bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Selective Anticancer Activity Evaluation of
2-phenylacrylonitrile Derivatives as Tubulin Inhibitors
Authors: Jin Ye-Zhi , Xin Ya-Bing , Li Yuan , Chen Xin-Yuan , Man De-Ao , Tian Yu-Shun
Published: October 2023

Objective:

This study aimed at synthesizing 13 series of novel derivatives
with 2-phenylacrylonitrile, evaluating antitumor activity both in vivo and in vitro, and
obtaining novel tubulin inhibitors.

Methods:

The 13 series of 2-phenylacrylonitrile derivatives were synthesized by Knoevenagel
condensation and the anti-proliferative activities were determined by MTT assay.
The cell cycle and apoptosis were analyzed by flow cytometer. Quantitative cell migration
was performed using 24-well Boyden chambers. The proteins were detected by
western blotting. in vitro kinetics of microtubule assembly was measured using ELISA
kit for Human β-tubulin (TUBB). Molecular docking was done by Discovery Studio (DS)
2017 Client online tool.

Results:

Among the derivatives, compound 1g2a possessed strong inhibitory activity
against HCT116 (IC50 = 5.9 nM) and BEL-7402 (IC50 = 7.8 nM) cells. Compound 1g2a
exhibited better selective antiproliferative activities and specificities than all the positive
control drugs, including taxol. Compound 1g2a inhibited proliferation of HCT116 and
BEL-7402 cells by arresting them in the G2/M phase of the cell cycle, inhibited the migration
of HCT116 and BEL-7402 cells and the formation of cell colonies. Compound
1g2a showed excellent tubulin polymerization inhibitory activity on HCT116 and
BEL-7402 cells. The results of molecular docking analyses showed that 1g2a may inhibit
tubulin to exert anticancer effects.

Conclusion:

Compound 1g2a shows outstanding antitumor activity both in vivo and in
vitro and has the potential to be further developed into a highly effective antitumor
agent with little toxicity to normal tissues.
Combinatorial Implications of Nrf2 Inhibitors with FN3K Inhibitor: In vitro Breast
Cancer Study
Authors: Beeraka Narasimha M. , Zhang Jin , Zhao Di , Liu Junqi , A U Chinnappa , Vikram PR Hemanth , Shivaprakash Priyanka , Bannimath Namitha , Manogaran Prasath , Sinelnikov Mikhail Y. , Bannimath Gurupadayya , Fan Ruitai
Published: October 2023

Background::

Platinum derivatives are chemotherapeutic agents preferred for the treatment of cancers
including breast cancer. Oxaliplatin is an anticancer drug that is in phase II studies to treat metastatic
breast cancer. However, its usage is constrained by chemoresistance and dose-related side effects.

Objective::

The objective of this study is to examine the combinatorial efficacy of brusatol, an Nrf2 blocker,
with oxaliplatin (a proven FN3K blocker in our study) in mitigating breast cancer growth in vitro.

Methods::

We performed cytotoxicity assays, combination index (CI) analysis, colony formation assays, apoptosis
assays, and Western blotting.

Results::

Results of our study described the chemosensitizing efficacy of brusatol in combination with lowdose
oxaliplatin against breast cancer through synergistic effects in both BT-474 and T47D cells. A significant
mitigation in the migration rate of these cancer cells was observed with the combination regimen, which is
equivalent to the IC-50 dose of oxaliplatin (125 μM). Furthermore, ROS-mediated and apoptotic modes of
cell death were observed with a combinatorial regimen. Colony formation of breast cancer cell lines was mitigated
with a combinatorial regimen of bursatol and oxaliplatin than the individual treatment regimen. FN3K
expression downregulated with oxaliplatin in T47D cells. The mitigation of FN3K protein expression with a
combination regimen was not observed but the Nrf2 downstream antioxidant signaling proteins were significantly
downregulated with a combination regimen similar to individual drug regimens.

Conclusion::

Our study concluded the combination efficacy of phytochemicals like brusatol in combination
with low-dose oxaliplatin (FN3K blocker), which could enhance the chemosensitizing effect in breast cancer
and minimize the overall dose requirement of oxaliplatin.
Understanding Alzheimer’s Disease and its Metal Chelation Therapeutics: A
Narrative Review
Authors: Thakur Ritik , Karwasra Ritu , Umar Tarana
Published: October 2023

The neurodegenerative disorders are age-related illnesses that cause the morphology or activity of
neurons to deteriorate over time. Alzheimer’s disease is the most frequent neurodegenerative illness in the
long run. The rate of advancement might vary, even though it is a progressive neurological illness. Various explanations
have been proposed, however the true etiology of Alzheimer’s disease remains unclear. Most pharmacological
interventions are based on the cholinergic theory, that is earliest idea. In accordance with the amyloid
hypothesis, the buildup of beta-amyloid in brain regions is the primitive cause of illness. There is no proof
that any one strategy is useful in avoiding Alzheimer’s disease, though some epidemiological studies have
suggested links within various modifiable variables, such as cardiovascular risk, diet and so on. Different metals
like zinc, iron, and copper are naturally present in our bodies. In metal chelation therapy drugs are used to
jam the metal ions from combining with other molecules in the body. Clioquinol is one of the metal chelation
drugs used by researchers. Research on metal chelation is still ongoing. In the present review, we go over the
latest developments in prevalence, incidence, etiology, or pathophysiology of our understanding of
Alzheimer’s disease. Additionally, a brief discussion on the development of therapeutic chelating agents and
their viability as Alzheimer’s disease medication candidates is presented. We also assess the effect of clioquinol
as a potential metal chelator.
The Biological Function of POLA2 in Hepatocellular Carcinoma
Authors: Yang Zhen , Shen Xingyuan , Wang Zhihuai , Li Renzhi , Hou Wenqiang , Liu Zengyuan , Gao Yuan , Zhu Chunfu , Qin Xihu
Published: October 2023

