Interplay of Cooper Pairs and Zero-Energy Quasiparticles in a Gapless Superconductor.

The interplay between Cooper pairs and Bogoliubov-de Gennes (BdG) quasiparticles is a topic of considerable interest in the quantum properties of solids, but its important ingredient, the sufficient amount of low-energy quasiparticles to interact with Cooper pairs remains elusive in conventional superconductors. Here a gapless superconductor with coupled paramagnetic atomic layers is used to generate a significant amount of zero-energy quasiparticles that Anderson-localize and bifurcate into regions of high and low zero-energy quasiparticle density of states. The enriched zero-energy quasiparticles induce puddled superconductivity and Josephson vortices. This discovery not only advances the understanding of the mutual interaction of Cooper pairs and BdG quasiparticles but also opens a new avenue for exploring and controlling exotic quantum phenomena where superconductivity, disorder, and spin degrees of freedom are entangled.

The role of cytoreductive nephrectomy in metastatic renal cell carcinoma in immune-oncology era (SEVURO-CN): study protocol for a multi-center, prospective, randomized trial.

BACKGROUND: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) remains unclear in the immuno-oncology (IO) era. The results of two randomized trials, CARMENA and SURTIME, questioned the role and timing of CN. However, despite the latest advances in the systemic treatment of mRCC, previous trials have only used targeted therapy, and no studies have fully investigated the role of CN in immune checkpoint inhibitor (CPI) settings, and there is an urgent need for future studies to better define the role and timing of CN. METHODS: This study is an open-label, multi-center, parallel, prospective, randomized, interventional clinical study to evaluate the efficacy of CN in combination with CPIs in mRCC patients with International mRCC Database Consortium (IMDC) intermediate- and poor-risk. Synchronous mRCC patients with ≤ 3 IMDC risk features will be randomly allocated to three groups (1, upfront CN; 2, deferred CN; and 3, systemic therapy [ST] only). For ST, the nivolumab plus ipilimumab combination regimen, one of the standard regimens for intermediate- and poor-risk mRCC, is chosen. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, objective response rate, number of participants with treatment-related adverse events, and number of participants with surgical morbidity. We will analyze the genetic mutation profiles of the tumor tissue, circulating tumor DNA, urine tumor DNA, and tumor-infiltrating lymphocytes. The gut and urine microbial communities will be analyzed. The study will begin in 2022 and will enroll 55 patients. DISCUSSION: This study is one of the few prospective randomized trials to evaluate the benefit of CN in the treatment of synchronous mRCC in the IO era. The SEVURO-CN trial will help identify the role and timing of CN, thereby rediscovering the value of CN. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05753839. Registered on 3 March 2023.

Tumor phagocytosis-driven STING activation invigorates antitumor immunity and reprograms the tumor micro-environment.

Immunogenic cell death (ICD) holds the potential for in situ tumor vaccination while concurrently eradicating tumors and stimulating adaptive immunity. Most ICD inducers, however, elicit insufficient immune responses due to negative feedback against ICD biomarkers, limited infiltration of antitumoral immune cells, and the immunosuppressive tumor microenvironment (TME). Recent findings highlight the pivotal roles of stimulators of interferon gene (STING) activation, particularly in stimulating antigen-presenting cells (APCs) and TME reprogramming, addressing ICD limitations. Herein, we introduced 'tumor phagocytosis-driven STING activation', which involves the activation of STING in APCs during the recognition of ICD-induced cancer cells. We developed a polypeptide-based nanocarrier encapsulating both doxorubicin (DOX) and diABZI STING agonist 3 (dSA3) to facilitate this hypothesis in vitro and in vivo. After systemic administration, nanoparticles predominantly accumulated in tumor tissue and significantly enhanced anticancer efficacy by activating tumor phagocytosis-driven STING activation in MC38 and TC1 tumor models. Immunological activation of APCs occurred within 12 h, subsequently leading to the activation of T cells within 7 days, observed in both the TME and spleen. Furthermore, surface modification of nanoparticles with cyclic RGD (cRGD) moieties, which actively target integrin αvß3, enhances tumor accumulation and eradication, thereby verifying the establishment of systemic immune memory. Collectively, this study proposes the concept of tumor phagocytosis-driven STING activation and its effectiveness in generating short-term and long-term immune responses.

