bluuebunny/crossref_metadata_2025 huggingface dataset:
Medicinal Chemistry of Pyrazolopyrimidine Scaffolds Substituted with Different Heterocyclic Nuclei
Authors: Elgemeie Galal H. , Azzam Rasha A. , Zaghary Wafaa A. , Khedr Mohammed A. , Elsherif Gihad E.
Published: November 2022

Background:

Medicinal chemistry of pyrazolopyrimidine scaffolds substituted with different heterocyclic nuclei has attracted great attention due to their wide range of biological activities that have been reported. Pyrazolopyrimidine scaffold is an important privileged heterocycle nucleus in drug discovery.

Methods:

All pharmacological activities of pyrazolopyrimidine scaffold have been mentioned, such as anticancer, anti-inflammatory, antihypertensive, antitubercular, antiviral, antibacterial, antifungal, antidiabetic, and anti-obesity agents. In addition, it was used in both osteoporosis and neurological disorders. The difference in potency and bioavailability of pyrazolopyrimidine derivatives refers to the substituent groups that can increase the activity against specific targets and enhance their selectivity.

Results:

This review provides an overview of different synthetic pathways, structure activity relationships, and preclinical studies of pyrazolopyrimidine scaffolds substituted with a variety of heterocyclic nuclei, as well as it provides a discussion on the significant biological findings of these important scaffolds. In addition, it provides some insights on the different macromolecular targets that pyrazolopyrimidine scaffold can effectively work on, such as; cyclin dependent kinases; CDK2, CDK7, and CDK9, checkpoint kinases; CHK1 and CHK2 and their correlation with the anticancer activity, PI3Kα, transient receptor potential canonical 6, B-Raf kinase, Interleukin- 1 receptor-associated kinase 4, B-cell lymphoma 6, TRKA-C kinase, potent kDa ribosomal protein S6 kinase, colon cancer cell line (CaCo-2), domain receptor kinase (KDR), HepG-2 carcinoma cell, FLT3. The antibacterial activity against B. subtilis and E. coli and antifungal activity against C. albicans, C. tropicalis, A. niger, and A. clavatus are discussed.

Conclusion:

This review provides an overview of the different pharmacological activities of the pyrazolopyrimidine scaffold and its correlation with chemical structure. Some exciting new developments in pyrazolopyrimidine scaffolds are also presented in this review.
An Overview of Recent Advances in Isatin-Based Multicomponent Reactions
Authors: Mohammadi Ziarani Ghodsi , Panahande Zahra , Mohajer Fatemeh , Goodarzi Mohammad , S. Varma Rajender
Published: November 2022

Isatin has been widely deployed in multicomponent reactions to prepare diverse heterocyclic compounds, which have garnered the attention of organic chemists considering their anti-inflammatory, anti-microbial, and antiviral activities, among others. This review discusses the applications of isatin in multicomponent reactions from 2019 to 2022. Isatin has been used as a raw material in multicomponent reactions due to its diverse biological and therapeutic activities. This overview may help stimulate the readers to exploit such convergent strategies in their synthetic endeavors.
Characterization of Oligomer Formation of Surfactant Protein-D (SP-D)
Using AF4-MALLS
Authors: Manning Mark Cornell , Manning Ryan R. , Holcomb Ryan E. , Katayama Derrick S. , Pauletti Giovanni M. , Grant Shawn N. , Rosenbaum Jan S.
Published: November 2022

Background:

Surfactant protein-S (SP-D) is a naturally occurring lung protein with the potential
to treat pulmonary infections. A recombinant surfactant protein-D (SP-D) has been produced
and was previously found to exist in multiple oligomeric states.

Introduction:

Separation and characterization of interconverting oligomeric states of a protein can be
difficult using chromatographic methods, so an alternative separation technique was employed for SPD
to characterize the different association states that exist.

Methods:

Samples of SP-D were analyzed using asymmetrical flow field-flow fractionation (AF4)
using UV and multi-angle laser light scattering (MALLS) detection. The AF4 method appears to be
able to separate species as small as the monomer up to the dodecamer (the dominant species) to much
larger species with a molar mass greater than 5 MDa.

Results:

Consistent elution of four distinct peaks was observed after repeated injections. The largest
species observed under the last peak (labeled as Peak 4) were termed “unstructured multimers” and
were resolved fairly well from the other species. The AF4-MALLS data suggest that only a small fraction
of Peak 4 truly corresponds to high molar mass unstructured multimers. All other peaks demonstrated
significant molar mass homogeneity consistent with AFM results.

Conclusion:

AF4-MALLS technology appears to be a powerful analytical approach to characterize the
complex and dynamic interplay among different protein oligomeric species of SP-D in an aqueous solution.
MicroRNAs in the Pathogenesis of Ankylosing Spondylitis and
their Clinical Implication
Authors: Fu Lanqing , Wang Guobo , Deng Wei , Lu Yu
Published: November 2022

