Wearable-Based Integrated System for In-Home Monitoring and Analysis of Nocturnal Enuresis.

Nocturnal enuresis (NE) is involuntary bedwetting during sleep, typically appearing in young children. Despite the potential benefits of the long-term home monitoring of NE patients for research and treatment enhancement, this area remains underexplored. To address this, we propose NEcare, an in-home monitoring system that utilizes wearable devices and machine learning techniques. NEcare collects sensor data from an electrocardiogram, body impedance (BI), a three-axis accelerometer, and a three-axis gyroscope to examine bladder volume (BV), heart rate (HR), and periodic limb movements in sleep (PLMS). Additionally, it analyzes the collected NE patient data and supports NE moment estimation using heuristic rules and deep learning techniques. To demonstrate the feasibility of in-home monitoring for NE patients using our wearable system, we used our datasets from 30 in-hospital patients and 4 in-home patients. The results show that NEcare captures expected trends associated with NE occurrences, including BV increase, HR increase, and PLMS appearance. In addition, we studied the machine learning-based NE moment estimation, which could help relieve the burdens of NE patients and their families. Finally, we address the limitations and outline future research directions for the development of wearable systems for NE patients.

Association between PDCD6-VNTR polymorphism and urinary cancer susceptibility.

BACKGROUND: Programmed cell death 6 (PDCD6) is known to be involved in apoptosis and tumorigenesis. Given the reported association with urinary cancer susceptibility through SNP analysis, we further analyzed the entire genomic structure of PDCD6. METHODS: Three VNTR regions (MS1-MS3) were identified through the analysis of the genomic structure of PDCD6. To investigate the association between these VNTR regions and urinary cancer susceptibility, genomic DNA was extracted from 413 cancer-free male controls, 267 bladder cancer patients, and 331 prostate cancer patients. Polymerase chain reaction (PCR) was performed to analyze the PDCD6-MS regions. Statistical analysis was performed to determine the association between specific genotypes and cancer risk. In addition, the effect of specific VNTRs on PDCD6 expression was also confirmed using a reporter vector. RESULTS: Among the three VNTR regions, MS1 and MS2 exhibited monomorphism, while the MS3 region represented polymorphism, with its transmission to subsequent generations through meiosis substantiating its utility as a DNA typing marker. In a case-control study, the presence of rare alleles within PDCD6-MS3 exhibited significant associations with both bladder cancer (OR = 2.37, 95% CI: 1.33-4.95, P = 0.019) and prostate cancer (OR = 2.11, 95% CI: 1.03-4.36, P = 0.038). Furthermore, through luciferase assays, we validated the impact of the MS3 region on modulating PDCD6 expression. CONCLUSIONS: This study suggests that the PDCD6-MS3 region could serve as a prognostic marker for urinary cancers, specifically bladder cancer and prostate cancer. Moreover, the subdued influence exerted by PDCD6-MS3 on the expression of PDCD6 offers another insight concerning the progression of urinary cancer.

QMAC-DST for Rapid Detection of Drug Resistance in Pulmonary Tuberculosis Patients: A Multicenter Pre-Post Comparative Study.

