Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be ...heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.
Highly specific Cas9 nucleases derived from SpCas9 are valuable tools for genome editing, but their wide applications are hampered by a lack of knowledge governing guide RNA (gRNA) activity. Here, we ...perform a genome-scale screen to measure gRNA activity for two highly specific SpCas9 variants (eSpCas9(1.1) and SpCas9-HF1) and wild-type SpCas9 (WT-SpCas9) in human cells, and obtain indel rates of over 50,000 gRNAs for each nuclease, covering ~20,000 genes. We evaluate the contribution of 1,031 features to gRNA activity and develope models for activity prediction. Our data reveals that a combination of RNN with important biological features outperforms other models for activity prediction. We further demonstrate that our model outperforms other popular gRNA design tools. Finally, we develop an online design tool DeepHF for the three Cas9 nucleases. The database, as well as the designer tool, is freely accessible via a web server, http://www.DeepHF.com/ .
Sodium‐ion batteries (SIBs) are considered as promising alternatives to lithium‐ion batteries (LIBs) for large‐scale electrical‐energy‐storage applications due to the wide availability and the low ...cost of Na resources. Along with the avenues of research on flexible LIBs, flexible SIBs are now being actively developed as one of the most promising power sources for the emerging field of flexible and wearable electronic devices. Here, the recent progress on flexible electrodes based on metal substrates, carbonaceous substrates (i.e., graphene, carbon cloth, and carbon nanofibers), and other materials, as well as their applications in flexible SIBs, are summarized. Also, some future research directions for constructing flexible SIBs are proposed, with the aim of providing inspiration to the further development of advanced flexible SIBs.
Flexible sodium‐ion batteries (SIBs) are being actively developed as one of the most promising power sources for the emerging field of flexible and wearable electronic devices. The recent progress on flexible electrodes based on metal substrates, carbonaceous substrates, and other materials, is summarized, along with their applications in flexible SIBs.
•Diabetic nephropathy is a serious complication of diabetes mellitus.•Hyperglycemia and other related factors are involved in the pathophysiology of diabetic nephropathy.•Understanding of the ...molecular mechanism may lead to effective therapies.
Diabetic nephropathy (DN) is a chronic disease characterized by proteinuria, glomerular hypertrophy, decreased glomerular filtration and renal fibrosis with loss of renal function. DN is the leading cause of end-stage renal disease, accounting for millions of deaths worldwide. Hyperglycemia is the driving force for the development of diabetic nephropathy. The exact cause of diabetic nephropathy is unknown, but various postulated mechanisms are: hyperglycemia (causing hyperfiltration and renal injury), advanced glycosylation products, activation of cytokines. In this review article, we have discussed a number of diabetes-induced metabolites such as glucose, advanced glycation end products, protein kinase C and oxidative stress and other related factors that are implicated in the pathophysiology of the DN. An understanding of the biochemical and molecular changes especially early in the DN may lead to new and effective therapies towards prevention and amelioration of DN.
Plant expansins are proteins involved in cell wall loosening, plant growth, and development, as well as in response to plant diseases and other stresses. In this study, we identified 128 expansin ...coding sequences from the wheat (Triticum aestivum) genome. These sequences belong to 45 homoeologous copies of TaEXPs, including 26 TaEXPAs, 15 TaEXPBs and four TaEXLAs. No TaEXLB was identified. Gene expression and sub-expression profiles revealed that most of the TaEXPs were expressed either only in root tissues or in multiple organs. Real-time qPCR analysis showed that many TaEXPs were differentially expressed in four different tissues of the two wheat cultivars-the cold-sensitive 'Chinese Spring (CS)' and the cold-tolerant 'Dongnongdongmai 1 (D1)' cultivars. Our results suggest that the differential expression of TaEXPs could be related to low-temperature tolerance or sensitivity of different wheat cultivars. Our study expands our knowledge on wheat expansins and sheds new light on the functions of expansins in plant development and stress response.
