De novo and salvage purine synthesis pathways across tissues and tumors.

Purine nucleotides are vital for RNA and DNA synthesis, signaling, metabolism, and energy homeostasis. To synthesize purines, cells use two principal routes: the de novo and salvage pathways. Traditionally, it is believed that proliferating cells predominantly rely on de novo synthesis, whereas differentiated tissues favor the salvage pathway. Unexpectedly, we find that adenine and inosine are the most effective circulating precursors for supplying purine nucleotides to tissues and tumors, while hypoxanthine is rapidly catabolized and poorly salvaged in vivo. Quantitative metabolic analysis demonstrates comparative contribution from de novo synthesis and salvage pathways in maintaining purine nucleotide pools in tumors. Notably, feeding mice nucleotides accelerates tumor growth, while inhibiting purine salvage slows down tumor progression, revealing a crucial role of the salvage pathway in tumor metabolism. These findings provide fundamental insights into how normal tissues and tumors maintain purine nucleotides and highlight the significance of purine salvage in cancer.

Coping with starvation: Cysteine keeps mTORC1 suppressed to ensure survival.

Jouandin et al. (2022) show that lysosomal-derived cysteine serves as a signal to promote the tricarboxylic acid (TCA) cycle and suppress TORC1 signaling for Drosophila to endure starvation periods.

Predictive Synthesis of Transition Metal Carbide via Thermochemical Oxocarbon Equilibrium.

Fabricating nanoscale metal carbides is a great challenge due to them having higher Gibbs free energy of formation (ΔG°) values than other metal compounds; additionally, these carbides have harsh calcination conditions, in which metal oxidation is preferred in the atmosphere. Herein, we report oxocarbon-mediated calcination for the predictive synthesis of nanoscale metal carbides. The thermochemical oxocarbon equilibrium of CO-CO2 reactions was utilized to control the selective redox reactions in multiatomic systems of Mo-C-O, contributing to the phase-forming and structuring of Mo compounds. By harnessing the thermodynamically predicted processing window, we controlled a wide range of Mo phases (MoO2, α-MoC1-x, and ß-Mo2C) and nanostructures (nanoparticle, spike, stain, and core/shell) in the Mo compounds/C nanofibers. By inducing simultaneous reactions of C-O (selective C combustion) and Mo-C (Mo carbide formation) in the nanofibers, Mo diffusion was controlled in C nanofibers, acting as a template for the nucleation and growth of Mo carbides and resulting in precise control of the phases and structures of Mo compounds. The formation mechanism of nanostructured Mo carbides was elucidated according to the CO fractions of CO-CO2 calcination. Moreover, tungsten (W) and niobium (Nb) carbides/C nanofibers have been successfully synthesized by CO-CO2 calcination. We constructed the thermodynamic map for the predictive synthesis of transition metal carbides to provide universal guideline via thermochemical oxocarbon equilibrium. We revealed that our thermochemical oxocarbon-mediated gas-solid reaction enabled the structure and phase control of nanoscale transition metal compounds to optimize the material-property relationship accordingly.

Robust Interlayer-Coherent Quantum Hall States in Twisted Bilayer Graphene.

We introduce a novel two-dimensional electronic system with ultrastrong interlayer interactions, namely, twisted bilayer graphene with a large twist angle, as an ideal ground for realizing interlayer-coherent excitonic condensates. In these systems, sub-nanometer atomic separation between the layers allows significant interlayer interactions, while interlayer electron tunneling is geometrically suppressed due to the large twist angle. By fully exploiting these two features we demonstrate that a sequence of odd-integer quantum Hall states with interlayer coherence appears at the second Landau level (N = 1). Notably the energy gaps for these states are of order 1 K, which is several orders of magnitude greater than those in GaAs. Furthermore, a variety of quantum Hall phase transitions are observed experimentally. All the experimental observations are largely consistent with our phenomenological model calculations. Hence, we establish that a large twist angle system is an excellent platform for high-temperature excitonic condensation.

Does body mass index affect outcomes following arthroscopic superior capsular reconstruction using fascia lata autograft for massive irreparable rotator cuff tear?

