bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a Novel Thermostable 7α-Hydroxysteroid Dehydrogenase
Authors: Lou Deshuai , Cao Yangyang , Duan Hongtao , Tan Jun , Li Binyan , Zhou Yuanjun , Wang Dong 
Published: January 2024

Background:
7α-Hydroxysteroid dehydrogenase (7α-HSDH) plays a pivotal role in
vivo in the biotransformation of secondary bile acids and has great potential in industrial biosynthesis
due to its broad substrate specificity. In this study, we expressed and characterized a novel
thermostable 7α-HSDH (named Sa 7α-HSDH).

Methods:
The DNA sequence was derived from the black bear gut microbiome metagenomic sequencing
data, and the coding sequence of Sa 7α-HSDH was chemically synthesized. The heterologous
expression of the enzyme was carried out using the pGEX-6p-1 vector. Subsequently, the
activity of the purified enzyme was studied by measuring the absorbance change at 340 nm. Finally,
the three-dimensional structure was predicted with AlphaFold2.

Results:
Coenzyme screening results confirmed it to be NAD(H) dependent. Substrate specificity
test revealed that Sa 7α-HSDH could catalyze taurochenodeoxycholic acid (TCDCA) with catalytic
efficiency (kcat/Km) 3.81 S-1 mM-1. The optimum temperature of Sa 7α-HSDH was measured to
be 75°C, confirming that it belongs to thermophilic enzymes. Additionally, its thermostability was
assessed using an accelerated stability test over 32 hours. The catalytic activity of Sa 7α-HSDH remained
largely unchanged for the first 24 hours and retained over 90% of its functionality after 32
hours at 50°C. Sa 7α-HSDH exhibited maximal activity at pH 10. The effect of metal ions-K+,
Na+, Mg2+ and Cu2+-on the enzymatic activity of Sa 7α-HSDH was investigated. Only Mg2+ was observed
to enhance the enzyme’s activity by 27% at a concentration of 300 mM. Neither K+ nor
Na+ had a significant influence on activity. Only Cu2+ was found to reduce enzyme activity.

Conclusion:
We characterized the thermostable 7α-HSDH, which provides a promising biocatalyst
for bioconversion of steroids at high reaction temperatures.
Part 2, Studies on the Synthesis of Quinolone Derivatives with their Biological
Activity
Authors: Saxena Nishtha , Shankhdhar Swapnil , Kumar Anil , Srivastava Nivedita 
Published: January 2024

Abstract:
Quinolones are among the class of antibiotics that are used most frequently worldwide and are used
for treating a variety of bacterial diseases in humans. Recent research has shown that new, improved analogues
of quinolones are being used as anticancer, antifungal, antiviral and other antimicrobial agents. In an earlier
review (Part 1) [8], we discussed the synthesis and antibacterial activity of quinolones in detail. This review
focuses on the detailed study of newly synthesized quinolone compounds and their biological activity in different
dimensions.
Two-step Continuous-flow Synthesis of 1,2-dimethyl-3-methylsulfanylbenzene via
Diazotization and Methanethiolation
Authors: Li Lixia , Zhang Qi , Bian Ce , Wei Wei , Sun Wenxuan , Ji Lu , Wang Hande , Zhou Chuan , Wang Ke , Gong Dangsheng , Yan Dongmao 
Published: January 2024

Abstract:
1,2-Dimethyl-3-methylsulfanylbenzene is the key intermediate of topramezone. This work designed a
two-step continuous-flow device to synthesize 1,2-dimethyl-3-methylsulfanylbenzene via diazotization and
methanethiolation. The results showed that compared with the batch process, the continuous-flow method greatly
shortened the residence time to 1 minute, avoided the accumulation of large amounts of diazonium salts to
reduce decomposition and increased the product yield to 91.7%. At the same time, the continuous-flow process
improved the safety and efficiency of the reactions, saved reaction time and had good prospects for industrial
application.
Innovations in Treating Sporotrichosis: Drug Repurposing and Lead Compound
Synthesis
Authors: de Carvalho Alcione S. , de Freitas Gabriel R.M. , Nicoletti Caroline D. , de C. da Silva Fernando , Futuro Débora O. , Ferreira Vitor F. , Ferreira Patricia G. 
Published: January 2024