Rates of Reoperation in Duane Retraction Syndrome.

Purpose: To investigate the types of strabismus surgeries performed and the reoperation rate in patients with Duane retraction syndrome (DRS). Design: Retrospective cohort analysis. Participants: An insurance claims data set was used to identify patients diagnosed with DRS between 2007 and 2021. Methods: We recorded the type of strabismus surgery performed and the timing and frequency of reoperations. The hazard ratios (HRs) for reoperation were estimated according to the surgical methods using Cox regression analysis. Results: Of the 9435 patients diagnosed with DRS, 1023 (10.8%) underwent ≥ 1 strabismus operation. The median age at surgery was 5.0 years, and patients were followed for an average of 3.8 ± 3.0 years after their initial strabismus surgery. Most of the surgeries only involved horizontal muscle(s) (n = 734 [71.7%]). However, some patients underwent surgeries on vertical muscle(s) (n = 132 [12.9%]), vertical muscle(s) with transposition (n = 102 [10.0%]), and horizontal muscle with transposition (n = 51 [5.0%]). The estimated 5-year rate of reoperation was 18.2% (95% confidence interval [CI], 15.0%-22.2%). Compared with surgery on horizontal muscle(s) only, vertical muscle surgery (HR, 2.01; 95% CI, 1.30-3.11; P = 0.002) and vertical muscle surgery coupled with transposition (HR, 1.79; 95% CI, 1.06-3.02; P = 0.03) had an increased risk of reoperation. Conclusions: Strabismus surgery on ≥ 1 horizontal muscles is the most common type of strabismus surgery performed on patients with DRS. Approximately 1 in 7 patients with DRS who had strabismus surgery underwent a reoperation. Patients who underwent vertical muscle surgery had a higher risk of undergoing a reoperation. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Emergent Quantum Phenomena of a Noncentrosymmetric Charge Density Wave in 1T-Transition Metal Dichalcogenides.

1T-transition metal dichalcogenides (TMDs) have been an exciting platform for exploring the intertwinement of charge density waves and strong correlation phenomena. While the David star structure has been conventionally considered as the underlying charge order in the literature, recent scanning tunneling probe experiments on several monolayer 1T-TMD materials have motivated a new, alternative structure, namely, the anion-centered David star structure. In this Letter, we show that this novel anion-centered David star structure manifestly breaks inversion symmetry, resulting in flat bands with pronounced Rashba spin-orbit couplings. These distinctive features unlock novel possibilities and functionalities for 1T-TMDs, including the giant spin Hall effect, the emergence of Chern bands, and spin liquid that spontaneously breaks crystalline rotational symmetry. Our findings establish promising avenues for exploring emerging quantum phenomena of monolayer 1T-TMDs with this novel noncentrosymmetric structure.

Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation.

Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, the existing literature on the role of adipocytes in the tumor microenvironment (TME) to elucidate the correlation between obesity and cancer remains insufficient. Here, we aim to investigate the formation of cancer-associated adipocytes (CAAs) and their contribution to tumor growth using mouse models harboring dysfunctional adipocytes. Specifically, we employ adipocyte-specific BECN1 KO (BaKO) mice, which exhibit lipodystrophy due to dysfunctional adipocytes. Our results reveal the activation of YAP/TAZ signaling in both CAAs and BECN1-deficient adipocytes, inducing adipocyte dedifferentiation and formation of a malignant TME. The additional deletion of YAP/TAZ from BaKO mice significantly restores the lipodystrophy and inflammatory phenotypes, leading to tumor regression. Furthermore, mice fed a high-fat diet (HFD) exhibit decreased BECN1 and increased YAP/TAZ expression in their adipose tissues. Treatment with the YAP/TAZ inhibitor, verteporfin, suppresses tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Overall, our findings provide insights into the key mediators of CAA and their significance in developing a TME, thereby suggesting a viable approach targeting adipocyte homeostasis to suppress cancer growth.