Ankylosing spondylitis (AS) is a chronic and progressive immunoinflammatory
disease, which mainly affects the spine and sacroiliac joints and shows a
high rate of late disability. Inflammation, bone destruction, and new bone formation are
typical pathological changes of AS. AS is dominated by inflammation at the early stage.
While bone destruction and heterotopic ossification, the two contradictory manifestations
of AS, occur at a later stage and reflect the imbalance between osteogenesis
and osteoclastogenesis in AS patients. Till now, the pathogenesis of AS remains unclear.
MicroRNAs (miRNAs) are a class of highly conserved single-stranded noncoding
RNAs (ncRNAs) with a length of about 22 bases characterized by temporal
sequence and tissue specificity. MiRNAs are key modulators in bone formation, resorption,
remodeling and regeneration by regulating the immune responses and the
differentiation and functions of osteoblasts, osteoclasts and chondrocytes. The present
review summarizes the roles and potential mechanisms of miRNAs’ involvement in AS
by regulating immuno-inflammatory responses, bone destruction, heterotopic ossification,
cell death and autophagy, and the involved signaling including the Wnt/β-catenin
and BMP/Smads pathways. In addition, the feasibility of miRNAs as diagnostic biomarkers
and therapeutic targets for AS are also discussed.
Hsa_circ_0004662 Accelerates the Progression of Osteoarthritis
via the microRNA-424-5p/VEGFA Axis
Authors: Xie Wei , Jiang Luoyong , Huang Xiaoyang , You Wei , Sun Wei
Published: November 2022

Objective:

Circular RNAs (circRNAs) have been extensively implicated in osteoarthritis (OA) progression. Therefore, this study explores the impact of hsa_circ_00046621 on OA progression and the related molecular mechanism.

Methods:

Human articular chondrocyte injury was induced by IL-1β to construct the OA model in vitro. hsa_circ_0004662 and microRNA (miR)-424-5p expression in chondrocytes was evaluated with qRT-PCR. Vascular endothelial growth factors A (VEGFA) expression was examined with qRT-PCR and western blot after hsa_circ_0004662 knockdown or miR-424-5p overexpression in chondrocytes. Subsequent to loss- and gain-of-function assays in IL-1β-induced chondrocytes, the proliferation and apoptosis of chondrocytes were assessed with CCK-8 assay and flow cytometry, respectively. The expression of MMP13, Aggrecan, and apoptosis-related proteins Bax and Bcl-2 was measured with western blot. The binding of miR-424-5p to hsa_circ_0004662 and VEGFA was assessed with a dual-luciferase reporter gene assay.

Results:

Hsa_circ_0004662 was up-regulated, but miR-424-5p was down-regulated in IL-1β-induced chondrocytes. Mechanistically, both hsa_circ_0004662 and VEGFA bound to miR-424-5p, and hsa_circ_0004662 enhanced VEGFA expression by down-regulating miR-424-5p. Hsa_circ_0004662 knockdown elevated cell proliferation, decreased apoptosis and MMP13 and Bax expression, and increased Aggrecan and Bcl-2 expression in IL-1β-induced chondrocytes, which was counteracted by further miR-424-5p down-regulation or VEGFA overexpression.

method:

Human articular chondrocyte injury was induced by IL-1β to mimic the OA model. hsa_circ_0004662 and microRNA (miR)-424-5p expression in chondrocytes was evaluated using qRT-PCR. Vascular endothelial growth factors A (VEGFA) expression was examined using qRT-PCR and western blot analysis following hsa_circ_0004662 knockdown or miR-424-5p overexpression in chondrocytes. Subsequent to the loss- and gain-of-function assays in IL-1β-induced chondrocytes, proliferation and apoptosis of chondrocytes were assessed using CCK-8 assay and flow cytometry, respectively. The expression of MMP13, Aggrecan, and apoptosis-related proteins Bax and Bcl-2 was measured using western blot analysis. The binding relationship of miR-424-5p to hsa_circ_0004662 and VEGFA was assessed using dual luciferase reporter gene assay.

Conclusion:

Hsa_circ_0004662 facilitates OA progression via the miR-424-5p/VEGFA axis.
Factors Related to Mechanical Thrombectomy Failure in Large Vessel
Occlusion: A Propensity Score Matching Analysis
Authors: Sung Jae Hoon , Yi Ho Jun , Lee Dong Hoon , Shin Dong-Seong , Kim Bum-Tae
Published: November 2022

Objective:

Mechanical thrombectomy (MT) is an effective treatment for large vessel
occlusion (LVO) with a high successful recanalization (SR) rate. However, MT fails in a proportion
of patients, leading to poor clinical outcomes. We analyzed the factors associated with the failure of
MT.

Methods:

Failed MT was observed in 97 patients (14.3%). Among them, 69 patients (10.2% of the
entire cohort, 71.1% of the failed MT group) were included in the RF group. Propensity matching
analysis with 69 patients in each group showed that the RF group had a higher rate of residual intracranial
atherosclerotic stenosis (ICAS) than the SR group (30.4% vs. 14.5% P = 0.003). The rates of
4 or more passages and no change of method were significantly higher in the RF group than in the
SR group (34.8% vs. 13.0%; P = 0.001 and 28.9% vs. 8.7%; P = 0.001).

Results:

Failed MT was observed in 97 patients (14.3%). Among them, 69 patients (10.2% of the
entire cohort, 71.1% of the failed MT group) were included in the RF group. Propensity matching
analysis with 69 patients in each group showed that the RF group had a higher rate of residual intracranial atherosclerotic stenosis (ICAS) than the SR group (30.4% vs. 14.5% P = 0.003). The rates of
4 or more passages and no change of method were significantly higher in the RF group than in the
SR group (34.8% vs. 13.0%; P = 0.001 and 28.9% vs. 8.7%; P = 0.001).