Abstract:
Sporotrichosis, recognized by the World Health Organization (WHO) as a neglected
tropical disease and classified among significant fungal health concerns, remains
both underestimated and underreported. There is a profound impact of sporotrichosis on
public health, affecting both humans and domestic animals. The causative agents are fungi
within the Sporothrix genus, primarily transmitted through traumatic exposure to contaminated
soil, plants, decomposing materials, or through scratches from infected animals, notably
cats. While sporotrichosis is a global concern, its prevalence is particularly noteworthy
in tropical and subtropical regions. The limited treatment options for sporotrichosis, with
itraconazole as the preferred choice, underscore the challenges posed by fungal infections.
Issues such as toxicity and drug resistance further complicate effective management. Consequently,
this review aims to elucidate key objectives: identification of novel synthetic compounds revealed in
the literature, highlighting ongoing efforts to develop new treatments against sporotrichosis, examining promising
anti-sporothrix natural products, and providing an overview of endeavors to repurpose approved drugs. The
key findings from the study underscore the urgent need for diversified and effective drugs for the treatment of
Sporotrichosis.
Synthesis, Characterization, Molecular Docking Studies and Biological Evaluation of
Some Novel 3,5-disubstituted-1-phenyl-4,5-dihydro-1H-pyrazole Derivatives
Authors: Tok Fatih , Bayrak İlayda Rumeysa , Karakaraman Elif , Soysal İrem , Çakır Cansel , Tuna Kübra , Özgüven Serap Yılmaz , Sıcak Yusuf , Öztürk Mehmet , Koçyiğit-Kaymakçıoğlu Bedia 
Published: January 2024

Abstract:
In this study, some new pyrazoline derivatives bearing cyano or nitro groups were synthesized. The
structures of the compounds were characterized by IR, 1H-NMR, 13C-NMR and elemental analysis data.
The ABTS·+, DPPH·, CUPRAC and β-Carotene/linoleic acid assays were carried out to determine the antioxidant
activity of the synthesized pyrazolines. Compound P14 showed higher antioxidant activity than the standard
substance BHA with IC50 values of 1.71±0.31 μM and 0.29±0.04 μM in ABTS+ and β-carotene/linoleic acid
assays, respectively. Compound P12 also exhibited higher antioxidant activities than BHA with an IC50 value of
0.36±0.14 μM in β-carotene/linoleic acid analysis.
In activity studies of pyrazolines against cholinesterase (AChE and BChE), tyrosinase, α-amylase and α-
glucosidase, compound P1 (IC50 = 39.51±3.80 μM) showed higher activity against α-amylase and compounds
P5 and P12 displayed higher activity against α-glucosidase than acarbose with IC50 values of 14.09±0.62 and
83.26±2.57 μM, respectively.
The drug-like properties such as Lipinski and Veber, bioavailability and toxicity risks of the synthesized compounds
were also evaluated. The compounds were predicted to be compatible with Lipinski and Veber rules,
have high bioavailability and low toxicity profiles. Moreover, molecular docking studies were performed to better
understand the high activity of the compounds against a-amylase and a-glucosidase enzymes.
(S)-10-Hydroxycamptothecin Inhibits EMT-evoked Osteosarcoma Cell
Growth and Metastasis by Activating the HIPPO Signaling Pathway
Authors: Ma Xiaoping , Chang Junli , Sun Xingyuan , Zhou Chujie , Zhao Peng , Yang Yanping 
Published: January 2024

Background:
Osteosarcoma is the most common primary bone cancer in children and
adolescents with high metastatic ability.

Aim:
This study aimed to explore the inhibitory effects of (S)-10-hydroxycamptothecin (HCPT)
on osteosarcoma cell growth and metastasis as well as the underlying mechanism.

Methods:
The osteosarcoma cells of 143B and U-2 OS (U-2), treated with HCPT (20, 100, or 300
nM), underwent detections, such as CCK-8, flow cytometry, Transwell, wound healing, and immunoblotting. EMT-related key proteins, like N-cadherin, Snail, and Vimentin, were found to be
down-regulated, while E-cadherin was up-regulated dose-dependently in HCPT-exposed 143B
and U-2 cells. Additionally, incubation of 143B and U-2 cells with HCPT for 3 hours dosedependently reduced the expression ratios of p-LATS1/LATS1, p-MST1/MST1, p-YAP/YAP,
and p-TAZ/TAZ.

Results:
Taken together, our study has demonstrated HCPT to inhibit osteosarcoma growth and
metastasis potentially by activating the HIPPO signaling pathway and reversing EMT.