Background/Objectives: This study explores the impact of QMAC-DST, a rapid, fully automated phenotypic drug susceptibility test (pDST), on the treatment of tuberculosis (TB) patients. Methods: This pre-post comparative study, respectively, included pulmonary TB patients who began TB treatment between 1 December 2020 and 31 October 2021 (pre-period; pDST using the Löwenstein-Jensen (LJ) DST (M-kit DST)) and between 1 November 2021 and 30 September 2022 (post-period; pDST using the QMAC-DST) in five university-affiliated tertiary care hospitals in South Korea. We compared the turnaround times (TATs) of pDSTs and the time to appropriate treatment for patients whose anti-TB drugs were changed based on these tests between the groups. All patients were permitted to use molecular DSTs (mDSTs). Results: A total of 182 patients (135 in the M-kit DST group and 47 in the QMAC-DST group) were included. The median TAT was 36 days for M-kit DST (interquartile range (IQR), 30-39) and 12 days for QMAC-DST (IQR, 9-15), with the latter being significantly shorter (p < 0.001). Of the total patients, 10 (5.5%) changed their anti-TB drugs based on the mDST or pDST results after initiating TB treatment (8 in the M-kit DST group and 2 in the QMAC-DST group). In the M-kit DST group, three (37.5%) patients changed anti-TB drugs based on the pDST results. In the QMAC-DST group, all changes were due to mDST results; therefore, calculating the time to appropriate treatment for patients whose anti-TB drugs were changed based on pDST results was not feasible. In the QMAC-DST group, 46.8% of patients underwent the first-line line probe assay compared to 100.0% in the M-kit DST group (p < 0.001), indicating that rapid QMAC-DST results provide quicker assurance of the ongoing treatment by confirming susceptibility to the current anti-TB drugs. Conclusions: QMAC-DST delivers pDST results more rapidly than LJ-DST, ensuring faster confirmation for the current treatment regimen.

Platycodi Radix Extract Prevents Hepatic Steatosis by Enhancing Bile Acid Synthesis in a High-Fat Diet-Induced Fatty Liver Mouse Model.

We aimed to identify the mechanism underlying the preventive effects of non-alcoholic fatty liver disease (NAFLD) through Platycodi Radix consumption using liver proteomic and bioinformatic analysis. C57BL/6J mice were categorized into three groups: those receiving a standard chow diet (NCD), those on a high-fat diet (HFD), and those on an HFD supplemented with 5% Platycodi Radix extract (PRE). After a 12-week period, PRE-fed mice exhibited a noteworthy prevention of hepatic steatosis. Protein identification and quantification in liver samples were conducted using LC-MS/MS. The identified proteins were analyzed through Ingenuity Pathway Analysis software, revealing a decrease in proteins associated with FXR/RXR activation and a concurrent increase in cholesterol biosynthesis proteins in the PRE-treated mouse liver. Subsequent network analysis predicted enhanced bile acid synthesis from these proteins. Indeed, the quantity of bile acids, which was reduced in HFD conditions, increased in the PRE group, accompanied by an elevation in the expression of synthesis-related proteins. Our findings suggest that the beneficial effects of PRE in preventing hepatic steatosis may be mediated, at least in part, through the modulation of FXR/RXR activation, cholesterol biosynthesis, and bile acid synthesis pathways.

Bottom Deposition Enables Stable All-Solid-State Batteries with Ultrathin Lithium Metal Anode.

Modern strides in energy storage underscore the significance of all-solid-state batteries (ASSBs) predicated on solid electrolytes and lithium (Li) metal anodes in response to the demand for safer batteries. Nonetheless, ASSBs are often beleaguered by non-uniform Li deposition during cycling, leading to compromised cell performance from internal short circuits and hindered charge transfer. In this study, the concept of "bottom deposition" is introduced to stabilize metal deposition based on the lithiophilic current collector and a protective layer composed of a polymeric binder and carbon black. The bottom deposition, wherein Li plating ensues between the protective layer and the current collector, circumvents internal short circuits and facilitates uniform volumetric changes of Li. The prepared functional binder for the protective layer presents outstanding mechanical robustness and adhesive properties, which can withstand the volume expansion caused by metal growth. Furthermore, its excellent ion transfer properties promote uniform Li bottom deposition even under a current density of 6 mA·cm-2. Also, scanning electron microscopy analysis reveals a consistent plating/stripping morphology of Li after cycling. Consequently, the proposed system exhibits enhanced electrochemical performance when assessed within the ASSB framework, operating under a configuration marked by a high Li utilization rate reliant on an ultrathin Li.

Promoting Homogeneous Zinc-Ion Transfer Through Preferential Ion Coordination Effect in Gel Electrolyte for Stable Zinc Metal Batteries.

