bluuebunny/crossref_metadata_2025 huggingface dataset:
Irreversible glacier change and trough water for centuries after overshooting 1.5°C
Authors: Schuster Lilian , Maussion Fabien , Rounce David , Ultee Lizz , Schmitt Patrick , Lacroix Fabrice , Frölicher Thomas , Schleussner Carl-Friedrich
Published: September 2024

Due to past climate inaction, exceeding a global mean temperature level of 1.5°C above pre-industrial levels has become a distinct possibility. Yet the consequences of such an overshoot are not well understood, including mountain glaciers' contribution to rising sea levels and regional water availability. Here we show that exceeding and then returning to the 1.5°C Paris Agreement limit has irreversible consequences for glacier mass and runoff over centuries. Novel global climate and glacier simulations project that a 3.0°C peak and decline scenario leads to 11% additional loss in global glacier mass by 2500 compared to limiting warming to 1.5°C without overshoot. In basins where glaciers regrow after peak temperature, glacier runoff reduces further than if the glaciers would stabilise, a newly documented phenomenon we call ″trough water″. Half of the studied glaciated basins show a lower glacier contribution to runoff with overshoot than without for decades to centuries post peak warming. These previously undocumented risks to glacier mass loss and runoff underscore the urgency of near-term emission reductions and limiting any potential climate overshoot.
Electrochemically-enhanced nuclear fusion of deuterium
Authors: Berlinguette Curtis , Chen Kuo-Yi , Schauer Phil , Issinski Sergey , Garcia Fatima H. , Oldford Ryan , Egoriti Luca , Higashino Shota , Maiwald Jannis , Vakili Aref E. , Wen Yunzhou , Koh Joseph , Schenkel Thomas , Stolar Monika , Brown Amanda K.
Published: September 2024

The ultimate goal of nuclear fusion research is to achieve a reaction that generates more energy than it consumes. Fuels such as deuterium need to be confined to increase the collision probability of particles. We therefore set out to investigate whether electrochemically loading a metal lattice with deuterium fuel could increase the probability of nuclear fusion events. Here, we report a benchtop fusion reactor that enabled us to bombard a palladium metal target with deuterium ions. These deuterium ions undergo deuterium-deuterium (D-D) fusion reactions within the palladium metal. We showed that the in situ electrochemical loading of deuterium into the palladium target resulted in a 15(2)% increase in D-D fusion rates. This experiment shows how electrochemical reactions at the eV energy scale can impact nuclear reactions at the MeV energy scale.
Contrasting human influences that shaped the vegetation of the Upano Valley, Ecuador.
Authors: Bush Mark , Sales Rachel , Neill David , León-Yánez Susana , Sinkler Wyllana , Stanley Amie , Bennett Isabel , Gomes Bianca Tacoronte , Land Klaas , McMichael Crystal
Published: September 2024

Long histories of human occupation are emerging for the wet forests of the Andean flank, even ones that are apparently ‘pristine’. The past habitations were societally and temporally complex with sophisticated cultures emerging, flourishing, and disappearing. The Upano River in eastern Ecuador supported such cultures, and yet the timing of occupation and whether their impact on the local ecosystem resulted in lasting ecological changes is not known. Here, using paleoecological reconstructions from Lake Cormorán, located immediately adjacent to the Upano Valley and within 5 km of abandoned mound complexes, we provide a timeline of human influence spanning the last 2770 years. We document the onset of maize cultivation c. 570 BCE, changes in land use within the occupation phase, with evidence of slash-and-burn, slash-and-mulch and silviculture. A gradual decline in forest exploitation presaged an apparent abandonment of the site c. 550 CE. A much later wave of land use that began about 1500 CE, coupled with a regional transition to a wetter climate, produced a distinctive forest composition unique to the last 120 years.
Macroeconomics Dynamics: Exploring the Impact of Stock Market Development on Economic Growth in Mali
Authors: CISSE Boubacar Amadou , TEME Aminata , KEITA Salimou , SÖNMEZ Yahya
Published: September 2024

Economic growth is often influenced by various factors, with stock market development playing a crucial role. This study investigates the relationship between the stock market development, specifically the Bourse Régionale des Valeurs Mobilières (BRVM), and economic growth in Mali. The BRVM serves eight West African countries, including Mali, and its development may impact regional economies. Utilizing monthly data from January 2009 to December 2020, this research examines the effects of BRVM Market Capitalization, BRVM Composite Index, Capital Flow, and Inflation on Mali's Gross Domestic Product (GDP). The study employs an Autoregressive Distributed Lag (ARDL) model and Vector Error Correction (VEC) model to analyze both short-run and long-run relationships. Findings suggest a significant long-run relationship between stock market development and economic growth in Mali, with inflation and capital flow having negative impacts, while market capitalization and the BRVM Composite Index show positive but less significant effects. The study contributes to understanding the macroeconomic dynamics within West African economies and the importance of stock market development in promoting economic growth.
Gel: E02, E20, O10, F43
Super-resolution upgrade for deep tissue imaging featuring easy implementation
Authors: Hellerer Thomas , Byers Patrick , Kellerer Thomas , Li Miaomiao , Chen Zhifen , Huser Thomas
Published: September 2024

