Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis.

The glycerol-3-phosphate shuttle (G3PS) is a major NADH shuttle that regenerates reducing equivalents in the cytosol and produces energy in the mitochondria. Here, we demonstrate that G3PS is uncoupled in kidney cancer cells where the cytosolic reaction is ∼4.5 times faster than the mitochondrial reaction. The high flux through cytosolic glycerol-3-phosphate dehydrogenase (GPD) is required to maintain redox balance and support lipid synthesis. Interestingly, inhibition of G3PS by knocking down mitochondrial GPD (GPD2) has no effect on mitochondrial respiration. Instead, loss of GPD2 upregulates cytosolic GPD on a transcriptional level and promotes cancer cell proliferation by increasing glycerol-3-phosphate supply. The proliferative advantage of GPD2 knockdown tumor can be abolished by pharmacologic inhibition of lipid synthesis. Taken together, our results suggest that G3PS is not required to run as an intact NADH shuttle but is instead truncated to support complex lipid synthesis in kidney cancer.

Tryptophanylation of insulin receptor by WARS attenuates insulin signaling.

Increased circulating amino acid levels have been linked to insulin resistance and development of type 2 diabetes (T2D), but the underlying mechanism remains largely unknown. Herein, we show that tryptophan modifies insulin receptor (IR) to attenuate insulin signaling and impair glucose uptake. Mice fed with tryptophan-rich chow developed insulin resistance. Excessive tryptophan promoted tryptophanyl-tRNA synthetase (WARS) to tryptophanylate lysine 1209 of IR (W-K1209), which induced insulin resistance by inhibiting the insulin-stimulated phosphorylation of IR, AKT, and AS160. SIRT1, but not other sirtuins, detryptophanylated IRW-K1209 to increase the insulin sensitivity. Collectively, we unveiled the mechanisms of how tryptophan impaired insulin signaling, and our data suggested that WARS might be a target to attenuate insulin resistance in T2D patients.

Unveiling the Twisted Aromatic Donor Effect on the Nonlinear Response of D-π-A Type Malononitrile-Derived Chromophores.

This study presents the design, synthesis, and comprehensive characterization of a novel series of D-π-A type malononitrile-derived chromophores, BTC-1-BTC-4. Combining various spectroscopic techniques, nonlinear Z-scan measurements, and quantum chemical calculations, we revealed the intricate relationship between nonlinear optical properties and the interplay of molecular structure, intramolecular charge transfer (ICT), and dipole moments (µ). Our experimental and computational findings corroborate that the polarization degree in the ground state, the charge separation in the excited state and twisted intramolecular charge transfer (TICT) collectively dictate the nonlinear optical properties of the compounds. Notably, BTC-1 exhibits an exceptional nonlinear absorption coefficient ß value (2×10-8 m W-1), attributed to its optimized charge transfer efficiency and pronounced degree of charge separation. Our findings provide actionable insights for the rational design of high-performance organic Nonlinear optics (NLO) materials with potential applications in advanced photonic devices.

In Situ Growth of MoN on Nickel Foam for Highly Efficient Hydrogen Evolution in Alkaline Solution.

Highly efficient, stable, and low-cost hydrogen evolution catalysts are urgently required for water electrolysis. Herein, a method for in situ growth of medium-nitrogen nanosheet MoN catalysts with a large electrochemical surface area on nickel foam (NF) is proposed. The results show that the morphology of the as-prepared catalysts greatly depends on the nitrogen sources and nitridation temperature. The MoN/NF catalyst nitride at 700 °C using melamine as a nitrogen source exhibits a spindle-like morphology consisting of stacked nanosheets, which is conducive to exposing more active sites, thereby increasing the catalyst activity. The N atoms in MoN could adjust the chemical environment of the metal by changing the density of the d-band electron state, which further improves the HER performance. Benefiting from the regulation of Mo charge distribution and exposure to more active sites through N doping and morphological control, the MoN/NF catalyst exhibits superior HER performance with an overpotential of 70 mV at a current density of 10 mA·cm-2, a Tafel slope of 44.3 mV dec-1, and an Rct of 1.83 Ω, indicating high HER catalytic activity, fast kinetics, and excellent conductivity. Theoretical calculations reveal that among the (002), (202), and (200) planes of MoN, the (202) plane exhibits the lowest value of |ΔGH*| (0.47 eV), which is close to that of Pt(111) (0.14 eV). More importantly, MoN(202) also has the smallest work function of 3.58 eV, indicating an enhanced capability to offer electrons. This work develops a strategy to design high-performance and low-cost transition-metal nitride HER catalysts.