Introduction::

The role and prognostic value of POLA2 in liver cancer were comprehensively
analyzed through TCGA, GEO, and ICGC databases, and the role of POLA2 in liver
cancer cells and the regulatory mechanism involved were further verified through cell experiments.
Hepatocellular carcinoma (HCC) is the most prevalent malignancy with high morbidity
and mortality. Consequently, it is critical to identify robust and reliable predictive biomarkers
and therapeutic targets for HCC patients. POLA2 is involved in the regulation of various tumors,
but the specific role of POLA2 in HCC has not been reported. The regulatory role and prognostic
value of POLA2 in HCC were determined by bioinformatics techniques and cell experiments.

Method::

The specific role and prognostic value of POLA2 in HCC were comprehensively analyzed
by combining the expression data of POLA2 in TCGA, GEO, and ICGC databases and
clinical data. In clinical samples, the expression of POLA2 in liver cancer was verified by
QPCR. Further, the regulatory role of POLA2 in HCC was explored through cell experiments
such as CCK-8, clonal formation experiment, EDU cell proliferation experiment, and flow cytometry.
In terms of mechanism exploration, western blot was used to verify the specific regulatory
mechanism that POLA2 participated in. Finally, the relationship between POLA2 and immune
invasion of HCC was analyzed by using the TIMER database.

Result::

A POLA2 expression and prognosis analysis of HCC patients was conducted using the
TCGA, GEO, and ICGC databases. We hypothesized that POLA2 might be one of the key factors
contributing to the HCC progression. According to a combined analysis of TCGA, ICGC,
and GEO databases, POLA2 was highly expressed in HCC. This was further confirmed in clinical
samples using the qPCR. POLA2 knockdown was also performed in vitro on HCC cell lines
to study the changes in their biological behavior. We confirmed that POLA2 was associated with
HCC proliferation by CCK-8, Colony Formation, and EDU assay. We verified the POLA2's involvement
in cell cycle regulation using flow techniques. The relationship between POLA2 and
PI3K/AKT/mTOR pathway was explored using Western Blotting experiments regarding its
mechanism. Further analysis revealed that the POLA2 expression was significantly associated
with HCC immune infiltration.

Conclusion::

Our study demonstrated POLA2's importance in HCC development and progression
and its potential role as a biomarker for disease progression on multiple levels. POLA2 has
an important role in regulating the cell cycle and cell proliferation. By interfering with the cell
cycle and proliferation, HCC cell growth is inhibited. Furthermore, POLA2 expression was significantly
associated with immune infiltration. POLA2 may play a role in HCC immunotherapy
based on its correlation with several immune cell types' genetic markers. The findings of this
study are expected to lead to new anticancer strategies for HCC.
Cortisol as a Target for Treating Mental Disorders: A Promising Avenue
for Therapy
Authors: Patel Vijay K , Vaishnaw Aayush , Shirbhate Ekta , Kore Rakesh , Singh Vaibhav , Veerasamy Ravichandran , Rajak Harish
Published: October 2023

Cortisol, commonly known as the "stress hormone," plays a critical role in the body's response
to stress. Elevated cortisol levels have been associated with various mental disorders, including
anxiety, depression, and post-traumatic stress disorder. Consequently, researchers have explored
cortisol modulation as a promising avenue for treating these conditions. However, the availability of
research on cortisol as a therapeutic option for mental disorders is limited, and existing studies employ
diverse methodologies and outcome measures. This review article aimed to provide insights
into different treatment approaches, both pharmacological and non-pharmacological, which can effectively
modulate cortisol levels. Pharmacological interventions involve the use of substances, such
as somatostatin analogs, dopamine agonists, corticotropin-releasing hormone antagonists, and cortisol
synthesis inhibitors. Additionally, non-pharmacological techniques, including cognitivebehavioral
therapy, herbs and supplements, transcranial magnetic stimulation, lifestyle changes, and
surgery, have been investigated to reduce cortisol levels. The emerging evidence suggests that cortisol
modulation could be a promising treatment option for mental disorders. However, more research
is needed to fully understand the effectiveness and safety of these therapies.
The Protective Effect of Curcumin Against Cardiotoxic Effects
Induced by Chronic Exposure to Chlorpyrifos
Authors: Abdollahi-Karizno Mahdi , Chahkandi Mahbobeh , Rajabi Shahnaz , Roshanravan Babak , Jafari-Nozad Amir Masoud , Aschner Michael , Samargahndian Saeed , Farkhondeh Tahereh
Published: October 2023

Aims::

This study aimed to evaluate the effect of Chlorpyrifos (CPF) in rat
heart tissue and the effect of Curcumin (Cur) on cardiac enzymes, oxidative indices,
and histopathological changes in the cardiac tissue.

Background::

CPF, the most used organophosphorus pesticide (OP), has been
reported to induce cardiotoxic effects.

Objective::

The cardioprotective effects of Cur against CPF-induced toxicity have not
been entirely investigated till now.

Method::

Forty male Wistar rats were randomized into five groups (n=8). C group
(Control animals that received olive oil), CPF group (10 mg/kg/day), CPF + Cur 25,
CPF + Cur 50, and CPF + Cur 100 groups (animals received 10 mg/kg/day CPF and
25, 50, and 100 mg/kg Cur, respectively). All treatments were administered via oral
gavage for 90 days. Cardiac enzymes (LDH & CPK) and oxidative stress (OS)
biomarkers in heart tissue (malondialdehyde, Superoxide Dismutase) were
measured. Histopathological changes in the heart tissue were also evaluated.