Deep tissue imaging with high contrast close to or even below the optical resolution limit is still challenging due to optical aberrations and scattering introduced by dense biological samples. This results in high complexity and cost of microscopes that can facilitate such challenges. Here, we demonstrate an easy to implement method to turn most two-photon laser-scanning microscopes into a super-resolution microscope for deep tissue imaging. We realize this by adding inexpensive optical devices, namely a cylindrical lens, a field rotator, and a sCMOS camera to these systems. By combining two-photon excitation with patterned line-scanning and subsequent image reconstruction, we achieve imaging of subcellular structures in Pinus radiata, mouse heart muscle and zebrafish. In addition, the penetration depth of super-resolved imaging in highly scattering tissue is considerably extended by using the camera's lightsheet shutter mode. The flexibility of our method allows the examination of a variety of thick samples with a free choice of fluorescent markers and microscope objective lenses. Thus, with an inexpensive modification of a multi-photon microscope, an up to twofold resolution enhancement is demonstrated down to at least 70 µm deep in tissue.
Analyzing Regional Disparities in E-Commerce Adoption Among Italian SMEs: Integrating Machine Learning Clustering and Predictive Models with Econometric Analysis
Authors: Leogrande Angelo , Drago Carlo , Arnone Massimo
Published: September 2024

The article explores the diffusion of online sales tools among Italian enterprises with at least ten employees, considering regional inequalities through methods that help address economic policy. The study gives an overall assessment of the adoption of e-commerce among Italian SMEs, using multiple methods that help to identify regional disparities and provide insight for policymakers. The data were obtained from the ISTAT-BES database. Analysis was applied using the k-Means machine learning algorithm by comparing the Silhouette coefficient vs. the Elbow method. The elbow method reveals greater expository capacity, and the optimal number of clusters equals 3. The econometric analysis used the following methods: Panel Data with Fixed Effects, Panel Data with Random Effects, Weighted Least Squares-WLS, and Dynamic Panels at 1 Stage. The results show that cultural and creative employment and regular internet users are positively associated with SMEs active in e-commerce while negatively associated with the family's availability of at least one computer and internet connection. Finally, the article compares different machine learning algorithms to predict the future value of SMEs active in e-commerce. The results are discussed critically.
JEL CODE: O3, O31, O32, O33, O34
On the Hyperparameters of PCTABU and PCHC Bayesian Network Learning Algorithms
Authors: Sevinç Volkan , Tsagris Michail
Published: September 2024

Various Bayesian network learning algorithms are proposed in the literature. This article aims to introduce PCTABU as a novel BN learning algorithm and examine and compare the estimation performances of PCTABU and PCHC algorithms, which are built on two different hyperparameters Tabu-Search (TABU) and Hill-Climbing (HC). Moreover, the estimation performances of the two algorithms are compared with respect to three different scoring functions, Bayesian Dirichlet equivalence (BDe), log-likelihood (LL), and Bayes information criterion (BIC) with both simulated and real-data-based Bayesian networks.
Antimicrobial Drug Sensitivity Pattern of Staphylococcus Aureus Isolated at Ringroad State Hospital, Ibadan.
Authors: Oparemi Mujeeb Opeyemi
Published: September 2024

Staphylococcus aureus is a gram-positive, catalase-positive, coagulase-positive bacteria. They are known to be the causative agent of various infections, including pyogenic infections, impetigo, urinary tract infections, food poisoning, septicemia, meningitis, and osteomyelitis. Staphylococcus aureus, like every other bacterium, is resistant to antimicrobial drugs and continues to defend against medical control and empirical treatments for infections caused by this microorganism; thus, there is a need for antimicrobial sensitivity testing to determine the appropriate drugs for the treatment of staphylococcal infections. This study investigated the antimicrobial drug sensitivity pattern of Staphylococcus aureus isolated from clinical samples at Ring Road State Hospital, Ibadan. One hundred thirty-two (132) isolates were obtained from clinical samples and were confirmed as S. aureus. Thereafter, the antimicrobial sensitivity test was performed via the Kirby–Bauer disc diffusion method. The sensitivity of each of the isolates was as follows: 92.4% of the isolates were resistant to amoxicillin, 88.6% were resistant to Zinnacef, and 65.9% were resistant to Pefloxacin. In addition, 65.2% of the isolates were resistant to Rocephin, and 56.8% of the isolates were resistant to methicillin. Most of the isolates were sensitive to ciprofloxacin (65.2%), streptomycin (56.8%), and erythromycin (50.8%). Antimicrobial drugs such as amoxicillin, Zinnacef, pefloxacin, rocephin, and methicillin were shown to be less likely to be effective in the empirical treatment of staphylococcal infections. In the study region, however, ciprofloxacin, streptomycin, and erythromycin are recommended as first-line antibiotics for the empirical treatment of staphylococcal infections. Statistical analysis revealed that age and sex had no influence on the sensitivity pattern of the isolates to amoxicillin, ciprofloxacin, pefloxacin, rocephin, streptomycin, erythromycin, or methicillin, whereas sex influenced the sensitivity pattern of the isolates to gentamycin and Zinnacef. This study underscores the importance of surveillance of Staphylococcus aureus antibiotic sensitivity patterns to select appropriate therapies, the need to effectively monitor and improve antimicrobial policies, and funding for appropriate research and therapy for Staphylococcus aureus in the health sector.
KSW: Khmer Stop Word based Dictionary for Keyword Extraction
Authors: THUON NIMOL
Published: September 2024