Aqueous zinc metal batteries (AZMBs) are emerging energy storage systems that are poised to replace conventional lithium-ion batteries owing to their intrinsic safety, facile manufacturing process, economic benefits, and superior ionic conductivity. However, the issues of inferior anode reversibility and dendritic plating during operation remain challenging for the practical use of AZMBs. Herein, a gel electrolyte based on zwitterionic poly(sulfobetaine methacrylate) (poly(SBMA)) dissolved with different concentrations of ZnSO4 is proposed. Two-dimensional correlation spectroscopy based on Raman analysis reveals an enhanced interaction priority between the polar groups in SBMA and the dissolved ions as electrolyte concentration increases, which establishes a robust interaction and renders homogeneous ion distribution. Attributable to the modified coordination, zwitterionic gel polymer electrolyte with 5 mol kg-1 of ZnSO4 (ZGPE-5) facilitates stable zinc deposition and improves anode reversibility. By taking advantage of preferential coordination, a symmetrical cell evaluation employing ZGPE-5 demonstrates a cycle life over 3600 h, where ZGPE-5 also exerts a beneficial effect on the full cell cycling when assembled with Zn0.25 V2 O5 cathode. This study elucidates changes in the internal ion behavior that are dependent on electrolyte concentrations and pave the way for durable AZMBs.

Hierarchical 3D Electrode Design with High Mass Loading Enabling High-Energy-Density Flexible Lithium-Ion Batteries.

Flexible lithium-ion batteries (LIBs) have attracted significant attention owing to their ever-increasing use in flexible and wearable electronic devices. However, the practical application of flexible LIBs in devices has been plagued by the challenge of simultaneously achieving high energy density and high flexibility. Herein, a hierarchical 3D electrode (H3DE) is introduced with high mass loading that can construct highly flexible LIBs with ultrahigh energy density. The H3DE features a bicontinuous structure and the active materials along with conductive agents are uniformly distributed on the 3D framework regardless of the active material type. The bicontinuous electrode/electrolyte integration enables a rapid ion/electron transport, thereby improving the redox kinetics and lowering the internal cell resistance. Moreover, the H3DE exhibits exceptional structural integrity and flexibility during repeated mechanical deformations. Benefiting from the remarkable physicochemical properties, pouch-type flexible LIBs using H3DE demonstrate stable cycling under various bending states, achieving a record-high energy density (438.6 Wh kg-1 and 20.4 mWh cm-2 ), and areal capacity (5.6 mAh cm-2 ), outperforming all previously reported flexible LIBs. This study provides a feasible solution for the preparation of high-energy-density flexible LIBs for various energy storage devices.

Azacyclic Anchor-Enabled Cohesive Graphite Electrodes for Sustainable Anion Storage.

Advanced energy-storage devices are indispensable for expanding electric mobility applications. While anion intercalation-type redox chemistry in graphite cathodes has opened the path to high-energy-density batteries, surpassing the limited energy density of conventional lithium-ion batteries , a significant challenge remains: the large volume expansion of graphite upon anion intercalation. In this study, a novel polymeric binder and cohesive graphite cathode design for dual-ion batteries (DIBs) is presented, which exhibits remarkable stability even under high voltage conditions (>5 V). The innovative binder incorporates an acrylate moiety ensuring superior oxidative stability and self-healing features, along with an azide moiety, which allows for azacyclic covalent bonding with graphite and interchain crosslinking. A simple 1-h ultraviolet treatment is sufficient for binder fixation within the electrode, leading to the covalent bond formation with graphite and the creation of a robust three-dimensional network. This modification facilitates deeper and more reversible anion intercalation, leading to improved capacity, extended lifespan, and sustainable anion storage. The binder design, exhibiting exceptional adhesive properties and effective stress mitigation, enables the construction of ultrathick graphite cathodes. These findings provide valuable insights for the development of advanced binders, paving the way for high-performance DIBs.

A fabrication of stable lithium metal anodes using HF scavenging films.

