Patients with osteogenesis imperfecta (OI) usually also show osteoporosis and bone fragility. Because these defects may also be combined with an airway that is difficult to manage, abnormal platelet ...function, and other problems, the perioperative management of anesthesia represents a substantial challenge. Therefore, it is important to be able to predict the risks during the perioperative period and to formulate and implement specific high-quality anesthesia management plans for such patients when they experience trauma. We report the case of a 59-year-old female patient with OI who experienced trauma resulting in fractures of the left proximal humerus and right hip. She required open reduction and internal fixation of her humerus and total hip arthroplasty. However, she also had obstructive sleep apnea syndrome, and an airway assessment indicated that her airway would be difficult to maintain. General anesthesia combined with a nerve block was administered. An ultrasound-guided bilateral superior laryngeal nerve block and cricothyroid membrane puncture were used to facilitate endotracheal intubation. An ultrasound-guided “hourglass-pattern” fascia iliaca block was performed for perioperative analgesia. The use of a regional block and preparation for the difficult airway access represented important and successful aspects of the management of anesthesia in this patient.
•A model of microwave heating process with translational motion and rotation was built.•Implicit function and level set method are used to express the elements’ motion.•Effects of samples' moving ...speeds and shape on the heating uniformity are analyzed.•This method can analyze the industrial microwave heating process with complex motion.
In practical chemical applications, in order to improve the microwave heating uniformity, moving elements, such as mode stirrers, turntables and conveyor belts, have been widely used as an easy way to implement. However, different moving elements may have different shapes, modes of motion and moving speed, which makes the simulation of the heating process very difficult. In this paper, a stepping algorithm based on implicit function and level set method is proposed to simulate the microwave heating process of multi-component with unequal moving speed. The accuracy of the algorithm is verified by discrete method and experiments. Moreover, the model was used to analyze the heating process with different components at different positions and speeds. The effect of different materials of mode stirrers and shapes of heated sample on heating process were also compared. The researches show that the proposed model can effectively improve the heating uniformity and heating efficiency.
Chemoresistance is a major cause of cancer progression and the mortality of cancer patients. Developing a safe strategy for enhancing chemosensitivity is a challenge for biomedical science. Recent ...studies have suggested that vitamin D supplementation may decrease the risk of many cancers. However, the role of vitamin D in chemotherapy remains unknown. We found that vitamin D sensitised oral cancer cells to cisplatin and partially reversed cisplatin resistance. Using RNA-seq, we discovered that lipocalin 2 (LCN2) is an important mediator. Cisplatin enhanced the expression of LCN2 by decreasing methylation at the promoter, whereas vitamin D enhanced methylation and thereby inhibited the expression of LCN2. Overexpression of LCN2 increased cell survival and cisplatin resistance both in vitro and in vivo. High LCN2 expression was positively associated with differentiation, lymph node metastasis, and T staging and predicted a poor prognosis in oral squamous cell carcinoma (OSCC) patients. LCN2 was also associated with post-chemotherapy recurrence. Moreover, we found that LCN2 promoted the activation of NF-κB by binding to ribosomal protein S3 (RPS3) and enhanced the interaction between RPS3 and p65. Our study reveals that vitamin D can enhance cisplatin chemotherapy and suggests that vitamin D should be supplied during chemotherapy; however, more follow-up clinical studies are needed.