Conclusion:

The failure rate for all of the MT was approximately 15%, and RF accounted for more
than 70% of the failed MT. RF was associated with residual ICAS. In cases with RF, even in repeated
attempts for recanalization, an alteration of the thrombectomy method should be considered.
Tandem Mass Tag (TMT) Quantitative Proteomic Analysis of Serum Exosomes in Cerebral Small-vessel Disease (CSVD) Patients With Depressive Symptoms
Authors: Zhao Zhong , Zhou Hua , Lu Yanjing , Shen Rong , Zhu Hao , Feng Qian , Li Yifan , Xu Wenxin , Zhang Dayong
Published: November 2022

Background:

Depressive symptoms are one of the main clinical features of the cerebral small-vessel disease (CSVD). However, the pathogenesis of depressive symptoms of CSVD has not been fully studied, and a lack of effective diagnostic methodseffective diagnostic methods exists. Recently, the emerging body of evidence regarding exosomes has rendered them potentially key players in the neuropsychiatric disease theragnostic. This study’s aim was to investigate serumexosome proteomic expression in CSVD patients with depressive symptoms and to screen and analyze potential biomarkers for clinical diagnosis.

Methods:

Serum samples were collected from 36 CSVD patients, including 18 cerebral small-vessel disease (CSVD+D) patients with depressive clinical manifestations and 18 cerebral small-vessel disease patients that did not present depression-related clinical manifestations (CSVD-D). This investigation employed tandem mass tag (TMT) combined with mass spectrometry for sample detection and quantitative analysis of proteins. The differential proteins with significant dysregulated expression levels in patient plasma exosomes were screened and analyzed through bioinformatics techniques.

Results:

This investigation focused on a global collection of 659 quantifiable proteins. Compared to the CSVD-D group, 7 up-regulated and 30 down-regulated proteins were identified in the CSVD+D group (P < 0.05). Gene ontology (GO) enrichment analyses revealed proteomic expression profile dysregulations within serum exosomes in patients with depression, such as desmosomes and keratins, rendering them as potential biomarkers. Kyoto encyclopedia of genes and genomes (KEGG) database investigations revealed the differentially expressed proteins to be highly aggregated within the estrogen signaling pathway.

Conclusion:

This investigation pioneered TMT proteomic evaluation of serum exosomes within CSVD patients suffering from depression and reveals the shifts in proteomic expression profiles by serum exosomes within such patients. This study identified several important molecular / signal pathway abnormalities related to depression. These results provide a possible means to further clarify the pathogenesis of depressive symptoms of cerebrovascular disease and its diagnosis and treatment in the future.
Aromatase Enzyme Activity and Liver Receptor Homolog-1 Levels in
Gestational Diabetes Mellitus
Authors: Bayraktar Nihayet , Tas Hasip , Bayraktar Mehmet , Koyuncu Ismail , Sarı İsmail , Uyanıkoğlu Hacer
Published: November 2022

Background:

Gestational diabetes mellitus (GDM) is one of the prediabetes conditions in which high blood sugar levels and body weight increase during pregnancy. The underlying molecular and biochemical mechanisms of GDM are poorly defined.

Introduction:

Aromatase enzyme activity is responsible for the conversion of androgens to estrogens and has a share in the regulation of body fat distribution and liver receptor homolog-1 (LRH-1), which plays a critical role in cholesterol transport, acid homeostasis, and steroidogenesis in GDM patients. This study aims to determine the levels of aromatase enzyme and LRH-1 in GDM patients and to investigate the relationship between the levels of aromatase enzyme and LRH-1 and the levels of insulin, HbA 1c and total cholesterol.

Method:

This prospective cross-sectional study was conducted over eleven months (September 2020 to July 2021). The study population was selected at Harran University Teaching and Research Hospital. The study included 32 GDM patients and 32 healthy pregnants. The automated assay measured serum fasting blood glucose, HbA1c, and insulin levels (AVIDA 1800 Chemistry System; Siemens). Aromatase enzyme activity and LRH-1 levels were determined by using a commercial enzyme-linked immunosorbent assay (ELISA) kit.

Result:

Aromatase activity decreased in GDM patients while LRH1 increased. Significant differences in means levels of fasting blood glucose (p=0.11), insulin (p= 0.001) and HbA1c (p= 0.001) between the patients and control groups. There was a significant negative correlation between the levels of aromatase and insulin (r=-370, p =0.037). In addition, a positive significant correlation coefficient (r=0.645, p=0.001) was found between HbA1c and total cholesterol among the patients' group.

Conclusion:

Our findings indicate that there is a negative relationship between aromatase activity and insulin levels. Aromatase and LRH 1 may play a role in the pathogenesis of GDM, and the use of LRH-1 agonists in treating the disease may be considered an alternative treatment in the future. However, additional studies are required to reveal the possible functions of these two proteins in GDM with their mechanisms.
CLABSI in Hemodialysis– New Face to an Old Foe; A Look at Current Trends and a Review of Literature
Authors: Jose Nisha , S. Manikantan , John Kevin , Prasad Ram , Jayakumar M.
Published: November 2022

Background:

Bloodstream infections are a potentially devastating complication of hemodialysis. This study aimed to elucidate the rates of CLABSI (Central Line Associated Blood Stream Infections)in a south Indian dialysis cohort and determine the catheter care and hygiene practices in the dialysis unit which might contribute to CLABSI

Methods:

A prospective observational study involving in-center dialysis patients with temporary access was conducted from June 2019 to December 2019. The catheter insertion and line handling techniques were monitored using a proforma adapted from the CDC (Center for Disease Control) guidelines. Adherence to infection control practices, rates of CLABSI identified using CDC surveillance definitions, and organisms identified were reported.