This paper introduces KSW, a Khmer-specific approach to keyword extraction that leverages a specialized stop word dictionary. Due to the limited availability of natural language processing resources for the Khmer language, effective keyword extraction has been a significant challenge. KSW addresses this by developing a tailored stop word dictionary and implementing a preprocessing methodology to remove stop words, thereby enhancing the extraction of meaningful keywords. Our experiments demonstrate that KSW achieves substantial improvements in accuracy and relevance compared to previous methods, highlighting its potential to advance Khmer text processing and information retrieval. The KSW resources, including the stop word dictionary, are available at the following GitHub repository: (https://github.com/back-kh/KSWv2-Khmer-Stop-Word-based-Dictionary-for-Keyword-Extraction.git).
Multi-target-based screening of phytochemicals found in aerial parts of Heliotropium indicum L. for identification of potential anti-urolithiatic agents using simulation methods
Authors: Kumar Vivek , Gupta Pawan , Sharma Vishnu , Dhiman Anju
Published: September 2024

BackGround:
Heliotropium indicum Linn., a plant also known as 'Indian heliotrope,' is found in tropical and temperate regions of the world, and throughout India. This plant exhibits varieties of therapeutic effects like anti-inflammatory, anti-bacterial, anti-fertility, anti-nociceptive, and anti-tumor activities. In addition, the Heliotropium indicum L. plant have been reported to have therapeutic effects in kidney stone or urolithiasis. But it is not reported to date which phytochemicals are responsible for this activity. The current studies deal with multi-targets-based virtual screening for identification of the phytochemicals found in Heliotropium indicumL. aerial parts against different targets and understanding their binding potential and pharmacokinetic profiles. The multitarget based virtual screening of phytochemical found in aerial part of Heliotropium indicum L. was performed against different anti-urolithiatic targets using molecular docking and molecular dynamic simulations.
Results
From the molecular docking-based screening, it was found that phytochemicals Pestalamide B, Rapanone, and Supinine possess had excellent binding modes against almost all the different targets selected for urolithiasis activities. Further validation in molecular dynamic simulations studies, these phytochemicals (Pestalamide B, Rapanone, Supinine) were supported docking results in term of stability and binding properties.
Conclusion:
Therefore, these phytochemicals (Pestalamide B, Rapanone, Supinine) from Heliotropium indicum L. aerial parts were found to have high potential most of the anti-urolithiatic targets as compared to other phytochemicals. However, these need to be proved experimentally. The results of the current studies can be exploited further for designing and discovering new anti-urolithiasis agents for the treatment of kidney stone/urolithiasis.
Detailed multivariate comparisons of environments with mobility oriented parity
Authors: Cobos Marlon E. , Owens Hannah L. , Soberón Jorge , Peterson A. Townsend
Published: September 2024

Multivariate model projections onto conditions that differ from those under which the models were calibrated can result in uncertainty owing to response extrapolation. Therefore, interpretations of models transferred to conditions not analogous to those of model calibration must be done carefully to avoid misleading conclusions. A good practice when producing model transfers is to assess the degree of dissimilarity between calibration and transfer conditions. The mobility oriented parity (MOP) metric is a tool commonly used to quantify such dissimilarities. Our study elucidated the details of MOP, and expanded the interpretability of results when transfer conditions are not analogous to those of model calibration. We implemented a more detailed characterization of non-analogous conditions previously only identified as outside calibration ranges. In addition, we quantified the sensitivity of MOP to the density and position of reference conditions in environmental space, and explored the effect of sample size on MOP results. We show that detailed characterizations of non-analogous conditions can help to determine which variables are different between the two areas and how. This information can be used to understand causes of environmental dissimilarity and to identify variables that could be excluded from ecological niche modeling owing to extrapolation risks associated with them. Our results also show that dissimilarity values calculated in comparisons offer good indicators of how reliable interpretations can be in areas with conditions not analogous to those of reference. The tools developed and implemented in this study provide a useful, quantitatively efficient means of characterizing extrapolation uncertainty in model transfer studies, a best practice when using multivariate ecological niche models to make predictions about species’ distributions.

An extended version of the mobility oriented parity metric helps identify variables for which risks of model extrapolations can be expected.

Distinct MOP metrics used to characterize dissimilarity show comparable general patterns in transfer areas, despite differences in values.

As MOP results are influenced by background sampling size, the definition of this sample should be aimed to appropriately characterize calibration areas.
Geography and ecology structure diversification in Ziziphus Mill. (Rhamnaceae)
Authors: Rickenback Jess , Lehmann Caroline E. R. , Hauenschild Frank , Hughes Mark J. , Pezzini Flávia Fonseca , Pennington R. Toby
Published: September 2024

Understanding the processes responsible for creating and preserving biodiversity within tropical ecosystems is essential for gaining deeper insights into the history, dynamics, and resilience of these environments. We investigated the biogeography and evolution of Ziziphus Mill. (Rhamnaceae), a genus of c.50 species found in all major tropical biomes and across Africa, Asia and Australasia to evaluate how ecology and geography structures its diversification, and their associations with functional traits. We used consistency and retention indices, as well as the delta statistic to test for phylogenetic signal in ecology, geography and functional traits. We constructed a time-calibrated phylogeny using BEAST, followed by the reconstruction of biome and geographical affinities in BioGeoBEARS, and ancestral functional trait evolution using phytools and ape. At a global scale, geography structures Ziziphus’ diversification more than ecology, as evidenced by higher phylogenetic signal in retention indices and the delta statistic. Multiple ecological switches among biomes are associated with dispersal events, which structure Ziziphus’ diversification at smaller scales. Biogeographic estimation suggests that Ziziphus evolved out of closed biomes in Asia during the Oligocene. Long distance dispersal from Asia to Africa resulted in the occupation of two novel biomes, the expanding tropical grassy biome and the desertic biome. Geographic transitions across continents that retain the same biome are fewer but are demonstrated by a dispersal from the closed biome in Asia to the same ecological setting in Australia. In keeping with the younger age of the savanna biome and the Pliocene radiation of geoxylic species, the youngest species in Ziziphus are mostly found in open biomes, and the youngest habit is geoxylic. Leaf hair appears to confer advantages across biomes whilst being a synapomorphy for open and desertic clades. One of two evolutions back into closed biomes is associated with the development of the liana habit.

