/ml, and clinical isolates of fluconazole (FLZ)-resistance C. tropicalis were highly susceptible to C18 with MIC value of 8 or 16 µg/ml. Additionally, C18 is superior to FLZ for killing planktonic C. albicans from inhibitory and killing kinetic curves. Moreover, C18 could attenuate the virulence of C. albicans, which includes damaging the cell structure, retarding hyphae transition, and inhibiting biofilm formation. Intriguingly, in the Galleria mellonella model with C. albicans infection, C18 could improve the survival rate of G. mellonella larvae to 70% and reduce C. albicans load from 5.01 × 107 to 5.62 × 104 CFU. For mechanistic action of C18, the level of reactive oxygen species (ROS) generation and cytosolic Ca2 + increased in the presence of C18, which is closely associated with mitochondrial dysfunction. Meanwhile, mitochondrial membrane potential (△Ψm) loss and ATP depletion of C. albicans occurred with the treatment of C18. We hypothesized that C18 might inhibit C. albicans via triggering mitochondrial dysfunction driven by ROS generation and Ca2 + accumulation. Our observation provides a basis for future research to explore the antifungal strategies and presents C18 as an attractive therapeutic candidate to be developed to treat candidiasis.

Vitamin C promotes anti-leukemia of DZNep in acute myeloid leukemia.

The epigenetic treatment by 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, shows great potential against acute myeloid leukemia (AML). However, the variant sensitivity and incomplete response to DZNep are commonly observed. Here, we reveal that vitamin C (Vc) dramatically promotes DZNep response against leukemic cells in different cell lines and primary AML samples. Vc enhances apoptosis and differentiation induced by DZNep in different AML cell lines in vitro and reduces leukemia progression in vivo. At the molecular level, Vc downregulates an enzyme of serine synthesis named D-3-phosphoglycerate dehydrogenase (PHGDH), as well as BCL2, an anti-apoptotic gene. Over-expression of PHGDH reverses the Vc-enhanced anti-leukemic effect of DZNep in AML cells. Therefore, our findings provide an effective approach to reduce the resistance against epigenetic treatment by Vc, which shows a potential improvement of their combination in AML patients.