Degradation of Rhodamine B by Visible Light Driven MoO3@TiO2 Core-Shell Photocatalyst.

In this study, a MoO3@TiO2 composite core-shell material was developed to remove Rhodamine B (RhB) dye through synergistic adsorption and photocatalytic degradation. n-n heterostructures were formed by coupling n-type semiconductors to enhance the efficiency of photocarrier separation and photocatalytic performance. MoO3, which possesses strong adsorption capacity, was primarily used as a dye adsorbent. Additionally, the formation of an n-n heterojunction with TiO2 enabled MoO3 to expand the photocorresponding range of TiO2, leading to the generation of superoxide (O2•) and hydroxyl (•OH) free radicals for dye degradation. The experimental results demonstrate that the MoO3@TiO2 core-shell composite exhibits excellent performance for RhB dye removal, with adsorption and degradation rates reaching 35.7 and 70.3%, respectively, even at low catalyst concentrations. This approach offers new insights into the development of MoO3 core-shell photocatalysts.

Control charts in healthcare quality monitoring: a systematic review and bibliometric analysis.

Control charts, used in healthcare operations to monitor process stability and quality, are essential for ensuring patient safety and improving clinical outcomes. This comprehensive research study aims to provide a thorough understanding of the role of control charts in healthcare quality monitoring and future perspectives by utilizing a dual methodology approach involving a systematic review and a pioneering bibliometric analysis. A systematic review of 73 out of 223 articles was conducted, synthesizing existing literature (1995-2023) and revealing insights into key trends, methodological approaches, and emerging themes of control charts in healthcare. In parallel, a bibliometric analysis (1990-2023) on 184 articles gathered from Web of Science and Scopus was performed, quantitatively assessing the scholarly landscape encompassing control charts in healthcare. Among 25 countries, the USA is the foremost user of control charts, accounting for 33% of all applications, whereas among 14 health departments, epidemiology leads with 28% of applications. The practice of control charts in health monitoring has increased by more than one-third during the last 3 years. Globally, exponentially weighted moving average charts are the most popular, but interestingly the USA remained the top user of Shewhart charts. The study also uncovers a dynamic landscape in healthcare quality monitoring, with key contributors, research networks, research hotspot tendencies, and leading countries. Influential authors, such as J.C. Benneyan, W.H. Woodall, and M.A. Mohammed played a leading role in this field. In-countries networking, USA-UK leads the largest cluster, while other clusters include Denmark-Norway-Sweden, China-Singapore, and Canada-South Africa. From 1990 to 2023, healthcare monitoring evolved from studying efficiency to focusing on conditional monitoring and flowcharting, with human health, patient safety, and health surveys dominating 2011-2020, and recent years emphasizing epidemic control, COronaVIrus Disease of 2019 (COVID-19) statistical process control, hospitals, and human health monitoring using control charts. It identifies a transition from conventional to artificial intelligence approaches, with increasing contributions from machine learning and deep learning in the context of Industry 4.0. New researchers and journals are emerging, reshaping the academic context of control charts in healthcare. Our research reveals the evolving landscape of healthcare quality monitoring, surpassing traditional reviews. We uncover emerging trends, research gaps, and a transition in leadership from established contributors to newcomers amidst technological advancements. This study deepens the importance of control charts, offering insights for healthcare professionals, researchers, and policymakers to enhance healthcare quality. Future challenges and research directions are also provided.

The predictive utility of cytokines, procalcitonin and C-reactive protein among febrile pediatric hematology and oncology patients with severe sepsis or septic shock.

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.

Ballistic PbTe Nanowire Devices.

Disorder is the primary obstacle in the current Majorana nanowire experiments. Reducing disorder or achieving ballistic transport is thus of paramount importance. In clean and ballistic nanowire devices, quantized conductance is expected, with plateau quality serving as a benchmark for disorder assessment. Here, we introduce ballistic PbTe nanowire devices grown by using the selective-area-growth (SAG) technique. Quantized conductance plateaus in units of 2e2/h are observed at zero magnetic field. This observation represents an advancement in diminishing disorder within SAG nanowires as most of the previously studied SAG nanowires (InSb or InAs) have not exhibited zero-field ballistic transport. Notably, the plateau values indicate that the ubiquitous valley degeneracy in PbTe is lifted in nanowire devices. This degeneracy lifting addresses an additional concern in the pursuit of Majorana realization. Moreover, these ballistic PbTe nanowires may enable the search for clean signatures of the spin-orbit helical gap in future devices.

