bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Microbial Communities in Mucilage and Surrounding Seawater: Metagenomic Insights into Mucilage Formation in the Marmara Sea
Authors: Gundogdu Aycan , Nalbantoglu Ozkan Ufuk , Karis Gizem , Sarikaya Ilknur , Erdogan Meryem N. , Hora Mehmet , Aslan Herdem
Published: June 2024

In 2021, the rapid emergence of mucilage in the Marmara Sea raised concerns about its environmental impact. This study compares mucilage and seawater samples from 16 stations across the Marmara Sea using shotgun metagenomic sequencing and bioinformatics. Sampling was conducted from April to September 2021 across varying oceanographic conditions, including different temperatures and salinity levels, to identify changes in the microbial community. Results showed that 58% of the reads in mucilage samples could not be assigned to any taxon, indicating significant microbial "dark matter." Clean seawater was characterized by a higher presence of Euryarchaeota, Proteobacteria, and Rhodothermaeota, while Chlamydiae and Fusobacteria were dominant in mucilage. Pre-mucilage seawater samples showed microbial compositions similar to mucilage, suggesting a link between microbiome imbalance and mucilage formation. These findings provide a comparative metagenomic analysis highlighting the need for further studies to understand mucilage's environmental impact and develop early warning strategies.
Study on microbial metabolic mechanism of activated sludge denitrification by A2O process under strong solar radiation in highland habitat
Authors: PENG Xianpai , ZONG Yongchen , WANG Jun , FU Chunhui , JI Jiaao , LIU Leran , LI Peifeng
Published: June 2024

The effects of plateau solar radiation on microbial abundance and diversity and metabolism during the formal operation of the A2O reactor were analyzed by running three parallel A2O units with solar radiation, constant temperature and room temperature laterally. The results showed that when the formal operation reached the 180th day, the nitrogen removal effect of the solar radiation A2O reactor decreased significantly compared with that of the constant temperature and room temperature units in general; the number of operational taxonomic units (OTUs) in the solar radiation, constant temperature and room temperature A2O systems were 1140, 972 and 1000, and the solar radiation reactor showed an increasing trend throughout the whole process, and the metabolic function of the dominant genera of microorganisms was dominated by organic matter degradation, denitrification and denitrogenation, and the metabolic pathways were dominated by carbon and nitrogen metabolism, and it was also found that the relative abundance of denitrifying bacteria (DNB) increased with the increase in the duration of solar radiation exposure. The bacterial diversity of the solar A2O system was lower than that of the constant and room temperature systems up to 90 days, and the relative abundance of some common dominant genera in the sludge was suppressed by solar radiation, but the abundance of some denitrification-related genera and their functional genes were instead strengthened in the solar radiation reactor.
Compound Kushen Injection improves radiation enteritis via cannabinoid receptor 1 in rats
Authors: Xu Wenjing , Gao Liping , Zou Wenjuan , Tang Xiaohui , Nian Weiqi , Zheng Weiqin , Huang Rongzhong , Wang Pei
Published: June 2024

Background: Clinical studies have shown that Compound Kushen Injection (CKI) can alleviate the inflammatory symptoms of radiation enteritis. However, the mechanism of action remains unclear. The aim of this study was to explore the possible targets and mechanisms of CKI in the treatment of radiation enteritis.
Methods: Network pharmacology was used to predict the potential targets of CKI for the treatment of radiation enteritis, and GO and KEGG enrichment analyses were subsequently performed. The therapeutic effects and signalling pathways were then verified in rats. The expression of inflammatory factors in ileal tissue was measured by qRT-PCR. The activities of SOD and GSH-Px in ileal tissue were measured by ELISA. The levels of MDA, ROS and NO were determined using biochemical kits. The expression of signalling pathway-related proteins was detected by Western blotting and immunofluorescence.
Results: According to network pharmacology, CB1 might be a target of CKI. GO and KEGG enrichment analyses revealed that CKI was significantly enriched in analgesic, endocannabinoid and inflammatory pathways. In the rat model, Compared with that in the radiotherapy group,the extent of ileal injury was significantly improved in the CKI group compared to the control group. In addition, the infiltration of CD68 and CD16b was significantly reduced, and the expression of MCP1, TNF-α, IL-1β and IL-10 was significantly decreased. In addition, the activities of SOD and GSH-Px were increased, and the activities of MDA, ROS and NO were decreased. The CKI group also showed inhibition of NF-κB signalling and a significant decrease in the expression of NOX4, CB1 and p-p38 MAPK/p38 MAPK. The use of a CB1 agonist could also alleviate radiation enteritis, whereas the addition of a CB1 antagonist could interfere with the ameliorative effect of CKI on radiation enteritis.
Conclusions: CKI might exert an anti-radiation enteritis effect by targeting the cannabinoid receptor 1.
Spark based parallelized FM algorithm research
Authors: deng fan , wang jiabin , lv sheng
Published: June 2024

