bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferumoxytol promotes hematopoietic stem cell post-injury regeneration as a ROS scavenger
Authors: Qian Pengxu , Wang Qiwei , Qian Wenchang , Mao Yu , Gao Zhenyue , Chen Yuxuan , Zeng Xin , Lu Huan , Jiang Lingli , Li Jinxin , Han Yingli , Gu Ning 
Published: July 2024

Abstract

Under stress conditions such as ex vivo culture, chemotherapy, irradiation and infection, hematopoietic stem cells (HSCs) actively divide to maintain blood cell production, during which reactive oxygen species (ROS) produces and accumulates, and eventually causes HSC exhaustion and hematopoietic failure. However, it remains largely elusive how to relieve ROS in stressed HSCs and facilitate the hematopoietic post-injury regeneration. Here, we report that ferumoxytol (Feraheme, FMT), an FDA-approved nanodrug, is a powerful ROS scavenger and could recover the functions of stress HSCs. Due to lower levels of TFEB expression and lysosomal activity in HSCs as compared to leukemia cells, FMT is less degraded and more distributed in the cytoplasm. Under ex vivo culture, chemotherapy and irradiation conditions, FMT effectively mitigates ROS and apoptosis in stressed HSCs and promotes hematopoietic post-injury regeneration. Mechanistically, the catalase (CAT)-like activity of FMT reduces intracellular levels of H2O2 and diminishes H2O2-induced DNA damage and cytotoxicity. Finally, FMT maintains long-term regenerative capacity of transplanted HSCs in pre-conditioned leukemic mice, and has an excellent biosafety profile. Collectively, our study deciphers the role of nanozymes in hematopoietic regeneration and highlights the potential clinical applications of FMT in promoting the stress-induced hematopoietic recovery.
Structure of the Nipah virus polymerase complex
Authors: Grimes Jonathan ,   Esra Balıkçı1, Günl Franziska , Carrique Loic , Keown Jeremy , Fodor Ervin 
Published: July 2024

Abstract

Nipah virus poses a recurring threat, causing severe respiratory and neurological disease in Southeast Asia. Since its first identification in Malaysia in 1998 and a subsequent outbreak in Singapore in early 1999, the virus has emerged as a highly virulent zoonotic paramyxovirus. Despite its lethality, there is currently no approved treatment for Nipah virus infection. The viral polymerase complex, composed of the large polymerase protein (L) and the phosphoprotein (P), is responsible for the replication of the viral RNA genome and transcription of viral genes. However, the mechanisms by which the L and P components perform these activities remain unknown. Here, we describe the structures of the Nipah virus L-P polymerase complex at a 2.5 Å resolution and the L protein’s Connecting Domain (CD) at a 1.85 Å resolution, determined by cryo-electron microscopy (cryo-EM) and X-ray crystallography, respectively. The L-P complex structure reveals the organization of the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, and how the P protein, which forms a tetramer, interacts with the RdRp domain of the L protein. Furthermore, the CD structure reveals the binding of Mg ions, which likely contribute to the functionality of the PRNTase domain. These findings offer insights into the structural details of the L-P polymerase complex and the molecular interactions between L and P, shedding light on the mechanisms of the replication machinery. This work will underpin efforts to develop antiviral drugs that target the polymerase complex of Nipah virus.
Ramsay hunt syndrome: A case report
Authors: sabouri Reza 
Published: July 2024

Abstract

Background:
Ramsay-Hunt syndrome (RSH) is a rare clinical condition characterized by herpes zoster oticus and ipslilateral facial nerve paralysis caused by reactivation of latent varicella-zoster virus( VZV ) in the sensory root of geniculate ganglia. This syndrome must be distinguished from other causes of facial palsy such as Bell’s palsy, stroke, Lyme disease and malignancies.
Accurate dignosis and treatment in the first 72 hours of are crucial to improve the prognosis and to prevent later complications including postherpetic neuralgia and corneal damage.
Case Report:
A 72-year-old female without any past medical history was admitted to emergency center of Vali Asr Hospital in Zanjan with hearing loss, ererythematous papules on the right external ear, otalgia, vertigo and dysgeusia. One day after hospitalization, the patient developed unilateral right-sided facial palsy and crusted erythematous papules on the right external ear.
Conclusion:
Ramsay-Hunt syndrome is an uncommon peripheral neuropathy of the facial nerve caused by reactivation of VZV in the geniculate ganglion. Most cases occur in immunocompromised and elderly. Pharmacological interventions can reduce recovery time and prevent complications. Specialists are not unanimous on the choice of medication, dosage and the duration of therapy, thus more research is warranted.
TRPV4 subserves physiological and pathological elevations in intraocular pressure
Authors: Redmon Sarah N. , Lakk Monika , Tseng Yun-Ting , Rudzitis Cristopher N. , Searle Jordan E. , Ahmed Feryan , Unser Andrea , Borrás Teresa , Torrejon Karen , Krizaj David 
Published: July 2024

