Complement C4, a key molecule in the complement system that is one of chief constituents of innate immunity for immediate recognition and elimination of invading microbes, plays an essential role for ...the functions of both classical (CP) and lectin (LP) complement pathways. Complement C4 is the most polymorphic protein in complement system. A plethora of research data demonstrated that individuals with C4 deficiency are prone to microbial infections and autoimmune disorders. In this review, we will discuss the diversity of complement C4 proteins and its genetic structures. In addition, the current development of the regulation of complement C4 activation and its activation derivatives will be reviewed. Moreover, the review will provide the updates on the molecule interactions of complement C4 under the circumstances of bacterial and viral infections, as well as autoimmune diseases. Lastly, more evidence will be presented to support the paradigm that links microbial infections and autoimmune disorders under the condition of the deficiency of complement C4. We provide such an updated overview that would shed light on current research of complement C4. The newly identified targets of molecular interaction will not only lead to novel hypotheses on the study of complement C4 but also assist to propose new strategies for targeting microbial infections, as well as autoimmune disorders.
In this paper, we study an initial-boundary value problem of the doubly dispersive quasilinear wave equation
u
tt
-
div
(
|
∇
u
|
p
-
2
∇
u
)
+
Δ
2
u
-
Δ
u
tt
=
|
u
|
q
-
2
u
log
|
u
|
in
Ω
×
(
0
,
T
...max
)
,
where
Ω
is an open bounded domain in
R
n
with smooth boundary;
T
max
(
≤
+
∞
)
denotes the maximal existence time;
p
,
q
>
2
are constants. We denote
q
=
p
the critical exponent for blow-up solutions. For
q
<
p
, we prove that all the weak solutions are globally bounded even if the initial energy is negative. For
q
≥
p
, we obtain the optimal classification of initial data on the existence of global and blow-up solutions, which is divided into the subcritical, critical, and super critical initial energy in the framework of potential well. By constructing new auxiliary functions, we obtain the upper bounds of blow-up time for different norms.
This study thoroughly investigates the dynamical properties, analytical solutions and chaotic behavior of the high-order nonlinear Schrödinger equation with conformal fractional derivative. After ...obtaining the dynamic properties by a third-order polynomial complete discriminant system, the study further utilizes a fourth-order polynomial complete discrimination system to derive all traveling wave solutions, including rational solutions, solitary wave solutions, triangular function periodic solutions, and Jacobian elliptic function periodic solutions. In addition, based on different phase diagrams and largest Lyapunov exponents, the chaotic behavior is numerically observed by considering different external perturbation terms and perturbation functions. The innovation of this work lies in using the same method to qualitatively and quantitatively analyze the proposed equation. The type of equation solution is predicted using the results of qualitative analysis, and the accuracy of the prediction can be verified through specific parameter values.
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•The crystallization inhibition ability of 12 CD derivatives was precisely assessed.•The crystallization inhibition effect is less related to the solubilization effect.•The ...hydrophobicity of CD derivative correlates to crystallization inhibition effect.
Cyclodextrin (CD) is used to solubilize poorly water-soluble drugs by inclusion complex formation. In this study, we investigated the effect of CD derivatives on stabilizing the supersaturation by inhibiting the crystallization of two poorly water-soluble drugs, carvedilol (CVD) and chlorthalidone (CLT). The phase solubility test showed that β-CD and γ-CD derivatives enhanced the solubility of CVD to a greater extent, whereas the solubility of CLT was enhanced more by β-CD derivatives. The solubilization efficacy of CD derivatives was dependent on the size fitness between the drug molecule and the CD cavity. In the drug crystallization induction time measurement, the same initial drug supersaturation ratio (S) was employed in all the CD solutions, and the methylated CD derivatives greatly outperformed unmethylated CD derivatives in stabilizing the supersaturation of both CVD and CLT. The crystallization inhibition strength of CD derivatives was strongly affected by the CD derivative substituent. Moreover, the calculated logarithm of octanol/water partition coefficients (log P) of CD derivatives showed a good correlation with drug crystallization inhibition ability. Thus, the high hydrophobicity of methylated CD plays an essential role in inhibiting crystallization. These findings can provide a valuable guide for selecting appropriate stabilizing agents for drug-supersaturation formulations.