For traditional Factorization Machines (FM) algorithms and various deep learning-based FM algorithms, although they perform well in tasks such as feature learning and recommender systems, they are often single-computer operations that require powerful computational and storage resources, and they have problems such as excessive irrelevant feature redundancy, slow convergence and low efficiency of parallelized training when running on large-scale datasets training efficiency, a Spark-based parallelized FM (SFM) algorithm is proposed. With the efficient distributed processing platform provided by Spark, the parallel computing of RDD datasets on multiple machines in the HDFS cluster can accelerate the processing speed, and at the same time ensure the scalability and fault tolerance when processing large-scale data. Part of the publicly available advertisement dataset is used for the experimental data. The experimental results show that the parallelized FM algorithm has better performance in recommendation accuracy, recall, F1 value, and scalability, and at the same time, it can significantly improve the operation efficiency in the case of large-scale data through multi-node parallelism.
Estimation of the high-cycle fatigue behaviour of timber connections with inclined screws under tension
Authors: Niebuhr Peter Lothar , Sieder Mike
Published: June 2024

Based on 31 quasistatic tests and 27 constant-amplitudefatigue tests the withdrawal behaviour of a self-tapping timber screw under cyclic loading is examined in two configurations with regard to the penetration length. Together with similar results from earlier withdrawal tests on threaded rods, indications of a dependence of the bearable load cycles on the penetration length are found where a larger penetration length yields inferior performance under cyclic loads. Further, in conjunction with results from earlier axial tensile tests on the examined screw, insights into the transition point between steel tensile failure and withdrawal are gained.
The obtained results on the withdrawal failure mode are combined with results from earlier studies to develop a proposal for a holistic verification concept for the high-cycle fatigue design of connections with inclined self-tapping screws. After a discussion of the state of knowledge regarding the relevant failure modes, the verification is reduced to the dominant failure modes withdrawal and steel tensile failure, while subsidiary effects such as bending in the fastener are inherentlyconsidered.
Bmlark is essential for embryo development
Authors: Peng Yuling , Li Jin , Niu Kangkang , Wang Man , Chen Yanfei , Tong Chunmei , Feng Qili
Published: June 2024

Background
Transcription factor lark has been demonstrated to play multiple functions in Drosophila, but the function of this gene in embryo development remains to be elucidated.
Results
In this study, CRISPR/Cas9 gene-editing method was used to construct a Bmlark mutant strain of Bombyx mori to investigate the roles of this gene. The results showed that the homozygous mutant Bmlark−/− was lethal. The Bmlark−/− embryos showed obvious developmental defects, such as defective sclerotization and melanization of exoskeleton. Transcriptomic comparison of Bmlark−/− and wild-type embryos showed that the differentially expressed genes (DEGs) were mainly enriched in the structure and metabolism processes of chitin and cuticles. While the expression levels of chitin metabolism-related enzyme genes did not significantly change, the expression levels of 63 putative cuticle protein genes showed significant difference in the mutant embryos as compared to the wild-type embryos. The expression levels of transcription factor POUM2 and eight wing disc cuticle protein genes (WCPs) were also changed. While the expression level of TH in the tyrosine-mediated pigmentation pathway was up-regulated in the mutant embryos, the expression levels of the four key pigment synthesis genes DDC, aaNAT, Laccase2A, and yellow-f2 were significantly down-regulated.
Conclusions
The expression levels of 63 putative cuticle protein genes, eight WCPs and five pigment synthesis genes were significantly changed in Bmlark mutants. These results suggest that Bmlark is essential for normal development of cuticle and tyrosine-mediated melanization in silkworm embryo.
Antibacterial Efficacy of Peppermint Oil Microcapsules on Denim: A Comparative Study of Washing Resistance
Authors: Doğan Merve , Göz Eda , Yüceer Mehmet
Published: June 2024

Incorporating Mentha piperita essential oils into denim fabrics was investigated using three distinct microencapsulation techniques: simple coacervation, interfacial polymerization, and microfluidics. The encapsulated essential oils were applied to 3/1Z, 100% cotton denim through novel finishing, coating, and coating-washing methodologies. A comprehensive evaluation of the performance characteristics of the fabric, including tensile strength, abrasion resistance, dry and wet rub fastness, and color difference, was conducted. Optical Microscopy, Scanning Electron Microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) meticulously characterized the microcapsules. Initial results demonstrated that the fabric maintained complete antibacterial efficacy up to the first home wash across all encapsulation methods. However, a gradual decline in antibacterial activity was observed in subsequent wash cycles. In conclusion, the microcapsules generated via the microfluidic technique exhibited superior durability, retaining 80% antibacterial activity after five wash cycles. These findings offer valuable insights into the sustainable application of natural antibacterial agents within the functional textile industry.
Mito-apocynin protects against kainic acid-induced excitotoxicity by ameliorating mitochondrial impairment
Authors: Lin Miaomiao , Wan Xiaorui , Wu Huanchen , Liu Na , Jiang Yiyue , Sheng Yichao , Wang Jing , Xu Haidong , Xue Jie , Qin Zhenghong , Wang Yan
Published: June 2024