Results and Discussion:

The median rate of CLABSI in this dialysis unit was 1.68 per 1000 catheter days. Gram-positive organisms were the majority – 69.2% and 72.27% were drug-resistant pathogens. The adherence to infection control practices in hand sterility, use of barriers, and sterile insertion technique were 100% with respect to existing CDC guidelines. The use of sterile semi-transparent dressings, however, was 98.2%. 65% of all patients had soiled dressings on arrival to the hospital. Line handling protocols were followed in accordance with CDC guidelines in 97.1% of cases

Conclusion:

CLABSI rates in this institute are in keeping with those around the world. There is a predominance of gram-positive organisms causing CLABSI. Drug-resistant organisms represent an alarming 72.27%of all infections. Soiled dressing and home care of the dialysis catheters represent a neglected aspect of catheter care and should be addressed.
What's the Relation between Iron Deficiency (ID) and Febrile Seizure (FS)? A Case Control Study in Tehran, Iran
Authors: Ehsanipour Fahimeh , Noorbakhsh Samileh , Tavasooli Azita , Tahernia Leila
Published: November 2022

Objective:

To evaluate the role of ID in the pathogenesis of FS.

Methods:

In this case-control study (2014-2016), 70 children were studied, 35 children with FS and 35 (controls)children with febrile diseases without convulsion (The mean age of cases was 2.191 ± 0946 vs. 1.93 ± 1.433 years in controls). Serum ferritin was estimated by the EIAS test. Data were compared between 2 groups, The ROC (receiver-operating-characteristic) curve was illustrated. The sensitivity, specificity, PPV, and NPV of the test, were calculated.

Results:

Serum ferritin levels had no significant difference between the 2 groups. The ferritin level (36ng/ml) had 74.3% sensitivity, 20% specificity, 56% PPV, and 52% NPV, with a Positive likelihood Ratio being 1.3 and a Negative likelihood Ratio: 0.93 to discriminate the 2 groups.

Conclusion:

Here the ferritin level (cut-off=36ng/ml) has an acceptable sensitivity (74.3%) but poor specificity (20%) and just 56% PPV and 52% NPV to differentiate the FS cases from non-convulsive febrile children. Although a different cut-off value 21.50 ng/ml provides 91% sensitivity and very low specificity . This lower threshold cut-off might have clinically relevant outcomes in FS children if considering the other comorbidities. In our opinion, ID could not lead to FS in all children, but in some cases, with a genetic basis; ID raises the threshold for seizures. The ferritin levels as an acute phase reactant are acceptable in every febrile case. The ferritin base level in each child (case /control) before infection was unknown, but in the present study, both groups were febrile in contrast to previous studies in which ferritin levels were compared with afebrile children. Due to the high prevalence of ID (26%), especially in the young Iranian population, adding iron to the diet might help decrease FS in susceptible cases. We recommend in the future study the FS cases selected with known iron levels before convulsion.
The Role of the World Health Organization in Increasing the Capacity of COVID-19 Laboratories in Indonesia
Authors: Candrawati Tanti Belinda , Mustikawati Inggrid Galuh , Wulandari Endah
Published: November 2022

Objective:

The aim of this research to explore the role of WHO in increasing the capacity of the COVID-19 laboratories in Indonesia.

Methods:

Explorative research, assesses deeply about issues or social phenomena that is not widely understood, new cases that have not been handled optimally. This study explores various data and information regarding the development of Corona cases and WHO program to solve the health crisis through data, literature review, and interview.

Results:

The role of WHO in increasing the capacity of COVID-19 laboratories in Indonesia can be seen in two sectors, namely surveillance activation and improvement of national laboratory diagnostics. To activate and strengthen the surveillance, several actions were taken by WHO, such as introducing the COVID-19 surveillance system to the Indonesian Government, supporting surveillance activities on various platforms, utilizing the Influenza Surveillance System to track COVID-19 cases, anticipating the increase of COVID-19 cases due to religious event, broadening the contact tracing network, developing an application to track close contact, and facilitating regular training for contact tracing officer. In the second sector, improvement of national laboratory diagnostic, WHO is actively supplying COVID-19 testing kits to Indonesia, conducting capacity building for laboratory staff, creating guidelines for COVID-19 testing, activating the existing Influenza Laboratory as COVID-19 Laboratory, and monitoring the quality of COVID-19 diagnostic.