Poly(ethylene oxide) Concentration Gradient-Based Microfluidic Isolation of Circulating Tumor Cells.

Circulating tumor cells (CTCs) have emerged as promising circulating biomarkers for non-invasive cancer diagnosis and management. Isolation and detection of CTCs in clinical samples are challenging due to the extreme rarity and high heterogeneity of CTCs. Here, we describe a poly(ethylene oxide) (PEO) concentration gradient-based microfluidic method for rapid, label-free, highly efficient isolation of CTCs directly from whole blood samples. Stable concentration gradients of PEO were formed within the microchannel by co-injecting the side fluid (blood sample spiked with 0.025% PEO) and center fluid (0.075% PEO solution). The competition between the elastic lift force and the inertial lift force enabled size-based separation of large CTCs and small blood cells based on their distinct migration patterns. The microfluidic device could process 1 mL of blood sample in 30 min, with a separation efficiency of >90% and an enrichment ratio of >700 for tumor cells. The isolated CTCs from blood samples were enumerated by immunofluorescence staining, allowing for discrimination of breast cancer patients from healthy donors with an accuracy of 84.2%. The concentration gradient-based microfluidic separation provides a powerful tool for label-free isolation of CTCs for a wide range of clinical applications.

Unveiling Superior Capacitive Behaviors of One-Pot Molten Salt-Engineered B, N Co-Doped Porous Carbon Sheets.

Heteroatom-doped porous carbon materials with distinctive surface properties and capacitive behavior have been accepted as promising candidates for supercapacitor electrodes. Currently, the researches mainly focus on developing facile synthetic method and unveiling the structure-activity relationship to further elevate their capacitive performance. Here, the B, N co-doped porous carbon sheet (BN-PCS) is constructed by one-pot pyrolysis of agar in KCl/KHCO3 molten salt system. In this process, the urea acts as directing agent to guide the formation of 2D sheet morphology, and the decomposition of KHCO3 and boric acid creates rich micro- and mesopores in the carbon framework. The specific capacitance of optimized BN-PCS reaches 361.1 F g-1 at a current density of 0.5 A g-1 in an aqueous KOH electrolyte. Impressively, the fabricated symmetrical supercapacitor affords a maximum energy density of 43.5 Wh kg-1 at the power density of 375.0 W kg-1 in 1.0 mol L-1 TEABF4 /AN electrolyte. It also achieves excellent long-term stability with capacitance retention of 91.1% and Columbic efficiency of 100% over 10 000 cycles. This study indicates one-pot molten salt method is effective in engineering advanced carbon materials for high-performance energy storage devices.

Downregulation of NUP93 aggravates hypoxia-induced death of cardiomyocytes in vitro through abnormal regulation of gene transcription.

Nuclear pore complex in the nuclear envelope plays an important role in controlling the transportation of RNAs, proteins and other macromolecules between the nucleus and cytoplasm. The relationship between abnormal expression of nucleoporins and cardiovascular diseases is unclear. In this study we investigated how myocardial infarction affected the expression and function of nucleoporins in cardiomyocytes. We separately knocked down 27 nucleoporins in rat primary myocardial cells. Among 27 nucleoporins, knockdown of Nup93, Nup210 and Nup214 markedly increased the expression of ANP and BNP, two molecular markers of cardiomyocyte function. We showed that Nup93 was significantly downregulated in hypoxic cardiomyocytes. Knockdown of Nup93 aggravated hypoxia-induced injury and cell death of cardiomyocytes, whereas overexpression of Nup93 led to the opposite effects. RNA-seq and bioinformatics analysis revealed that knockdown of Nup93 did not affect the overall transportation of mRNAs from the nucleus to the cytoplasm, but regulated the transcription of a large number of mRNAs in cardiomyocytes, which are mainly involved in oxidative phosphorylation and ribosome subunits. Most of the down-regulated genes by Nup93 knockdown overlapped with the genes whose promoters could be directly bound by Nup93. Among these genes, we demonstrated that Nup93 knockdown significantly down-regulated the expression of YAP1. Overexpression of YAP1 partially rescued the function of Nup93 knockdown and attenuated the effects of hypoxia on cell injury and cardiomyocyte death. We conclude that down-regulation of Nup93, at least partially, contributes to hypoxia-induced injury and cardiomyocyte death through abnormal interaction with the genome to dynamically regulate the transcription of YAP1 and other genes. These results reveal a new mechanism of Nup93 and might provide new therapeutic targets for the treatment of ischemia-induced heart failure.