PURPOSE: This study aimed to evaluate the effect of increased body mass index (BMI) on patient-reported outcomes (PROs) and clinically significant outcomes (CSOs) obtained > two years postoperatively following arthroscopic superior capsular reconstruction (ASCR). METHODS: A retrospective study was conducted on patients who underwent ASCR with a minimum two year follow-up. All patients were divided into normal (BMI < 25.0), overweight (BMI 25-30.0), and obese (BMI ≥ 30) according to preoperative BMI. Patients were assessed using the PROs preoperatively and at six months, one year, and two years postoperatively, including the visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES), and Constant-Murley scores. The time required to achieve each CSO was analyzed and compared. Multivariate analyses evaluated the predictor variables and time required to achieve CSOs. RESULTS: This study included 63 patients with a mean age of 64.8 ± 8.6 years, including 31 normal BMI, 25 overweight, and seven obese patients. Significant improvements in VAS and ASES scores after ASCR were observed in all three groups. Normal and overweight patients had significant improvements in the Constant score; however, no difference was observed in obese patients. No significant difference was observed in the probability distributions of CSOs between the BMI groups. Similarly, no significant differences were observed in the probability distributions of the CSOs, ASES, and Constant scores at each time point, among the BMI groups. CONCLUSION: Patients in the normal and overweight groups had significant improvements in the VAS, ASES, and Constant scores after ASCR. Patients in the obese group had a significant improvement in VAS score; however, there is no difference for the ASES and Constant scores in the obese group. However, no differences were observed in all PROMs and the likelihood of achieving CSOs among the different BMI groups.

Fresnel-type solid immersion lens for efficient light collection from quantum defects in diamond.

Quantum defects in diamonds have been studied as a promising resource for quantum science. The subtractive fabrication process for improving photon collection efficiency often require excessive milling time that can adversely affect the fabrication accuracy. We designed and fabricated a Fresnel-type solid immersion lens using the focused ion beam. For a 5.8 µm-deep Nitrogen-vacancy (NV-) center, the milling time was highly reduced (1/3 compared to a hemispherical structure), while retaining high photon collection efficiency (> 2.24 compared to a flat surface). In numerical simulation, this benefit of the proposed structure is expected for a wide range of milling depths.

Effective Healing of Staphylococcus aureus-Infected Wounds in Pig Cathelicidin Protegrin-1-Overexpressing Transgenic Mice.

Antimicrobial peptides (AMPs) are promising alternatives to existing treatments for multidrug-resistant bacteria-infected wounds. Therefore, the effect of protegrin-1 (PG1), a potent porcine AMP with broad-spectrum activity, on wound healing was evaluated. PG1-overexpressing transgenic mice were used as an in vivo model to evaluate its healing efficiency against Staphylococcus aureus-infected (106 colony forming units) wounds. We analyzed the wounds under four specific conditions in the presence or absence of antibiotic treatment. We observed the resolution of bacterial infection and formation of neo-epithelium in S. aureus-infected wounds of the mice, even without antibiotic treatment, whereas all wild-type mice with bacterial infection died within 8 to 10 days due to uncontrolled bacterial proliferation. Interestingly, the wound area on day 7 was smaller (p < 0.01) in PG1 transgenic mice than that in the other groups, including antibiotic-treated mice, suggesting that PG1 exerts biological effects other than bactericidal effect. Additionally, we observed that the treatment of primary epidermal keratinocytes with recombinant PG1 enhanced cell migration in in vitro scratch and cell migration assays. This study contributes to the understanding of broad-spectrum endogenous cathelicidins with potent antimicrobial activities, such as PG1, on wound healing. Furthermore, our findings suggest that PG1 is a potent therapeutic candidate for wound healing.

Approaching Ideal Visibility in Singlet-Triplet Qubit Operations Using Energy-Selective Tunneling-Based Hamiltonian Estimation.