Conclusion:

In order to increase the capacity of COVID-19 Laboartory in Indonesia, WHO actively contributes in strengthening the surveillance system and improving national laboratories' diagnostic.
Current Remedial Strategies for the Treatment of Rheumatoid Arthritis
through the Oral Route with Janus Kinase Inhibitors
Authors: Mathur Pooja , Verma Ravinder , Kumar Manish , Jhawat Vikas , Dutt Rohit , Bhatt Shailendra
Published: November 2022

Rheumatoid arthritis (RA) is a well-known chronic inflammatory disease that results in
articular degradation, comorbidities, and body part functional loss. In the last two decades, the development of effective biologics and small compounds, such as Janus kinase inhibitors (Jakinibs),
has significantly improved clinical outcomes. Low-molecular-weight chemicals known as jakinibs
are currently used for effective treatment of RA. Jakinibs are a new class of drugs being developed
to treat RA, and several of them are now in different phases of clinical trials to establish their safety
and efficacy in humans. Jakinibs can be very different in their selectivity against JAK inhibitors.
For an efficient therapy of RA, it is critical to fully comprehend the properties of JAK inhibitors as
well as their mechanism of action. Tofacitinib, Baricitinib, Upadacitinib, Peficitinib, Filgotinib, Decernotinib, Itacitinib, Ruxolitinib, and PF-06651600 are a few selective orally active Jakinibs that
have entered clinical trials to treat RA. This review aims to elaborate on Jakinibs for the treatment
of Rheumatoid Arthritis (RH), including their mechanism of action (MOA), efficacy and safety profiles, clinical trials of adverse effects (AEs) associated with Jakinibs and combination therapy with
other DMARDs.
Optimization and Fabrication of Curcumin Loaded Solid Lipid Nanoparticles
Using Box-Behnken Design for Nasal Delivery
Authors: Bhatt Shailendra , Sharma Sherry , Sharma Jai Bharti , Kumar Manish
Published: November 2022

Aims:

To prepare curcumin loaded solid lipid nanoparticles for nasal administration using
Box-Behnken design.

Background:

The effectiveness of curcumin in neurological disorders is widely studied by various researchers,
but its use is limited due to its poor bioavailability. The brain-targeting efficiency of curcumin
can be improved using solid lipid nanoparticles via nasal administration.

Objective:

In the present work, Curcumin loaded solid lipid nanoparticles (CUR-SLN) were formulated
and optimized for nasal administration.

Methods:

Based on solubility studies, cetostearyl alcohol and poloxamer 407 were selected as lipid and
surfactant, respectively. Box-Behnken design (BBD) was used to analyze the effects of drug-to-lipid ratio
(X1), surfactant concentration (X2) and homogenization time (X3) on particle size (Y1) and % entrapment
efficiency (Y2). The CUR-SLN were formulated by the high shear homogenization method. The
optimized formulation was evaluated for DSC, TEM, drug release and ex-vivo studies.

Results:

Good results were obtained for the particle size and entrapment efficiency analyzed using BBD.
The optimized formulation of CUR-SLN obtained using BBD was observed with a particle size of 96.09
nm and % EE of 78.23. In-vitro release of the drug was found to be 82.93± 0.15% after 8 hours. DSC
studies revealed that crystalline form of curcumin changed to an amorphous form in SLN. TEM results of
optimized CUR-SLN were in correlation with the results obtained using a zeta sizer. No harmful effects
were observed on nasal mucosa in the histopathology study.

Conclusion:

The SLN can be safely utilized for the intranasal administration of curcumin.
Effect of the Surfactant Charge on the Characteristics and Anticancer
Effects of Docetaxel-loaded Poloxamer Polymeric Micelles
Authors: Harry Nugraha Dwianto , Anggadiredja Kusnandar , Rachmawati Heni
Published: November 2022

Background:

The main problem in the use of docetaxel as a potent chemotherapeutic agent is its solubility. Practically insoluble docetaxel requires a harsh formulation with high surfactant and alcohol concentrations to comply with the product quality. However, this formulation is inconvenient for patients. Polymeric micelles using a biocompatible polymer, poloxamer, seem to be a promising approach to increase the solubility of docetaxel, avoiding the high polysorbate and alcohol contents in the commercial product and yielding similar or better anticancer effects.

Objective:

This study aims to investigate the effects of surfactant with three different charges on the particle size, chemical stability, in vitro drug release and anticancer efficacy of the docetaxel-loaded poloxamer-based polymeric micelle formulation.

Methods:

The freeze drying method was used to prepare polymeric micelles of docetaxel. Dynamic light scattering was used to determine particle size. The morphology of particles was investigated using a transmission electron microscope. High Pressure Liquid Chromatography was used to measure encapsulation efficiency, drug loading, and percentage of drug released. MTT assay was used to assess the anticancer effect.

Result:

Nonionic and anionic surfactants tended to increase the particle size, while cationic surfactants
had no effect. Furthermore, the addition of cationic surfactant increased the chemical stability
of docetaxel. Poloxamer polymeric micelles have sustained drug release, and the addition of
a surfactant can increase polymeric micelle drug release. All surfactant charges increased the anticancer
efficacy of docetaxel compared to the commercial formulation Taxotere, except for the
formulation prepared with an anionic surfactant.

Conclusion:

The charge of the surfactant affects the particle size, chemical stability, drug release and anticancer properties of docetaxel-loaded poloxamer polymeric micelles. Cationic surfactant formulations have shown to be promising, resulting in the most stable and highest anticancer effect.
Preparation of Ionic Liquid Supported Organocatalysts for the Synthesis
of Stereoselective (R)-9-Methyl-5(10)-Octaline-1,6-Dione
Authors: Srivastava Vivek
Published: November 2022

:

The synthesis of Proline-2-triethyl-ethylamide hexafluorophosphate (ILPA-PF6) (with
96% yield) and further the application during the synthesis of (R)-9-Methyl-5(10)-octaline-1,6-dione
(Wieland-Miescher ketone molecule) are defined in this manuscript. The suggested protocol signifies
one of the most efficient methods for the synthesis of these flexible chiral building blocks in good
yield. The evident solubility of ionic liquids allows straightforward isolation of the (R)-9-Methyl-
5(10)-octaline-1,6-dione product from reaction mass. Additionally, six times catalyst recycling was
considered the main conclusion of this proposed procedure.