Spectrum and clinical features of gene mutations in Chinese pediatric acute lymphoblastic leukemia.

PURPOSE: The 5-year survival rate of children with acute lymphoblastic leukemia (ALL) is 85-90%, with a 10-15% rate of treatment failure. Next-generation sequencing (NGS) identified recurrent mutated genes in ALL that might alter the diagnosis, classification, prognostic stratification, treatment, and response to ALL. Few studies on gene mutations in Chinese pediatric ALL have been identified. Thus, an in-depth understanding of the biological characteristics of these patients is essential. The present study aimed to characterize the spectrum and clinical features of recurrent driver gene mutations in a single-center cohort of Chinese pediatric ALL. METHODS: We enrolled 219 patients with pediatric ALL in our single center. Targeted sequencing based on NGS was used to detect gene mutations in patients. The correlation was analyzed between gene mutation and clinical features, including patient characteristics, cytogenetics, genetic subtypes, risk stratification and treatment outcomes using χ2-square test or Fisher's exact test for categorical variables. RESULTS: A total of 381 gene mutations were identified in 66 different genes in 152/219 patients. PIK3R1 mutation was more common in infants (P = 0.021). KRAS and FLT3 mutations were both more enriched in patients with hyperdiploidy (both P < 0.001). NRAS, PTPN11, FLT3, and KMT2D mutations were more common in patients who did not carry the fusion genes (all P < 0.050). PTEN mutation was significantly associated with high-risk ALL patients (P = 0.011), while NOTCH1 mutation was common in middle-risk ALL patients (P = 0.039). Patients with ETV6 or PHF6 mutations were less sensitive to steroid treatment (P = 0.033, P = 0.048, respectively). CONCLUSION: This study depicted the specific genomic landscape of Chinese pediatric ALL and revealed the relevance between mutational spectrum and clinical features of Chinese pediatric ALL, which highlights the need for molecular classification, risk stratification, and prognosis evaluation.

The optimal control chart selection for monitoring COVID-19 phases: a case study of daily deaths in the USA.

Epidemiologists frequently adopt statistical process control tools, like control charts, to detect changes in the incidence or prevalence of a specific disease in real time, thereby protecting against outbreaks and emergent health concerns. Control charts have proven essential in instantly identifying fluctuations in infection rates, spotting emerging patterns, and enabling timely reaction measures in the context of COVID-19 monitoring. This study aims to review and select an optimal control chart in epidemiology to monitor variations in COVID-19 deaths and understand pandemic mortality patterns. An essential aspect of the present study is selecting an appropriate monitoring technique for distinct deaths in the USA in seven phases, including pre-growth, growth, and post-growth phases. Stage-1 evaluated control chart applications in epidemiology departments of 12 countries between 2000 and 2022. The study assessed various control charts and identified the optimal one based on maximum shift detection using sample data. This study considered at Shewhart ($\bar X$, $R$, $C$) control charts and exponentially weighted moving average (EWMA) control chart with smoothing parameters λ = 0.25, 0.5, 0.75, and 1 were all investigated in this study. In Stage-2, we applied the EWMA control chart for monitoring because of its outstanding shift detection capabilities and compatibility with the present data. Daily deaths have been monitored from March 2020 to February 2023. Control charts in epidemiology show growing use, with the USA leading at 42% applications among top countries. During the application on COVID-19 deaths, the EWMA chart accurately depicted mortality dynamics from March 2020 to February 2022, indicating six distinct stages of death. The third and fifth waves were extremely catastrophic, resulting in a considerable loss of life. Significantly, a persistent sixth wave appeared from March 2022 to February 2023. The EWMA map effectively determined the peaks associated with each wave by thoroughly examining the time and amount of deaths, providing vital insights into the pandemic's progression. The severity of each wave was measured by the average number of deaths $W5(1899)\,\gt\,W3(1881)\,\gt\,W4(1393)\,\gt\,W1(1036)\,\gt\,W2(853)\,\gt\,(W6(473)$. The USA entered a seventh phase (6th wave) from March 2022 to February 2023, marked by fewer deaths. While reassuring, it remains crucial to maintain vaccinations and pandemic control measures. Control charts enable early detection of daily COVID-19 deaths, providing a systematic strategy for government and medical staff. Incorporating the EWMA chart for monitoring immunizations, cases, and deaths is recommended.