We inferred the most complete phylogeny for Ziziphus to date.

Ziziphus
originated in closed biomes in Asia in the Oligocene.

At a global scale, geography structures diversification more than ecology (biome preference) in Ziziphus.

Biome shifts are frequently associated with long distance dispersal events.

Shifts in growth form are frequently associated with biome shifts.
Acceleration from a clustering environment
Authors: Holtzman Roi , Maes Christian
Published: September 2024

We study the effects of correlations in a random environment on a random walker. The dependence of its asymptotic speed on the correlations is a nonperturbative effect as it is not captured by a homogeneous version of the same environment. For a slowly cooling environment, the buildup of correlations modifies the walker’s speed and, by so, realizes acceleration. We remark on the possible relevance in the discussion of cosmic acceleration as traditionally started from the Friedmann equations, which, from a statistical mechanical point of view, would amount to a mean-field approximation. Our environment is much simpler though, with transition rates sampled from the one-dimensional Ising model and allowing exact results and detailed velocity characteristics.
Morpholine-tethered Novel Hydrazones as Promising Non-peptidic Prolyl Oligopeptidase (POP) Inhibitors: Synthesis In Vitro and In Silico Studies
Authors: Khalid Urwa , Fatima Noor , Ullah Saeed , Halim Sobia Ahsan , Khan Ajmal , Mali Suraj N. , El-kott Attalla F. , AlShehri Mohammed A. , Kashtoh Hamdy , Al-Harrasi Ahmed , Shafiq Zahid
Published: September 2024

Introduction:

Prolyl oligopeptidase (POP) is a pivotal druggable target implicated
in diverse biological processes and linked to the development of various ailments,
including neurodegenerative disorders. While conventional peptide-based inhibitors
have been a centerpiece, their limitations, such as restricted bioavailability, necessitate
exploration of non-peptidic inhibitors for their therapeutic potential.

Method:

This study focuses on designing, synthesizing, and assessing morpholine-based
hydrazones targeting the catalytic serine residue of POP. The hydrazones (5a-o), reported
as moderately potent analogs compared to the renowned Z-Pro-Prolinal, demonstrated
in vitro POP inhibition with IC50 values ranging from 13.60 ± 2.51 to 36.51 ± 1.82
μM. The derivative 5h, with an IC50 of 13.60 ± 2.51 μM, emerged as the most potent inhibitor.

Results:

Moreover, the in vitro kinetic study of compound 5h indicated that it exhibited
concentration-dependent type of inhibition. in silico docking studies of 5h revealed robust
interactions in the POP enzyme's active site, yielding a docking score of ˗6.30 Kcal/-
mol, consistent with experimental results.

Conclusion:

All findings underscored the potential of synthesized derivatives for drug
development.
Discovery of Small Molecule Inhibitors Targeting CTNNB1 (β-catenin) for Endometrial cancer: Employing 3D QSAR, Drug-Likeness Assessment, ADMET Predictions, Molecular Docking and Simulation
Authors: Fatima Israr , Rehman Abdur , Wang Peng , He Zhijie , Liao Mingzhi
Published: September 2024

Background:

Endometrial carcinoma (EC) is a type of cancer that originates in the lining
of the uterus, known as the endometrium. It is associated with various treatment options such
as surgery, radiation therapy, chemotherapy, and hormone therapy, each presenting unique challenges
and limitations. Beta-catenin, a protein involved in the development and progression of several
cancers, including EC, plays a crucial role. Abnormal beta-catenin signaling is often linked to
the emergence of specific EC subtypes, affecting tumor growth and invasion.

Objectives:

The study's objective is to identify compounds targeting the beta-catenin protein for
treating endometrial cancer (EC) using in silico drug design. Our approach includes molecular
docking to evaluate binding affinities, ADME profiling for pharmacokinetic properties, toxicity assessments,
and molecular dynamics simulations to assess compound stability and interactions.

Methods:

Approximately one thousand anti-cancer phytochemicals were sourced from PubChem
and subjected to molecular docking simulations against the beta-catenin protein. The compounds
were evaluated based on their binding affinities, with the top five selected for further analysis. These
five molecules underwent toxicity and ADME profiling. The Prediction of Activity Spectra
for Substances (PASS) tool was used to identify compounds targeting CTNNB1. Comparative
molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)
were employed to establish quantitative structure-activity relationship (QSAR) models for the
five CTNNB1 antagonist molecules.