Background:

The synthesis of WMK starts with the Michael Addition step, where the α, β-
unsaturated ketone reacts with 2-methyl-1,3-cyclohexanedione followed by the nucleophilic attack
and produces the triketone. Further, the isolated triketone goes to intramolecular Aldol Condensation,
(in the Robinson Annulation reaction cascade) to get an enolate. Later, followed by the dehydrogenation
reaction of enolate (to expel hydroxide ion) the desired product Wieland Miescher Ketone
was isolated in good yield. The above conventional method suffers from several drawbacks like
a slow reaction rate, the requirement of high boiling point solvent systems, and low reaction yield.

Objective::

To prepare ionic liquid-supported organocatalysts for the synthesis of stereoselective (R)-
9-Methyl-5(10)-octaline-1,6-dione

Method:

This report summarizes the synthesis and its application of triethyl salt-supported prolinebased
organocatalysts as recyclable and highly efficient for the asymmetric Wieland-Miescher ketone
((R)-9-Methyl-5(10)-octaline-1,6-dione). An ionic liquid-supported proline (as a catalyst) is
equipped with basic proline and a significantly acidic amide moiety to promote the reaction rate, and
synchronously having a specialty of ionic liquid could be easy to separate and recycle.

Results::

The report simply defined the WMK molecule in good yield and enantioselectivity followed
by minimal ether washing. During the reaction, low catalyst loading i.e., 0.5 g of catalyst was found
enough to attain the maximum yield and enantioselectivity in 2 hours. Furthermore, catalyst recycling
was observed 6 times as a significant element of the suggested catalytic method.

Conclusion::

The synthesis of an extremely dynamic and enantioselective ILPA-PF6 catalytic approach
is demonstrated in the report. The ILPA-PF6 catalyst was further modified after its characterization
for use in the synthesis of the WMK molecule and the subsequent intramolecular aldol reaction
of triketone. The WMK molecule was isolated with good yield and enantioselectivity followed
by minimal ether washing. During the reaction, low catalyst loading i.e., 0.5 g of catalyst was found
enough to get the maximum yield and enantioselectivity in 2 hours. Additionally, catalyst recycling
was observed 6 times as a significant element of the suggested catalytic method.
Performance of Indoor 5G 3GPP Systems
Authors: Khruahong Sanya , Lam Sinh Cong , Tran Duc-Tan
Published: November 2022

Background:

The 5G cellular networks are expected to provide high data rates for indoor
environments by utilizing the mmWave bands. Due to a lack of general path loss models of these
bands, various works have been carried out to find the most appropriate model that can provide accurate
values of path loss over distance for different indoor scenarios. This paper focuses on some
well-known path loss models, e.g., mixed and OpenOffice models introduced by 3GPP; the dualstripe
model was presented by Alcatel-Lucent, picoChip Designs, and Vodafone at the 3GPP meeting;
single and dual ABG models were designed by leading academic and industrial labs.

Methods:

Two network scenarios, e.g., single-cell and 3-cell networks, are utilized in simulation to
analyze the effects of path loss models on network performance.

Results:

The simulation results indicate that the single-slop and dual-slop models can derive a similar
performance when only a cell is deployed. However, in a 3-cell network system with intercell
interference, the achieved performance in these systems is significantly different.

Conclusion:

The dual-slop model is better than the single–slope model in terms of path loss modeling
since it can capture more characteristics of wireless transmission links, particularly the Light-of-
Sight (LoS) and Non-LoS (NLoS) effects.
Building on firm competitive advantage through core competence manufacturing firm
Authors: Igho Okpewho Lucky
Published: November 2022

The study examined the effect of core competence and firm competitive advantage in the Nigeria Brewing industry, with a focus on selected Brewing firms in Enugu, Onitsha and Benin City. The study employed a descriptive survey research design. Instrument adopted for the study is a structured questionnaire based on simple random sampling method. In addition, interview was also employed to serve as a compliment for the questionnaire. Reliability of the research instrument was tested using the Cronbach Alpha method which revealed that the instrument is reliable. The result of Durbin Watson revealed that the data is free from autocorrelation. Data analysis was done using both descriptive and inferential analysis technique. Descriptive statistics was used to give insight on the respondents profile while inferential statistics was used in the conducting of hypotheses. The two research questions for the study were analyzed using multiple regression model. The study shows that the two null hypotheses were rejected while the two alternative hypotheses were accepted (intellectual capital (p=0.000<0.05, ?=0.325) and customer services (p=0.000<0.05, ?=0.708).
Ultra-High Protein Soybeans for Food and Aquaculture
Authors:   Amfora, Inc., Lassner Michael
Published: November 2022