High-temperature concomitant metal-insulator and spin-reorientation transitions in a compressed nodal-line ferrimagnet Mn3Si2Te6.

Symmetry-protected band degeneracy, coupled with a magnetic order, is the key to realizing novel magnetoelectric phenomena in topological magnets. While the spin-polarized nodal states have been identified to introduce extremely-sensitive electronic responses to the magnetic states, their possible role in determining magnetic ground states has remained elusive. Here, taking external pressure as a control knob, we show that a metal-insulator transition, a spin-reorientation transition, and a structural modification occur concomitantly when the nodal-line state crosses the Fermi level in a ferrimagnetic semiconductor Mn3Si2Te6. These unique pressure-driven magnetic and electronic transitions, associated with the dome-shaped Tc variation up to nearly room temperature, originate from the interplay between the spin-orbit coupling of the nodal-line state and magnetic frustration of localized spins. Our findings highlight that the nodal-line states, isolated from other trivial states, can facilitate strongly tunable magnetic properties in topological magnets.

SIRT1 regulates the localization and stability of telomerase protein by direct interaction.

Telomerase reverse transcriptase (TERT) not only upholds telomeric equilibrium but also plays a pivotal role in multiple non-canonical cellular mechanisms, particularly in the context of aging, cancer, and genomic stability. Though depletion of SIRT1 in mouse embryonic fibroblasts has demonstrated telomere shortening, the impact of SIRT1 on enabling TERT to regulate telomeric homeostasis remains enigmatic. Here, we reveal that SIRT1 directly interacts with TERT, and promotes the nuclear localization and stability of TERT. Reverse transcriptase (RT) domain of TERT and N-terminus of SIRT1 mainly participated in their direct interaction. TERT, concomitantly expressed with intact SIRT1, exhibits nuclear localization, whereas TERT co-expressed with N-terminal-deleted SIRT1 remains in the cytosol. Furthermore, overexpression of SIRT1 enhances the nuclear localization and protein stability of TERT, akin to overexpression of deacetylase-inactive SIRT1, whereas N-terminal-deleted SIRT1 has no effect on TERT. These findings suggest a novel regulatory role of SIRT1 for TERT through direct interaction. This interaction provides new insights into the fields of aging, cancer, and genome stability governed by TERT and SIRT1.

Preoperative smoking and robot-assisted radical cystectomy outcomes & complications in multicenter KORARC database.

To investigate the influence of preoperative smoking history on the survival outcomes and complications in a cohort from a large multicenter database. Many patients who undergo radical cystectomy (RC) have a history of smoking; however, the direct association between preoperative smoking history and survival outcomes and complications in patients with muscle-invasive bladder cancer (MIBC) who undergo robot-assisted radical cystectomy (RARC) remains unexplored. We conducted a retrospective analysis using data from 749 patients in the Korean Robot-Assisted Radical Cystectomy Study Group (KORARC) database, with an average follow-up duration of 30.8 months. The cohort was divided into two groups: smokers (n = 351) and non-smokers (n = 398). Propensity score matching was employed to address differences in sample size and baseline demographics between the two groups (n = 274, each). Comparative analyses included assessments of oncological outcomes and complications. After matching, smoking did not significantly affect the overall complication rate (p = 0.121). Preoperative smoking did not significantly increase the occurrence of complications based on complication type (p = 0.322), nor did it increase the readmission rate (p = 0.076). There were no perioperative death in either group. Furthermore, preoperative smoking history showed no significant impact on overall survival (OS) [hazard ratio (HR) = 0.87, interquartile range (IQR): 0.54-1.42; p = 0.589] and recurrence-free survival (RFS) (HR = 1.12, IQR: 0.83-1.53; p = 0.458) following RARC for MIBC. The extent of preoperative smoking (≤ 10, 10-30, and ≥ 30 pack-years) had no significant influence on OS and RFS in any of the categories (all p > 0.05). Preoperative smoking history did not significantly affect OS, RFS, or complications in patients with MIBC undergoing RARC.