Result::

Chronic exposure to CPF significantly increased cardiac enzyme levels and
OS biomarkers. Histological changes were found, including disorganization of the
cardiac muscle fibers with disorganization and degeneration in myocardial fibers with
separation of myofibrils and cytoplasmic vacuolization of cardiac muscle fibers.
Administration of Cur (100 mg/kg) reversed serum LDH concentration and OS
biomarkers to normal levels in CPF-exposed animals (p < 0.05) and significantly
improved cardiac damage.

Conclusion::

According to the results of this study, Cur can reduce the adverse
effects of long-term exposure to CPF in rat heart tissue by modulating OS.
Antiviral Effects and Mechanisms of Green Tea Catechins on Influenza: A
Perception on Combating Symptoms from COVID-19
Authors: Man Gene Chi Wai , Zheng Xu , Hung Sze Wan , Chan Loucia Kit Ying , Zhang Tao , Chen Xiaoyan , Chu Kai On , Huen Ian Chung Yuen , Lui Darren Wang Yip , Wong Alfred Ding , Wang Chi Chiu
Published: October 2023

Over the centuries, influenza and its associated epidemics have been a serious public
health problem. Although vaccination and medications (such as neuraminidase inhibitors) are the
mainstay of pharmacological approaches to prevent and treat influenza, however, frequent mutations
in the influenza genome often result in treatment failure and resistance to standard medications
which limit their effectiveness. In recent years, green tea catechins have been evaluated as
potential anti-influenza agents. Herein, in this review, we highlighted the effects and mechanisms
underlying the inhibitory effects of epigallocatechin 3-gallate (EGCG), the most abundant ingredient
in green tea, against different influenza viral infections, and their clinical benefits toward prevention
and treatment. In addition, as the severe acute respiratory syndrome coronavirus 2 (SARSCoV-
2) causes the outbreak of COVID-19 pandemic, our review also delineates the current perspective
on SARS-CoV-2 and future insights as to the potential application of EGCG on suppressing
the flu-like symptoms caused by COVID-19.
Nutritional Profile, GC-MS Analysis and In-silico Anti-diabetic Phytocompounds
Candidature of Jatropha gossypifolia Leaf Extracts
Authors: Awote Olasunkanmi Kayode , Kanmodi Rahmon Ilesanmi , Ebube Success Chidera , Abdulganniyyu Zainab Folashade
Published: October 2023

Background::

Diabetes mellitus (DM) is a metabolic disorder known to impair many
physiological functions via reactive oxygen species (ROS). Aldose reductase, Sorbitol dehydrogenase,
Dipeptidyl peptidase IV, α-amylase and α-glucosidase are pharmacotherapeutic protein targets
in type-2 diabetes. Inhibitors of these enzymes constitute a new class of drugs used in the treatment
and management of type-2 diabetes mellitus. Some reports claim that medicinal plant extracts used
as food (antioxidant source) can reduce these alterations by eliminating ROS caused by DM. Ethnobotanical
survey claims Jatropha gossypifolia commonly called “fig-nut” and “Lapa-lapa” in the
Yoruba land of South-western Nigeria, to be used for the treatment and management of diabetes, in
addition to its nutritive value.

Objective::

The nutritional composition and in-silico antidiabetic potential of the bioactive constituents
of J. gossypifolia leaf extracts were investigated.

Methods::

Proximate, minerals and gas chromatography–mass spectroscopy (GC-MS) analysis were
carried out using standard procedures. Phytocompounds present in J. gossypifolia methanol (JGM)
and ethyl acetate (JGE) leaf extracts were tested as potential antagonists of selected protein targets
via in-silico techniques. Drug-likeness, pharmacokinetic properties and toxicity of the promising
docked ligands were also predicted.

Results::

The proximate and mineral analysis revealed good nutritional composition and mineral
content. Moreso, cyclo-pentadecane and dibutyl phthalate from methanol extract, and benzene-
1,2,4,5-tetramethyl, benzene-1,2,3,5-tetramethyl, and benzene-1,3-dimethyl-5-(1-methylethyl) from
ethyl acetate extract were present in J. gossypifolia leaf which exhibited better binding affinity than
the clinically prescribed standard, metformin.

Conclusion::

Benzene-1,2,4,5-tetramethyl from JGE extracts exhibited the most promising antidiabetic
potential in-silico, suggesting its candidature as diabetes-target-protein inhibitor which may be
developed for the treatment of type-2 diabetes mellitus.
From Gut to Glucose: A Comprehensive Review on Functional Foods and
Dietary Interventions for Diabetes Management
Authors: Patel Nirali , Dinesh Susha , Sharma Sameer
Published: October 2023

Background::

In the realm of diabetes research, considerable attention has been
directed toward elucidating the intricate interplay between the gastrointestinal tract and glucose
regulation. The gastrointestinal tract, once exclusively considered for its role in digestion and
nutrient assimilation, is presently acknowledged as a multifaceted ecosystem with regulatory
supremacy over metabolic homeostasis and glucose metabolism. Recent studies indicate that
alterations in the composition and functionality of the gut microbiota could potentially influence
the regulation of glucose levels and glucose homeostasis in the body. Dysbiosis, characterized
by perturbations in the equilibrium of gut microbial constituents, has been irrevocably linked to
an augmented risk of diabetes mellitus (DM). Moreover, research has revealed the potential
influence of the gut microbiota on important factors, like inflammation and insulin sensitivity,
which are key contributors to the onset and progression of diabetes. The key protagonists
implicated in the regulation of glucose encompass the gut bacteria, gut barrier integrity, and the
gut-brain axis. A viable approach to enhance glycemic control while concurrently mitigating the
burden of comorbidities associated with diabetes resides in the strategic manipulation of the gut
environment through adapted dietary practices.