Conclusion:
HCPT might be a candidate agent for the prevention and treatment of osteosarcoma
Heparin Oligosaccharides as Vasoactive Intestinal Peptide Inhibitors via
their Binding Process Characterization
Authors: Li Meixin , Xue Yaqi , Chi Lianli , Jin Lan 
Published: January 2024

Background:
It has been proven that vasoactive intestinal peptide (VIP) was involved
in the pathogenesis of prostate cancer. Cardin et al. found that by an alanine scan, the heparin-binding site on VIP was exactly the same sequence in VIP and its receptor. Therefore, heparin could
competitively block the binding of VIP and its receptor. However, the structure-activity relationship between heparin and VIP has not been reported, especially in terms of the sequence and sulfation patterns of heparin oligosaccharides upon binding to VIP.

Objective:
The binding process between heparin oligosaccharides and VIPA variety of experiments was designed to study the structure-activity relationship between heparin oligosaccharides
and VIP.

Methods:
Heparin was enzymatically digested and purified to produce heparin oligosaccharides,
and the structures were characterized by NMR. The binding capacity between heparin oligosaccharides and VIP was analyzed by GMSA and ITC experiments. The binding between heparin oligosaccharides and VIP was simulated using a molecular docking program to show the
complex. ELISA assay was used to investigate the effect of non-anticoagulant heparin oligosaccharides on the VIP-mediated cAMP/PKA signaling pathway in vitro.

Results:
The results indicated that both the length and the sulfation pattern of heparin oligosaccharides affected its binding to VIP. VIP could induce the expression of cAMP at a higher
level in PC3 cells, which could be regulated by the interaction of heparin oligosaccharides and
VIP.

Conclusion:
The binding between heparin oligosaccharides and VIP could block the binding between VIP and its receptor on tumor cells. Downloading the regulation of the expression level of
cAMP could possibly further affect the subsequent activation of PKA. These non-anticoagulant heparin oligosaccharides may block the VIP-mediated cAMP/PKA signaling pathway and thus exert
their antitumor activity.
Targeting Ferroptosis: A Novel Strategy for the Treatment of Atherosclerosis
Authors: Zhang Yifan , Jiang Chengshi , Meng Ning 
Published: January 2024

Abstract:
Since ferroptosis was reported in 2012, its application prospects in various diseases have
been widely considered, initially as a treatment direction for tumors. Recent studies have shown that
ferroptosis is closely related to the occurrence and development of atherosclerosis. The primary
mechanism is to affect the occurrence and development of atherosclerosis through intracellular iron
homeostasis, ROS and lipid peroxide production and metabolism, and a variety of intracellular signaling
pathways. Inhibition of ferroptosis is effective in inhibiting the development of atherosclerosis,
and it can bring a new direction for treating atherosclerosis. In this review, we discuss the mechanism
of ferroptosis and focus on the relationship between ferroptosis and atherosclerosis, summarize
the different types of ferroptosis inhibitors that have been widely studied, and discuss some issues
worthy of attention in the treatment of atherosclerosis by targeting ferroptosis.
Pharmacological Treatment of Heart Failure: Recent Advances
Authors: Chan Jonathan C.H. , Siddiqui Areeb 
Published: January 2024

Background:
Heart failure is a clinical condition with high mortality and morbidity
that occurs when the heart is unable to pump enough blood to meet the metabolic demands of
the body. The pharmacological management of heart failure has been revolutionized over the
past decade with novel treatments.

Objective:
The aim of the review is to highlight the recent pharmacological advances in the
management of heart failure.

Results:
Sodium-glucose cotransporter-2 inhibitor (SGLT2i), iron carboxymaltose, finerenone,
omecamtiv mecarbil, and vericiguat have been shown to reduce hospitalization for heart failure.
However, only SGLT2i, vericiguat, and omecamtiv mecarbil have been shown to reduce cardiovascular death. Finerenone has been shown to reduce cardiovascular events and renal adverse
outcomes in patients with diabetes and kidney disease.
Currently, only SGLT2i has been studied in patients beyond the heart failure-reduced ejection
fraction population.

Conclusion:
The current quadruple therapy in the treatment of heart failure has demonstrated a
reduction in the hospitalization of patients and a decrease in mortality associated with the condition. Individualized heart failure therapy research have shown some benefit in select heart failure patients. Further research on novel therapies will help improve heart failure patient outcomes.
The Sentinel Node and Occult Lesion Localization (SNOLL) Technique Using a
Single Radiopharmaceutical in Non-palpable Breast Lesions
Authors: Okudan Berna , Seven Bedri , Arıcan Pelin 
Published: January 2024

Background::
In order to perform a full surgical resection on non-palpable breast lesions, a current method necessitates correct intraoperative localization.
Additionally, because it is an important prognostic factor for these patients, the examination of the lymph node status is crucial.

