Obesity is a chronic lifestyle issue with devastating results. Behavioral changes are one of the initial lines of management strategies for obesity, but they are not very efficient management ...strategies. Many people also use surgical intervention to maintain a healthy weight, now considered to be the most common and effective obesity management. Chemically synthesized medicines fill the gap between lifestyle interventions and minimally invasive surgical management of obesity. The most common issue associated with monotherapy without side effects is its moderate effectiveness and higher dose requirement. Combination therapy is already used for many serious and complicated disease treatments and management and has shown efficacy as well. Generally, we use two or more medicines with different mechanisms of action for a better effect. The commonly used combination therapy for obesity management includes low-dose phentermine and prolonged and slow-releasing mechanism topiramate; naltrexone, and bupropion. Phentermine with inhibitors of Na-glucose cotransporter-2 or glucagon-like peptide-1 (GLP-1) agonists with gastric hormone or Na-glucose cotransporter-2 are two more viable combo therapy. This combination strategy aims to achieve success in bariatric surgery and the scientific community is working in this direction.
A
bstract
Understanding the loss landscape is an important problem in machine learning. One key feature of the loss function, common to many neural network architectures, is the presence of ...exponentially many low lying local minima. Physical systems with similar energy landscapes may provide useful insights. In this work, we point out that black holes naturally give rise to such landscapes, owing to the existence of black hole entropy. For definiteness, we consider 1/8 BPS black holes in
N
= 8 string theory. These provide an infinite family of potential landscapes arising in the microscopic descriptions of corresponding black holes. The counting of minima amounts to black hole microstate counting. Moreover, the exact numbers of the minima for these landscapes are a priori known from dualities in string theory. Some of the minima are connected by paths of low loss values, resembling mode connectivity. We estimate the number of runs needed to find all the solutions. Initial explorations suggest that Stochastic Gradient Descent can find a significant fraction of the minima.
Bone is a highly integrative and dynamic tissue of the human body. It is continually remodeled by bone cells such as osteoblasts, osteoclasts. When a fraction of a bone is damaged or deformed, stem ...cells and bone cells under the influence of several signaling pathways regulate bone regeneration at the particular locale. Effective therapies for bone defects can be met via bone tissue engineering which employs drug delivery systems with biomaterials to enhance cellular functions by acting on signaling pathways such as Wnt, BMP, TGF-β, and Notch. This review provides the current understanding of polymers/bioceramics/bioactive compounds as scaffolds in activation of signaling pathways for the formation of bone.
In the Internet of Vehicles (IoV), vehicles communicate wirelessly with other vehicles, sensors, pedestrians, and roadside units. IoV is aimed at improving road safety, driving comfort, and traffic ...efficiency. However, IoV is exposed to a range of threats to security and privacy. The presence of dishonest and misbehaving peers in the system is of a major concern, which may put lives in danger. Thus, establishing trust among these probable untrusted vehicles is one of the most significant challenges of such a network. The critical pitfalls of existing and traditional mechanisms are scalability, a single point of failure, maintaining the quality of service, verification, and revocation and dealing with sparsity, consistency, availability, efficiency, robustness, privacy concerns are some of the biggest challenges to be addressed. Blockchain technology, with its great success in applications like cryptocurrencies and smart contracts, is considered as one of the potential candidates to build trust in IoV. In this paper, we propose a blockchain-based decentralized trust management scheme using smart contracts. Specifically, we introduce the concept of blockchain sharding for reducing the load on the main blockchain and increasing the transaction throughput. Our proposal has two key contributions: blockchain to maintain and update reliable and consistent trust values across the network and incentive scheme to encourage peers to perform well. We also conduct extensive experiments, which demonstrate the implementation feasibility of proposed mechanisms in the real world.
Let
S
denote the class of functions analytic and univalent (i.e. one-to-one) in the unit disk
D
=
{
z
∈
C
:
|
z
|
<
1
}
normalized by
f
(
0
)
=
0
=
f
′
(
0
)
-
1
. The logarithmic coefficients
γ
n
of
...f
∈
S
are defined by
log
f
(
z
)
z
=
2
∑
n
=
1
∞
γ
n
z
n
.
Let
F
1
(
F
2
and
F
3
resp.
)
denote the class of functions
f
∈
A
such that
Re
(
1
-
z
)
f
′
(
z
)
>
0
(
Re
(
1
-
z
2
)
f
′
(
z
)
>
0
and
Re
(
1
-
z
+
z
2
)
f
′
(
z
)
>
0
resp.
)
in
D
.
The classes
F
1
,
F
2
and
F
3
are subclasses of the class of close-to-convex functions. In the present paper, we determine the sharp upper bound for
|
γ
1
|
,
|
γ
2
|
and
|
γ
3
|
for functions
f
in the classes
F
1
,
F
2
and
F
3
.
Recently in China, a novel coronavirus outbreak took place which caused pneumonia-like symptoms. This coronavirus belongs to the family of SARS and MERS and causes respiratory system disease known as ...COVID-19. At present we use polymerase chain reaction (PCR) based molecular biology methods for the detection of coronavirus. Other than these PCR based methods, some improved methods also exist such as microarray-based techniques, Real time-quantitative PCR, CRISPR-Cas13 based tools but almost all of the available methods have advantages and disadvantages. There are many limitations associated with this method and hence there is a need for a fast, more sensitive, and specific diagnostic tool which can detect a greater number of samples in less time. Here we have summarised currently available nucleic acid-based diagnostic methods for the detection of coronavirus and the need for developing a better technique for a fast and sensitive detection of coronavirus infections.