Objective::

This review aimed to provide a deep understanding of the complex relationship
between gut health, glucose metabolism, and diabetes treatment.

Conclusion::

This study has presented an exhaustive overview of dietary therapies and
functional foods that have undergone extensive research to explore their potential advantages in
the management of diabetes. It looks into the role of gut health in glucose regulation, discusses
the impact of different dietary elements on the course of diabetes, and evaluates how well
functional foods can help with glycemic control. Furthermore, it investigates the mechanistic
aspects of these therapies, including their influence on insulin sensitivity, β-cell activity, and
inflammation. It deliberates on the limitations and potential prospects associated with
integrating functional foods into personalized approaches to diabetes care.
A Prerequisite for need of Harmonized Nutrient Reference Values & its
Standardized Terminology for Better access of Nutritional Supplements
Globally
Authors: Bhatt Mayank , Patel Shreyansh , Tank Sampann , Soni Navdha , Shah Jignesh , Maheshwari Dilip
Published: October 2023

To reduce the risk of insufficient nutrient intake, nutrient reference values for humans
are set at the average nutrient need level without a safety margin. The vast majority of nations and
areas in the globe set nutritional intake guidelines for their citizens. Currently, no harmonized nutrient
reference value has been published, as well as the development of standards cannot be
achieved through the use of formalized frameworks or terminology. The study's objective was to
create recommendations for appropriate and secure micronutrient intake ranges that could be used
to inform dietary advice. As relevant to the study, we examined micronutrient data from food intake
surveys from representative nations. The comparison of national standards illustrates that the
level of reference values for nutrient for individual countries is dependent on variables such as
methodology, data sources, physical activity exemptions, standard body weights, and age range.
In the current study, iron, calcium, magnesium, vitamin A, B12, D and folate were identified as
the most commonly under-consumed micronutrients. In this article, the level of six countries' standards
are compared to the current reference values for nutrients. Further, numerous words for different
dietary standards components are discussed, and a final set of harmonized reference nutrient
intake for the dietary advice is provided.
Fetal Aortic and Umbilical Doppler Flow Velocity Waveforms in
Pregnancy: The Concept of Aortoumbilical Column
Authors: Ana Beatriz De Almeida , Ana Rita Morais , Miguel Ferreira , Ana Rita Gaio , Luís Guedes-Martins
Published: October 2023

Low impedance within the uteroplacental circulation is crucial for fetal development.
Flow velocity waveforms (FVW) have been established for the aortic and umbilical arteries in
low-risk pregnancies during the second half of pregnancy, but data regarding early gestation is
limited. Both vascular territories exhibit higher impedance patterns in pregnancies complicated
by fetal growth restriction (FGR), hypertensive disorders, fetal anemia, and chromosomal abnormalities.
Early identification of these complications is critical in obstetric practice, to reduce
perinatal morbidity and mortality through prevention and close antenatal surveillance. Available
data suggest that aortic and umbilical impedances follow the same variation pattern as pregnancy
progresses. This observation implies that both vessels may be considered as a single artery, referred
to as the “aortoumbilical column”. Our hypothesis posits that changes in the hemodynamic
pattern of this column could identify high-risk pregnancies, particularly those complicated by
preeclampsia, FGR, intrauterine fetal demise, fetal aneuploidies, and fetal anemia. Understanding
vascular embryogenesis and the FVWs of the aortic and umbilical arteries enables comprehension
of impedance changes throughout normal pregnancies. The continuous variation in impedance
along a single vessel supports our concept of the aortoumbilical column. Deviations
from the regular pattern could assist in identifying compromised fetuses during early pregnancy.
Further research on normal aortoumbilical column FVW and the development of reference charts
is necessary to consider this arterial column as a screening tool in clinical practice.
Chest CT Image based Lung Disease Classification – A Review
Authors: Kondamuri Shri Ramtej , Thadikemalla Venkata Sainath Gupta , Suryanarayana Gunnam , Karthik Chandran , Reddy Vanga Siva , Sahithi V. Bhuvana , Anitha Y. , Yogitha V. , Valli P. Reshma
Published: October 2023

Computed tomography (CT) scans are widely used to diagnose lung conditions due to their ability to provide a detailed overview of the body's
respiratory system. Despite its popularity, visual examination of CT scan images can lead to misinterpretations that impede a timely diagnosis.
Utilizing technology to evaluate images for disease detection is also a challenge. As a result, there is a significant demand for more advanced
systems that can accurately classify lung diseases from CT scan images. In this work, we provide an extensive analysis of different approaches and
their performances that can help young researchers to build more advanced systems. First, we briefly introduce diagnosis and treatment procedures
for various lung diseases. Then, a brief description of existing methods used for the classification of lung diseases is presented. Later, an overview
of the general procedures for lung disease classification using machine learning (ML) is provided. Furthermore, an overview of recent progress in
ML-based classification of lung diseases is provided. Finally, existing challenges in ML techniques are presented. It is concluded that deep
learning techniques have revolutionized the early identification of lung disorders. We expect that this work will equip medical professionals with
the awareness they require in order to recognize and classify certain medical disorders.
Recent Progress in the Composites of Perovskite Nanocrystals and II-VI
Quantum Dots: Their Synthesis, Applications, and Prospects
Authors: Wu Qiaoyun , Hu Rongrong , Yang Bobo , Peng Wenfang , Shi Mingming , Li Yuefeng , Cheng Lin , Liang Pan , Zou Jun
Published: October 2023