Results:

The selected five compounds, namely Pazopanib, Binimetinib, Telatinib, 4-(2,3-Dihydrobenzo[
b][1,4]dioxin-6-yl)-3-((5-nitrothiazol-2-yl)thio)-1H-1,2,4-triazol-5(4H)-one, and Ribavirin,
demonstrated efficacy against CTNN1. MD simulations of the docked complexes confirmed
the stability of these drugs in binding to the target protein. All five molecules showed
promising safety and effectiveness profiles according to their ADME and toxicity evaluations.

Conclusion:

Through a comprehensive screening process employing in silico drug design methods,
this study successfully identified five potential human anticancer drug candidates targeting
the beta-catenin protein. These findings offer a foundation for further experimental validation and
development towards the treatment of EC.
Vincristine in Cancer Therapy: Mechanisms, Efficacy, and Future Perspectives
Authors: Garg Nitika , Farhat Joviana , Dhankhar Sanchit , Chauhan Samrat , Bala Rajni , Madaan Reecha , Sharma Himanshu , Saini Monika , Singh Thakur Gurjeet , Aldahish Afaf Ahmed , Almarhoon Zainab , Al-Omari Basem , Sharifi-Rad Javad
Published: September 2024

Cancer remains one of the predominant causes of mortality globally, accounting
for over 10 million deaths each year. Despite advancements in medical treatments, the challenge
of resistance and treatment failure persists, necessitating innovative approaches. Traditional
cancer treatments include surgery, chemotherapy, radiation therapy, and pharmaceutical
therapy. In recent years, significant attention has been directed towards plant-derived
compounds as potential chemotherapeutic agents and preventive measures against cancer.
Vincristine, a distinguished alkaloid derived from plant secondary metabolites, has shown
considerable efficacy in cancer treatment. As a member of the antimitotic class of compounds,
vincristine disrupts the cell cycle by causing aberrations in microtubule function,
thereby inhibiting cell division and proliferation. This mechanism of action positions vincristine
as a potent agent against various malignancies. Its role in combination therapy is crucial,
as it is often administered in low doses alongside other chemotherapeutic agents to enhance
its efficacy and reduce the risk of resistance. In the realm of medicinal chemistry, understanding
vincristine's molecular mechanism is paramount. Detailed investigations into its
interaction with cellular components can provide insights into its antineoplastic properties.
This review aimed to elucidate vincristine's mechanism of action and structure-activity relationship,
and summarize current in vitro and in vivo studies evaluating its efficacy. Moreover,
it discusses innovative strategies, including nanotechnology-based delivery systems,
designed to optimize vincristine formulations. These advanced delivery systems aim to improve
bioavailability, target specificity, and minimize systemic toxicity. This comprehensive
analysis underscores the critical role of vincristine in contemporary cancer treatment
and highlights future directions for research and development in this field.
Unravelling Peptic Ulcers: Comprehensive Insights into Etiology, Diagnosis, Screening Techniques, and Treatment
Authors: Pathak Rashmi , Chandra Phool , Sachan Neetu
Published: September 2024

The risk of illnesses is increasing in the modern era due to unhealthy and modern lifestyles. Research
has shown that the most frequent acid-induced abrasion, which often occurs in the stomach and proximal
duodenum, is gastric and Peptic Ulcer Disease (PUD), which is a primary worldwide health concern. The
deformity is characterized by denuded mucosa and spreads into the submucosa. Non-steroidal antiinflammatory
drugs (NSAIDs) and H. pylori infections are two common offenders. In the past, it has been
thought that dietary variables, stress, and an acidic hypersecretory state encourage mucosal disruption in peptic
acid disease patients. Peptic ulcers continue to be a significant health issue because of their potential for
substantial consequences, including bleeding, blockage, and perforation, even with advancements in detection
and treatment. This review discusses current screening methods for peptic ulcers and the challenges in diagnosis
and treatment, emphasizing the need for precise diagnosis and more effective therapies.
The Causal Role of Uterine Fibroid in Keloid and Hypertrophic Scar: A Bidirectional Mendelian Randomization Study on European Populations
Authors: Zhou Xiaobo , Lin Jui-Ming , Wang Hui , Gong Yiyi , Lin Jinran , Wu Wenyu , Huang Jia
Published: September 2024

Background:

The relationship between uterine fibroids and keloid/hypertrophic scars
has been contradictory. Our research employs a bidirectional Mendelian Randomization (MR)
approach to establish a clearer understanding of this potential causal link.

Objective:

This study aimed to determine the effect of uterine fibroids on keloid/hypertrophic
scars and the effect of keloid/hypertrophic scars on uterine fibroids.

Purpose:

We aimed to demonstrate the relationship between uterine fibroids and keloid/
hypertrophic scars.

Method:

Our bidirectional MR study utilized summarized data from genome-wide association
studies (GWAS) focused on European populations. Our primary tool for establishing causality
was the Inverse-Variance Weighted (IVW) method. To reinforce the IVW findings, we also applied
four alternative MR methods: MR-Egger, Maximum Likelihood, Weighted Mode, and
Weighted Median.

Result:

The IVW method indicated a significant causal link, with uterine fibroids greatly raising
the likelihood of developing keloids (Odds Ratio [OR] = 1.202, 95% Confidence Interval [CI]:
1.045-1.381; P=0.010) and hypertrophic scars (OR = 1.256, 95% CI: 1.039-1.519; P=0.018).
Parallel results were observed with the MR-Egger, Maximum Likelihood, Weighted Mode, and
Weighted Median methods. Sensitivity analyses indicated robustness in these findings, with no
evidence of heterogeneity or horizontal pleiotropy. Conversely, the reverse MR analysis did not
demonstrate an increased risk of uterine fibroids due to keloids or hypertrophic scars.