A stable lithium metal anode was fabricated using a functional lithiophilic thin film polymer. The functional film captures HF impurities in the electrolyte and provides a fluorine-rich surface. In addition, the lithiophilic properties and in situ formed stable solid-electrolyte-interphase layer induced uniform lithium electrodeposition and exhibited outstanding cell performance in both liquid and solid electrolytes.

Peroxiredoxin 5 regulates osteogenic differentiation through interaction with hnRNPK during bone regeneration.

Peroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, its function in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes in Prdx5 knockout (Prdx5Ko) male mice. To investigate the function of Prdx5 in the bone, osteoblasts were analyzed through immunoprecipitation (IP) and liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) methods, while osteoclasts were analyzed through RNA-sequencing. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as a potential binding partner of Prdx5 during osteoblast differentiation in vitro. Prdx5 acts as a negative regulator of hnRNPK-mediated osteocalcin (Bglap) expression. In addition, transcriptomic analysis revealed that in vitro differentiated osteoclasts from the bone marrow-derived macrophages of Prdx5Ko mice showed enhanced expression of several osteoclast-related genes. These findings indicate that Prdx5 might contribute to the maintenance of bone homeostasis by regulating osteoblast differentiation. This study proposes a new function of Prdx5 in bone remodeling that may be used in developing therapeutic strategies for bone diseases.

Exploring the Relationship between CLPTM1L-MS2 Variants and Susceptibility to Bladder Cancer.

CLPTM1L (Cleft Lip and Palate Transmembrane Protein 1-Like) has previously been implicated in tumorigenesis and drug resistance in cancer. However, the genetic link between CLPTM1L and bladder cancer remains uncertain. In this study, we investigated the genetic association of variable number of tandem repeats (VNTR; minisatellites, MS) regions within CLPTM1L with bladder cancer. We identified four CLPTM1L-MS regions (MS1~MS4) located in intron regions. To evaluate the VNTR polymorphic alleles, we analyzed 441 cancer-free controls and 181 bladder cancer patients. Our analysis revealed a higher frequency of specific repeat sizes within the MS2 region in bladder cancer cases compared to controls. Notably, 25 and 27 repeats were exclusively present in the bladder cancer group. Moreover, rare alleles within the medium-length repeat range (25-29 repeats) were associated with an elevated bladder cancer risk (odds ratio [OR] = 5.78, 95% confidence interval [CI]: 1.49-22.47, p = 0.004). We confirmed that all MS regions followed Mendelian inheritance, and demonstrated that MS2 alleles increased CLPTM1L promoter activity in the UM-UC3 bladder cancer cells through a luciferase assay. Our findings propose the utility of CLPTM1L-MS regions as DNA typing markers, particularly highlighting the potential of middle-length rare alleles within CLPTM1L-MS2 as predictive markers for bladder cancer risk.

Prediction of anticancer drug resistance using a 3D microfluidic bladder cancer model combined with convolutional neural network-based image analysis.

Bladder cancer is the most common urological malignancy worldwide, and its high recurrence rate leads to poor survival outcomes. The effect of anticancer drug treatment varies significantly depending on individual patients and the extent of drug resistance. In this study, we developed a validation system based on an organ-on-a-chip integrated with artificial intelligence technologies to predict resistance to anticancer drugs in bladder cancer. As a proof-of-concept, we utilized the gemcitabine-resistant bladder cancer cell line T24 with four distinct levels of drug resistance (parental, early, intermediate, and late). These cells were co-cultured with endothelial cells in a 3D microfluidic chip. A dataset comprising 2,674 cell images from the chips was analyzed using a convolutional neural network (CNN) to distinguish the extent of drug resistance among the four cell groups. The CNN achieved 95.2% accuracy upon employing data augmentation and a step decay learning rate with an initial value of 0.001. The average diagnostic sensitivity and specificity were 90.5% and 96.8%, respectively, and all area under the curve (AUC) values were over 0.988. Our proposed method demonstrated excellent performance in accurately identifying the extent of drug resistance, which can assist in the prediction of drug responses and in determining the appropriate treatment for bladder cancer patients.