Neurodegenerative diseases are major global health problems with increasing incidence rates. A large amount of data suggests that excitotoxicity is a potential target of neurodegenerative diseases. However, effective pharmacological interventions against excitotoxicity are lacking. We aimed to elucidate the neuroprotective effect and mechanism of the mitochondrion-targeted NOX inhibitor mito-apocynin on kainic acid (KA)-induced excitotoxicity. We found that KA impaired mitochondrial morphology and led to impaired mitochondrial energy metabolism and dysfunction. In Western blotting experiments, KA disrupted mitochondrial quality control. In Nissl staining and CCK8 experiments, Mito-apocynin attenuated the death of neurons due to excitotoxic damage induced by KA both in vivo and in vitro. Mito-apocynin ameliorated neurobehavior induced by KA deficits in vivo and mitochondrial dysfunction in vitro. Mito-apocynin significantly reversed the increase in NOX4 levels caused by KA in the mitochondria of the striatum, decreased phosphorylated DRP1 (Ser616)/total DRP1 and increased PGC-1α, PINK1 and Parkin protein expression in the total striatum. In summary, Mito-apocynin alleviated oxidative stress, maintained normal mitochondrial function and energy metabolism levels, and promoted the balance of mitochondrial quality control by regulating the expression of NOX in mitochondria, thus reducing KA-induced excitatory toxic damage.
Reviewing the Effectiveness of Medical Teaching Institute Reforms on Tertiary Health Care in Pakistan: Perspectives from Management, Faculty, and Administration
Authors: Qamar Wajiha , Qayum Mehran , Nisa Waqar-un , Ali Asma
Published: June 2024

Objective: The study was conducted with an objective to assess the impact of the Medical Teaching Institution (MTI) promulgated in tertiary health care, on autonomy and overall performance within healthcare institutions in the Khyber Pakhtunkhwa (KP) province of Pakistan.
Methodology: A cross-sectional study was carried out from September 2023 to March 2024, involving interviews with frontline staff, administrative personnel, and senior management within MTI-affiliated institutions. A mixed-methods approach was employed, using both qualitative and quantitative data analysis techniques.
Results: The study showed that institutional staff members' knowledge and understanding of the MTI changes differed. Some observed very minor adjustments, while others saw advances in hospital operations and service delivery. Administrative complexity, political meddling, and resource allocation problems were noted as challenges. Positive results were also observed, though, and they included improved infrastructure, possibilities for staff training, and decision-making procedures.
Conclusion: Despite the improvements brought about by the MTI reforms, problems still exist, underscoring the necessity of multifaceted strategies and teamwork to properly address them. Sustaining improvement necessitates constant assessment, flexible approaches, and a dedication to improving KP healthcare delivery.
Millennial-Scale Microbiome Analysis Reveals Ancient Antimicrobial Resistance Conserved Despite Modern Selection Pressures
Authors: Gomathinayagam Sankaranarayanan , Kanagalingam Swathi , Chandrasekaran Srimathi , Thirumoorthy Krishnan , Muthukaliannan Gothandam Kodiveri
Published: June 2024

Background Antimicrobial resistance presents a formidable challenge, yet its existence predates the introduction of antibiotics. Our study delves into the presence of antimicrobial resistance determinants (ARDs) in ancient permafrost microbiomes, comparing them with contemporary soil and pristine environments. Majority of the samples are from regions around Beringia, encompassing parts of Russia and Alaska, with only one sample originating from the Tien Shan Mountain range in Kyrgyzstan.Results From over 2.3 tera base pairs of raw metagenomic data, we assembled about 1.3 billion metagenomic contigs and explored the prevalence of ARDs in them. Our findings reveal a diverse array of ARDs in ancient microbiomes, akin to contemporary counterparts. On average, we identified 2 ARDs per ribosomal protein gene in ancient samples. Actinomycetota, Bacillota, and several thermophiles were prominent carriers of ARDs in Chukochi and Kamchatkan samples. Conversely, ancient permafrost from the Tien Shan Mountain range exhibited no Thermophiles or Actinomycetota carrying ARDs. Both ancient and contemporary microbiomes showcased numerous divergent ARDs, majority of which have identity between 40%-60% to genes in antibiotic resistance gene databases. Antibiotic inactivation-type ARDs exhibited purifying selection with contemporary resistance genes, as estimated by dN/dS ratio.Conclusion Antibiotic resistance has always existed and will continue to do so, as it is inherently encoded in the genomes of microbes. The classes of antimicrobial resistance genes profiled and the function of antibiotic-inactivating enzymes from ancient permafrost microbiomes do not seem to be very different from the genes found in the antibiotic era. Additionally, we retrieved 359 putative complete viruses from ancient microbiomes and none of them harboured any ARDs.
The Impact of COVID-19 Vaccination Rate on Traffic Recovery
Authors: Zhang Suyanpeng , Jin Jing , Yu Han , Hong Ying , Sood Neeraj , Suen Sze-chuan
Published: June 2024

At the beginning of the COVID-19 pandemic in the US, traffic sharply fell due to social distancing policies in many locations. Correspondingly, many regions observed an increase in traffic volume (traffic recovery) as the pandemic eased in 2022. We examine how vaccination rates influence traffic recovery in Los Angeles County (LAC), controlling for differences in case counts, demographics, and socioeconomic factors across areas with different vaccination rates. We use arterial road sensor data as a proxy for the traffic volume near each ZIP code, alongside their respective demographic and socioeconomic characteristics. We find that a higher vaccination rate is statistically significantly associated with a larger traffic recovery, a finding that remains consistent across all explored models. This implies that a rise in the vaccination rate might enhance the public's perception of protection, leading to a larger traffic recovery. Moreover, we found that variables including population, income, race, work industry, and commuting preferences were correlated with vaccination rates. This highlights potential inequalities based on race, income, and industry sectors in the COVID-19 vaccination and a return to normal traffic flow.
Can the digital economy imporve the efficiency of synergistic management of pollution and carbon emissions?Evidence from cities in China
Authors: Yan Jian Jun , Deng Nan
Published: June 2024