We report energy-selective tunneling readout-based Hamiltonian parameter estimation of a two-electron spin qubit in a GaAs quantum dot array. Optimization of readout fidelity enables a single-shot measurement time of 16 µs on average, with adaptive initialization and efficient qubit frequency estimation based on real-time Bayesian inference. For qubit operation in a frequency heralded mode, we observe a 40-fold increase in coherence time without resorting to dynamic nuclear polarization. We also demonstrate active frequency feedback with quantum oscillation visibility, single-shot measurement fidelity, and gate fidelity of 97.7%, 99%, and 99.6%, respectively, showcasing the improvements in the overall capabilities of GaAs-based spin qubits. By pushing the sensitivity of the energy-selective tunneling-based spin to charge conversion to the limit, the technique is useful for advanced quantum control protocols such as error mitigation schemes, where fast qubit parameter calibration with a large signal-to-noise ratio is crucial.

Single-Shot Readout of a Driven Hybrid Qubit in a GaAs Double Quantum Dot.

We report a single-shot-based projective readout of a semiconductor hybrid qubit formed by three electrons in a GaAs double quantum dot. Voltage-controlled adiabatic transitions between the qubit operations and readout conditions allow high-fidelity mapping of quantum states. We show that a large ratio both in relaxation time vs tunneling time (≈50) and singlet-triplet splitting vs thermal energy (≈20) allows energy-selective tunneling-based spin-to-charge conversion with a readout visibility of ≈92.6%. Combined with ac driving, we demonstrate high visibility coherent Rabi and Ramsey oscillations of a hybrid qubit in GaAs. Further, we discuss the generality of the method for use in other materials, including silicon.

Conditioned Medium of Human Pluripotent Stem Cell-Derived Neural Precursor Cells Exerts Neurorestorative Effects against Ischemic Stroke Model.

Previous studies have shown that early therapeutic events of neural precursor cells (NPCs) transplantation to animals with acute ischemic stroke readily protected neuronal cell damage and improved behavioral recovery through paracrine mechanisms. In this study, we tested the hypothesis that administration of conditioned medium from NPCs (NPC-CMs) could recapitulate the beneficial effects of cell transplantation. Rats with permanent middle cerebral artery occlusion (pMCAO) were randomly assigned to one of the following groups: PBS control, Vehicle (medium) controls, single (NPC-CM(S)) or multiple injections of NPC-CM(NPC-CM(M)) groups. A single intravenous injection of NPC-CM exhibited strong neuroregenerative potential to induce behavioral recovery, and multiple injections enhanced this activity further by suppressing inflammatory damage and inducing endogenous neurogenesis leading to histopathological and functional recovery. Proteome analysis of NPC-CM identified a number of proteins that are known to be associated with nervous system development, neurogenesis, and angiogenesis. In addition, transcriptome analysis revealed the importance of the inflammatory response during stroke recovery and some of the key hub genes in the interaction network were validated. Thus, our findings demonstrated that NPC-CM promoted functional recovery and reduced cerebral infarct and inflammation with enhanced endogenous neurogenesis, and the results highlighted the potency of NPC-CM in stroke therapy.

Quantum control and process tomography of a semiconductor quantum dot hybrid qubit.

The similarities between gated quantum dots and the transistors in modern microelectronics--in fabrication methods, physical structure and voltage scales for manipulation--have led to great interest in the development of quantum bits (qubits) in semiconductor quantum dots. Although quantum dot spin qubits have demonstrated long coherence times, their manipulation is often slower than desired for important future applications, such as factoring. Furthermore, scalability and manufacturability are enhanced when qubits are as simple as possible. Previous work has increased the speed of spin qubit rotations by making use of integrated micromagnets, dynamic pumping of nuclear spins or the addition of a third quantum dot. Here we demonstrate a qubit that is a hybrid of spin and charge. It is simple, requiring neither nuclear-state preparation nor micromagnets. Unlike previous double-dot qubits, the hybrid qubit enables fast rotations about two axes of the Bloch sphere. We demonstrate full control on the Bloch sphere with π-rotation times of less than 100 picoseconds in two orthogonal directions, which is more than an order of magnitude faster than any other double-dot qubit. The speed arises from the qubit's charge-like characteristics, and its spin-like features result in resistance to decoherence over a wide range of gate voltages. We achieve full process tomography in our electrically controlled semiconductor quantum dot qubit, extracting high fidelities of 85 per cent for X rotations (transitions between qubit states) and 94 per cent for Z rotations (phase accumulation between qubit states).