We study the core mass function (CMF) within 32 dense clumps in seven infrared dark clouds (IRDCs) with the Atacama Large Millimeter/submillimeter Array via 1.3 mm continuum emission at a resolution ...of ∼1″. We have identified 107 cores with the dendrogram algorithm, with a median radius of about 0.02 pc. Their masses range from 0.261 to 178 M . After applying completeness corrections, we fit the combined IRDC CMF with a power law of the form and derive an index of 0.86 0.11 for M ≥ 0.79 M and 0.70 0.13 for M ≥ 1.26 M , which is a significantly more top-heavy distribution than the Salpeter stellar initial mass function index of 1.35. We also make a direct comparison of these IRDC clump CMF results to those measured in the more evolved protocluster G286 derived with similar methods, which have 1.29 0.19 and 1.08 0.27 in these mass ranges, respectively. These results provide a hint that, especially for the M ≥ 1.26 M range where completeness corrections are modest, the CMF in high pressure, early-stage environments of IRDC clumps may be top-heavy compared to that in the more evolved, global environment of the G286 protoclusters. However, larger samples of cores probing these different environments are needed to better establish the robustness of this potential CMF variation.
•Novel chondroitin sulfate-based nanoparticles (PTX/CQE NPs) were initially prepared.•PTX/CQE NPs could exert enhanced chemo-photodynamic therapy in vitro and in vivo.•PTX/CQE NPs exhibited in vivo ...MDR inhibition and anti-metastasis efficacy.
As a major therapeutic approach for cancer treatment, the effectiveness of chemotherapy is challenged by multidrug resistance (MDR). Herein, we fabricated novel redox-responsive, chondroitin sulfate-based nanoparticles that could simultaneously deliver quercetin (chemosensitizer), chlorin e6 (photosensitizer) and paclitaxel (chemotherapeutic agent) to exert enhanced chemo-photodynamic therapy for overcoming MDR and lung metastasis of breast cancer. In vitro cell study showed that nanoparticles down-regulated the expression of P-glycolprotein (P-gp) on MCF-7/ADR cells and thereby improved the anticancer efficacy of PTX against MCF-7/ADR cells. Moreover, NIR laser irradiation could induce nanoparticles to generate cellular reactive oxygen species (ROS), leading to mitochondrial membrane potential loss, and meanwhile facilitating lysosomal escape of drugs. Importantly, the novel nanoplatform exhibited effective in vivo MDR inhibition and anti-metastasis efficacy through enhanced chemo-photodynamic therapy. Thus, the study suggested that the multifunctional nanoplatform had good application prospect for effective breast cancer therapy.
Muscle fibrosis and fatty infiltration (FI) are common complications seen in various muscle disease states. Recent studies indicate that muscle residential fibro/adipogenic progenitors (FAPs) are the ...major cellular source for muscle fibrosis and FI. We previously showed that MMP13 knockout (KO) mice have significantly increased FI, suggesting an important role of MMP13 in muscle FI. However, how MMP13 affects the differentiation of FAPs remains unknown.
In order to assess the role of MMP-13 on FAP differentiation, we isolated FAPs from wildtype C57BL/6 and MMP13 knock out mice with FACS using CD31-, CD45-, Integrin α7- and Sca-1+ markers. FAPs were cultured in 24 well plate after FACS.in standard media till 80% confluent and then switched to adipogenic medium. In order to study the role of TGFβ and BMP in their differentiation, FAPs from both wildtype and MMP13 KO mice were treated with TGFβ1 (5 ng/ml). For MMP13 inhibitor treatment, FAPs from wildtype mice were incubated in adipogenic medium containing 10 µM MMP13 inhibitor (or vehicle) for 2 weeks. Immunofluorescence and gene expression analysis were used to assess FAP adipogenic and fibrogenic differentiation. FAPs were stained with Perilipin A (FITC, adipogenesis marker) and αSMA (Red, fibroblast marker), and DAPI. Real time PCR was performed for gene expression evaluation. A two-tailed Anova was used for statistical comparisons between groups, with p ≤ 0.05. Data are presented as mean ± standard deviation.
In this study, we isolated FAPs from wildtype C57BL/6 and MMP13 KO mice and evaluated their adipogenic and fibrogenic differentiation in vitro. MMP13 KO FAPs demonstrated enhanced adipogenesis but reduced fibrogenesis compared to wildtype FAPs. Treating wildtype FAPs with an MMP13 inhibitor simulated phenotypes seen in MMP13 KO FAPs. In order to assess the role of MMP13 on TGFβ/BMP signaling in regulating FAP differentiation, we treated wildtype and MMP13 KO FAPs with TGFβ1, BMP7, TGFβ inhibitor, and BMP inhibitor. TGFβ1 treatment significantly enhanced fibrogenesis, but inhibited adipogenesis of wildtype FAPs. However, treatment with BMP7 showed the opposite effect. Interestingly, the effect of TGFβ1/BMP7 was voided in MMP13 KO FAPs. Treating wildtype FAPs with MMP13 inhibitor also abolished the effect of TGFβ1/BMP7 in FAP differentiation.