Rapid and Accurate On-Site Immunodiagnostics of Highly Contagious Severe Acute Respiratory Syndrome Coronavirus 2 Using Portable Surface-Enhanced Raman Scattering-Lateral Flow Assay Reader.

In early 2022, the number of people infected with the highly contagious mutant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), called Omicron, was increasing worldwide. Therefore, several countries approved the lateral flow assay (LFA) strip as a diagnostic method for confirming SARS-CoV-2 instead of reverse transcription-polymerase chain reaction (RT-PCR), which takes a long time to generate the results. However, owing to the limitation of detection sensitivity, commercial LFA strips have high false-negative diagnosis rates for patients with low virus concentrations. Therefore, in this study, we developed a portable surface-enhanced Raman scattering (SERS)-LFA reader based on localized surface plasmon effects to solve the sensitivity problem of the commercial LFA strip. We tested 54 clinical samples using this portable SERS-LFA reader, which generated 49 positive and 5 negative results. Out of the 49 positive results, SERS-LFA classified only 2 as false negative, while the commercial LFA classified 21 as false negative. This confirmed that the false-negative rate had significantly improved compared to that of commercial LFA strips. We believe that the proposed SERS-LFA system can be utilized as a point-of-care diagnostic system to quickly and accurately determine a virus infection that could spread significantly within a short period.

Development of selective mercury recovery technology by using iron iodide from waste sludge of non-ferrous metal smelting process.

The waste sludge from non-ferrous metal smelter contains high concentrations of mercury (Hg), arsenic (As) and sulfur (S). The Article 11 of the Minamata Convention on Mercury mandates the recovery of Hg before the disposal stage of Hg waste. However, As compounds have similar boiling points with Hg compounds, and they are considered interfering substances in the recovery of Hg. Moreover, a high concentration of S requires significant energy to volatilize Hg. This study examined the optimal conditions for selective recovery of Hg and energy reduction by introducing FeI2 as an additive during thermal treatment. Thermogravimetric analysis was utilized to evaluate the conversion of HgS to HgI2 under the influence of FeI2. The optimal conditions for thermal treatment such as temperature, treatment time, and molar ratio of [Hg]:[As]:[FeI2] were explored. The simulated waste indicated that the maximum separation efficiency of Hg was ∼95%, thereby allowing a selective separation of 81.5% of Hg from waste sludge with an Hg content of 0.33%, As content of 23.8%, and S content of 30.7%. Sequential extraction procedure was applied to evaluate the stability of Hg and As for residues. As a result, most Hg was vaporized and As was stabilized in sulfide, crystalline, and amorphous forms.

Heterotypic cell-in-cell structures between cancer and NK cells are associated with enhanced anticancer drug resistance.

The heterotypic CIC structures formed of cancer and immune cells have been observed in tumor tissues. We aimed to assess the feasibility of using heterotypic CICs as a functional biomarker to predict NK susceptibility and drug resistance. The heterotypic CIC-forming cancer cells showed a lower response to NK cytotoxicity and higher proliferative ability than non-CIC cancer cells. After treatment with anticancer drugs, cancer cells that formed heterotypic CICs showed a higher resistance to anticancer drugs than non-CIC cancer cells. We also observed the formation of more CIC structures in cancer cells treated with anticancer drugs than in the non-treated group. Our results confirm the association between heterotypic CIC structures and anticancer drug resistance in CICs formed from NK and cancer cells. These results suggest a mechanism underlying immune evasion in heterotypic CIC cancer cells and provide insights into the anticancer drug resistance of cancer cells.

Serum proteomics of severe fever with thrombocytopenia syndrome patients.