Fabrication of Hierarchically Porous CuBTC@PA-PEI Composite for High-Efficiency Elimination of Cyanogen Chloride.

Cyanogen chloride (CNCl) is highly toxic and volatile, and it is difficult to effectively remove via porous substances such as activated carbon due to the weak interaction between CNCl and the adsorbent surface. Developing a highly effective elimination material against CNCl is of great importance in military chemical protection. In this work, a new metal-organic framework (MOF) CuBTC@PA-PEI (polyacrylate-polyethyleneimine) composite was prepared and exhibited excellent CNCl elimination performance in the breakthrough tests. PEI was used for the functionalization of PA with amino groups, which is beneficial to anchor with metal ions of MOF. Afterward, the growth of MOF occurred on the surface and in the pores of the matrix by molecular self-assembly via our newly proposed stepwise impregnation layer-by-layer growth method. Breakthrough tests were performed to evaluate the elimination performance of the composites against CNCl. Compared with the pristine CuBTC powder, the CuBTC@PA-PEI composite exhibited better adsorption capacity and a longer breakthrough time. By compounding with the PA matrix, a hierarchically porous structure of CuBTC@PA-PEI composite was constructed, which provides a solution to the mass transfer problem of pure microporous MOF materials. It also solves the problems of MOF molding and lays a foundation for the practical application of MOF.

Caspase-6-cleaved tau is relevant in Alzheimer's disease and marginal in four-repeat tauopathies: Diagnostic and therapeutic implications.

AIM: Tau truncation (tr-tau) by active caspase-6 (aCasp-6) generates tau fragments that may be toxic. Yet the relationship between aCasp-6, different forms of tr-tau and hyperphosphorylated tau (p-tau) accumulation in human brains with Alzheimer's disease (AD) and other tauopathies remains unclear. METHODS: We generated two neoepitope monoclonal antibodies against tr-tau sites (D402 and D13) targeted by aCasp-6. Then, we used five-plex immunofluorescence to quantify the neuronal and astroglial burden of aCasp-6, tr-tau, p-tau and their co-occurrence in healthy controls, AD and primary tauopathies. RESULTS: Casp-6 activation was strongest in AD and Pick's disease (PiD) but almost absent in 4-repeat (4R) tauopathies. In neurons, the tr-tau burden was much more abundant in AD and PiD than in 4R tauopathies and disproportionally higher when normalising by p-tau pathology. Tr-tau astrogliopathy was detected in low numbers in 4R tauopathies. Unexpectedly, about half of tr-tau positive neurons in AD and PiD lacked p-tau aggregates, a finding we confirmed using several p-tau antibodies. CONCLUSIONS: Early modulation of aCasp-6 to reduce tr-tau pathology is a promising therapeutic strategy for AD and PiD but is unlikely to benefit 4R tauopathies. The large percentage of tr-tau-positive neurons lacking p-tau suggests that many vulnerable neurons to tau pathology go undetected when using conventional p-tau antibodies. Therapeutic strategies against tr-tau pathology could be necessary to modulate the extent of tau abnormalities in AD. The disproportionally higher burden of tr-tau in AD and PiD supports the development of biofluid biomarkers against tr-tau to detect AD and PiD and differentiate them from 4R tauopathies at a patient level.

HFIP as Protonation Reagent and Solvent for Regioselective Alkylation of Indoles with All-Carbon Centers.

The regio- and chemoselective construction of indole bearing an all-carbon center at the C3-position, a versatile bioactive building block, by C(sp2)-C(sp3) formation with olefins has been achieved through utilization of hexafluoroisopropanol (HFIP) as the protonation reagent and solvent. The catalytic reactions are operationally simple and green compared with previous reports utilizing elaborated olefins and catalysts. This protocol allows for alkylation of a variety of substituted indoles with diverse of styrene type alkenes in excellent yields and with high selectivity. Application of this protocol to the synthesis of drug was pursued and with an improved yield in contrast to previous art. Catalytic kinetics and deuterium-labeling experiments suggest that the rate-determining step involves the protonation of olefin by HFIP to generate carbocation, followed by electrophilic addition to indole derivative.

Cardiovascular-specific PSEN1 deletion leads to abnormalities in calcium homeostasis.