Achieving synergies in reducing pollution and carbon emissions has emerged as a crucial strategic goal in the new development phase. To investigates whether digital economy(DE), as a novel dynamic energy in this stage, can effectively contribute to the reduction of pollutants and carbon emissions. Accordingly, this study focuses on 265 cities in China spanning from 2011 to 2019. The study introduces the concept of the efficiency of synergistic management of pollutants and carbon emissions (SEPC). It utilizes an econometric model to empirically examine the pollution and carbon reduction effects of digital ecomomy, along with its implementation path. The findings reveal the following: (1) The impact of DE on SEPC exhibits a noticeable non-linear pattern, resembling a “U” shape. Moreover, significant spatial spillovers resulting from this nonlinearity are observed. (2) The mechanism analysis indicates that DE influences SEPC by affecting the energy framework, promoting green technology innovation, shaping industrial composition, and influencing public concern for the environment. (3) Heterogeneity analysis suggests that the influence of DE on SEPC is more pronounced in innovative cities, smart cities, and cities with higher levels of government intervention. This study validates the pivotal role of DE in advancing synergies for pollution and carbon reduction. Furthermore, it serves as a valuable reference for achieving dual carbon objectives.
Bee venom reduces early inflammation and oxidative stress associated with lipopolysaccharide-induced alpha-synuclein in the substantia nigra-striatum axis
Authors: Lomeli-Lepe Alma Karen , Castañeda-Cabral José Luis , Ureña-Guerrero Mónica E. , Cabrera Graciela Gudiño , López-Pérez Silvia Josefina
Published: June 2024

Neuroinflammation and oxidative stress are important features in the pathogenesis and development of synucleinopathies, the glial activation and upregulation of pro-inflammatory and oxidative mediators induce alpha-synuclein (α-syn) accumulation. Recent studies have shown that bee venom (BV) has beneficial effects on symptoms of these neurodegenerative diseases. BV is known to exert anti-inflammatory and anti-oxidative effects. Here, we investigated the effects of BV over the different inflammatory and oxidative markers, and in the expression of α-syn and tyrosine hydroxylase (TH) in a lipopolysaccharide (LPS)-induced rat model of synucleinopathies. We examined whether BV (1.5 mg/kg by acupoint injection ST36 six times every 48 hours) could change the α-syn and TH expression measured by western blotting, also, observed the activation of microglia and astrocytes by immunofluorescence, quantify the proinflammatory cytokines levels (TNF-α and IL-1β) by ELISA, and estimated the lipid peroxidation and the activity of superoxide dismutase (SOD) and catalase (CAT) by colorimetric kits in LPS-treated rats (2.5 µg by a single dose intranigral injection) in substantia nigra (SN) and striatum (STR) brain areas. In the LPS-injected rat brain, BV treatment reduced α-syn levels and increased the TH levels. In addition, we observed lower microglia and astrocyte activation in SN and STR. Furthermore, BV decreases IL-1β and lipid peroxidation and increases the CAT activity in the STR. These results indicate that BV can restore the α-syn and TH levels possibly by the inhibition of LPS-induced neuroinflammation and oxidation, also, these results suggest that BV could be a promising treatment option for synucleinopathies.
The spread of the invasive mosquito Aedes albopictus (Diptera: Culicidae) in Portugal: a first genetic analysis
Authors: Zé-Zé Líbia , Freitas Inês Campos , Silva Manuel , Soares Patrícia , Alves Maria João , Osório Hugo Costa
Published: June 2024

Background
Aedes albopictus, commonly known as the Asian tiger mosquito, has become one of the most invasive mosquito species, introduced and established in various tropical and temperate regions worldwide over the last five decades. First reported in Europe in 1979 in Albania and later in Italy in 1990, the species is now established in 13 EU/EEA countries and 337 regions (2023). In Portugal, Ae. albopictus was first detected in the Algarve and Penafiel regions in 2017, followed by Alentejo in 2022 and Lisbon in 2023. This mosquito species poses a significant public health risk as a vector for numerous pathogenic viruses, including dengue, Zika and chikungunya.
Methods
Aedes albopictus collected in Lisbon in 2023, were analyzed using COX gene sequencing to understand their genetic relationships.
Results
Our data indicate that the Ae. albopictus mosquito populations detected in three different locations in Lisbon in 2023 correspond to recent, but distinct introduction events.
Conclusions
Although there has been no local transmission of Aedes-transmitted viruses in mainland Portugal to date, the spread of the mosquito and increased international travel increase the risk of Aedes-borne disease outbreaks. The ongoing spread of Ae. albopictus in the country and the confirmed multiple introductions in new locations raise awareness of the need to monitor mosquito vectors in order to control and prevent autochthonous Aedes-borne disease outbreaks.
Sex-mediated gene flow of grayfoot chacma baboons (Papio ursinus griseipes) in a highly seasonal habitat in Gorongosa National Park
Authors: Silva Maria J Ferreira da , Tralma Paula , Colmonero-Costeira Ivo , Mota Mariana , Farassi Rassina , Hammond Philippa , Lewis-Bevan Lynn , Bamford Marion K. , Biro Dora , Lüdecke Tina , Mathe Jacinto , Bobe René , Capelli Cristian , Carvalho Susana , Martinez Felipe I.
Published: June 2024