Graphic abstract
Nucleic acid based detection tool for SARS-CoV-2.
Amino acid-based cationic lipids, which have proven their efficacy as plasmid DNA nanocarriers, were employed as dicationic forms to transfect genes into cancer and non-cancer cells in this study. ...Proline, methionine, and serine amino acids are involved as hydrophilic moieties and the hydrocarbon long-chain serves as a hydrophobic tail. In a multicultural investigation, cationic lipids were employed as nano-vectors in conjunction with the helper lipid DOPE. To quantify the lipid efficient size, charge, and pDNA binding, biophysical analyses such as hydrodynamic diameter, zeta potential, agarose gel electrophoresis, and serum stability were done primarily. The liposomal particle composition was examined by scanning electron microscopy (SEM). Synthesized dicationic vector lipoplex formulations with reporter genes were found to be non-toxic to the cells investigated by MTT assay, and in addition, therapeutic gene p53 transfected into oral and brain cancer cells causing cell death was examined. In vitro investigations further validated that the proline-based lipid (C14-P) has high gene knockdown efficacy than methionine-based lipid (C14-M) and serine-based lipid (C14-S) at optimal N/P ratios as measured by β-galactosidase protein and eGFP expression. C14-P lipid shows superior cellular internalization compared to C14-M and C14-S in HEK-293 and CAL-27 cells attested by confocal study. These findings could include the proline-based lipid vector's exceptional gene delivery activity.
Huanglongbing (HLB, also known as citrus greening) is considered to be the most devastating disease that has significantly damaged the citrus industry globally. HLB is caused by the Candidatus ...Liberibacter asiaticus (CLas), the fastidious phloem-restricted gram-negative bacterium, vectored by the asian citrus psyllid. To date, there is no effective control available against CLas. To alleviate the effects of HLB on the industry and protect citrus farmers, there is an urgent need to identify or develop inhibitor molecules to suppress or eradicate CLas from infected citrus plant. In this paper, we demonstrate for the first time an in planta efficacy of two antimicrobial compounds against CLas viz. 2S albumin (a plant based protein; ~12.5 kDa), Nano-Zinc Oxide (Nano-ZnO; ~ 4.0 nm diameter) and their combinations. Aqueous formulations of these compounds were trunk-injected to HLB affected Mosambi plants (Citrus sinensis) grafted on 3-year old rough lemon (C. jambhiri) rootstock with known CLas titer maintained inside an insect-free screen house. The effective concentration of 2S albumin (330 ppm) coupled with the Nano-ZnO (330 ppm) at 1:1 ratio was used. The dynamics of CLas pathogen load of treated Mosambi plants was assessed using TaqMan-qPCR assay every 30 days after treatment (DAT) and monitored till 120 days. We observed that 2S albumin-Nano-ZnO formulation performed the best among all the treatments decreasing CLas population by 96.2%, 97.6%, 95.6%, and 97% of the initial bacterial load (per 12.5 ng of genomic DNA) at 30, 60, 90, and 120 DAT, respectively. Our studies demonstrated the potency of 2S albumin-Nano-ZnO formulation as an antimicrobial treatment for suppressing CLas in planta and could potentially be developed as a novel anti CLas therapeutics to mitigate the HLB severity affecting the citrus industry worldwide.
The steroid hormone receptors (SHRs) among nuclear hormone receptors (NHRs) are steroid ligand‐dependent transcription factors that play important roles in the regulation of transcription of genes ...promoted via hormone responsive elements in our genome. Aberrant expression patterns and context‐specific regulation of these receptors in cancer, have been routinely reported by multiple research groups. These gave an window of opportunity to target those receptors in the context of developing novel, targeted anticancer therapeutics. Besides the development of a plethora of SHR‐targeting synthetic ligands and the availability of their natural, hormonal ligands, development of many SHR‐targeted, anticancer nano‐delivery systems and theranostics, especially based on small molecules, have been reported. It is intriguing to realize that these cytoplasmic receptors have become a hot target for cancer selective delivery. This is in spite of the fact that these receptors do not fall in the category of conventional, targetable cell surface bound or transmembrane receptors that enjoy over‐expression status. Glucocorticoid receptor (GR) is one such exciting SHR that in spite of it being expressed ubiquitously in all cells, we discovered it to behave differently in cancer cells, thus making it a truly druggable target for treating cancer. This review selectively accumulates the knowledge generated in the field of SHR‐targeting as a major focus for cancer treatment with various anticancer small molecules and nanotherapeutics on progesterone receptor, mineralocorticoid receptor, and androgen receptor while selectively emphasizing on GR and estrogen receptor. This review also briefly highlights lipid‐modification strategy to convert ligands into SHR‐targeted cancer nanotherapeutics.
This article is categorized under:
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Biology‐Inspired Nanomaterials > Lipid‐Based Structures
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Targeting steroid hormone receptors for anticancer therapy.
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