Amfora is developing two categories of soybeans with increased protein content. One product is designed to increase the protein content of commodity soybeans by at least 10% with minimal impact on oil and yield. A second product is designed to deliver an ultra-high protein (ULTRAHIPRO TM) soymeal with more than 60% protein. A soybean meal with 60% protein can be used to displace soy protein concentrate in multiple applications including plant-based meats and as a high value ingredient in aquaculture feed. Amfora’s core technology is using gene editing to drive increased expression of NF-YC4, which results in a phenotype of increased protein at the expense of carbohydrates. We are using a combination of unique germplasm, modern genomics-based crop breeding and new breeding technologies to develop and commercialize valuable products for food and aquaculture applications.
Lipidomic analysis in food: The role of a detailed elucidation of intact lipids in functional foods for investigating on nutritional aspects
Authors:   Universita Di Messina, Dugo Paola , Rigano Francesca , Mondello Luigi
Published: November 2022

The growing demand in natural matrices, representing a source of dietary and nutraceutical molecules, placed, as direct consequence, the urgent need for the development of suitable analytical methods able to provide a comprehensive characterization of both “conventional” and “unconventional” products. In the last decades, lipidomic has emerged as a cutting-edge approach among omics- techniques, since lipids revealed to be essential molecules in the regulation of metabolic pathways. To this regard, the content of essential fatty acids (EFAs), as well as nutritional indices such as the levels of omega-3 and omega-6 FAs and their ratio are essential parameter to evaluate the beneficial properties of food products. In addition, the investigation of complex lipids in their native forms is proved to be crucial to obtain additional information about lipids role and on FA arrangement into each species. For this reason, the present study is aimed to a detailed elucidation of intact lipids in different functional foods, including the profiling of microalgae, hemp products and the wastes of the fish industry. Phospholipids and triacylglycerols were the most representative lipid classes. However, mono- and diacylglycerols, pigments and carotenoids were also detected, representing an added value for the investigated matrices. From an analytical point of view, the use of a recently introduced linear retention index (LRI) approach in LC paved the way for the automatization of the identification process in LC. Furthermore, the use of high-resolution chromatographic techniques (that is UHPLC), even combined with selective tandem MS operation mode allowed for the determination of the entire lipidome with high sensitivity. Finally, the UHPLC-MS/MS platform was coupled to a preparative workstation to fully automatize the analytical work-flow. This also entailed the miniaturization of the lipid extraction procedure, which was compared with a conventional manual procedure, resulting in quite similar quali-quantitative profiles.
Supercritical extracts from olive leaves as natural antioxidants: extraction optimization, characterization and evaluation
Authors:   PEDECIBA Quimica-Udelar, Vieitez Osorio Ignacio , Gambaro Adriana ,   Universidad de la República, Dauber Cecilia ,   Universidad de la República, Ibanez Elena ,   Institute of Food Science Research (CIAL-CSIC), Gonzalez Laura ,   Universidad de la República, Carreras Tatiana ,   Universidad de la República
Published: November 2022

Olive leaves (OL) are considered a potential source of bioactive compounds mainly due to its high content of polyphenols, widely known as natural antioxidants. The objective of this study was to optimize supercritical fluid extraction conditions from OL in order to obtain natural extracts with high antioxidant activity. OL (belong to the Arbequina cultivar) were collected from a local producer (Uruguay) and subjected to a drying and milling (1 mm particle size) pre-treatment. Supercritical fluid extractions were carried out using a laboratory-built system equipped with a 25 mL stainless steel vessel filled with 10 g of OL. A total of 10 extractions were carried out following a Central Composite Design in which the two independent variables considered were: extraction temperature (40–60 °C) and extraction pressure (150-350 bar). In all cases, extraction solvent was CO2 with 10% of ethanol as modifier. A constant flow rate of 0.5 L/min CO2 was set and each run was finished when 100 L of CO2 were measured in the flow totalizer. Extraction yield (% wt), total phenolic content (Folin-Ciocalteau) and antioxidant activity (ABTS+. assay) of the extracts were considered as response variables. Extraction yield was positively correlated with temperature and pressure, while total phenolic content and antioxidant activity were negatively correlated with temperature. Phenolic content of the extracts varied from 22.9 to 53.6 mg GAE/g. For the extract obtained at optimal conditions, the identification of individual polyphenols was performed by RP/HPLC-Q-TOF MS/MS, being phenolic acids, simple phenols and secoiridoids the most abundant compounds. Finally, oxidative stability of canola oil with or without the incorporation of 250 ppm of some extracts was assessed during five weeks of storage at 60°C. Peroxide, K232, K270, and Rancimat values, besides tocopherol content were determined. Results obtained reinforce the use of supercritical fluid technology to obtain antioxidants compounds from natural sources.
Development of a method for the identification and quantification of terpenes and cannabinoids in hemp using multidimensional gas chromatography and quadrupole-orbitrap mass spectrometry
Authors:   U.S. Food and Drug Administration, Prebihalo Sarah , Dubrow Geoffrey , Delmonte Pierluigi , Pawar Rahul
Published: November 2022