The remarkable photoelectric characteristics of perovskite nanocrystals (NCs), including
high fault tolerance, tunable photoluminescence (PL) emission, and high carrier mobility,
contribute to making them especially attractive for photonic and optoelectronic applications.
Unfortunately, the poor environmental thermal and light stability set obstacles to their industrial
applications. Over the past 40 years, II-VI semiconductor quantum dots (QDs) have achieved
many important photophysics findings and optoelectronic applications. Compared with perovskite
NCs, II-VI semiconductor QDs still have a relatively weaker molar absorbance coefficient.
Whereas, significant enhancement of both the stability and the optical performance of the composites
of perovskite NCs and II-VI QDs are of interest for photovoltaic and optoelectronic devices.
The composites of perovskite NCs and II-VI QDs come in two primary types: core/shell
structures and heterojunction structures. To better understand the composites of perovskite NCs
and II-VI QDs, the approaches of synthesis methods, their optoelectronic properties, carrier dynamics
and potential applications in solar cells, light emitting diodes (LEDs) and photodetectors
are summarized. Furthermore, the unmet problems and the potential applications are also presented.
GDF15 Interference Regulates Proliferation, Inflammation, and Autophagy
of Lipopolysaccharide-induced Mesangial Cells by Inhibiting PI3K/
AKT/mTOR Signaling
Authors: Chen Zhen , Gao Liping , Li Cailing , Sun Wenzhu
Published: October 2023

Background:

Chronic glomerulonephritis (CGN) is a primary glomerular disease. As
a circulating protein, growth and differentiation factor 15 (GDF15) participates in a variety of
biological processes.

Objective:

We aimed to investigate the role of GDF15 in CGN.

Methods:

HBZY-1 cells were induced by lipopolysaccharide (LPS). Cell viability was detected
using a cell counting kit-8 (CCK-8) assay, and a western blot was applied for the detection of
GDF15 protein expression. After GDF15 silencing, cell proliferation was evaluated by CCK-8
assay and 5-ethynyl-2'-deoxyuridine (EDU) staining. Enzyme-linked immunosorbent assay
(ELISA) kits were used to detect the levels of inflammatory cytokines. Autophagy was assessed
by GFP-LC3B assay. Besides, the expression of NF-κB signaling-, autophagy- (LC3II/I, Beclin
l and p62) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of
rapamycin (mTOR) signaling-related proteins were measured by western blot. Afterwards,
PI3K agonist 740Y-P was used to clarify whether GDF15 affected LPS-induced HBZY-1 cells
via PI3K/AKT/mTOR signaling.

Results:

LPS induction increased cell viability and elevated GDF15 expression in HBZY-1
cells. After GDF15 expression depletion, the increased proliferation of LPS-induced HBZY-1
cells was decreased. Additionally, GDF15 knockdown suppressed the release of inflammatory
factors in LPS-induced HBZY-1 cells and activated autophagy. Moreover, the PI3K/AKT/
mTOR signal was evidenced to be activated by GDF15 deficiency. The further addition of
740Y-P reversed the impacts of GDF15 deficiency on the proliferation, inflammation, and autophagy
of LPS-induced HBZY-1

Conclusion:

Collectively, GDF15 downregulation could protect against CGN via blocking
PI3K/AKT/mTOR signaling.
Meta-analysis of the Relationship between Type 2 Diabetes Mellitus and
Renal Cancer Risk
Authors: Wang Yingxin , Cao Ying , Zhu Chenchen
Published: October 2023

Objective::

This study aimed to investigate the relationship between type 2 diabetes
mellitus and the risk of renal cancer.

Methods::

A search was carried out on PubMed, Embase, Web of Science, China Biology Medicine
disc (CBM), China National Knowledge Infrastructure (CNKI), Wanfang and other databases.
The search period was from 2000 to 2022. The two authors independently conducted literature
screening, extracted literature data, and then conducted a literature quality evaluation.
The type of study is a cohort study. Meta-analysis was carried out on the included literature
through Stata12.0 software, and the combined value was calculated with RR value and 95% confidence
interval. Subgroup analysis was carried out to explore the impact of different factors on
the overall results.

Results::

A total of 10 articles were included. Through cohort study, the meta-analysis on the risk
of type 2 diabetes and renal cancer showed that the combined effect value Risk Ratio (RR) =
1.57 with 95% Confidence Intervals (CI) (1.36, 1.82) and P<0.05. The difference had a significant
impact, indicating that the risk of renal cancer in type 2 diabetes patients was 1.55 times
higher than that in non-type 2 diabetes patients. The subgroup analysis showed that the combined
effect value RR and 95% CI for men was 1.49 (1.26, 1.75), and the combined effect value
RR and 95% CI for women was 1.60 (1.35, 1.88), which was basically consistent.

Conclusion::

Type 2 diabetes can significantly increase the risk of renal cell carcinoma, and the
former is a risk factor for the latter. It is suggested that multi-center studies with larger sample
sizes should be conducted in the future, and adjustments should be made according to the type of
diabetes, the source of the study population, the pathological type of renal cell carcinoma, the
use of hypoglycemic drugs, and other factors, to provide a reliable basis for the study of the relationship
between diabetes and renal cell carcinoma. At present, the specific mechanism of diabetes
increasing the risk of renal cell carcinoma and whether diabetes increases mortality due to
renal cell carcinoma is still unclear and needs further research.
Clinical, Biochemical and Molecular Features of a Cohort of 8 Patients with Inherited Disorders of Vitamin B12 Metabolism in a Metabolic Reference Center
Authors: Padeira Gonçalo , Jacinto Sandra , Ribeirinho Augusto , Ferreira Ana Cristina
Published: October 2023

Background:

Vitamin B12, or cobalamin (Cbl), undergoes a complex series of absorptive
and intracellular processing steps before serving as a cofactor for the enzymes
methylmalonyl-CoA mutase and methionine synthase. Disorders of intracellular cobalamin metabolism
have variable phenotypes and age of onset related to the location of the defect in the
metabolic pathway leading to a combined methylmalonic acidemia and homocystinuria (cblC,
cblD, cblF and cblJ), Isolated methylmalonic acidemia (cblA, cblB and cblDv2) and isolated
homocystinuria (cblDv1, cblE and cblG).