Topological Complex Charge Conservation in Nontrivial Z2 × Z2 Domain Walls.

Localized topological modes such as solitons, Majorana Fermions, and skyrmions are attracting great interest as robust information carriers for future devices. Here, a novel conserved quantity for topological domain wall networks of a Z2 × Z2 order generated with spin-polarized current in Sr2VO3FeAs is discovered. Domain walls are mobilized by the scanning tunneling current, which also observes in atomic scale active dynamics of domain wall vertices including merge, bifurcation, pair creation, and annihilation. Within this dynamics, the product of the topological complex charges defined for domain wall vertices is conserved with a novel boundary-charge correspondence rule. These results may open an avenue toward topological electronics based on domain wall vertices in generic Z2 × Z2 systems.

PIBF1 regulates trophoblast syncytialization and promotes cardiovascular development.

Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as the heart, is crucial for a normal pregnancy. However, the mechanism through which the placenta influences the development of embryonic organs remains unclear. Trophoblasts fuse to form multinucleated syncytiotrophoblasts (SynT), which primarily make up the placental materno-fetal interface. We discovered that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is vital for trophoblast differentiation and fusion into SynT in humans and mice. PIBF1 facilitates communication between SynT and adjacent vascular cells, promoting vascular network development in the primary placenta. This process affected the early development of the embryonic cardiovascular system in mice. Moreover, in vitro experiments showed that PIBF1 promotes the development of cardiovascular characteristics in heart organoids. Our findings show how SynTs organize the barrier and imply their possible roles in supporting embryogenesis, including cardiovascular development. SynT-derived factors and SynT within the placenta may play critical roles in ensuring proper organogenesis of other organs in the embryo.

Dual Higgs modes entangled into a soliton lattice in CuTe.

Recently discovered Higgs particle is a key element in the standard model of elementary particles and its analogue in materials, massive Higgs mode, has elucidated intriguing collective phenomena in a wide range of materials with spontaneous symmetry breaking such as antiferromagnets, cold atoms, superconductors, superfluids, and charge density waves (CDW). As a straightforward extension beyond the standard model, multiple Higgs particles have been considered theoretically but not yet for Higgs modes. Here, we report the real-space observations, which suggest two Higgs modes coupled together with a soliton lattice in a solid. Our scanning tunneling microscopy reveals the 1D CDW state of an anisotropic transition metal monochalcogenide crystal CuTe is composed of two distinct but degenerate CDW structures by the layer inversion symmetry broken. More importantly, the amplitudes of each CDW structure oscillate in an out-of-phase fashion to result in a regular array of alternating domains with repeating phase-shift domain walls. This unusual finding is explained by the extra degeneracy in CDWs within the standard Landau theory of the free energy. The multiple and entangled Higgs modes demonstrate how novel collective modes can emerge in systems with distinct symmetries broken simultaneously.

Kinkless Electronic Junction along 1D Electronic Channel Embedded in a Van Der Waals Layer.

Here, the formation of type-I and type-II electronic junctions with or without any structural discontinuity along a well-defined 1 nm-wide 1D electronic channel within a van der Waals layer is reported. Scanning tunneling microscopy and spectroscopy techniques are employed to investigate the atomic and electronic structure along peculiar domain walls formed on the charge-density-wave phase of 1T-TaS2 . Distinct kinds of abrupt electronic junctions with discontinuities of the band gap along the domain walls are found, some of which even do not have any structural kinks and defects. Density-functional calculations reveal a novel mechanism of the electronic junction formation; they are formed by a kinked domain wall in the layer underneath through substantial electronic interlayer coupling. This work demonstrates that the interlayer electronic coupling can be an effective control knob over nanometer-scale electronic property of 2D atomic monolayers.

