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A cost-effective conversion of lignocellulosic biomass into bioethanol requires that the xylose released from the hemicellulose fraction (20-40% of biomass) can be fermented. Baker's yeast, Saccharomyces cerevisiae, efficiently ferments glucose but it lacks the ability to ferment xylose. Xylose-fermenting yeast such as Pichia stipitis requires accurately controlled microaerophilic conditions during the xylose fermentation, rendering the process technically difficult and expensive. In this study, it is demonstrated that under anaerobic conditions Spathaspora passalidarum showed high ethanol production yield, fast cell growth, and rapid sugar consumption with xylose being consumed after glucose depletion, while P. stipitis was almost unable to utilize xylose under these conditions. It is further demonstrated that for S. passalidarum, the xylose conversion takes place by means of NADH-preferred xylose reductase (XR) and NAD^sup +^-dependent xylitol dehydrogenase (XDH). Thus, the capacity of S. passalidarum to utilize xylose under anaerobic conditions is possibly due to the balance between the cofactor's supply and demand through this XR-XDH pathway. Only few XRs with NADH preference have been reported so far. 2-Deoxy glucose completely inhibited the conversion of xylose by S. passalidarum under anaerobic conditions, but only partially did that under aerobic conditions. Thus, xylose uptake by S. passalidarum may be carried out by different xylose transport systems under anaerobic and aerobic conditions. The presence of glucose also repressed the enzymatic activity of XR and XDH from S. passalidarum as well as the activities of those enzymes from P. stipitis. [PUBLICATION ABSTRACT]

The symmetry of Cooper pairs in iron-based superconductors is an issue under continued investigation. A scanning tunnelling study of Fe(Te,Se) reveals a robust zero-energy bound state, providing evidence for a non-trivial pairing symmetry. In superconductors, electrons are paired and condensed into the ground state. An impurity can break the electron pairs into quasiparticles with energy states inside the superconducting gap. The characteristics of such in-gap states reflect accordingly the properties of the superconducting ground state 1 . A zero-energy in-gap state is particularly noteworthy, because it can be the consequence of non-trivial pairing symmetry 1 or topology 2 , 3 . Here we use scanning tunnelling microscopy/spectroscopy to demonstrate that an isotropic zero-energy bound state with a decay length of ∼10 Å emerges at each interstitial iron impurity in superconducting Fe(Te,Se). More noticeably, this zero-energy bound state is robust against a magnetic field up to 8 T, as well as perturbations by neighbouring impurities. Such a spectroscopic feature has no natural explanation in terms of impurity states in superconductors with s -wave symmetry, but bears all the characteristics of the Majorana bound state proposed for topological superconductors 2 , 3 , indicating that the superconducting state and the scattering mechanism of the interstitial iron impurities in Fe(Te,Se) are highly unconventional.

SummaryWe investigated the secular trends of the incidence and hospitalization cost of hip fracture in Tangshan, China. The incidence of hip fracture and the hospitalization cost were both increasing during the observation period.IntroductionThe present study aimed to determine sex-, age-, and fracture type-specific incidence and annual changes in hip fractures in Tangshan, China, between 2007 and 2018.MethodsWe analyzed annual hip fracture incidence using urban hospital data during 2007–2018 and calculated incidence rate/100,000 person years in each age group and sex. We assessed annual changes in incidence among people aged >60 years using linear-by-linear association tests and evaluated hospitalization costs with the Kruskal–Wallis test.ResultsDuring the study period, we observed an increasing proportion of hip fractures in people >60 years old from 14.2 to 22.79%. Crude hip fracture incidence increased markedly from 140.87 to 306.56/100,000 in women (p < 0.01) and from 124.83 to 167.19/100,000 in men (p < 0.01) in the age group >60 years. Type-specific analysis indicated significantly increased trends in incidence of cervical and trochanteric fractures among women and cervical fracture among men (p < 0.01). In people aged 36–60 years, the trend of hip fracture increased significantly in both sexes. The total and cervical-to-trochanteric ratio in men increased, with significant upward trends (p < 0.01). The proportion of cervical fracture was higher than that for trochanteric fracture in women, with stable levels from 2007 to 2018. Hospitalization costs for cervical and trochanteric fractures increased by 51.91% and 53.20%, respectively, during 2011–2018.ConclusionTangshan will have an increasing burden on health care resources attributable to a considerable rise in hip fracture incidence and the older population. Further investigation of risk factors and subsequent implementation of effective measures to prevent hip fracture are needed.