Investigating primates’ behavioral variation at the inter-population level is important for the understanding of the evolutionary processes leading to species-specific patterns. The study of behavioral diversity among populations also contributes to improving’ primate conservation efforts. Dispersal patterns tend to be similar among close phylogenetic lineages but may vary in response to individual-based responses. Here, we investigate dispersal patterns of chacma baboons (Papio ursinus griseipes) living in Gorongosa National Park (GNP) and the Catapu Forest Reserve (CFR) in central Mozambique. The park consists of a mosaic landscape, located in a seasonally variable area. GNP was the epicenter of a major war, which severely reduced most apex predators resulting in limited mammalian predation on baboons and a steep increase in number of groups and/or group’s fission. We used a genetic dataset of 121 non-invasive DNA samples analyzed for uni- and bi-parentally inherited markers aiming to characterize the spatial distribution of genetic variation and investigate the extent and direction of sex-mediated gene flow at different time scales. We found high levels of genetic diversity as estimated using autosomal microsatellite loci data and no evidence for a significant contraction of the population size in the last generations. A very distinct mitochondrial DNA haplotype was sampled in CFR. We found evidence for historical and instantaneous male-biased dispersal and female philopatry, estimated among localities and at short distances in GNP, respectively. Our study highlights the strong conservation of sex-biased dispersal patterns and philopatry in chacma baboons and suggests that dispersal behaviors in chacma baboons are resilient to environmental changes and seasonality.
EMPREENDEDORISMO SOCIAL
Authors: Lamberti Tatiane Balbinot , Ávila Lucas Veiga , Rosa Carmen Brum
Published: June 2024

Em vista do crescimento de pesquisas sobre empreendedorismo social e assuntos relacionados, notou-se a necessidade de analisar as principais características, tendências e desafios sobre o estudo do empreendedorismo social dos últimos anos, a fim de sintetizar os principais avanços e trilhar um caminho para pesquisas futuras. Para isso, realizou-se uma Revisão Sistemática da Literatura, utilizando a base de dados Web of Science. O período estabelecido foi de 01/01/2018 a 30/06/2023 e, para a coleta de dados, foram utilizados o conjunto de palavras-chaves e operadores booleanos: “inovação social” & “negócios” & “empreendedorismo social”. Foi utilizado filtro para selecionar “Artigos” e “Artigos de Revisão”. Foram encontrados 321 artigos que, após a aplicação da pergunta filtro, somaram 186 artigos. Para auxiliar na organização e análise dos estudos, foram utilizados os softwares Mendeley e VOSviewer Como resultado, observou-se que os países desenvolvidos tiveram predominância na quantidade de publicações, com destaque para os Estados Unidos da América e a Inglaterra. Entretanto, quando se analisa a quantidade de publicações por instituição e por autores, países em desenvolvimento lideram esse ranking, representados por instituições como a Tecnológico de Monterrey (México) e a Thapar Institute of Engineering Technology (Índia), sendo esta a instituição com maior número de citações. A principal área de pesquisa é a de “Economia de Negócios”, contida em 62,9% dos estudos. Novas vertentes de pesquisa são identificadas  nos temas de “Relacionamentos em Rede” e “Capacidade de Escala das Inovações”, apresentando as principais lacunas atuais.
Non-surgical Synergistic Interventions for the Treatment of Skin Cancer
Authors: Abobaker Magdi , Govender Mershen , Choonara Yahya E.
Published: June 2024

Skin cancer is broadly classified into two categories i.e., non-melanoma skin cancer (NMSC) and
malignant melanoma (MM), with MM having a greater fatality rate than NMSC. A large number of treatment
strategies currently exist for these skin cancer types, ranging from monotherapies to complex multifaceted synergistic
interventions including dual therapies, trimodality therapy, and multicomponent combinations therapy.
These combinatorial cancer treatments have delivered more favorable results when compared with monotherapies,
and although combination treatments increase the cost of treatment, these regimens have lower side effect
profiles, decreased resistance, high efficacy and an improved long-term response. Synergistic combination
treatments for skin cancer are often complex, wide-ranging and encompass diverse platforms with various
mechanisms of action. An understanding of the physiological potential, as well the efficacy of such treatments,
is therefore vital to ensure patients receive the best possible treatment. This review therefore focuses on the
current advancements and existing non-surgical combinative drug delivery methods utilized for treating skin
cancer. It encompasses the diverse pharmaceutical delivery systems, clinical outcomes, and oncology strategies
employed and aims to highlight the role of non-surgical combination therapies in enhancing patient compliance,
reducing treatment durations, and improving overall survival rates while addressing relapses and metastasis.
The promising outlook of the research being conducted in this field has also been provided, as well as
the barriers to the effective treatment of this complex condition.
Novel Therapies for ANCA-associated Vasculitis: Apilimod Ameliorated Endothelial Cells Injury through TLR4/NF-κB Pathway and NLRP3 Inflammasome
Authors: Liu Siyang , Cao Chenlin , Wang Yiru , Hu Liu , Liu Qingquan
Published: June 2024

Background:

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a rapidly progressive
form of glomerulonephritis for which effective therapeutic drugs are currently lacking, and its underlying
mechanism remains unclear.

Aims:

This study aimed to investigate new treatment options for AAV through a combination of bioinformatics
analysis and cell molecular experiments.

Methods:

The research utilized integrated bioinformatics analysis to identify genes with differential expression,
conduct enrichment analysis, and pinpoint hub genes associated with AAV. Potential therapeutic compounds
for AAV were identified using Connectivity Map and molecular docking techniques. In vitro experiments
were then carried out to examine the impact and mechanism of apilimod on endothelial cell injury induced
by MPO-ANCA-positive IgG.