Conclusion:

This study elucidates a significant causal effect of uterine fibroids on the development
of keloid and hypertrophic scars, offering valuable insights into their pathogenesis and
potential therapeutic targets.
Deoxypodophyllotoxin Mediates Autophagy Death through Inhibition of
GRP78 in Human Osteosarcoma
Authors: Tang Xiao-jun , Luo Ling-li , Zhou Wen-chao , Shi Gang-qing , Wang Xiao-xu , Zeng Tian , Tan Xiong-jin , Guo Wei-ming , Gao An-bo , Li Yukun , Zou Juan
Published: September 2024

Background:

Glucose-regulated protein 78 (GRP78), as a chaperone protein, can
protect the endoplasmic reticulum of cells and is expressed to influence chemoresistance and
prognosis in cancer. Deoxypodophyllotoxin (DPT) is a compound with antitumor effects on
cancers. DPT inhibits the proliferation of osteosarcoma by inducing apoptosis, necrosis, or
cell cycle arrest.

Object:

This study was performed to demonstrate the molecular mechanism by which DPT
attenuates osteosarcoma progression through GRP78.

Methods:

Natural compound libraries and western blot (WB) were used to screen the inhibitors of osteosarcoma GRP78. The expression of mitochondria-related genes in cancer cells of
the treatment group was detected by quantitative real-time PCR (qPCR) and WB. 3-(4,5)-
Dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-ethynyl-2'-
deoxyuridine (EDU) were used to discover the activity and proliferation of osteosarcoma
cells treated with DPT. We constructed an in vivo mouse model of DPT drug therapy and carried out immunohistochemical detection of xenografts. The treated osteosarcoma cells were
analyzed using bioinformatics and electron microscopy. The data were analyzed finally

Results:

DPT inhibited osteosarcoma cell survival and the growth of tumor xenografts. It
promoted up-regulation of BCL2-associated X protein (Bax) and B-cell CLL/lymphoma 2
(Bcl-2), which serves to mediate and attenuate, respectively, the killing activities of DPT
through mitochondria dysfunction. The effect of DPT against cancer cells could be attenuated
by the overexpression of GRP78, characterized by the inactivation of the caspase cascade.
The loss of GRP78 in osteosarcoma cells negatively mediated the basal level of autophagyassociated genes. DPT stimulated autophagy via the phosphoinositide 3-kinase (PI3K)-v-akt
murine thymoma viral oncogene homolog (AKT), a mechanistic target of rapamycin (mTOR)
axis. The autophagy caused by DPT played an active role in the osteosarcoma of humans and
blocked the apoptotic cascade.

Conclusion:

Combination treatment with the GRP78 inhibitor DPT and pharmacological autophagy inhibitors will be a meaningful method of obviating osteosarcoma cells.
In Silico Analysis and Molecular Docking of Human Antimicrobial Peptides for Targeting Monkeypox Virus: Potential Therapeutic Implications of Histatin 5 Peptide
Authors: Radhakumar Deeksha Sarojini Devi , Thiyagarajan Sundar , Rajaram Kaushik , Parsanathan Rajesh
Published: September 2024

Background:

Monkeypox, a viral zoonotic disease akin to smallpox, has posed significant
public health challenges, particularly in Africa. Recent outbreaks, including those in India,
underscore the global threat it poses.

Objective:

In this study, we explore a novel approach to combat monkeypox virus (MPXV) infection
by targeting its surface proteins, crucial for viral entry and fusion.

Methods:

Employing advanced computational techniques, we predict and refine the 3D structures
of MPXV surface proteins and human antimicrobial peptides (hAMPs), specifically Histatin 1, 3,
and their cleaved product, Histatin 5 (HIS 5). Further, molecular docking was carried out for
MPXV surface proteins with hAMP HIS using HDOCK and Cluspro 2.0. Protein-peptide interactions
were analyzed using PdbSum. Finally, the physicochemical properties of HIS peptides were
determined using CamSol.

Results:

Our findings suggest HIS 5 as a potential therapeutic peptide against MPXV, warranting
further investigation through in vitro and in vivo studies.

result:

Compared to HIS 1 and 3, HIS 5 has higher solubility, an estimated half-life, cell permeability, stability, and a good docking score. Hence, based on the physicochemical properties of HIS 5, it may be used as a novel potential therapeutic peptide against MPXV.

Conclusion:

This study sheds light on the efficacy of the HIS family in targeting MPXV and advocates
for continued exploration of HIS 5's antiviral effects.
Phytochemical and Pharmacological Profile of Plants from Genus Buxus: A Review
Authors: Yan Yuxin
Published: September 2024

Buxus is an evergreen shrub of the Buxaceae family. A comprehensive survey of the literature
has been conducted, revealing that alkaloids are the predominant metabolites characterized
by their noteworthy biological activities. Of particular interest are the alkaloids that have exhibited
significant cytotoxic activity against various cell lines, including HL-60, SMMC-7721, A549, MCF-
7, SW480, ES2, and A2780 cell lines. CVB-D, buxbodine B, and buxmicrophyllines F can inhibit
the growth of tumor cells and induce tumor cell apoptosis. This article reviews the chemical constituents,
antitumor effect, and mechanism of Buxus alkaloids in recent years so as to provide a reference
for its further development and utilization of medicinal plants of the genus Buxus.
Synthesis of Palladium Nanomaterials Using Plant Leaf Extract and their Enhanced Photocatalytic Activities against Organic Dyes
Authors: Kaur Gurcharn , Aulakh Jatinder Singh
Published: September 2024

Aims and Objectives:

This study aimed to carry out the green synthesis of palladium nanoparticles
(Pd NPs) using the aqueous leaves extract of Eclipta alba. The appearance of a characteristic
surface plasmon resonance peak at 410 nm confirmed the synthesis of Pd NPs.