The aim of this study was to develop a widely accepted prognostic nomogram for extranodal NK/T-cell lymphoma, nasal-type (NKTCL). The clinical data from 1383 patients with NKTCL treated at 10 participating institutions between 2000 and 2011 were reviewed. A nomogram was developed that predicted overall survival (OS) based on the Cox proportional hazards model. To contrast the utility of the nomogram against the widely used Ann Arbor staging system, the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI), we used the concordance index (C-index) and a calibration curve to determine its predictive and discriminatory capacity. The 5-year OS rate was 60.3% for the entire group. The nomogram included five important variables based on a multivariate analysis of the primary cohort: stage; age; Eastern Cooperative Oncology Group performance status; lactate dehydrogenase; and primary tumor invasion. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.72 for both cohorts, which was superior to the predictive power (range, 0.56–0.64) of the Ann Arbor stage, IPI and KPI in the primary and validation cohorts. The proposed nomogram provides an individualized risk estimate of OS in patients with NKTCL.

Cancer stem cells (CSCs) may be responsible for treatment resistance, tumor metastasis, and disease recurrence. Here we demonstrate that the Arf1-mediated lipid metabolism sustains cells enriched with CSCs and its ablation induces anti-tumor immune responses in mice. Notably, Arf1 ablation in cancer cells induces mitochondrial defects, endoplasmic-reticulum stress, and the release of damage-associated molecular patterns (DAMPs), which recruit and activate dendritic cells (DCs) at tumor sites. The activated immune system finally elicits antitumor immune surveillance by stimulating T-cell infiltration and activation. Furthermore, TCGA data analysis shows an inverse correlation between Arf1 expression and T-cell infiltration and activation along with patient survival in various human cancers. Our results reveal that Arf1-pathway knockdown not only kills CSCs but also elicits a tumor-specific immune response that converts dying CSCs into a therapeutic vaccine, leading to durable benefits. Cancer stem cells (CSC) have been shown as the origin for therapeutic resistance and patient relapse. Here, the authors show that targeting Arf1-mediated lipid metabolism in CSC induces cell death but also an immunogenic anti-cancer response.

Attenuating the lipolysis pathway in Drosophila melanogaster by modulation of the COP1–Arf1 signalling complex induced necrosis in stem cells and led to their engulfment by differentiated cells. Cancer stem cells dependent on lipid utilization In an effort to establish the molecular mechanism behind the resistance of cancer stem cells to chemotherapy, Steven Hou and colleagues turned to Drosophila melanogaster . They find that the lipolysis pathway protects stem cells from chemotherapy-induced necrosis. Attenuating the lipolysis pathway by modulation of COPI–Arf1 signalling complex led to engulfment of dying stem cells by differentiated cells. The authors also present evidence that the same survival pathway may be active in human cancer cell lines with stem cell characteristics. This work implies that quiescent stem or cancer stem cells may depend on lipid reserves for energy, and that agents that block lipolysis might therefore be of therapeutic use. Cancer stem cells (CSCs) may be responsible for tumour dormancy, relapse and the eventual death of most cancer patients 1 . In addition, these cells are usually resistant to cytotoxic conditions. However, very little is known about the biology behind this resistance to therapeutics. Here we investigated stem-cell death in the digestive system of adult Drosophila melanogaster . We found that knockdown of the coat protein complex I (COPI)–Arf79F (also known as Arf1) complex selectively killed normal and transformed stem cells through necrosis, by attenuating the lipolysis pathway, but spared differentiated cells. The dying stem cells were engulfed by neighbouring differentiated cells through a draper–myoblast city–Rac1–basket (also known as JNK)-dependent autophagy pathway. Furthermore, Arf1 inhibitors reduced CSCs in human cancer cell lines. Thus, normal or cancer stem cells may rely primarily on lipid reserves for energy, in such a way that blocking lipolysis starves them to death. This finding may lead to new therapies that could help to eliminate CSCs in human cancers.