Results from this study showed that TGFβ1 inhibits FAP adipogenesis but stimulates FAP fibrogenesis. BMP7 was shown to promote FAP adipogenesis but reduce its fibrogenesis. The role of the TGFβ/BMP signaling pathway regulating FAP differentiation was found to be MMP13 dependent. This study suggests that MMP13 is a critical downstream effector in TGFβ/BMP pathway which may serve as a new therapeutic target for muscle fibrosis and FI.
We study the core mass function (CMF) of the massive protocluster G286.21+0.17 with the Atacama Large Millimeter/submillimeter Array via 1.3 mm continuum emission at a resolution of 1 0 (2500 au). We ...have mapped a field of 5 3 × 5 3 centered on the protocluster clump. We measure the CMF in the central region, exploring various core detection algorithms, which give source numbers ranging from 60 to 125, depending on parameter selection. We estimate completeness corrections due to imperfect flux recovery and core identification via artificial core insertion experiments. For masses M 1 M , the fiducial dendrogram-identified CMF can be fit with a power law of the form dN/dlog M ∝ M− with 1.24 0.17, slightly shallower than, but still consistent with, the index of the Salpeter stellar initial mass function of 1.35. Clumpfind-identified CMFs are significantly shallower with 0.64 0.13. While raw CMFs show a peak near 1 M , completeness-corrected CMFs are consistent with a single power law extending down to ∼0.5 M , with only a tentative indication of a shallowing of the slope around ∼1 M . We discuss the implications of these results for star and star cluster formation theories.
Main conclusion
A putative powdery mildew effector can elicit defense responses including reactive oxygen species and callose accumulations in model plants
Nicotiana benthamiana
and
Arabidopsis ...thaliana
and host plant
Hevea brasiliensis
.
Powdery mildew fungi cause severe diseases in many agricultural plants, such as the mildew fungus
Erysiphe quercicola
infecting the rubber tree (
Hevea brasiliensis
), causing latex yield losses. However, effectors of
E
.
quercicola
were rarely functionally characterized. In this study, we identified a highly specific candidate-secreted effector protein, EqCSEP04187, from
E
.
quercicola
. This putative effector is expressed at the late stage but not the early stage during infection. The constitutive expression of EqCSEP04187 in model plants
Nicotiana benthamiana
and
Arabidopsis thaliana
elicited defense responses, as did transient expression of EqCSEP04187 in protoplasts of
H
.
brasiliensis
. Introducing EqCSEP04187 into another
H
.
brasiliensis-
associated fungal pathogen,
Colletotrichum gloeosporioides
, inhibited
H
.
brasiliensis
infection, and infection by
E
.
quercicola
was decreased in the
A
.
thaliana eds1
mutant expressing EqCSEP04187. Further analysis suggests that these reductions in infection were the consequences of EqCSEP04187 eliciting defense responses. Our study suggests that this putative effector has elicitor activity that can improve plant resistance.
Three-dimensional graphene–carbon nanotubes were prepared by the chemical reduction of a mixed aqueous solution of carboxylated multiwalled carbon nanotubes (C-MWCNTs) and graphene oxide, followed by ...freeze-drying. C-MWCNTs were then introduced into a three-dimensional graphene aerogel. The obtained three-dimensional graphene–carbon nanotubes were used as a solid-phase adsorbent for the determination of four organophosphorus pesticides (OPPs) in water using GC–MS. Under the optimal extraction conditions, good linearity was achieved between 0.5 and 500 μg L
−1
with a correlation coefficient of 0.9993–0.9998. The limits of detection (
S
/
N
= 3) and limits of quantification (
S
/
N
= 10) for the OPPs ranged from 0.28 to 0.52 and 0.96 to 1.64 μg L
−1
, respectively. The accuracy of the proposed method was evaluated by measuring the recovery of spiked samples, which ranged from 94.8 to 103.5%, with relative standard deviations lower than 7.0% (
n
= 3). This method was applied to the determination of target analytes in wetland water, lake water, and river water, and the results showed that the three-dimensional graphene–carbon nanotubes have great potential for the determination of OPPs in real water samples.
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