Since the passage of the 2018 Farm Bill, hemp-containing food products, including those marketed as dietary supplements, have proliferated in the U.S. marketplace, necessitating the development of analytical methods for the identification and quantification of cannabinoids in hemp. Reports suggesting a possible contribution of terpenes on the effects of cannabinoids further expands the demand for analytical methods that can accurately determine the terpenes profile for these products. Due to the complex composition of hemp, one-dimensional chromatographic methods may be proven to be insufficient for unmasking trace level terpenes which may play an important role in the chemical properties of hemp-materials. To address this challenge, a method combining multidimensional gas chromatography (GC×GC) and high-resolution quadrupole-orbitrap mass spectrometry has been developed. The reported method provides accurate analysis of fifty-six terpenes and nine cannabinoids, including but not limited to, CBD and D-9-THC, in various varieties of hemp plant material.
Quantitative and predictive modelling of lipid oxidation in mayonnaise
Authors:   Unilever, Van Duynhoven John ,   Wageningen University, Swager Andries ,   Wageningen University, Merkx Donny ,   Unilever, van Velzen Ewoud ,   Unilever
Published: November 2022

In the food industry, the oxidative stability mayonnaise is typically assessed by accelerated shelf-life tests. Even under accelerated conditions (50 °C) it can take weeks before the onset of volatile off-flavor (aldehydes) can be observed. To enable earlier assessment of compromised shelf-life a predictive model for aldehyde generation was developed. The model was based on formation kinetics of hydroperoxides, which are early oxidation products and precursors of volatile aldehydes. Under accelerated conditions (50 °C) hydroperoxide concentration over time shows a sigmoidal curvature followed by an acceleration phase that occurs at a LOOH-concentration between 38–50 mmol/kg, here interpreted as a critical LOOH concentration (CCLOOH). The time at which CCLOOH was reached was hypothesized to be related to the onset of aldehyde generation. We further hypothesized that long-term LOOH-generation could be predicted from formation kinetics in the first days. These hypotheses were tested using the semi-empirical Foubert model to describe the autocatalytic character of hydroperoxide formation in combination with the CCLOOH. From the prediction of long-term LOOH generation, the onset of aldehyde generation could be predicted. In addition, model parameters could be used to recognize antioxidant mechanisms at play.
Enzyme-based soy processing
Authors:   University of Akron, Ju Lu-Kwang , Loman Abdullah Al ,   Biogen, Kabir Md Fauzul ,   The University of Akron, Li Qian ,   Catalent, Islam S.M. Mahfuzul ,   Archer Daniels Midland Company
Published: November 2022

Soybeans contain three major components: protein (ca. 40%), carbohydrate (25–30%) and oil (18–20%). To maximize value and minimize waste in soy processing, all these components should be collected and utilized. Current processing was originally designed to maximize oil extraction. It tends to make protein and carbohydrate separation from the remaining meal more difficult and, as a result, can limit their uses and reduce their value. We have been developing an enzyme-based processing method which, in a single step, enables the recovery of oil, protein, and sugar in separate streams. Further, oil and protein present in soybeans as individually “packaged” oil bodies (oleosomes) and protein bodies. This solvent-free, enzyme-based processing allows collection of intact oleosomes and protein bodies without alteration by heat, solvent, or mechanical pressing. This new processing method can maximize the recovery of nutritional and industrial/economic value of all major soybean components. We also develop and optimize the production of enzyme particularly suitable for soy processing.
Molecular simulation as a tool for the design of biosurfactant-based cosmetic formulations
Authors:   Schrodinger, Coscia Benjamin , Browning Andrea , Sanders Jeffrey , Halls Mat
Published: November 2022

There is growing consumer-driven demand in the cosmetic industry to replace petroleum-based surfactants with environmentally friendly alternatives. Biologically derived surfactants, or biosurfactants, are a promising class of molecules which may be suitable towards this end. However, separate from challenges in producing these materials which have been increasingly addressed throughout the last decade, formulations built around these new surfactants must perform competitively compared to existing formulations. There are a number of subclasses of biosurfactant molecules and modifications which can be made to those. The cosmetic science community is in need of lucid design principles for reformulating existing products using this set of ingredients. We believe that this presents an optimization challenge which molecular simulation is well-equipped to solve. In this work, we demonstrate how physics-based molecular simulation paired with chemistry-oriented informatics software can aid in the prospective design of new formulations. Simulation trivializes the enumeration of possible formulation compositions, allowing us to systematically study and gain a molecular-level understanding of surfactant aggregates at a variety of conditions. We test aqueous mixtures of four different types of biosurfactants at various concentrations and pH and present our analysis of aggregate size, shape and composition as well as solution properties such as viscosity and diffusivity.
Unlocking the next generation of row crop quality traits through genome editing
Authors:   Bayer Crop Science, Stevens Julia
Published: November 2022

Climate smart farming practices; low-impact, high quality raw materials; equitable access to nutrition. The agricultural challenges of the future require innovative technologies today. Expansion of our biotechnology toolbox to include genome editing enables us to design crops that will revolutionize agriculture. At Bayer Crop Science we are developing a Quality Trait portfolio to deliver a safe and sustainable food supply from the beginning of the supply chain while reducing agriculture’s environmental impact. Through our knowledge of endogenous molecular pathways for traits like flavor, nutrient composition, disease resistance, and crop efficiency, we can use modern technology to specifically target and create genetic variation for desired phenotypes. This product development pipeline moves us closer to delivering improved nutritional sustainability, with the flexibility to solve emerging agricultural challenges. In this talk I will cover, why genome editing is needed as a bridge between breeding and biotechnology, the importance of multiplexed editing to deliver quality traits, and an example of success in our pipeline with the short stature corn concept.