Control over Electron-Phonon Interaction by Dirac Plasmon Engineering in the Bi2Se3 Topological Insulator.

Understanding the mutual interaction between electronic excitations and lattice vibrations is key for understanding electronic transport and optoelectronic phenomena. Dynamic manipulation of such interaction is elusive because it requires varying the material composition on the atomic level. In turn, recent studies on topological insulators (TIs) have revealed the coexistence of a strong phonon resonance and topologically protected Dirac plasmon, both in the terahertz (THz) frequency range. Here, using these intrinsic characteristics of TIs, we demonstrate a new methodology for controlling electron-phonon interaction by lithographically engineered Dirac surface plasmons in the Bi2Se3 TI. Through a series of time-domain and time-resolved ultrafast THz measurements, we show that, when the Dirac plasmon energy is less than the TI phonon energy, the electron-phonon coupling is trivial, exhibiting phonon broadening associated with Landau damping. In contrast, when the Dirac plasmon energy exceeds that of the phonon resonance, we observe suppressed electron-phonon interaction leading to unexpected phonon stiffening. Time-dependent analysis of the Dirac plasmon behavior, phonon broadening, and phonon stiffening reveals a transition between the distinct dynamics corresponding to the two regimes as the Dirac plasmon resonance moves across the TI phonon resonance, which demonstrates the capability of Dirac plasmon control. Our results suggest that the engineering of Dirac plasmons provides a new alternative for controlling the dynamic interaction between Dirac carriers and phonons.

Does final component alignment correlate with alignment of the bone resection surfaces in cemented total knee arthroplasty?

PURPOSE: To examine, with a navigation, whether the final component alignments correlate with alignment of the bone resection surfaces in cemented total knee arthroplasty (TKA), and to evaluate the factors affecting alignment deviation. METHODS: A total of 222 patients (276 knees) who underwent navigation-assisted TKA between September 2012 and January 2014 due to osteoarthritis were retrospectively reviewed. The deviation between the alignment of bone resection surfaces and the final alignment of femoral and tibial components was measured. Factors associated with alignment deviation of greater than 2° (outliers) were evaluated. These included age, sex, body mass index, bone mineral density (T score), preoperative and postoperative mechanical femorotibial angle, preoperative and postoperative flexion contractures, and the difference between medial and lateral gaps in knee extension or flexion. RESULTS: Outliers consisted of 24 cases (8.6%) on the femoral coronal plane, 4 cases (1.4%) on the tibial coronal plane, and 48 cases (17.4%) on the tibial sagittal plane. In the coronal plane (femur and tibia), the outliers were associated with preoperative [p < 0.001; odds ratio (OR) 0.774; 95% confidence interval (CI) 0.672-0.891] and postoperative (p < 0.001; OR 0.240; 95% CI 0.123-0.468) flexion contractures; a difference of 3 mm or more between the medial and lateral gaps in knee extension (p < 0.041; OR 5.805; 95% CI 1.075-31.343); and a T score of less than -2.5(p < 0.024; OR 5.899; 95% CI 1.258-27.664). In the sagittal plane of the tibia, the outliers were associated with preoperative (p < 0.001; OR 0.886; 95% CI 0.829-0.946) and postoperative (p < 0.031; OR 0.803; 95% CI 0.659-0.980) flexion contractures. CONCLUSION: There was a deviation between the alignments of the bone resection surfaces and the final alignments of components. With larger preoperative and postoperative flexion contractures in the coronal and sagittal planes, there were more outlier risks. The outliers in the coronal plane were associated with a difference of 3 mm or more between the medial and lateral gaps in knee extension and poor bone quality. Awareness of such alignment deviation and related factors can help diminish the outliers after TKA. LEVEL OF EVIDENCE: IV.

Two-axis control of a singlet-triplet qubit with an integrated micromagnet.