Objective and Methods:

We conducted a retrospective study of the clinical biochemical and
molecular features of a cohort of patients with disorders of intracellular Cbl metabolism followed
in our Reference Centre of Inherited Metabolic Diseases (CR-IMD) for the last 23 years
(2000-2023).

Results:

CblC: P1 and P2, pré-newborn screening (NBS), had an early and severe presentation
evolving to multiorgan failure and death. P3 was asymptomatic at NBS with an excellent evolution
except for nystagmus and retinitis pigmentosa. P4 presented at 19Y with an atypical hemolytic
uremic syndrome and is presently on hemodialysis. CblD: P5 had a developmental delay
(DD) and hypotonia and presented at 14m with seizures. CblDv2: P6 had DD and failure to
thrive (FTT) and presented at 4Y with acute metabolic acidosis. CblDv1: P7 had DD, FTT, and
hypotonia and presented at 16m with seizures and anemia. CblG: P8 had DD and FTT and presented
at 15m with macrocytic anemia. In all, characteristic biochemical profiles guided the diagnosis,
afterward confirmed by genetic analysis (4 MMACHC, 3 MMADHC, 1 MTR). All
patients received either betaine, hydroxycobalamin, or both (P3 is on a very high dosage).

Conclusion:

Our cohort of patients has similar clinical and biochemical characteristics to the
ones described in the literature. Outcomes of patients reinforce the importance of newborn
screening and the need for consensus guidelines for optimal doses of parenteral hydroxocobalamin.
Metabolic Myopathies: Experience of a Reference Center of Inherited Metabolic Diseases
Authors: Rebelo Mafalda , Pires Madalena , Azurara Laura , Câmara Lara , Pereira Márcia , Ribeirinho Augusto , Padeira Gonçalo , Silva Patrícia Gaspar , Jacinto Sandra , Vieira José Pedro , Ferreira Ana Cristina
Published: October 2023

Introduction: Metabolic myopathies (MM) are a heterogeneous group of genetic disorders
affecting metabolic pathways involved in energy production during rest, exercise and
physiologic stress (fever, fasting, …). Impairments in the pathways of glycolysis/
glycogenolysis, fatty acid transport/oxidation or in the mitochondrial respiratory chain present
primarily with exercise intolerance, myalgias, weakness, cramps, or rhabdomyolysis. Depending
on aetiology, the diagnosis can be made through neonatal screening, pre-symptomatic
or in the set of clinical manifestations for which a high level of suspicion is important.

Methods: Retrospective descriptive study of the clinical, biochemical, and molecular features of
patients with a confirmed diagnosis of MM followed by the multidisciplinary team of the Reference
Center of Inherited Metabolic Diseases of Centro Hospitalar Universitário de Lisboa Central
from 2009 to 2022.
Results: Twenty-three patients with MM were included: 9 (39%) glycogen storage diseases (7
McArdle and 2 Pompe), 7 (30%) fatty acid oxidation disorders (3 CPT2, 3 LCHAD and 1 MAD
deficiencies), 6 (26%) mitochondrial disease with significant muscle involvement (2 Pearson, 1
Kearns Sayre, 1 VARS2, 1 SUCLA2 and 1 MT-TL1 deficiencies), and 1 myoadenylate deaminase
deficiency. Ages varied from 15 months to 35 years. Eighteen (78%) patients were diagnosed
by clinical symptoms, 3 by newborn screening (LCHAD) and 2 were asymptomatic (1
Pompe and 1 McArdle). Frequent symptoms were rhabdomyolysis triggered by illness or exercise
12 (52%), fatigue 11 (48%), exercise intolerance 10 (43%), and myalgia 9 (43%). Eight
(35%) patients (LCHAD and mitochondrial) had multisystemic involvement. In 20 (87%) patients,
the diagnosis was confirmed by biochemical and/or genetic analysis and 3 (McArdle) by
muscle biopsy.

Conclusion: MM are a heterogeneous set of disorders, but a careful history may guide the differential
diagnosis among biochemical pathways and other etiologies. Nowadays, molecular
testing has become a powerful tool for diagnosis confirmation, surpassing muscular biopsy in
most cases. Accurate diagnosis is important to identify who may benefit from specific therapeutic
options, such as enzyme replacement therapy, restricted diets, emergency regime and cofactors.
All patients benefit from adequate lifestyle modifications, individualized exercise prescription,
nutritional intervention, and genetic counselling.
A Comprehensive Review on Sophora japonica: Ethnomedicinal,
Phytochemistry & Pharmacological Aspects
Authors: Ghatti Srivalli Susmitha , Garaga Machiraju , Chatterjee Arnab , Thimmannagari Sravani , Cherupalli Sree Ramya , Hebbani Nagarajappa Shivaprasad , Krishnamani Madhu , Soni Gaurav
Published: October 2023