Method:

The average particle sizes of 13 nm were observed by using the leaf concentrations of 10
mL with a certain amount of PdCl2 (0.001 M) at 25 ̊ C. The Pd NPs, as synthesized under the optimized
conditions (10 mL extract + 60 ̊ C + 0.001 M PdCl2), were spherical in shape, small in size,
and uniformly distributed, as depicted by HR-TEM images.

Results:

FTIR, XRD, DLS, and zeta potential further confirmed the formation of Pd NPs. The Pd
NPs synthesized at optimized conditions exhibited strong catalytic activity in dye Eosin yellow, Rose
Bengal, Tartrazine, and Ponceau S degradation by discoloration of dyes in 3 hrs. The removal of all
dyes by the Pd NPs was optimized by varying specific operating parameters, such as initial dye concentration,
solution pH, irradiation time, and temperature.

Conclusion:

This high activity of Pd NPs may be due to their small size, high dispersion, and surface-
capping phytochemicals.

result:

Bio-fabrication of metallic Pd NPs using different plant extracts compared to other reducing agents is more scalable, rapid, and cost-effective for generating bulk nanoparticles. The phytochemical principles, such as phytoconstituents, reduce the PdCl2 to Pd NPs and are implicated in the capping and stability of the nanoparticles. Hence, the leaves of Eclipta alba have different polyols and are well known. Apart from this, hydroxyl groups in phenolic compounds may participate in the bio-reduction of PdCl2. Such compounds can chelate metal ions to form their quinones form, which is an intermediate palladium complex. Then, stabilization of the intermediate form and reduction of Pd2+ to Pd0 occurred due to free electrons or nascent hydrogen produced during the bio-reduction reaction. Finally, Pd-NPs were prepared due to the collision of neighboring Pd0 atoms. These significant conjugations exist in the keto-enol system within the quinone form of the compound.
The Acute Kidney Injury Induced by Cisplatin in Mice is Exacerbated by the Conditioned Medium Derived from the Cultivation of Mesenchymal
Stem Cells under Hypoxic Conditions
Authors: Temnov Andrey A. , Sklifas Alla N. , Sharapov Mars G. , Fadeev Roman S. , Klychnikova Elena V. , Dolbnya Andrey D. , Pekov Stanislav I. , Popov Igor A.
Published: September 2024

Background:

Acute Kidney Injury (AKI) is a severe complication of cisplatin-based
chemotherapy. Thus, searching for novel therapeutic approaches to reduce system toxicity is vital
for improving patient outcomes. The use of stem cells or the paracrine factors released by these
cells during cultivation is currently being explored as a potential method for AKI prevention during
chemotherapy. However, the conditions of stem cell cultivation considerably affect the composition
of paracrine factors released by cells.

Objective:

In this study, we aimed to investigate the impact of paracrine factors derived from mesenchymal
stem cells cultured under hypoxic conditions on the progression of AKI induced by cisplatin.

Methods:

AKI was induced in mice by intraperitoneal administration of cisplatin with the simultaneous
injection of fractions of conditioned medium obtained from the cultivation of mesenchymal
stem cells under hypoxic conditions. The survival rate of animals was assessed alongside qRTPCR
implementation to assess gene expression of cytokines.

Results:

The total fraction of conditioned medium and >30 kDa fraction had no impact on cisplatin
nephrotoxicity in mice. However, either subcutaneous or intraperitoneal administration of
<30 kDa fraction of conditioned medium exacerbated animal mortality and led to severe damage
to renal tissues. The effect was in a good correlation with KIM-1 and CDKN1A gene expression.

Conclusion:

The conditioned medium obtained during mesenchymal stem cells under hypoxic
conditions has been found to markedly amplify the toxicity of cisplatin, which should be considered
in stem cell therapy of AKI patients.
Evaluating the Reliability of Machine Learning Predictors in m6A-SNP Association Analysis: A Comparative Study Using m6A-QTL Data
Authors: Mao Zhongzheng , Wei Zhen
Published: September 2024

Introduction:

N6-Methyladenosine (m6A) plays a crucial role in determining the fate of
RNA after transcription. Understanding the downstream functions of individual m6A sites is of critical
interest in epitranscriptomics. In published studies, two main approaches have been used to decipher
the specific impact of m6A sites on gene expression and disease/traits: the m6A quantitative
trait loci (m6A-QTL) and in-silico mutation prediction by Machine Learning (ML) models. However,
earlier works still lack independent validation for the performance of ML-based methods.

Methods:

In this study, we use m6A-QTL as ground truth to evaluate the outcomes of in-silico mutation
models. We benchmark both the newly trained machine learning models using genomic or
sequence features and the existing model inference results published in in-silico mutationdependent
databases against m6A-QTL.

Results:

We found that the consistency between in-silico mutation and m6A-QTL is weak, regardless
of the ML algorithms and predictive features used. This trend was also consistent across multiple
published databases based on in-silico mutation, including RMDisease2, m6AVar, and RMVar.