Abstract
Based on the properties of photodynamic therapy (PDT) and magnetic resonance imaging (MRI), combining them to construct multifunctional nanotheranostics can leverage strengths and avoid ...weaknesses for tumor diagnosis and treatment. However, certain problems remain unsolved, notably the short observation window caused by insufficient retention time. In this study, a GSH‐responsive shape‐transformable nanotheranostics Gd‐Ce6‐FFVLGGGC‐SS‐PEG are designed (abbreviated as GdCFS) by combining a single metal Gd with Ce6, and peptide (Phe‐Phe‐Val‐Leu‐Gly‐Gly‐Gly‐Cys) disulfide‐conjugated with polyethylene glycol (PEG) to perform dual‐modal T
1
/T
2
MRI specifically at the tumor site. Due to its amphiphilic features, GdCFS can self‐assemble to spherical nanoparticles, while transforming to nanofibers (NFs) in the presence of intracellular overexpressed GSH stimuli. After NFs formation, the hydrophobic core of GdCFS is exposed, resulting in T
1
positive contrast enhancement, whereas NFs can simultaneously achieve T
2
negative contrast enhancement. Furthermore, GSH depletion can cause imbalance in intracellular redox state, ultimately improving PDT efficacy. GdCFS benefits from the shape‐transformation in terms of sufficient retention time, thus positively minimizing the toxicity risk. On the tumor model of nasopharyngeal carcinoma, in vivo and in vitro outcomes confirm that GdCFS can be a promising candidate for early diagnosis, real‐time monitoring, and precise treatment of tumors with great biocompatibility.
Candida tropicalis
is a globally distributed human pathogenic yeast, and its increasing resistance to azoles makes clinical treatment difficult. In this study, we investigated the clinical features, ...azole resistance and genetic relatedness of 87
C. tropicalis
isolates from central China and combined with the global database to explore the relationship between genetic information and fluconazole susceptibility. Of the 55 diploid sequence types (DSTs) identified by multilocus sequence typing (MLST), 27 DSTs were new to the
C. tropicalis
MLST database. Fluconazole-nonsusceptible (FNS) isolates were genetically closely related. goeBURST analysis showed that DST225, DST376, DST506, and DST546 formed a distinct and unique FNS clonal complex (CC) in Wuhan. The local FNS CC belongs to the large FNS CC (CC2) in China, in which the putative founder DST225 has been reported from the environment. The three most prevalent types (DST506, DST525, and DST546) in Wuhan had high minimum inhibitory concentrations (MICs) for antifungal azoles, and the six possible nosocomial transmissions we captured were all FNS strains, most of which were from CC2. Unique FNS CCs have been found in Singapore (CC8) and India (CC17) and are close to China’s CC2 in the minimum spanning tree. There were no FNS CCs outside Asia. This study is the first to reveal a significant correlation between genetic information and fluconazole susceptibility worldwide and to trace geographical locations, which is of great value for molecular epidemiological surveillance and azole-resistance study of
C. tropicalis
globally.
The International Council for Harmonisation revised the E14 guideline through the questions and answers process to allow concentration-QTc (C-QTc) modeling to be used as the primary analysis for ...assessing the QTc interval prolongation risk of new drugs. A well-designed and conducted QTc assessment based on C-QTc modeling in early phase 1 studies can be an alternative approach to a thorough QT study for some drugs to reliably exclude clinically relevant QTc effects. This white paper provides recommendations on how to plan and conduct a definitive QTc assessment of a drug using C-QTc modeling in early phase clinical pharmacology and thorough QT studies. Topics included are: important study design features in a phase 1 study; modeling objectives and approach; exploratory plots; the pre-specified linear mixed effects model; general principles for model development and evaluation; and expectations for modeling analysis plans and reports. The recommendations are based on current best modeling practices, scientific literature and personal experiences of the authors. These recommendations are expected to evolve as their implementation during drug development provides additional data and with advances in analytical methodology.
Bacterial infection often leads to inflammatory responses and delays wound healing. Chitosan (CS)-based composite hydrogels can hold desirable mechanical properties and maintain excellent ...antibacterial abilities, and thus may be promising as wound dressings. Although CS-based hydrogels have been widely studied on the antibacterial and wound-healing abilities, their immunomodulatory abilities were rarely evaluated. Herein, we developed a multifunctional CS/Poly2-(methacryloyloxy)ethyl trimethyl ammonium chloride (PMETAC) hydrogel. In vitro, this hydrogel exhibited self-healing ability and excellent biocompatibility, promoted macrophage polarization towards M2 phenotype, and showed desirable antibacterial activity. In vivo, this hydrogel accelerated the wound regeneration process by reducing bacterial burden, increasing collagen deposition, stimulating angiogenesis, promoting macrophage polarization to M2 direction, and shifting the balance of T helper type 17 (Th17) cells towards anti-inflammatory regulatory T (Treg) cells. This work revealed the potential immunomodulatory effect of CS-based wound dressings and thus may provide a novel target for developing efficient wound healing tools.