Abstract

Ocular hypertension (OHT) caused by mechanical stress and chronic glucocorticoid exposure reduces the hydraulic permeability of the conventional outflow pathway. It increases the risk for irreversible vision loss, yet healthy individuals experience nightly intraocular pressure (IOP) elevations without adverse lifetime effects. It is not known which pressure sensors regulate physiological vs. pathological OHT nor how they impact the permeability of the principal drainage pathway through the trabecular meshwork (TM). We report that OHT induced by the circadian rhythm, occlusion of the iridocorneal angle and glucocorticoids requires activation of TRPV4, a stretch-activated cation channel. Wild-type mice responded to nocturnal topical administration of the agonist GSK1016790A with IOP lowering, while intracameral injection of the agonist elevated diurnal IOP. Microinjection of TRPV4 antagonists HC067047 and GSK2193874 lowered IOP during the nocturnal OHT phase and in hypertensive eyes treated with steroids or injection of polystyrene microbeads. Conventional outflow-specific Trpv4 knockdown induced partial IOP lowering in mice with occluded iridocorneal angle and protected retinal neurons from pressure injury. Indicating a central role for TRPV4-dependent mechanosensing in trabecular outflow, HC067047 doubled the outflow facility in TM-populated steroid-treated 3D nanoscaffolds. Tonic TRPV4 signaling thus represents a fundamental property of TM biology as a driver of increased in vitroand in vivo outflow resistance. The TRPV4-dependence of OHT under conditions that mimic primary and secondary glaucomas could be explored as a novel target for glaucoma treatments.
Is BDSM in the eye of the beholder? Variations in Conventional and non-Conventional Sexual Behaviors by Self-Identification vs. BDSM Practice Frequency in the General Population
Authors: Quintana Gonzalo R. , Aguilera Elías , Santibáñez-Palma Francisco , Escudero-Pastén Javier , Consortium CSSS Research , Barrientos Jaime 
Published: July 2024

Abstract

Studies concerning BDSM sexual practices within the general population often use different criteria to differentiate between those who practice or identify by them vs. those who do not. Yet, using criteria such as BDSM self-identification or measuring the actual frequency of these practices incur in limitations that likely over or underestimate the prevalence of these behaviors, making the interpretation and comparison of the results inaccurate across studies. Therefore, the following study examined the magnitude of difference between using BDSM self-identification vs. BDSM practice frequency as criteria, across conventional and non-conventional sexual behaviors, as well as sexual function in the general population. This study was composed of 3904 Chilean men and women. Sexual function was measured using the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI). Results revealed differences in the prevalence of BDSM individuals by criteria varying by behavior, whereas correlations between BDSM criteria were positive, yet of low magnitude. The practice frequency criterion yielded a larger prevalence of BDSM practitioners, with higher engagement in BDSM-specific behaviors, greater pleasure derived from these practices, and better sexual function compared to non-BDSM individuals, especially among highly frequent practitioners. Lastly, differences in sexual function dimensions according to BDSM criteria were found more frequently, and by a larger magnitude, through the BDSM practice frequency criterion, especially in women, compared to non-BDSM people. This study findings demonstrate the importance of considering both self-identification and practice frequency criteria in understanding BDSM and its implications for sexual health in future studies.
A hypothalamic circuit for circadian regulation of corticosterone secretion
Authors: Ramirez-Plascencia Oscar D. , De Luca Roberto , Machado Natalia L. S. , Eghlidi Dominique , Khanday Mudasir A. , Bandaru Sathyajit S. , Raffin Francesca , Vujovic Nina , Arrigoni Elda , Saper Clifford B. 
Published: July 2024