Objective::
The aim of this study was to evaluate the efficiency of the sentinel node and occult lesion localization (SNOLL) technique in localizing nonpalpable
breast lesions together with sentinel lymph node (SLN) using a single radiotracer, that is, nanocolloid particles of human serum albumin
(NC) labeled with technetium-99m (99mTc).

Methods::
39 patients were included, each having a single non-palpable breast lesion and clinically no evidence of axillary disease. Patients received 99mTc-
NC intratumorally on the same day as surgery under the guidance of ultrasound. Planar and single-photon emission computed
tomography/computed tomography lymphoscintigraphy were performed to localize the breast lesion and the SLN. The occult breast lesion and
SLN were both localized using a hand-held gamma-probe, which was also utilized to determine the optimal access pathway for surgery. In order to
ensure a radical treatment in a single surgical session and reduce the amount of normal tissue that would need to be removed, the surgical field was
checked with the gamma probe after the specimen was removed to confirm the lack of residual sources of considerable radioactivity.

Results::
Breast lesions were successfully localized and removed in all patients. Pathological findings revealed breast carcinoma in 11/39 patients (28%) and
benign lesions in 28 (72%). Axillary SLNs were detected in 31/39 (79.5%) patients. The metastatic involvement of SLN was only seen in two
cases.

Conclusion::
While the identification rate of the SNOLL technique performed with an intratumoral injection of 99mTc-NC as the sole radiotracer in non-palpable
breast lesions was great, it was not fully satisfactory in SLNs.
Pharmacokinetic Studies of Gypenoside XLVI in Rat Plasma using
UPLC-MS/MS Method
Authors: Li Han , Yang Aiping , Yang Meng , Zhou Fengjuan , Zhang Rui , Zheng Zongping , Wang Xiachang 
Published: January 2024

Background:
Gynostemma pentaphyllum (Thunb.) Makino has been linked to a number
of pharmacological benefits, including hepatoprotective, anti-inflammatory, antioxidative, and antihyperlipidemic
activities. Gypenoside XLVI (Gyp XLVI) was a significant triterpenoid saponin reported
from a sweet-taste varietas G. pentaphyllum, which has inhibitory effects and causes apoptosis
on human hepatocytes and hepatoma cells.

Methods:
A quick, precise, and sensitive method for the quantification and pharmacokinetic research
of Gyp XLVI in rats was developed utilizing UPLC-MS/MS. When extracting blood
samples, protein was precipitated using methanol. An internal standard (IS) was employed,
which was tolbutamide. For the chromatographic separation, a C18 column (Waters Acquity)
was used with mobile phases as 0.1% formic acid and acetonitrile. Multiple reaction monitoring
was used as MS detection manner with electrospray ionization in negative mode.

Results:
Gyp XLVI had good linearity in the 1.36‒1000.00 ng/mL concentration range. The intra-
day and inter-day precisions (RSD%) and accuracy (RE%) were less than 12.7% or 8.29%,
respectively. Gyp XLVI’s extraction recovery ranged from 89.5% to 104.2%. The matrix effects
ranged from 75.3%‒94.3%. The outcomes of matrix interference and recovery investigations
complied with the necessary variability limitations. After three hours at room temperature
(25°C), 24 hours in an auto-sampler (4°C), three freeze-thaw cycles, and 30 days of storage
at -20°C, the analyte in rat plasma remained stable. Gyp XLVI pharmacokinetic investigations
and quantification were conducted using the validated method. The AUC0-∞ values for intravenous
administration (1 mg/kg) and oral administration (10 mg/kg) were 2213.9 ± 561.5
ng·h/mL and 1032.8 ± 334.8 ng·h/mL, respectively. Gyp XLVI had a half-life (t1/2z) of 2.5 ±
0.4 h in the rats after intravenous injection and 4.2 ± 0.9 h after oral administrations. Gyp
XLVI had a comparatively low oral bioavailability of 4.56%.