Successful robotic kidney transplantation for surgeons with no experience in minimally invasive surgery: a single institution experience.

BACKGROUND: Robotic kidney transplantation (RKT) is a novel and welcomed innovation yielding good surgical outcomes. However, data on the feasibility and safety of performing RKT by surgeons with a lack of prior minimally invasive surgery (MIS) experience are limited. The authors aimed to evaluate the surgical and functional results of RKT and present the learning curves (LC) of RKT by a single surgeon with no prior experience in MIS. MATERIALS AND METHODS: This was a retrospective study of all RKT performed between November 2019 and April 2023 at Severance Hospital in Seoul, South Korea. The authors analyzed surgical and functional outcomes, as well as complication rates of RKT in comparison to open kidney transplantation (OKT). The authors evaluated LCs using the cumulative summation method to describe the number of cases associated with the competency of a single surgeon. RESULTS: A total of 50 patients who underwent RKT and 104 patients who underwent OKT were included in this study. In RKT group, the median surgical console time was 193 min (interquartile range, 172-222) and the median vascular anastomoses time was 38 min (35-44). Total operation time was 323 min (290-371) and rewarming time was 62.5 min (56.0-70.0) in RKT group compared to 210 min (190-239) and 25 min (21-30), respectively, in OKT group. Despite extended surgical durations with a robotic technique, both groups had comparable intraoperative and postoperative outcomes, as well as renal function. Estimated blood loss and post-transplant hospital stays were significantly lower in RKT group than in OKT group. LC analysis of RKT by the single surgeon revealed that surgical competence was achieved after 15 cases. CONCLUSION: Even if surgeons do not have prior experience with MIS, they can rapidly overcome the LC and safely perform RKT with adequate preparation and acquisition of basic robotic surgical techniques.

Fully Automated Segmentation of Human Eyeball Using Three-Dimensional U-Net in T2 Magnetic Resonance Imaging.

Purpose: To develop and validate a fully automated deep-learning-based tool for segmentation of the human eyeball using a three-dimensional (3D) U-Net, compare its performance to semiautomatic segmentation ground truth and a two-dimensional (2D) U-Net, and analyze age and sex differences in eyeball volume, as well as gaze-dependent volume consistency in normal subjects. Methods: We retrospectively collected 474 magnetic resonance imaging (MRI) scans, including different gazing scans, from 119 patients. A 10-fold cross-validation was applied to separate the dataset into training, test, and validation sets for both the 3D U-Net and 2D U-Net. Performance accuracy was measured using four quantitative metrics compared to the ground truth, and Bland-Altman plot analysis was conducted. Age and sex differences in eyeball volume and variability in eyeball volume differences across gazing directions were analyzed. Results: The 3D U-Net outperformed the 2D U-Net with mean accuracy scores >0.95, showing acceptable agreement in the Bland-Altman plot analysis despite a tendency for slight overestimation (mean difference = -0.172 cm³). Significant sex differences and age effects on eyeball volume were observed for both methods (P < 0.05). No significant volume differences were found between the segmentation methods or within each method for the different gazing directions. Significant differences in performance accuracy were identified among the five gazing directions, with the upward direction showing a notably lower performance. Conclusions: Our study demonstrated the effectiveness of 3D U-Net human eyeball volume segmentation using T2-weighted MRI. The robustness and reliability of 3D U-Net across diverse populations and gaze directions support enhanced ophthalmic diagnosis and treatment strategies. Translational Relevance: Our findings demonstrate the feasibility of using the proposed 3D U-Net model for the automatic segmentation of the human eyeball, with potential applications in various ophthalmic research fields that require the analysis of 3D geometric eye globe shapes or eye movement detection.

Targeting FLT3-TAZ signaling to suppress drug resistance in blast phase chronic myeloid leukemia.