Treating the light-flavor constituent quarks and antiquarks whose momentum information is extracted from the data of soft light-flavor hadrons in
pp
collisions at
s
=
7
TeV as the underlying source ...of chromatically neutralizing the charm quarks of low transverse momenta (
p
T
), we show that the experimental data of
p
T
spectra of single-charm hadrons
D
0
,
+
,
D
∗
+
D
s
+
,
Λ
c
+
and
Ξ
c
0
at mid-rapidity in the low
p
T
range (
2
≲
p
T
≲
7
GeV/
c
) in
pp
collisions at
s
=
7
TeV can be well understood by the equal-velocity combination of perturbatively created charm quarks and those light-flavor constituent quarks and antiquarks. This suggests a possible new scenario of low
p
T
charm quark hadronization, in contrast to the traditional fragmentation mechanism, in
pp
collisions at LHC energies. This is also another support for the exhibition of the soft constituent quark degrees of freedom for the small parton system created in
pp
collisions at LHC energies.
We apply a quark combination model with equal-velocity combination (EVC) approximation to study the elliptic flow (
v
2
) of hadrons in heavy-ion collisions in a wide collision energy range (
s
NN
=
...27–5020 GeV). Utilizing the simple relationship between
v
2
of hadrons and those of quarks under EVC, we find that
v
2
of up/down quarks obtained by experimental data of proton is consistent with that obtained by data of
Λ
and
Ξ
.
v
2
of strange quarks obtained by data of
Ω
is consistent with that obtained by data of
Λ
and
Ξ
, and at RHIC energies it is also consistent with that obtained by data of
ϕ
. This means that
v
2
of these hadrons have a common quark-level source. Using data of
D
0
, we obtain
v
2
of charm quarks with
p
T
≲
6
GeV/c. We find that under EVC charm quark dominates
v
2
of
D
mesons at low
p
T
but light-flavor quarks significantly contribute to
v
2
of
D
mesons in the range
3
≲
p
T
≲
8
GeV/c. We predict
v
2
of charmed baryons
Λ
c
+
and
Ξ
c
0
which show a significant enhancement at intermediate
p
T
due to the double contribution of light-flavor quarks. The properties of the obtained quark
v
2
under EVC are studied and a regularity for
v
2
of quarks as the function of
p
T
/
m
is found.
Aims and objectives
To examine the effectiveness of a nurse‐led transitional care programme on readmission, self‐efficacy to implement health‐promoting behaviours, functional status and life quality ...among Chinese patients with coronary artery disease.
Background
Coronary artery disease is a major cause of mortality in China. Transitional care could help to ensure improved patient outcomes. Nevertheless, our knowledge of how to perform transitional care for patients with coronary artery disease is insufficient in mainland China.
Design
Randomised controlled trial.
Methods
The nurse‐led transitional care intervention in the experimental group adopted the Omaha system and Pender's health‐promoting model as its frameworks. The control group received a comparable length routine care and follow‐up contacts. Evaluations were conducted at baseline before discharge and after 7 months after discharge using hospital readmission rate, self‐rated abilities for health practices scale and Seattle Angina Questionnaire for functional status and life quality. Data were collected between March 2014–October 2014.
Results
Compared with the control group, participants in the experimental group showed greater self‐efficacy to implement health‐promoting behaviours, more angina stability, less angina frequency, more satisfaction with treatment and better quality of life. The difference in readmission rate and physical limitations was not significant between the two groups.
Conclusion
This study provides evidence for the effectiveness of a nurse‐led transitional care programme in improving the ability to implement health‐promoting behaviours, the functional status and life quality among Chinese patients with coronary artery disease.
Relevance to clinical practice
The nurse‐led transitional care programme is helpful for coronary artery disease patients to promote their effective transfer from hospital to community and provide an evidence for nursing managers to train their nurses for transitional care knowledge and skills.
Herein, we describe an unprecedented cascade reaction to β‐stereogenic γ‐lactams involving Pd(II)‐catalyzed enantioselective aliphatic methylene C(sp3)−H alkenylation–aza‐Wacker cyclization through ...syn‐aminopalladation. Readily available 3,3′‐substituted BINOLs are used as chiral ligands, providing the corresponding γ‐lactams with broad scope and high enantioselectivities (up to 98 % ee).
An unprecedented cascade reaction to β‐stereogenic γ‐lactams involving Pd(II)‐catalyzed enantioselective aliphatic methylene C(sp3)−H alkenylation–aza‐Wacker cyclization through syn‐aminopalladation is reported. Readily available 3,3′‐substituted BINOLs are used as chiral ligands, providing the corresponding γ‐lactams with broad scope and high enantioselectivities (up to 98 % ee).
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