Mutations of PSEN1 have been reported in dilated cardiomyopathy pedigrees. Understanding the effects and mechanisms of PSEN1 in cardiomyocytes might have important implications for treatment of heart diseases. Here, we showed that PSEN1 was downregulated in ischemia-induced failing hearts. Functionally, cardiovascular specific PSEN1 deletion led to spontaneous death of the mice due to cardiomyopathy. At the age of 11 months, the ratio of the heart weight/body weight was slightly lower in the Sm22a-PSEN1-KO mice compared with that of the WT mice. Echocardiography showed that the percentage of ejection fraction and fractional shortening was significantly reduced in the Sm22a-PSEN1-KO group compared with the percent of these measures in the WT group, indicating that PSEN1-KO resulted in heart failure. The abnormally regulated genes resulted from PSEN1-KO were detected to be enriched in muscle development and dilated cardiomyopathy. Among them, several genes encode Ca2+ ion channels, promoting us to investigate the effects of PSEN1 KO on regulation of Ca2+ in isolated adult cardiomyocytes. Consistently, in isolated adult cardiomyocytes, PSEN1-KO increased the concentration of cytosolic Ca2+ and reduced Ca2+ concentration inside the sarcoplasmic reticulum (SR) lumen at the resting stage. Additionally, SR Ca2+ was decreased in the failing hearts of WT mice, but with the lowest levels observed in the failing hearts of PSEN1 knockout mice. These results indicate that the process of Ca2+ release from SR into cytoplasm was affected by PSEN1 KO. Therefore, the abnormalities in Ca2+ homeostasis resulted from downregulation of PSEN1 in failing hearts might contribute to aging-related cardiomyopathy, which might had important implications for the treatment of aging-related heart diseases.

Treatment of Relapsed and Refractory ALK-Positive Anaplastic Large Cell Lymphoma With ALK-Specific Tyrosine Kinase Inhibitor in Children: A Case Series.

Relapsed and refractory ALK-positive anaplastic large cell lymphoma (ALCL) has a poor prognosis. In this report, we present 3 relapsed/refractory pediatric ALCL patients, 1 of these with central nervous system involvement. All 3 patients were treated with ALK inhibitor and achieved complete response. Both crizotinib and alectinib have shown significant activity in pediatric patients with refractory ALK-positive ALCL.

A Novel NUP98/RARG Gene Fusion in Pediatric Acute Myeloid Leukemia Resembling Acute Promyelocytic Leukemia.

Here, we introduced the first case of acute myeloid leukemia (AML) with RARG-NUP98 in a pediatric patient. The young male presented with structural and functional abnormalities similar to hypergranular acute promyelocytic leukemia, but was resistant to all transretinoic acids and arsenic trioxide. Till date, only 12 adult AML cases involving RARG rearrangement have been reported. At present, there is no standardized or optimal treatment option for this AML subtype. Disease management may typically require a joint treatment strategy involving chemotherapy, immunotherapy, and support therapy. In this study, we report the clinical manifestations and experimental results of a 10-year-old male and review other cases of RARG gene rearrangement reported in the literature.

Transferrin receptors/magnetic resonance dual-targeted nanoplatform for precise chemo-photodynamic synergistic cancer therapy.

Various drug delivery strategies to improve cancer therapeutic efficacy have been actively investigated. One major challenge is to improve the targeting ability. Here elaborately designed nanocarriers (NCs) named as Tf-5-ALA-PTX-NCs are demonstrated to address this problem. In this nanostructure, paclitaxel (PTX) and 5-aminolevulinic acid (5-ALA) were co-encapsulated within magnetic nanocarriers to achieve synergistic chemotherapy and photodynamic therapy, while transferrin (Tf) was conjugated with modified copolymer Pluronic P123 and embedded in the surface of the nanocarriers, which endows nanocarriers with Tf targeting and magnetic targeting to enhance the anti-tumor outcome. Results demonstrated that Tf-5-ALA-PTX-NCs significantly enhanced the targeting drug delivery to MCF-7 cells and synergistically induced apoptosis and death of MCF-7 cells in vitro and highly efficient tumor ablation in vivo. Intriguingly, Tf-5-ALA-PTX-NCs have a controllable "on/off" switch to enhance the drug release. The dual-targeted nanocarriers would be a promising versatile anti-tumor drug delivery and imaging-guided cancer chemo-photodynamic synchronization therapy strategy.