Abstract

The secretion of cortisol in humans and corticosterone (Cort) in rodents follows a daily rhythm which is important in readying the individual for the daily active cycle and is impaired in chronic depression. This rhythm is orchestrated by the suprachiasmatic nucleus (SCN) which governs the activity of neurons in the paraventricular nucleus of the hypothalamus that produce the corticotropin-releasing hormone (PVHCRH neurons). The dorsomedial nucleus of the hypothalamus (DMH) serves as a crucial intermediary, being innervated by the SCN both directly and via relays in the subparaventricular zone, and projecting axons to the PVH, thereby exerting influence over the cortisol/corticosterone rhythm. However, the role and synaptic mechanisms by which DMH neurons regulate the daily rhythm of Cort secretion has not been explored. We found that either ablating or acutely inhibiting the DMH glutamatergic (DMHVglut2) neurons resulted in a 40-70% reduction in the daily peak of Cort. Deletion of the Vglut2 gene within the DMH produced a similar effect, highlighting the indispensable role of glutamatergic signaling. Chemogenetic stimulation of DMHVglut2 neurons led to an increase of Cort levels, and optogenetic activation of their terminals in the PVH in hypothalamic slices directly activated PVHCRH neurons through glutamate release (the DMHVglut2 → PVHCRH pathway). Similarly, ablating, inhibiting, or disrupting GABA transmission by DMH GABAergic (DMHVgat) neurons diminished the circadian peak of Cort, particularly under constant darkness conditions. Chemogenetic stimulation of DMHVgat neurons increased Cort, although with a lower magnitude compared to DMHVglut2 neuron stimulation, suggesting a role in disinhibiting PVHCRH neurons. Supporting this hypothesis, we found that rostral DMHVgat neurons project directly to GABAergic neurons in the caudal ventral part of the PVH and adjacent peri-PVH area (cvPVH), which directly inhibit PVHCRH neurons, and that activating the DMHVgat terminals in the cvPVH in brain slices reduced GABAergic afferent input onto the PVHCRH neurons. Finally, ablation of cvPVHVgat neurons resulted in increased Cort release at the onset of the active phase, affirming the pivotal role of the DMHVgat → cvPVHVgat → PVHCRH pathway in Cort secretion. In summary, our study delineates two parallel pathways transmitting temporal information to PVHCRH neurons, collectively orchestrating the daily surge in Cort in anticipation of the active phase. These findings are crucial to understand the neural circuits regulating Cort secretion, shedding light on the mechanisms governing this physiological process and the coordinated interplay between SCN, DMH, and PVH.
ZIF-8/Cellulose Nanocomposites: Scalable Electrode Materials for Solar Powered Capacitive Deionization Desalination
Authors: khanghah zahra kamali 
Published: July 2024

Abstract

Saline water poses a significant challenge specifically for agricultural irrigation. Solar-powered capacitive deionization (CDI) offers an energy-efficient solution for desalination. This study explores zeolite imidazolate framework/cellulose acetate (ZIF-8/CA) nanocomposite electrodes as a promising option for solar-powered CDI technology. This nanocomposite boasts several advantages, including high surface area, simple synthesis, and well-developed porosity, making it scalable and potentially commercially viable for desalination applications. Notably, the ZIF-8 component exhibits homogenous intergrowth onto the cellulose surface, forming a ten-layered structure. To evaluate their performance, electrochemical performance was assessed through cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) within a CDI unit. The ZIF-8/CA nanocomposite demonstrates a high specific capacitance of approximately 156.20 F/g, suggesting its potential as a promising, scalable, and eco-friendly adsorbent for CDI, particularly well-suited for agricultural applications.
Hybrid approach of Hypothesis Testing to test the mean difference between two groups utilising Gaussian Distribution and Confidence Interval
Authors: Hasan Kazi Sakib 
Published: July 2024

Abstract

This paper presents an easier and new robust method for hypothesis testing to conclude significant mean differences between two independent or paired samples using the concepts of location, variability, confidence intervals and Gaussian distribution. For hypothesis testing of two samples, t-test is widely used. Beside this, Wilcoxon signed-rank test and often permutation test is also conducted. Each of these methods have their own rigorousness and drawbacks for which general people and non-statistics students often find it hard to conduct experiments using these. To fix these issues, a new method of hypothesis testing is proposed in this paper that basically utilises the properties of normally distributed data and resampling, and is relatively easier to calculate using only pen and paper. The time complexity analysis of each program is also conducted to give a concise overview about which hypothesis testing algorithm is more efficient and faster to execute, since statisticians use a lot of software nowadays for their analytical tasks.
Ferrate as a coagulant prior to sand filters treating secondary wastewater effluent for reuse
Authors: Gaber Omar , Elbarki Walid , Fayed Mai , Aly Samia Ahmed Abdelrahman 
Published: July 2024