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•A chitosan/poly 2-(methacryloyloxy)ethyl trimethyl ammonium chloride hydrogel was developed to prevent wound infection.•The hydrogel possessed self-healing properties, exhibited desirable antibacterial properties, and promoted wound healing.•The accelerated wound healing may be due to the ability on regulating macrophage polarization and modulating T cell balance.
In this paper, we mainly study variational formulae of functionals determined by the
k
-curvature of the modified Schouten tensor which is defined on the space
G
(
M
)
of Riemannian metrics on a ...compact manifold
M
. Firstly, we consider the functional
F
k
τ
given by
F
k
τ
(
g
)
:
=
V
-
n
-
2
k
n
∫
M
σ
k
(
P
τ
)
d
v
g
,
g
∈
G
(
M
)
,
where
σ
k
(
P
τ
)
is the
k
-curvature of the modified Schouten tensor
P
τ
with
τ
∈
R
, and then prove that, for a critical metric
g
of the functional
F
k
τ
,
k
≥
3
, the
k
-curvature
σ
k
(
P
τ
)
is constant if the corresponding Cotton tensor vanishes. Secondly, we study a more general functional
F
3
τ
,
θ
also given by the modified Schouten tensor
P
τ
. As the result, we establish the corresponding Euler–Lagrange equation and then compute the second variational formulae for the functional
F
3
τ
,
θ
restricted to a given conformal metric class.
•A coupling anaerobic-aerobic biofilm was established on semi-suspended bio-carriers.•The coupling biofilm created suitable multi-habitats for diverse microorganisms.•The coupling biofilm stimulated ...the simultaneous removal of organics and nutrients.•The microbial community on bio-carrier was dominated by functional microorganisms.
This work aims at establishing a coupling anaerobic-aerobic biofilm within a single bioreactor and revealing its microbial community and succession. By using a semi-suspended bio-carrier fabricated with 3D printing technique, an obvious DO gradient was gradually created within the biofilm, which demonstrated that a coupling anaerobic-aerobic biofilm was successfully established on the surface of bio-carriers. The results of metagenomic analysis revealed that the microbial community on the bio-carriers experienced a continuous succession in its structure and dominant species along with the operational time. The formed coupling biofilm created suitable micro multi-habitats for the co-existence of these microorganisms, including nitrifying and denitrifying bacteria, which were beneficial to the removing of organic pollutants and converting nutrients. Along with the succession, the microbial community was gradually dominated by several functional microorganisms. Overall, the results presented an approach to improve the microbial biodiversity by constructing a new structure and floating status of bio-carriers.
Abstract
How convective boundary‐layer (CBL) processes modify fluxes of sensible (
SH
) and latent (
LH
) heat and CO
2
(
F
c
) in the atmospheric surface layer (ASL) remains a recalcitrant problem. ...Here, large eddy simulations for the CBL show that while
SH
in the ASL decreases linearly with height regardless of soil moisture conditions,
LH
and
F
c
decrease linearly with height over wet soils but increase with height over dry soils. This varying flux divergence/convergence is regulated by changes in asymmetric flux transport between top‐down and bottom‐up processes. Such flux divergence and convergence indicate that turbulent fluxes measured in the ASL underestimate and overestimate the “true” surface interfacial fluxes, respectively. While the non‐closure of the surface energy balance persists across all soil moisture states, it improves over drier soils due to overestimated
LH
. The non‐closure does not imply that
F
c
is always underestimated;
F
c
can be overestimated over dry soils despite the non‐closure issue.
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