Conclusion:

These results highlight the importance of critical empirical evaluations for ML models
in future SNP-m6A association studies and suggest the need for more high-quality m6A-QTL experiments
to guide model development.
Mechanisms of Cinnamomi Cortex against Diabetes Mellitus Explored by Network Pharmacology combined with Molecular Docking and Experimental Validation
Authors: Yu Jianqin , Song Zijun , Wang Lusheng , Yang Hongyu , Fan Hui
Published: September 2024

Objective:

Cinnamomi cortex (CC), a traditional Chinese herbal medicine, exhibits
antidiabetic properties, yet the underlying mechanisms are not fully understood. Our study
combined network pharmacology, molecular docking, and experimental validation to elucidate
the antidiabetic mechanisms of CC.

Methods:

Active components of CC and their potential antidiabetic targets were identified
through TCMSP, DisGeNET, and GeneCards. The PPI networks were constructed with
STRING and analyzed with Cytoscape, while GO and KEGG analyses utilized the DAVID database.
Molecular docking with core targets was performed using Autodock Vina. The efficacy
of CC in diabetes mellitus was evaluated through H&E staining, qPCR, and Western blot in the
T2DM mouse.

Results:

Eleven active components and sixty-six potential antidiabetic targets of CC were identified.
The enrichment analysis revealed 288 GO terms and 37 pathways. The molecular docking
showed high affinity for PPAR-γ and IL-6 receptors. In vivo studies further confirmed CC's
ability to modulate PPAR-γ and IL-6, contributing to its antidiabetic effects.

Conclusion:

CC manages diabetes by regulating the PPAR-γ pathway and suppressing associated
inflammation, providing a multi-pathway therapeutic approach.
Likelihood of Laryngeal Involvement in Autoimmune Thyroid Disorder Patients: A Meta-Analysis
Authors: Yue Chuan , Gu Li , Guo Wei
Published: September 2024

Background:

The involvement of the larynx in many situations can have a substantial
impact on a person's voice, breathing, and general health. Individuals with autoimmune thyroid
disorders can experience a variety of conditions affecting the larynx. Autoimmune thyroid
disorders, such as Hashimoto's thyroiditis [HT] and Graves' disease [GD], are prevalent conditions
affecting the thyroid gland. Beyond their established impact on thyroid function, these disorders
have been associated with laryngeal involvement. The current study aims to explore the
likelihood of laryngeal involvement in patients with Autoimmune Thyroid Disorders [AITD].

Method:

This study involved a retrospective analysis of medical records from patients diagnosed
with autoimmune thyroid disorders. Inclusion criteria were a confirmed diagnosis through
laboratory investigations and clinical assessment. Patients with pre-existing laryngeal pathologies
or other conditions affecting the larynx were not considered. We collected data from 4 research
articles and 3 clinical trials from Embase, PubMed, and NCBI-Trials portals, focusing on
reported laryngeal symptoms. The severity of laryngeal involvement was assessed and categorized
based on its extent and impact on vocal function.

Results:

Preliminary analysis of the collected data indicated a significant proportion of patients
with autoimmune thyroid disorders reporting laryngeal symptoms. Among these patients, various
manifestations of laryngeal involvement were observed, including vocal changes, hoarseness,
and throat discomfort.

Conclusion:

The findings show that laryngeal symptoms may be an underappreciated feature of
these diseases, potentially impacting vocal function and quality of life in affected people. Further
research is also needed for more precise projections in this direction.
LINCRNA01094 Promotes Renal Interstitial Fibrosis via the Mir-513b-5p/MELK/Smad3 Axis
Authors: Zhang Xingguang , Jia Binghan , Zhang Yanqi , Zhang Sen
Published: September 2024

Background:

Chronic Kidney Disease (CKD) is a common chronic disease that is a
threat to human health. Accumulating evidence showed that long noncoding RNAs (lncRNAs)
are associated with various diseases and can function as competing endogenous RNAs (ceRNAs).
However, the roles and functions of the lncRNA‒miRNA-mRNA network in CKD are
still unclear.

Methods:

In this study, we performed differential expression analysis of lncRNAs, miRNAs,
and mRNAs in CKD using the datasets GSE66494 and GSE80247 from the Gene Expression
Omnibus. A total of 33 lncRNAs, 20 miRNAs, and 240 mRNAs were differentially expressed
between CKD patients and healthy controls. Two ceRNA interaction modules composed of 11
hub nodes, namely, 2 lncRNAs (LINC01086, LINC01094), 2 miRNAs (hsa-miR-197-3p, hsamiR-
513b-5p) and 7 mRNAs (CENPF, TOP2A, ARHGAP11A, CEP55, MELK, DTL, and
ANLN) were constructed. In vitro knockdown of LINC01094 expression in renal tubular epithelial
HK2 cells significantly attenuated the phenotype of TGFβ1-induced cell fibrosis.

Results:

The results of RNA immunoprecipitation (RIP) experiments and dual-luciferase reporter
experiments based on constructed mutants confirmed that LINC01094 could mediate
MELK expression by sponging miR-513b-5p.

Conclusion:

Our observations indicated that lowering the expression of LINC01094 can significantly
attenuate the TGFβ1-induced fibrosis phenotype in HK2 cells and renal inflammation
through the miR-513b-5p/MELK/Smad3 signalling axis.