Results:

The findings revealed a set of 374 common genes from differentially expressed genes and key modules
of WGCNA, which were notably enriched in immune and inflammatory response processes. A proteinprotein
interaction network was established, leading to the identification of 10 hub genes, including TYROBP,
PTPRC, ITGAM, KIF20A, CD86, CCL20, GAD1, LILRB2, CD8A, and COL5A2. Analysis from Connectivity
Map and molecular docking suggested that apilimod could serve as a potential therapeutic cytokine inhibitor
for ANCA-GN based on the hub genes. In vitro experiments demonstrated that apilimod could mitigate
tight junction disruption, endothelial cell permeability, LDH release, and endothelial activation induced by
MPO-ANCA-positive IgG. Additionally, apilimod treatment led to a significant reduction in the expression of
proteins involved in the TLR4/NF-κB and NLRP3 inflammasome-mediated pyroptosis pathways.

Conclusion:

This study sheds light on the potential pathogenesis of AAV and highlights the protective role of
apilimod in mitigating MPO-ANCA-IgG-induced vascular endothelial cell injury by modulating the TLR4/
NF-kB and NLRP3 inflammasome-mediated pyroptosis pathway. These findings suggest that apilimod may
hold promise as a treatment for AAV and warrant further investigation.
Exploring the Therapeutic Potential of Triptonide in Salivary Adenoid Cystic Carcinoma: A Comprehensive Approach Involving Network Pharmacology and Experimental Validation
Authors: Geng Shikai , Chen Li , Lin Wanzun , Wan Fangzhu , Le Ziyu , Hu Wei , Chen Huaiyuan , Liu Xingyu , Huang Qingting , Zhang Haojiong , Lu Jiade J. , Kong Lin
Published: June 2024

Background:

Salivary Adenoid Cystic Carcinoma (ACC) is characterized by a highly invasive and
slow-growing pattern, and its etiology remains unidentified. Triptonide (TN) has demonstrated efficacy as a
pharmacotherapeutic agent against ACC. Nonetheless, the specific targets and mechanism of molecular action
underlying the effectiveness of TN in treating ACC have not been elucidated.

Objectives:

By integrating network pharmacology within laboratory experiments, this research delves into the
prospective targets and molecular mechanisms associated with the application of TN in treating ACC.

Methods:

Initially, pertinent targets associated with TN against ACC were acquired from public databases.
Subsequently, a combination of network pharmacology and bioinformatics analysis was utilized to screen the
top 10 hub targets and key signal pathways of TN-treating ACC. Finally, in vitro experiments involving various
molecular assays were conducted to evaluate the biological phenotypes of cells following TN treatment,
encompassing assessments of apoptosis levels, plate migration, and other parameters, thereby validating pivotal
genes and pathways.

Results:

A total of 23 pertinent targets for TN in relation to ACC were identified, with the top 10 hub genes being
MAPK8, PTGS2, RELA, MAPK14, NR3C1, HDAC1, PPARG, NFKBIA, AR, and PGR. There was a significant
correlation between the TNF signaling pathway and the treatment of ACC with TN. In vitro experiments
demonstrated that TN treatment elevated RELA phosphorylation while concurrently reducing MAPK14
phosphorylation and inducing G2/M arrest. TN exhibited the ability to enhance the apoptosis rate through increased
caspase-3 activity, elevated levels of Reactive Oxygen Species (ROS), mitochondrial dysfunction, and
inhibition of cell migration.

Conclusion:

There is a potential therapeutic role for TN in the treatment of ACC through the activation of the
TNF signaling pathway. Among the identified candidates, MAPK8, HDAC1, PTGS2, RELA, NR3C1,
PPARG, NFKBIA, AR, and PGR emerge as the most pertinent therapeutic targets for TN in the context of
ACC treatment.
Study on the Mechanism of the Combination of Methotrexate and Leflunomide in the Treatment of Rheumatoid Arthritis Based on Network
Pharmacology, Molecular Docking, and in vitro Experimental Verification
Authors: Shi Jinyang , Cui Xinhua , Wang Yang , Song Yuli , Tang Xudong , Fan Junwen , Xu Hongyue , Zhu Mingmei , Yu Wanlu , Yu Lu
Published: June 2024

Background:

To date, disease-modifying antirheumatic drugs (DMARDs) are widely
used as the primary first-line treatment option for patients with rheumatoid arthritis (RA), and
the curative effect of methotrexate (MTX) and leflunomide (LEF; MTX + LEF) is greater than
that of single-agent MTX therapy, but the synergistic mechanism of MTX + LEF is unclear.

Methods:

First, we explored the mechanism of action of MTX + LEF in RA through network
pharmacology and molecular docking. Venn diagram analysis revealed 97 overlapping gene
targets of MTX + LEF-RA and STRING, along with Cytoscape plug-in MOCDE and cytoHubba;
and GO enrichment analysis revealed that the functions of 97 synergistic targets were related
to 123 molecular functions (MF), 63 cell components (CC), and 1,068 biological processes
(BP). The Cytoscape plug-in ClueGO demonstrated that these targets were enriched in KEGG
pathways of 52 terms, whereas 9 pivotal genes were mainly involved in the signaling pathways
of estrogen, Ras, Rap1, PI3K-Akt, relaxin, TNF, AMPK, FoxO, prolactin, IL-17, and adherens
junction. Finally, CETSA and DARTS validated the direct binding of MTX or LEF to the selected
target proteins EGFR, PPARG, MMP9, and SRC in RAW264.7 cells.