Conclusion:
This is the first time that Gyp XLVI’s pharmacokinetic properties have been investigated
through various administration routes. These findings will aid in our understanding
of how Gyp XLVI was metabolized in rats and how it behaved pharmacologically in vivo.
Anticancer Properties of Baicalin against Breast Cancer and other
Gynecological Cancers: Therapeutic Opportunities based on Underlying
Mechanisms
Authors: Pourhanifeh Mohammad Hossein , Farrokhi-Kebria Hossein , Mostanadi Parsa , Farkhondeh Tahereh , Samarghandian Saeed 
Published: January 2024

Abstract:
Gynecological cancers are serious life-threatening diseases responsible for high morbidity and mortality around the world. Chemotherapy,
radiotherapy, and surgery are considered standard therapeutic modalities for these cancers. Since the mentioned treatments have undesirable side
effects and are not effective enough, further attempts are required to explore potent complementary and/or alternative treatments. This study was
designed to review and discuss the anticancer potentials of baicalin against gynecological cancers based on causal mechanisms and underlying
pathways. Traditional medicine has been used for thousands of years in the therapy of diverse human diseases. The therapeutic effects of natural
compounds like baicalin have been widely investigated in cancer therapy. Baicalin was effective against gynecological cancers by regulating key
cellular mechanisms, including apoptosis, autophagy, and angiogenesis. Baicalin exerted its anticancer property by regulating most molecular
signaling pathways, including PI3K/Akt/mTOR, NFκB, MAPK/ERK, and Wnt/β-catenin. However, more numerous experimental and clinical
studies should be designed to find the efficacy of baicalin and the related mechanisms of action.
Challenges and Opportunities in Mental Health Care for
Transitional Age Youth (TAY): Lessons Learned from the
COVID-19 Pandemic
Authors: Kim Hyun Jung , Wilson Cynthia , Van Deusen Timothy , Millard Hun , Qayyum Zheala , Parke Susan 
Published: January 2024

Abstract:
COVID-19, caused by the SARS-CoV-2 virus, began in late 2019. On
March 11th, 2020, the World Health Organization (WHO) declared the virus a
pandemic, and by March 13th, 2020, the United States (US) government declared the
pandemic a national emergency and, subsequently, a global pandemic. Since then, the
world has experienced an upheaval affecting every age group in almost every aspect
of life. This was particularly true for young people. Globally, a number of studies
indicated that the COVID-19 pandemic has had a significant impact on youth mental
health measures. In the US, the Centers for Disease Control and Prevention (CDC)
2022 report showed that more than a third of high school students reported that they
experienced poor mental health during the pandemic, and 44 percent reported feeling
persistently sad or hopeless in the last 12 months. More than half (55 percent)
reported experiencing emotional abuse by a parent or other adult at home, and 11
percent reported experiencing physical abuse. In addition, more than a quarter (29
percent) reported that a parent or other adult in the home lost their job. The pandemic
upended not only daily life but also healthcare delivery throughout the world. Its vast
impact on the healthcare system has disproportionately affected transitional age youth
(TAY) between 15 to 25 years old. While the pandemic caused unprecedented
changes and challenges, it was also a learning experience that deepened our
understanding of our system of care, its strengths and vulnerabilities. This paper will
discuss many challenges and opportunities associated with the delivery of psychiatric
services for TAY in college mental health, emergency departments, and inpatient and
outpatient settings, as well as in specialized programs, such as those for early
psychotic disorders.
Strengthening Youth Resilience via Social Work Internship Placements
within Boys and Girls Clubs: A Process Evaluation
Authors: Taylor Michelle , Madrigal Leilani , Dolezal-Ng Jeremy , Cox Tory 
Published: January 2024

Background:
There is a growing mental health crisis among youth in the United
States. The objective of the current study was to conduct a process evaluation of Strengthening
Youth Resilience (SYR), a unique program aimed at decreasing youth anxiety and depression via
social work internship placements within after-school programs in three historically underserved
communities in a large city in Southern California. The SYR program utilizes the School Social
Work Practice Model as a framework for interacting with youth within community settings by
providing a tiered system of service delivery.

Methods:
Focus group discussions and interviews were used to examine the unique perspectives
of social work interns, program leaders, and Boys and Girls Clubs of America (BGCA) staff.

Results:
Results emphasized the importance of trust, clear communication, and shared decisionmaking as a foundation for successful program site integration. Additionally, several unanticipated barriers to implementation arose, including difficulty obtaining informed parental consent to
work individually with youth, challenges aligning internship schedules with the fluid structure of
after-school programs, and the need for a private welcoming space to work.

Conclusion:
In conclusion, the SYR program successfully integrated within BGCA sites and was
able to provide support to youth. BGCA sites expressed great satisfaction with the program and
were eager to continue and expand upon their collaboration with the local university