BACKGROUND: Although the development of BCR::ABL1 tyrosine kinase inhibitors (TKIs) rendered chronic myeloid leukemia (CML) a manageable condition, acquisition of drug resistance during blast phase (BP) progression remains a critical challenge. Here, we reposition FLT3, one of the most frequently mutated drivers of acute myeloid leukemia (AML), as a prognostic marker and therapeutic target of BP-CML. METHODS: We generated FLT3 expressing BCR::ABL1 TKI-resistant CML cells and enrolled phase-specific CML patient cohort to obtain unpaired and paired serial specimens and verify the role of FLT3 signaling in BP-CML patients. We performed multi-omics approaches in animal and patient studies to demonstrate the clinical feasibility of FLT3 as a viable target of BP-CML by establishing the (1) molecular mechanisms of FLT3-driven drug resistance, (2) diagnostic methods of FLT3 protein expression and localization, (3) association between FLT3 signaling and CML prognosis, and (4) therapeutic strategies to tackle FLT3+ CML patients. RESULTS: We reposition the significance of FLT3 in the acquisition of drug resistance in BP-CML, thereby, newly classify a FLT3+ BP-CML subgroup. Mechanistically, FLT3 expression in CML cells activated the FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway, which conferred resistance to a wide range of BCR::ABL1 TKIs that was independent of recurrent BCR::ABL1 mutations. Notably, FLT3+ BP-CML patients had significantly less favorable prognosis than FLT3- patients. Remarkably, we demonstrate that repurposing FLT3 inhibitors combined with BCR::ABL1 targeted therapies or the single treatment with ponatinib alone can overcome drug resistance and promote BP-CML cell death in patient-derived FLT3+ BCR::ABL1 cells and mouse xenograft models. CONCLUSION: Here, we reposition FLT3 as a critical determinant of CML progression via FLT3-JAK-STAT3-TAZ-TEAD-CD36 signaling pathway that promotes TKI resistance and predicts worse prognosis in BP-CML patients. Our findings open novel therapeutic opportunities that exploit the undescribed link between distinct types of malignancies.

Enhanced Interfacial Properties of Carbon Fiber/Maleic Anhydride-Grafted Polypropylene Composites via Two-Step Surface Treatment: Electrochemical Oxidation and Silane Treatment.

The interfacial adhesion between carbon fibers (CFs) and a thermoplastic matrix is an important aspect that should be improved in manufacturing CF-reinforced thermoplastics with high strength and rigidity. In this study, the effects of a two-step surface treatment comprising electrochemical oxidation and silane treatment of the CF surface on the mechanical properties of CF/maleic anhydride-grafted polypropylene (MAPP) composites were confirmed. The surface characteristics of the treated CFs were analyzed via scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The tensile testing of a single CF and interfacial adhesion of the samples before and after the surface treatment were analyzed using a single-fiber testing machine and a universal testing machine. After the silane treatment, the roughness of the CF surface increased due to the formation of a siloxane network. In addition, the interfacial shear strength increased by ∼450% compared to that of the untreated CFs due to the covalent bond between the -NH2 end group of siloxane and MAPP. This two-step surface treatment, which can be performed continuously, is considered an effective method for improving the mechanical interface strength between the CF and polymer matrix.

Robust Luttinger Liquid State of 1D Dirac Fermions in a Van der Waals System Nb9Si4Te18.

We report on the Tomonaga-Luttinger liquid (TLL) behavior in fully degenerate 1D Dirac Fermions. A ternary van der Waals material Nb9Si4Te18 incorporates in-plane NbTe2 chains, which produce a 1D Dirac band crossing Fermi energy. Tunneling conductance of electrons confined within NbTe2 chains is found to be substantially suppressed at Fermi energy, which follows a power law with a universal temperature scaling, hallmarking a TLL state. The obtained Luttinger parameter of ∼0.15 indicates a strong electron-electron interaction. The TLL behavior is found to be robust against atomic-scale defects, which might be related to the Dirac electron nature. These findings, combined with the tunability of the compound and the merit of a van der Waals material, offer a robust, tunable, and integrable platform to exploit non-Fermi liquid physics.