BACKGROUND: Dabie bandavirus, also termed as severe fever with thrombocytopenia syndrome virus (SFTSV), was first isolated in China in 2010. At this time, the virus was found to have spread to South Korea, Japan, and other countries. A high case fatality rate is reported for SFTS, ranging from 12-50% within various sources. Several omics for clinical studies among SFTS patients as well as studies of cultured SFTSV have attempted to characterize the relevant molecular biology and epidemiology of the disease. However, a global serum proteomics analysis among SFTS patients has not yet been reported to date. METHODS: In the current study, we evaluated comparative serum proteomics among SFTS patients (eight recovered patients and three deceased patients) with the goal of identifying the protein expression patterns associated with the clinical manifestations of SFTS. RESULTS: The proteomic results in the current study showed that the coagulation factor proteins, protein S and protein C, were statistically significantly downregulated among the deceased patients. Downregulation of the complement system as well as prolonged neutrophil activation were also observed. Additionally, the downstream proteins of tumour necrosis factor alpha, neutrophil-activating cytokine, and interleukin-1ß, an inflammatory cytokine, were overexpressed. CONCLUSIONS: Thrombocytopenia and multiple organ failure are the major immediate causes of death among SFTS patients. In this study, serum proteomic changes related to thrombocytopenia, abnormal immune response, and inflammatory activation were documented in SFTS patients. These findings provide useful information for understanding the clinical manifestations of SFTS.

Upregulation of CYP1B1 by hypoxia is mediated by ERα activation in breast cancer cells.

Endocrine therapy for breast cancer often leads to drug resistance and tumor recurrence; tumor hypoxia is also associated with mortality and tumor relapse. Cytochrome P450 1B1 (CYP1B1) regulates estrogen metabolism in breast cells and is known to be overexpressed in breast cancer tissue. Although the individual association of hypoxia-induced hypoxia-inducible factor-1-alpha (HIF-1α) and CYP1B1 with tumorigenesis is well known, the association between HIF-1α and CYP1B1 leading to tumorigenesis has not been investigated. Here, we investigated the correlation between hypoxia and CYP1B1 expression in breast cancer cells for tumorigenesis-related mechanisms. Hypoxia was induced in the human breast cancer cell lines MCF-7 (Er-positive) and MDA-MB-231 (triple-negative) and the normal breast epithelial cell line MCF10A; these cell lines were then subjected to immunoblotting, transient transfection, luciferase assays, gene silencing using small interfering RNA, polymerase chain reaction analysis, chromatin immunoprecipitation, co-immunoprecipitation, and mammalian two-hybrid assays. Furthermore, immunofluorescence analysis of the tumor microarrays was performed, and the pub2015 and the Cancer Genome Atlas patient datasets were analyzed. HIF-1α expression in response to hypoxia occurred in both normal and breast cancer cells, whereas CYP1B1 was induced only in estrogen receptor α (ERα)-positive breast cancer cells under hypoxia. HIF-1α activated ERα through direct binding and in a ligand-independent manner to promote CYP1B1 expression. Therefore, we suggested the mechanism by which hypoxia and ER-positivity orchestrate breast cancer relapse.

Proteomics-based diagnostic peptide discovery for severe fever with thrombocytopenia syndrome virus in patients.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) virus is an emerging infectious virus which causes severe hemorrhage, thrombocytopenia, and leukopenia, with a high fatality rate. Since there is no approved therapeutics or vaccines for SFTS, early diagnosis is essential to manage this infectious disease. METHODS: Here, we tried to detect SFTS virus in serum samples from SFTS patients by proteomic analysis. Firstly, in order to obtain the reference MS/MS spectral data of SFTS virus, medium from infected Vero cell culture was used for shotgun proteomic analysis. Then, tryptic peptides in sera from SFTS patients were confirmed by comparative analysis with the reference MS/MS spectral data of SFTS virus. RESULTS: Proteomic analysis of culture medium successfully discovered tryptic peptides from all the five antigen proteins of SFTS virus. The comparative spectral analysis of sera of SFTS patients revealed that the N-terminal tryptic peptide of the nucleocapsid (N) protein is the major epitope of SFTS virus detected in the patient samples. The prevalence of the peptides was strongly correlated with the viral load in the clinical samples. CONCLUSIONS: Proteomic analysis of SFTS patient samples revealed that nucleocapsid (N) protein is the major antigen proteins in sera of SFTS patients and N-terminal tryptic peptide of the N protein might be a useful proteomic target for direct detection of SFTS virus. These findings suggest that proteomic analysis could be an alternative tool for detection of pathogens in clinical samples and diagnosis of infectious diseases.