The qubit is the fundamental building block of a quantum computer. We fabricate a qubit in a silicon double-quantum dot with an integrated micromagnet in which the qubit basis states are the singlet state and the spin-zero triplet state of two electrons. Because of the micromagnet, the magnetic field difference ΔB between the two sides of the double dot is large enough to enable the achievement of coherent rotation of the qubit's Bloch vector around two different axes of the Bloch sphere. By measuring the decay of the quantum oscillations, the inhomogeneous spin coherence time T2* is determined. By measuring T2* at many different values of the exchange coupling J and at two different values of ΔB, we provide evidence that the micromagnet does not limit decoherence, with the dominant limits on T2* arising from charge noise and from coupling to nuclear spins.

Effects of Resection of Posterior Condyles of Femur on Extension Gap of Knee Joint in Total Knee Arthroplasty.

BACKGROUND: When evaluating the effects of the preparation of the flexion gap on the extension gap in total knee arthroplasty (TKA), the effects of posterior condylar resection and osteophyte removal on the extension gap should be differentiated. Although the amount of osteophytes differs between patients, posterior condylar resection is a procedure that is routinely implemented in TKA. The aim of this study was to assess the effects of the resection of the posterior condyle of the femur on the extension gap in posterior-stabilized (PS) TKA. METHODS: We enrolled 40 knees that underwent PS TKA between July 2010 and February 2011 with no or minimal osteophytes in the posterior compartment and a varus deformity of <15°. We measured the extension gap before and after the resection of the posterior condyle of the femur using a tensor under 20 and 40 lb of distraction force. RESULTS: Under 20 lb of distraction force, the average extension gap was 13.3 mm (standard deviation [SD], 1.6) before and 13.8 mm (SD, 1.6) after posterior condylar resection. Under 40 lb of distraction force, the average extension gap was 15.1 mm (SD, 1.5) before and 16.1 mm (SD, 1.7) after posterior condylar resection. CONCLUSION: The resection of the posterior condyle of the femur in PS TKA increased the extension gap. However, this increase was only by approximately 1 mm. In conclusion, posterior condylar resection does increase the extension gap by approximately 1 mm. However, in most case, this change in unlikely to be clinically important.

Wave-Tunable Lattice Equivalents toward Micro- and Nanomanipulation.

The assembly of micro- and nanomaterials is a key issue in the development of potential bottom-up construction of building blocks, but creating periodic arrays of such materials in an efficient and scalable manner still remains challenging. Here, we show that a cymatic assembly approach in which micro- and nanomaterials in a liquid medium that resonate at low-frequency standing waves can be used for the assembly in a spatially periodic and temporally stationary fashion that emerges from the wave displacement antinodes of the standing wave. We also show that employing a two-dimensional liquid, rather than a droplet, with a coffee-ring effect yields a result that exhibits distinct lattice equivalents comprising the materials. The crystallographic parameters, such as the lattice parameters, can be adjusted, where the parameters along the x- and y-axes are controlled by the applied wave frequencies, and the one along z-axis is controlled by a transparent layer as a spacer to create three-dimensional crystal equivalents. This work represents an advancement in assembling micro- and nanomaterials into macroscale architectures on the centimeter-length scale, thus establishing that a standing wave can direct micro- and nanomaterial assembly to mimic plane and space lattices.

Unintended Pulmonary Artery Ligation during PDA Ligation.

A 10-day-old boy was transferred to our hospital due to tachypnea. Patent ductus arteriosus (PDA), 4.8 mm in diameter, with small ASD was diagnosed on echocardiography. Surgical ligation of the ductus was performed after failure of three cycles of ibuprofen. However, the ductus remained open on routine postoperative echocardiography on the second postoperative day, and chest CT revealed inadvertent ligation of the left pulmonary artery (LPA) rather than the PDA. Emergent operation successfully reopened the clipped LPA and ligated the ductus on the same (second postoperative) day.Mechanical ventilator support was weaned on postoperative day 21, and the baby was discharged on postoperative day 47 with a normal left lung shadow.

Tuning bulk and surface conduction in the proposed topological Kondo insulator SmB(6).