Results:

We identified 292 MTX targets and 247 LEF targets from 7 databases. Furthermore,
2,814 potential targets of RA were identified by merging 1,925 targets from 7 databases and 999
differentially expressed genes (DEGs) between normal controls and patients with RA extracted
from 5 GEO databases. Nine pivotal genes, ESR1, ALB, CASP3, EGFR, HSP90AA1, SRC,
MMP9, PPARG, and IGF1, were identified. Molecular docking verified that both MTX and
LEF strongly bind to most of the 9 pivotal proteins except ESR1 and IGF1.

Conclusion:

These results contribute to our understanding of the enhancement mechanism of
MTX combined with LEF and provide a targeted basis for the clinical treatment of RA.
Multi-target Compounds against Trypanosomatid Parasites and
Mycobacterium tuberculosis
Authors: Gomes Midiane Correia , Padilha Emanuelly Karla Araújo , Diniz Gustavo Rafael Angelo , Gomes Edilma Correia , da Silva Santos-Júnior Paulo Fernando , Zhan Peng , da Siva-Júnior Edeildo Ferreira
Published: June 2024

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Multi-target drug treatment has become popular as a substitute for traditional monotherapy.
Monotherapy can lead to resistance and side effects. Multi-target drug discovery is gaining
importance as data on bioactivity becomes more abundant. The design of multi-target drugs is expected
to be an important development in the pharmaceutical industry in the near future. This review
presents multi-target compounds against trypanosomatid parasites (Trypanosoma cruzi, T.
brucei, and Leishmania sp.) and tuberculosis (Mycobacterium tuberculosis), which mainly affect
populations in socioeconomically unfavorable conditions. The article analyzes the studies, including
their chemical structures, viral strains, and molecular docking studies, when available. The objective
of this review is to establish a foundation for designing new multi-target inhibitors for these
diseases.
A Low-cost and Rapid Method for Determination of Five Flavonoids in Herbal Medicines with Rutin by HPLC-UV at Equal Absorption Wavelength
Authors: Qian Zhengming , He Zhuobin , Lian Dongyin , Huang Qi , Tan Guoying , Xie Juying
Published: June 2024

Background:

Flavonoid is a type of active constituent in herbs and always used as the
quality control markers of herbal medicines. Owing to the extensive diversity of flavonoids, numerous
reference compounds are necessitated for the analysis of flavonoids, and some are usually very
expensive, which engenders challenges in the analysis of flavonoids in herbal medicines. Consequently,
the development of a simple, rapid, and reference compounds saving method is important
for the determination of flavonoids in herbal medicines.

Objective:

In order to develop a high-performance liquid chromatography (HPLC) method for the
determination of 5 flavonoids (mangiferin, hesperidin, baicalin, buddleoside, and rutin) in five herbal
medicines (Anemarrhenae rhizome, Sophorae flos, Citri reticulatae pericarpium, Scutellariae radix,
and Chrysanthemi indici flos) with rutin.

Methods:

Five herbal medicine samples were prepared according to the Chinese Pharmacopoeia
which includes ultrasound and reflux methods. The separation of the sample was performed on a
PoroShell 120 EC-C18 (4.6 mm×100 mm, 2.7 μm) by gradient elution with 0.1% formic acid and
acetonitrile at a flow rate of 1.0 mL/min. The wavelengths were set as follows: Anemarrhenae rhizome
(363 nm), Sophorae flos (256 nm), Citri reticulatae pericarpium (236 nm), Scutellariae radix
(263 nm), Chrysanthemi indici flos (354 nm).

Results:

The method validation showed that the established HPLC method was accurate and stable
for quantitative analysis of flavonoids in five herbal medicines. The comparative analysis revealed
that the determination results of the current HPLC method and Chinese Pharmacopoeia method are
consistent, exhibiting less than 1% relative error. Remarkably, the developed HPLC method needs
one cheapest reference compound (rutin) and costs 8 min for sample HPLC analysis.

Conclusion:

The developed HPLC method for quantitative analysis of five flavonoids in five herbal
medicines is simple, rapid, and reference compound saving, which provides a good alternative method
for quality control of flavonoids in herbal medicines.
Phage Therapy: Clinical Applications, Efficacy, and Implementation Hurdles
Authors: Fowoyo Patience Temitope
Published: June 2024

The increasing resistance of bacteria to antibiotics has brought back attention to phages with the need to determine their efficacy and possible use in treating antibiotic-resistant infections. Over the years, there has been a gradual uptick in the integration of phages for treatment, although primarily centered around compassionate usage. Despite the recognition of phage’s capacity to counter bacterial infections over a century ago, utilizing with this therapy has encountered numerous impediments. Currently, the efficacy of phages finds validation in numerous favorable case studies centered on individual patients. Nonetheless, a necessity exists for conducting clinical trials and streamlining the research and development procedures to ease the assimilation of these experimental treatments into a widely accepted adjunct to antibiotics. Integrating bacteriophage therapy into standard clinical practice will necessitate substantial, dedicated investments from research institutions and healthcare establishments, demanding collaboration with the international scientific and medical communities. This endeavor should encompass consensus among regulatory agencies and an adaptable perspective that evolves alongside our deepening understanding of the nuances of this promising therapeutic approach.
A Comprehensive Review on History, Sources, Biosynthesis, Chemical Synthesis and Applications of Stilbenes
Authors: Shafiq Nusrat , Jannat Asna , Rashid Maryam , Parveen Shagufta , Noor Nadia
Published: June 2024