Additive Effect of CD73 Inhibitor in Colorectal Cancer Treatment With CDK4/6 Inhibitor Through Regulation of PD-L1.

BACKGROUND & AIMS: Although cancer immunotherapies are effective for advanced-stage cancers, there are no clinically approved immunotherapies for colon cancers (CRCs). Therefore, there is a high demand for the development of novel therapies. Extracellular adenosine-mediated signaling is considered a promising target for advanced-stage cancers that are nonresponsive to programmed death 1 (PD-1)-/programmed death-ligand 1 (PD-L1)-targeted immunotherapies. In this study, we aimed to elucidate novel tumorigenic mechanisms of extracellular adenosine. METHODS: To investigate the effects of extracellular adenosine on tumor-associated macrophages, peripheral blood-derived human macrophages were treated with adenosine and analyzed using flow cytometry and Western blot. Changes in adenosine-treated macrophages were further assessed using multi-omics analysis, including total RNA sequencing and proteomics. Colon cancer mouse models were used to measure the therapeutic efficacy of AB680 and palbociclib. We also used tissue microarrays of patients with CRC, to evaluate their clinical relevance. RESULTS: Extracellular adenosine-mediated reduction of cyclin D1 (CCND1) was found to be critical for the regulation of immune checkpoint molecules and PD-L1 levels in human macrophages, indicating that post-translational modification of PD-L1 is affected by adenosine. A potent CD73 selective inhibitor, AB680, reversed the effects of adenosine on CCND1 and PD-L1. This result strongly suggests that AB680 is a combinatory therapeutic option to overcome the undesired side effects of the cyclin-dependent kinase 4/6 inhibitor, palbociclib, which increases PD-L1 expression in tumors. Because palbociclib is undergoing clinical trials for metastatic CRC in combination with cetuximab (clinical trial number: NCT03446157), we validated that the combination of AB680 and palbociclib significantly improved anti-tumor efficacy in CRC animal models, thereby highlighting it as a novel immunotherapeutic strategy. We further assessed whether the level of CCND1 in tumor-associated macrophages was indeed reduced in tumor sections obtained from patients with CRC, for evaluating the clinical relevance of this strategy. CONCLUSIONS: In this study, we demonstrated that a novel combination therapy of AB680 and palbociclib may be advantageous for the treatment of CRC.

Breathable Artificial Interphase for Dendrite-Free and Chemo-Resistive Lithium Metal Anode.

A dendrite-free and chemically stabilized lithium metal anode is required for extending battery life and for the application of high energy density coupled with various cathode systems. However, uneven Li metal growth and the active surface in nature accelerate electrolyte dissipation and surface corrosion, resulting in poor cycle efficiency and various safety issues. Here, the authors suggest a thin artificial interphase using a multifunctional poly(styrene-b-butadiene-b-styrene) (SBS) copolymer to inhibit the electrochemical/chemical side reaction during cycling. Based on the physical features, hardness, adhesion, and flexibility, the optimized chemical structure of SBS facilitates durable mechanical strength and interphase integrity against repeated Li electrodeposition/dissolution. The effectiveness of the thin polymer film enables high cycle efficiency through the realization of a dendrite-free structure and a chemo-resistive surface of Li metal. The versatile anode demonstrates an improvement in the electrochemical properties, paired with diverse cathodes of high-capacity lithium cobalt oxide (3.5 mAh cm-2 ) and oxygen for advanced Li metal batteries with high energy density.