Bulk and surface state contributions to the electrical resistance of single-crystal samples of the topological Kondo-insulator compound SmB_{6} are investigated as a function of crystal thickness and surface charge density, the latter tuned by ionic liquid gating with electrodes patterned in a Corbino disk geometry on a single (100) surface. By separately tuning bulk and surface conduction channels, we show conclusive evidence for a model with an insulating bulk and metallic surface states, with a crossover temperature that depends solely on the relative contributions of each conduction channel. The surface conductance, on the order of 100 e^{2}/h, exhibits a field-effect mobility of 133 cm^{2}/Vs and a large carrier density of ∼2×10^{14} cm^{-2}, in good agreement with recent photoemission results. With the ability to gate modulate surface conduction by more than 25%, this approach provides promise for both fundamental and applied studies of gate-tuned devices structured on bulk crystal samples.

Treatment outcomes of adjuvant resectional surgery for nontuberculous mycobacterial lung disease.

BACKGROUND: Outcomes of antibiotic treatment for lung disease caused by nontuberculous mycobacteria (NTM) are unsatisfactory. The role of adjunctive surgery in the treatment of NTM lung disease is still unclear. METHODS: We conducted a retrospective review of 70 patients who underwent pulmonary resection for NTM lung disease from March 2007 to February 2013. All patients received recommended antibiotic treatment before and after the surgery. RESULTS: A total of 70 patients underwent 74 operations. The median age of the patients was 50 years. Of the 70 patients, 45 (64%) had Mycobacterium avium complex infection (24 M. intracellulare and 21 M. avium) and 23 (33%) had M. abscessus complex infection (15 M. abscessus and 8 M. massiliense). Thirty-eight (54%) patients had the nodular bronchiectatic form and 28 (40%) had the fibrocavitary form of NTM lung disease. The indications for surgery were a poor response to drug therapy (n=52), remnant cavitary lesions and severe bronchiectasis (n=14), and hemoptysis (n=4). Preoperative sputum acid-fast bacilli staining results were positive in 44 (63%) patients, and sputum culture was positive in 54 (76%). The surgery included lobectomy or lobectomy plus segmentectomy (n=50, 68%), segmentectomy (n=11, 15%), pneumonectomy or completion pneumonectomy (n=8, 11%), bilobectomy or bilobectomy plus segmentectomy (n=4, 5%), and wedge resection (n=1, 1%). Postoperative complications occurred in 15 (21%) patients, including one postoperative death and bronchopleural fistula in 5 patients with the fibrocavitary form of the disease. A negative sputum culture was achieved and maintained in 57 (81%) patients. CONCLUSIONS: Although adjuvant pulmonary resection is associated with a relatively high complication rate, this procedure may provide a high level of treatment success for selected patients with NTM lung disease, such as those with a poor response to antibiotic treatment alone.

Central Lung Cancer Management: Impact of Bronchial Resection Margin Length.

PURPOSE: The purpose of this study was to analyze the clinical impact of bronchial resection margin length in centrally located, non-small cell lung cancer. MATERIALS AND METHODS: A total of 1,854 pulmonary resections were performed between January 1994 and December 2005. Central lung cancer was defined as a tumor that was confirmed by bronchoscopy or a malignancy proven by bronchoscopic washing. Cases with neoadjuvant treatment that could alter the malignancy on the margin and those without documentation of margin length were excluded. To divide the study group into two groups, the cutoff value for the margin length was calculated by the minimum p-value approach. Clinical variables were then compared between the two groups and prognostic factors for survival were analyzed. RESULTS: A total of 573 patients were included. The patients were divided into two groups based on margin length, short (< 19 mm) and long (≥ 19 mm). Overall survival and disease-free survival were superior in the short length group by univariate analysis (p = 0.03, 0.02). With multivariate analysis, advanced age (p < 0.00, 0.00), pneumonectomy (p < 0.00, 0.00), advanced pathologic stage (p < 0.00, 0.00), and no adjuvant chemotherapy (p < 0.00, 0.01) were poor prognostic factors for survival; however, bronchial resection margin length was not a statistically significant factor (p = 0.90, 0.96). CONCLUSION: A long bronchial resection margin length may not guarantee better oncologic outcomes in central lung cancer patients. Rather, avoiding pneumonectomy and the application of adjuvant chemotherapy should be considered to survival.