This review is about a class of plant polyphenols known as Stilbenes. Resveratrol – the
first stilbene was extracted from White Hellebore in 1940, since then 400 plus stilbene derivatives
have been discovered. The core purpose of this paper is to summarize the history, extraction
sources, biosynthesis and chemical synthesis and applications of stilbenes. Apart from biosynthesis,
its novel derivatives are being synthesized in laboratories. This class of compounds has extensive
clinical (including antioxidant, anticancer, anti-inflammatory activities etc.) and industrial applications
such as optical dyes, laser dyes, scintillators, etc.
Deciphering the Cardiovascular Conundrum of COVID-19: An In-depth
Review
Authors: Yadav Shiv Kumar , Chand Sharad
Published: June 2024

The coronavirus disease pandemic raised a notable deal of discussion among scientists
and the public, in addition to necessitating the adaptation of healthcare staff for nearly two years.
COVID-19 caused various respiratory symptoms and lung damage. In addition, it also played a major role in insulting the circulatory system. The frequency of heart-lung involvement with its inverse
relationship with prognosis is highlighted in the review. Direct cardiac involvement (COVID-19
myocarditis) was followed by subsequent cardiac involvement (myocardial damage, myocardial
infarction, and arrhythmias). The coronavirus disease vaccination's continual effects, cardiovascular
problems, and the way the virus aggravated preexisting cardiovascular illness were ultimately studied in this review.
Strategies to Overcome the Impact of Neglected Diseases on the World
Authors: MP Namratha , Mittal Pooja , Sharma Anjali , Mittal Vishnu
Published: June 2024

Neglected tropical diseases (NTDs) are highly prevalent in Sub-Saharan
Africa. In the World Bank's definition of poverty, nearly all people suffer from at least
one NTD. Among the most widespread NTDs are malaria, HIV, and soil-transmitted
helminths like lymphatic filariasis, schistosomiasis, trachoma, and onchocerciasis. A
recent study suggests that NTDs may influence the evolution of HIV and AIDS,
malaria, and tuberculosis. These interactions may be influenced by epidemiological,
immunological, and clinical factors, which may impair the prognosis for those with
HIV/AIDS, TB, or malaria. World Health Organization (WHO) suggests five main
strategies for preventing and controlling NTDs for public health-intensified case
management, vector control, preventive chemotherapy, sanitation, the provision of safe
water, veterinary public health, and hygiene. Despite only using one method and doing
it locally, to control, and eliminate the NTDs, these methods can be used as a mark for
achieving the Sustainable Development Goals as they are mainly found in
disadvantaged regions and environments. The development of pilot projects and
initiatives can help achieve the Millennium Development Goals. The poor and
marginalised could gain from innovative treatments for neglected diseases (particularly
parasite infections) based on sustainability concepts and knowledge of key factors
affecting health.
Rethinking the Role of Customary Elites: The Flexibility of Adat and the Interest of Customary Elites in Local Politics in Lampung, Indonesia
Authors: Kaneko Masanori , Nurdin Bartoven Vivit , Sari Ifaty Fadliliana , Asnani Asnani , Turki Syifaa Sabianova Addina , Thesalonica Denysha
Published: June 2024

This study examines the customary elites' role in the local socio-political landscape in Lampung, Indonesia. The problem is that so far, the role of customary elites is often ignored in regional development, where they only become political symbols and are used for local political interests in the region. In this case study, customary elites attempt to manage their adat communities so that they make positive contributions to society. Adat still has a significant influence and plays an important role in the daily lives of the Lampung people. However, this is not just community-level regulation or customary law; it also has important cultural and social significance for the nation. This study uses qualitative research methods and an ethnographic approach. Data was collected through in-depth interviews and participant observation with analysis using data reduction, verification, data display, and data triangulation. The result showed that adat helps form and maintain social ties among local communities, contributing to government development programs and administrative changes. In the adat government, traditional elites also represent their adat communities. Adat shows flexibility towards change while preserving local wisdom and contributing to regional development. Customary elites and adat communities have great influence in society, and they are valued and respected by their collective members. Their role should be maximized by local governments in regional development because one of the keys to successful development is utilizing local wisdom because local wisdom is the element that is most adaptable and flexible in change.
Literacy Festival Program as a Means of Ecology Education for Society
Authors: Mulyono Dinno , Hufad Ahmad , Wahyudin Uyu
Published: June 2024

Literacy is one of the supporting concepts for development, including community empowerment. The approach is forming a literacy community that regularly holds literacy festivals. With literacy, society is expected to understand its role in development. The theories used in this study were the concepts of literacy and ecological education. This study applied a descriptive qualitative approach using interviews, observations, and documentation studies. The main reason for choosing the research method was to understand the existing phenomena in-depth and completely, especially in the program implemented by the Bening Saguling Foundation. This study showed that community empowerment developed using a dialogic approach had positive implications for developing the community's ecological and economic awareness. This study concluded that the social literacy approach could develop public awareness of various potentials to direct society to establish economic independence.