ABSTRACT

Wastewater reuse is one of the crucial water resources in Egypt due to the ongoing need to increase water resources and close the supply-demand gap. In this study, a new coagulant has been investigated before sand filters as an advanced wastewater treatment method. The sand filter pilot was run at a hydraulic loading rate of 0.75 m/h and two different dosages of three coagulants (Alum, FeCl3, and Ferrate VI) were selected using the jar tests. The sand filter without coagulant removed 12% of BOD5 and 70% of turbidity. Applying in-line coagulation before the sand filter provided effluents with better quality, especially for turbidity, organics, and microorganisms. Ferrate provided the highest removal of turbidity (90%) and BOD5 (93%) at very low dosages and lower costs compared with other coagulants, however, it adversely impacted both conductivity and dissolved solids. A significant effect on reducing bacteria was obtained with 40.0 mg/L of alum. According to the study's findings, the ferrate coagulant enhanced the sand filter's performance producing effluents with high quality, enabling it to meet strict water reuse regulations as well as aquatic environmental and health preservations.
LAMTOR5-AS1 Regulates Chemotherapy-induced Oxidative Stress via the miR-34a-3p/SIRT1/HNF4A Axis in Osteosarcoma Cells
Authors: Zhao Fangfang , Wei Chao , Pu Youguang , Zang Chunbao 
Published: July 2024

Introduction:
Osteosarcoma (OS) drug resistance often leads to a poor prognosis.
Recent evidence suggests that long non-coding RNAs play a crucial role in regulating
tumor drug resistance.

Method:
This study aims to investigate the involvement of lncRNA LAMTOR5-AS1 in
OS. RNA-seq and qRT-PCR were performed, and the relationship between LAMTOR5-
AS1, miR-34a-3p, SIRT1, and HNF4A was determined using Dual-luciferase reporter
assays and RNA immunoprecipitation assays. Gain- and loss-of-function assays
were measured using CCK-8, cell proliferation, and colony formation assays.

Result:
The study found that the dysregulated LAMTOR5-AS1 acts as a competing endogenous
RNA (ceRNA) and competitively protects the HNF4A mRNA 3’ UTR from
miR-34a-3p. In addition, in vitro functional studies showed that HNF4A can physically
interact with SIRT1 to synergistically inhibit osteosarcoma drug resistance. The study
found that LAMTOR5-AS1 regulates drug resistance in osteosarcoma through the
miR-34a-3p/HNF4A or miR-34a-3p/SIRT1/HNF4A axis.

Conclusion:
These findings offer new insights into lncRNA-mediated drug resistance in
cancer and may serve as potential biomarkers for cancer therapy.
Dental Caries: Unveiling the State-of-the-art Insights and Crafting Hypotheses for Oral Health
Authors: Kaur Palwinder , Vyas Manish , Sharma Sandeep 
Published: July 2024

:
The pathophysiological understanding of dental caries explains that the primary factor responsible
is linked to an imbalance in microbial composition within the oral cavity, stemming from both artificial and natural
sources. Streptococcus mutans (S. mutans) is the most accountable and prevalent pathogen for caries development
among the diverse pool. S. mutans, an acidogenic bacterium, lowers oral pH through the metabolic
conversion of dietary sugar into organic acids, leading to enamel demineralization and dental caries. Numerous
antibacterial interventions have been employed in the past to address this issue. However, adopting such
an approach poses the risk of exacerbating concerns related to Antimicrobial Resistance (AMR) and long-term
oral cytotoxicity. In response to this, a sustainable strategy is suggested, involving the utilization of L-Arginine
(L-Arg) as a probiotic nutrient supplement for non-pathogenic microbes. It will help in creating a natural
competitive environment against the pathogenic microbes responsible for initiating dental caries. The hypothesis
involves utilizing a combination of a nutrient supplement and the repurposed drug Piceatannol, specifically
for its anti-biofilm properties. This combination synergistically improves the effectiveness of the therapy by
converting the complex microbial biofilm into a planktonic state.
In silico Screening and in vitro Cytotoxicity Study of Achyranthes aspera Phytochemicals Against Oral Cancer: A Possible Step towards the
Development of Anti-cancer Agents
Authors: Israr Juveriya , Khan Mohsin Ali , Misra Sankalp , Gupta Divya , Singh Nootan , Ahmad Rumana , Siddiqui Sahabjada 
Published: July 2024

Background:
Oral cancer poses a significant threat to public health worldwide. In
addition, because many chemotherapy treatments have negative side effects, natural herbs may
be beneficial for oral cancer therapy. Achyranthes aspera (AA), a potential medicinal herb, exerts
various pharmacological and biochemical activities.