The plasma membrane protein Orai forms the pore of the calcium release—activated calcium (CRAC) channel and generates sustained cytosolic calcium signals when triggered by depletion of calcium from the endoplasmic reticulum. The crystal structure of Orai from Drosophila melanogaster, determined at 3.35 angstrom resolution, reveals that the calcium channel is composed of a hexameric assembly of Orai subunits arranged around a central ion pore. The pore traverses the membrane and extends into the cytosol. A ring of glutamate residues on its extracellular side forms the selectivity filter. A basic region near the intracellular side can bind anions that may stabilize the closed state. The architecture of the channel differs markedly from other ion channels and gives insight into the principles of selective calcium permeation and gating.

Solid-state spin sensors have the capacity to act as quantum microscopes for probing material properties and physical processes. However, so far, these tools have relied on quantum defects hosted in rigid, three-dimensional (3D) crystals such as diamond, limiting their ability to closely interface with the sample. Here we demonstrate a versatile quantum microscope using point defects embedded within a thin layer of the van der Waals material hexagonal boron nitride. To showcase the multi-modal capabilities of this platform, we assemble two different heterostructures of a van der Waals material in combination with a quantum-active boron nitride flake. We demonstrate time-resolved, simultaneous temperature and magnetic imaging near the Curie temperature of a van der Waals ferromagnet, as well as map out charge currents and Joule heating in an operating graphene device. The straightforward integration of the hexagonal boron nitride quantum sensor with other van der Waals materials will yield substantial practical benefits for the design and measurement of 2D devices.Hexagonal boron nitride is a common component of 2D heterostructures. Defects implanted in boron nitride crystals can be used to perform spatially resolved sensing of properties, including temperature, magnetism and current.

To ward off a wide variety of pathogens, the human adaptive immune system harbors a vast array of T-cell receptors (TCRs) and B-cell receptors (BCRs), collectively referred to as the immune repertoire. High-throughput sequencing (HTS) of TCR/BCR genes allows in-depth molecular analysis of T/B-cell clones, providing an unprecedented level of detail when examining the T/B-cell repertoire of individuals. It can evaluate TCR/BCR complementarity-determining region 3 (CDR3) diversity and assess the clonal composition, including the size of the repertoire; similarities between repertoires; V(D)J segment use; nucleotide insertions and deletions; CDR3 lengths; and amino acid distributions along the CDR3s at sequence-level resolution. Deep sequencing of B-cell and T-cell repertoires offers the potential for a quantitative understanding of the adaptive immune system in healthy and disease states. Recently, paired sequencing strategies have also been developed, which can provide information about the identity of immune receptor pairs encoded by individual T or B lymphocytes. HTS technology provides a previously unimaginable amount of sequence data, accompanied, however, by numerous challenges associated with error correction and interpretation that remain to be solved. The review details some of the technologies and some of the recent achievements in this field.

Isotopic ratios of radioactive releases into the environment are useful signatures for contamination source assessment. Uranium is known to behave conservatively in sea water so that a ratio of uranium trace isotopes may serve as a superior oceanographic tracer. Here we present data on the atomic 233 U/ 236 U ratio analyzed in representative environmental samples finding ratios of (0.1–3.7) ⋅ 10 − 2 . The ratios detected in compartments of the environment affected by releases of nuclear power production or by weapons fallout differ by one order of magnitude. Significant amounts of 233 U were only released in nuclear weapons fallout, either produced by fast neutron reactions or directly by 233 U-fueled devices. This makes the 233 U/ 236 U ratio a promising new fingerprint for radioactive emissions. Our findings indicate a higher release of 233 U by nuclear weapons tests before the maximum of global fallout in 1963, setting constraints on the design of the nuclear weapons employed. The dominant emission sources of anthropogenic radionuclides come from either atmospheric nuclear weapons tests or the nuclear industry (i.e., reprocessing plants or reactor accidents). Here, the authors identify a new environmental isotope tracer ( 233 U/ 236 U) which can help distinguish emissions from nuclear weapons tests, and can also provide constraints on past weapon designs and fuel sources, for which many details remain classified or lost.