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
+
-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
.
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. A zero-energy in-gap state is particularly noteworthy, because it can be the consequence of non-trivial pairing symmetry or topology. 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, indicating that the superconducting state and the scattering mechanism of the interstitial iron impurities in Fe(Te,Se) are highly unconventional.
Functional mature cells are continually replenished by stem cells to maintain tissue homoeostasis. In the adult Drosophila posterior midgut, both terminally differentiated enterocyte (EC) and ...enteroendocrine (EE) cells are generated from an intestinal stem cell (ISC). However, it is not clear how the two differentiated cells are generated from the ISC. In this study, we found that only ECs are generated through the Su(H)GBE(+) immature progenitor enteroblasts (EBs), whereas EEs are generated from ISCs through a distinct progenitor pre-EE by a novel lineage-tracing system. EEs can be generated from ISCs in three ways: an ISC becoming an EE, an ISC becoming a new ISC and an EE through asymmetric division, or an ISC becoming two EEs through symmetric division. We further identified that the transcriptional factor Prospero (Pros) regulates ISC commitment to EEs. Our data provide direct evidence that different differentiated cells are generated by different modes of stem cell lineage specification within the same tissues.
Summary
We 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.
Introduction
The 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.
Methods
We 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.
Results
During 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.
Conclusion
Tangshan 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.
•New results on the stability of terminator and heliotropic orbits.•First global study of dynamics around asteroids with SRP and the C20 term.•Influence of the asteroid’s orbit eccentricity on the ...secular stability is studied.
This study focuses on the secular dynamics of orbital motion around asteroids with joint effects of C20 term and solar radiation pressure (SRP). With their combined influences, two specific orbits are firstly studied, namely the solar terminator orbit (STO) and the heliotropic orbit. Then, the global orbital motion other than the two specific ones is investigated. Finally, the influence of the asteroid’s orbital eccentricity around the Sun on the secular dynamics is discussed.
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 tumour dormancy, relapse and the eventual death of most cancer patients. 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.
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.
Ampelopsis grossedentata, an indigenous plant in southern China, has been used for treating pharyngitis in traditional Chinese medicine for hundreds of years. In this study, we explored the ...anti-inflammatory activity of dihydromyricetin (1), its major bioactive component, and the underlying mechanism of this action. We demonstrated that 1 suppressed the levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as increased the level of the anti-inflammatory cytokine interleukin-10 (IL-10) in lipopolysaccharide (LPS)-treated mice. Moreover, 1 was found to markedly inhibit the production of nitric oxide (NO) and the levels of TNF-α, IL-1β, and IL-6, whereas it increased the level of IL-10 in LPS-induced RAW 264.7 macrophage cells. Compound 1 also reduced the protein expression of inducible nitric oxide synthase (iNOS), TNF-α, and cyclooxygenase-2 (COX-2) in macrophage cells. Furthermore, 1 suppressed the phosphorylation of NF-kappa B (NF-κB) and IκBα as well as the phosphorylation of p38 and JNK but not ERK1/2 in LPS-stimulated macrophages. Taken together, the present results suggest that 1 exerts its topical anti-inflammatory action through suppressing the activation of NF-κB and the phosphorylation of p38 and JNK. Thus, 1 may be a potentially useful therapeutic agent for inflammatory-related diseases.
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.
PDF