Sophora japonica, a species of Sophora, one of the prominent genera, belongs to the family
Fabaceae, native to China, which is commonly known as a pagoda tree. Sophora, includes nearly
52 species, nineteen varieties and many of these species have been used in traditional Chinese medicine
to cure various ailments. This review compiles its ethnomedical uses, diverse phytochemicals
reported from the various parts of S. japonica, and their pharmacological effects to elucidate its therapeutic
potential against a wide range of diseases. Traditionally it is used to treat various hematic
disorders such as hypertension, hemorrhoids, hemorrhage, hematuria, hematochezia, dysentery, arteriosclerosis,
etc. Moreover, each and every part of this plant, including the flowers, buds, leaves,
bark, fruits, seeds, pericarp, stems, and roots are used as medicine, particularly in China, Japan, Korea,
and Asia. Chinese Pharmacopoeia and European Pharmacopoeia describe the utility of this plant
since ancient times. The enhanced use of S. japonica in Chinese medicine resulted in the exploration
of various phytochemicals and their pharmacological properties includes in vitro, in vivo, and clinical
studies. It is enchanted with steroids, phospholipids, flavonoids, isoflavonoids, alkaloids, triterpenes,
and other phenolic compounds that are characterized by therapeutic activities such as anti-oxidant,
anticancer, anti-asthmatic, anti-neoplastic, antimicrobial, antiviral, antidote, anti-pyretic, cardiotonic,
anti-inflammatory, diuretic, anti-platelet, anti-hyperglycemic, immunomodulatory, anti-diabetic,
estrogenic and anti-osteoporotic activity in post-menopausal women etc. and this is also used as a
remedy for skin diseases like eczema, colpitis and psoriasis. Despite its health benefits, supplementary
data is still required in order to bridge the gaps and ensure the possible safety profile by conducting
clinical studies for its therapeutic applications as a natural and eminent safe drug.
PV Array Reconfiguration for Global Maximum Power Optimizing under Partial Shading Conditions based on PV Switched System
Authors: Abdelaziz Mohamed M. , Sharaf Soliman M. , El Zoghby Helmy M.
Published: October 2023

Background:

Due to the partial shading effects on different photovoltaic (PV) modules
in a PV array, PV module operating conditions are inconsistent, and PV array output power is significantly
reduced. Although the maximum power point (MPP) of a non-uniform irradiance PV
array can be observed through global maximum power point tracking (GMPPT), no evaluation of
the array's energy potential has been done.

Objective:

One of the most effective solutions to overcome the negative effects of partial shading
in PV systems is the PV array reconfiguration process. To optimize the electrical structure of the
PV array as the PV modules are partially shaded in a non-uniform manner, this study proposes a
promising technique for dynamic reconfiguring a PV array in order to improve the extracted maximum
power from a PV array under partial shading conditions (PSC).

Methods:

PV modules are rearranged by iteratively sorting them to allow the PV array with nonuniform
irradiance to produce as much power as possible. This is conducted by applying a switching
matrix to implement a PV-switched system approach. The proposed system with different PV
array dimensions (e.g., 3×4, 4×6, and 5×8) is assessed in order to validate the proposed algorithm. A
MATLAB/Simulink PV array developed model is used to find the global maximum power point for
the different PV array dimensions in both pre-reconfiguration and post-reconfiguration states.

Results:

A detailed numerical comparison of the extracted power from the proposed system has
been provided.

Conclusion:

The results show that the proposed system has the potential to extract the exact global
maximum power for a PV-switched system under PSC, irrespective of array dimensions, according
to simulation results.
High-precision Prediction Method of Electric Vehicle Trading Power
based on Neural Network
Authors: Wei Wei , Ye Li , Fang Yi , Wang Yingchun , Zhong Yue , Zhang Chenghao , Li Zhenhua
Published: October 2023

Introduction:

Electric vehicles have become a development trend due to their good
environmental protection and energy saving, etc. Prediction of electric vehicle charging volume
can help relevant departments optimize power supply, service, and construction.

Methods:

In this paper, the Support Vector Machine (SVM) model and the combined Long Short
Term Memory (LSTM) and Support Vector Regression (SVR) prediction model are constructed for
the prediction of charging capacity, and simulated by actual trading power data in Hubei Province.

Results:

The results show that the prediction effect of the two methods is good, and the LSTMSVR
algorithm is judged to have better performance and less error in predicting the fluctuation of
transaction power.

Conclusion:

LSTM-SVR can be used as a charging prediction method to provide a reference basis
for the power control strategy of electric vehicles charging management platform, which is conducive
to the healthy development of electric vehicles industry.
A Shunt DC Electric Spring Control Strategy for MVDC Bus Voltage Stability Onboard AES
Authors: Radhakrishnan Remna , Chacko Mariamma
Published: October 2023

Background:

The recent trend in the all-electric ship (AES) electrical systems, especially
in military vessels, is to move towards medium voltage direct current (MVDC) distribution.
Bus voltage instability is a major issue in direct current (DC) distribution systems. Nowadays,
direct current electric springs (DCES) are extensively used in low-voltage direct current (LVDC)
microgrids to address voltage instability issues. This paper extends the use of a shunt DCES to
stabilize the bus voltage in an MVDC grid. The work proposes an addition to the MVDC onboard
ship distribution system architecture, described in IEEE 1709, by integrating a shunt DCES with a
novel control strategy to stabilize the bus voltage under various loading conditions, including propulsion
motor (PM) and online pulsed power load (PPL).

Methods:

The shunt DCES is designed to provide current into the MVDC bus, which reduces the
bus current ripple to attain a stable bus voltage with reduced ripple. A dual loop control with a
battery management system (BMS) is proposed for the shunt DCES and simulated in
MATLAB/Simulink. BMS is designed based on the state of charge (SOC) of the battery and bus
current ripple extracted from the system's source and load side currents. The current supplied by
the shunt DCES and the extracted ripple current validate the effectiveness of the proposed control.
Total harmonic distortions (THDs) as a measure of voltage ripple of the MVDC bus voltage at
different intervals are measured and compared for both systems, with and without shunt DCES.