Objective:
The present study aimed to predict the anti-oral cancer potential of AA using in silico
tools and cell death by in vitro testing.

Methods:
A total of fourteen bioactive constituents from AA herb were selected using phytochemical
databases. The toxicity of AA herb extract was analysed through MTT assay against
oral carcinoma A253 cell line. The binding activities of the phytocomponents against serine/
threonine-specific protein kinases isoforms, namely Akt1 (PDB ID: 3qkk) and Akt2 (PDB
ID: 2jdo) proteins, were analysed using Discovery Studio 2021 and PyRx docking software.

Results:
Cell viability data revealed that AA extract decreased the viability and reduced the
number of live cells of the oral carcinoma A253 cell line in a dose-dependent manner. The halfmaximal
concentration (IC50) value of AA was assessed as 204.74 μg/ml. Based on binding affinity,
saponin C (-CDOCKER energy = -77.9862), oleanolic acid (-CDOCKER energy = -
49.4349), spinasterol (-CDOCKER energy = -38.1246), 36,47-dihydroxyhenpentacontan-4-one
(-CDOCKER energy = -32.4386), and 20-hydroxyecdysone (-CDOCKER energy = -31.9138)
were identified as the best compounds against Akt1, while, compounds saponin C (-CDOCKER
energy = -134.412), oleanolic acid (-CDOCKER energy = -90.0846), spinasterol (-CDOCKER
energy = -78.3213), 20-hydroxyecdysone (-CDOCKER energy = -80.1049), and ecdysone (-
CDOCKER energy = -73.3885) were identified as Akt2 inhibitors. These top compounds fulfilled
drug score values, pharmacokinetic and physicochemical characteristics, and druglikeness
parameters.

Conclusion:
The present findings reveal that the lead phytomolecules of AA could be effective
and developed as a prospective drug against oral cancer.
Network Pharmacology and Molecular Docking Integrated with Molecular Dynamics Simulations Investigate the Pharmacological Mechanism of
Yinchenhao Decoction in the Treatment of Non-alcoholic Fatty Liver Disease
Authors: Yang Rong , Jiang Dansheng , Xu Hongling , Yang Huili , Feng Lian , Wu Qibiao , Xing Yufeng 
Published: July 2024

Background:
Non-Alcoholic Fatty Liver Disease (NAFLD) has become a significant
health and economic burden globally. Yinchenhao decoction (YCHD) is a traditional Chinese
medicine formula that has been validated to exert therapeutic effects on NAFLD.

Object:
The current study aimed to explore the pharmacological mechanisms of YCHD on
NAFLD and further identify the potential active compounds acting on the main targets.

Methods:
Compounds in YCHD were screened and collected from TCMSP and published studies,
and their corresponding targets were obtained from the SWISS and SEA databases.
NAFLD-related targets were searched in the GeneCards and DisGeNet databases. The “compound-
intersection target” network was constructed to recognize the key compounds. Moreover,
a PPI network was constructed to identify potential targets. GO and KEGG analyses were performed
to enrich the functional information of the intersection targets. Then, molecular docking
was used to identify the most promising compounds and targets. Finally, molecular dynamics
(MD) simulations were performed to verify the binding affinity of the most potential compounds
with the key targets.

Results:
A total of 53 compounds and 556 corresponding drug targets were collected. Moreover,
2684 NAFLD-related targets were obtained, and 201 intersection targets were identified.
Biological processes, including the apoptotic process, inflammatory response, xenobiotic metabolic
process, and regulation of MAP kinase activity, were closely related to the treatment of
NAFLD. Metabolic pathways, non-alcoholic fatty liver disease, the MAPK signaling pathway,
and the PI3K-Akt signaling pathway were found to be the key pathways. Molecular docking
showed that quercetin and isorhamnetin were the potential active compounds, while AKT1,
IL1B, and PPARG were the most promising targets. MD simulations further verified that the
binding of PPARG-isorhamnetin (-35.96 ± 1.64 kcal/mol) and AKT1-quercetin (-31.47 ± 1.49
kcal/mol) was due to their lowest binding free energy.

Conclusion:
This study demonstrated that YCHD exerts therapeutic effects for the treatment of
NAFLD through multiple targets and pathways, providing a theoretical basis for further pharmacological
research on the potential mechanisms of YCHD in NAFLD.