Results:

It was observed that the shunt DCES could reduce the voltage ripple well below the permissible
limit, which is 5% as per IEEE 1709.

Conclusion:

The proposed control strategy could attain a reduction of 68-85% in THD under peak
to off-peak loading conditions with the addition of shunt DCES.
Insights on Natural Products Against Amyotrophic Lateral Sclerosis
(ALS)
Authors: Monteiro Kadja Luana Chagas , dos Santos Alcântara Marcone Gomes , de Aquino Thiago Mendonça , da Silva-Júnior Edeildo Ferreira
Published: October 2023

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes
the death of motor neurons and consequent muscle paralysis. Despite many efforts to address it, current
therapy targeting ALS remains limited, increasing the interest in complementary therapies. Over
the years, several herbal preparations and medicinal plants have been studied to prevent and treat this
disease, which has received remarkable attention due to their blood-brain barrier penetration properties
and low toxicity. Thus, this review presents the therapeutic potential of a variety of medicinal herbs
and their relationship with ALS and their physiopathological pathways.
Inflammation, Autoimmunity and Neurodegenerative Diseases,
Therapeutics and Beyond
Authors: Garmendia Jenny Valentina , De Sanctis Claudia Valentina , Das Viswanath , Annadurai Narendran , Hajduch Marián , De Sanctis Juan Bautista
Published: October 2023

Neurodegenerative disease (ND) incidence has recently increased due to improved life expectancy. Alzheimer's (AD) or Parkinson's disease (PD) are the most prevalent NDs. Both diseases are poly genetic, multifactorial and heterogenous. Preventive medicine, a healthy diet, exercise, and controlling comorbidities may delay the onset. After the diseases are diagnosed, therapy is needed to slow progression. Recent studies show that local, peripheral and age-related inflammation accelerates NDs' onset and progression. Patients with autoimmune disorders like inflammatory bowel disease (IBD) could be at higher risk of developing AD or PD. However, no increase in ND incidence has been reported if the patients are adequately diagnosed and treated. Autoantibodies against abnormal tau, β amyloid and α- synuclein have been encountered in AD and PD and may be protective. This discovery led to the proposal of immune-based therapies for AD and PD involving monoclonal antibodies, immunization/vaccines, pro-inflammatory cytokine inhibition and anti-inflammatory cytokine addition.
All the different approaches have been analysed here. Future perspectives on new therapeutic strategies for both disorders are concisely examined.
Smoking, Symptoms Improvement, and Total Antioxidant Capacity in
Patients with Drug-naive First-episode Schizophrenia: A Prospective
Cohort Study
Authors: Gao Zhiyong , Xiu Meihong , Liu Jiahong , Wu Fengchun , Zhang Xiangyang
Published: October 2023

Background:

It has been hypothesized that smoking is associated with the severity of negative
symptoms. Until now, no studies have investigated whether the impact of smoking on negative
symptoms is dependent on antioxidants. This study was designed to evaluate the effect of smoking on
therapeutic response and total antioxidants capacity (TAOC) in antipsychotic-naïve first-episode
(ANFE) patients.

Methods:

The severity of the patient’s symptoms was assessed using the Positive and Negative
Syndrome Scale (PANSS). A total of 237 ANFE patients were recruited and treated with risperidone
(oral tablets, 4-6 mg/day twice a day) for 12 weeks. PANSS was assessed at baseline and a 12-week
follow-up. Plasma TAOC levels were also assayed at baseline and week 12.

Results:

Relative to nonsmokers with ANFE SZ, smokers had higher PANSS negative subscores.
There was no significant difference in TAOC changes after 12 weeks of treatment with risperidone between
smokers and non-smokers. However, we found greater improvement in negative symptoms in
smokers compared to non-smokers. Further analysis in smokers with SZ demonstrated that improvements
in negative symptoms were not associated with changes in TAOC.

Conclusion:

Our study suggested that smoking affected the severity of baseline negative symptoms
and further contributed to their reduction after risperidone treatment. However, improvement in negative
symptoms was not dependent on the changes in TAOC.
Enhancement Techniques for the Reduction of Heating and Cooling Loads in Buildings: A Review
Authors: Ismail kamal , Lino Fatima , Henriquez Jorge , Teggar Mohamed , Laouer Abdelghani , Arici Muslum , Benhorma Amani , Rodríguez Daniel
Published: October 2023

The building sector is rated as a big consumer of electric energy and emissions, responsible for about 40% of final electric energy consumption. As a result, the Paris Agreement 2015 set a goal for buildings and the construction sector to reach a nearly zero-carbon stage by 2050. This urged most countries to create regulations for the construction sector and invest in energy efficiency programs. The present paper aims to present an updated review of building energy-saving solutions and techniques to contribute to carbon emission mitigation in the building sector. The high energy consumption of a building is mainly due to heating and cooling, which is directly related to the thermal properties of the materials used. Natural ventilation and illumination are other aspects that contribute to the high energy consumption. Considering these issues, the review covers energy-efficient construction materials such as mortars, concrete with PCM, new construction materials with PCM such as 3d printing concrete and geopolymer concrete, and bricks usually used in buildings. Also, the review covers the methods and solutions for energy saving for building heating and cooling. Since transparent windows and façades are essential for structures, their thermal and visual performance is crucial. Established and under-development techniques for windows and façades are presented and discussed. Walls and roofs are usually rated at the top of the weak barriers against a building's heat losses and energy gains. The present paper reviews existing and still under research and development techniques to improve the thermal performance of walls and roofs, such as cool roof and cool walls, walls and roofs with phase change materials (PCM), and ventilated walls and ceilings.Some authors’ comments are presented at the end of each topic. Some possible opportunities for future research and developments are also presented.