bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Whole Genome Screen of Nutrient-Starved Mycobacterium tuberculosis Identifies Genes Involved in Rifampin Tolerance
Authors: Matern William M. , Harris Harley T. , Danchik Carina , McDonald Marissa , Patel Gopi , Srivastava Aashish , Ioerger Thomas R. , Bader Joel S. , Karakousis Petros C.
Published: September 2023

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), poses a global health challenge and is responsible for over a million deaths each year. Current treatment is lengthy and complex, and new, abbreviated regimens are urgently needed. Mtb adapts to nutrient starvation, a condition experienced during host infection, by shifting its metabolism and becoming tolerant to the killing activity of bactericidal antibiotics. An improved understanding of the mechanisms mediating antibiotic tolerance in Mtb can serve as the basis for developing more effective therapies. We performed a forward genetic screen to identify candidate Mtb genes involved in tolerance to the two key first-line antibiotics, rifampin and isoniazid, under nutrient-rich and nutrient-starved conditions. In nutrient-rich conditions, we found 220 mutants with differential antibiotic susceptibility (218 in the rifampin screen and 2 in the isoniazid screen). Following Mtb adaptation to nutrient starvation, 82 mutants showed differential antibiotic susceptibility (80 in the rifampin screen and 2 in the isoniazid screen). Using targeted mutagenesis, we validated the rifampin-hypersusceptible phenotype under nutrient starvation in Mtb mutants lacking the following genes: ercc3, moeA1, rv0049, and rv2179c. These findings shed light on potential therapeutic targets, which could help shorten the duration and complexity of antitubercular regimens.
Chemotaxis of Meloidogyne incognita Response to Rhizosphere Bacteria
Authors: Li Beiyang , Wang Pinyi , Yang Liangliang , Rang Xiaozhan , Zhou Wenzhen , Liu Yajun
Published: September 2023

Rhizosphere microorganisms and the volatile organic compounds (VOCs) produced by them take part in the regulation of the chemotaxis of nematodes. A total of 150 strains of rhizosphere bacteria were screened via a chemotaxis experiment with Meloidogyne incognita. Some isolates affected the behavior of the nematodes, including attraction, randomness, and repulsion. Volatile metabolites produced via the selected bacteria were associated with the chemotaxis of nematodes. M. incognita was highly attracted to decanal. In addition, dimethyl disulfide, 2,5-dimethylpyrazine, pentadecanoic acid, and palmitic acid were found to attract weakly M. incognita. Furthermore, the chemotaxis of M. incognita was tested in a pot experiment. The bacteria Bacillus sp. 1-50, Brevibacillus brevis 2-35, B. cereus 5-14, Chryseobacterium indologens 6-4, and VOC decanal could regulate the movement of M. incognita in the pot with or without plants. The results provide insights into rhizosphere microorganisms and their VOCs and how they regulate the chemotaxis of the nematodes.
Occurrence of a New Variant of Salmonella Infantis Lacking Somatic Antigen
Authors: Alessiani Alessandra , La Bella Gianfranco , Donatiello Adelia , Occhiochiuso Gilda , Faleo Simona , Didonna Antonella , D’Attoli Luigi , Selicato Patrizia , Pedarra Carmine , La Salandra Giovanna , Mancini Maria Emanuela , Di Taranto Pietro , Goffredo Elisa
Published: September 2023

Salmonella Infantis is one of the most frequent serovars reported in broilers and is also regularly identified in human salmonellosis cases, representing a relevant public health problem. In the laboratories of the Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata (IZSPB), six Salmonella Infantis strains with antigenic formula -:r:1,5 have been isolated from the litter and carcass of broilers between 2018 and 2022. The strains were investigated to evaluate their phenotype, antibiotic resistance and genomic profiles. Genomic analysis confirmed that the isolates belonged to the Infantis serotype and to the sequence type ST32. Moreover, all strains showed a multidrug-resistant (MDR) profile and were characterised by the presence of the IncFIB plasmid incompatibility group. Three strains had the blaCTX-M-1 gene, and one of them carried IncX1. The presence of this new variant of S. Infantis is particularly relevant because it could expand the landscape of the S. Infantis population. The absence of the somatic antigen could pose a problem in both isolation and serotyping and a consequent public health concern due to the spread of Salmonella infection.
Identification of Two Clusters in Renal Pelvis Urobiome of Unilateral Stone Formers Using 2bRAD-M
Authors: Hong Sen-Yuan , Miao Lin-Tao , Zhang Jia-Qiao , Wang Shao-Gang
Published: September 2023

Urolithiasis is a common urological disease with increasing incidence and a high recurrence rate, whose etiology is not fully understood. The application of sequencing and culturomics has revealed that urolithiasis is closely related to the urinary microbiome (urobiome), shedding new light on the pathogenesis of stone formation. In this study, we recruited 30 patients with unilateral stones and collected their renal pelvis urine from both sides. Then, we performed 2bRAD-M, a novel sequencing technique that provides precise microbial identification at the species level, to characterize the renal pelvis urobiome of unilateral stone formers in the both sides. We first found that the urobiome in the stone side could be divided into two clusters (Stone1 and Stone2) based on distance algorithms. Stone2 harbored higher microbial richness and diversity compared to Stone1. The genera Cupriavidus and Sphingomonas were overrepresented in Stone1, whereas Acinetobacter and Pseudomonas were overrepresented in Stone2. Meanwhile, differential species were identified between Stone1 and Stone2. We further constructed a random forest model to discriminate two clusters which achieved a powerful diagnostic potential. Moreover, the urobiome of the non-stone side (Control1/2) was compared with that of the stone side (Stone1/2). Stone1 and Control1 showed different microbial community distributions, while Stone2 was similar to Control2 based on diversity analysis. We also identified differentially abundant species among all groups. We assumed that there might be different mechanisms of how microbiota contribute to stone formation in two clusters. Our findings might assist in the selection of suitable medical treatments for urolithiasis.
Phenotypic and Genomic Characteristics of Campylobacter gastrosuis sp. nov. Isolated from the Stomachs of Pigs in Beijing
Authors: Wang Hairui , Gu Yixin , He Lihua , Sun Lu , Zhou Guilan , Chen Xiaoli , Zhang Xin , Shao Zhujun , Zhang Jianzhong , Zhang Maojun
Published: September 2023

Campylobacter is among the four main causes of gastroenteritis worldwide. Most reported Campylobacter infections are caused by C. jejuni and C. coli. However, other emerging Campylobacter pathogens have been recognized as important pathogens in humans and animals. A novel bacterial strain, PS10T, was isolated from the gastric mucous of pigs in 2022 in Beijing, China. The cell was Gram-negative, microaerobic, motile, and negative for catalase, oxidase, and urease. Phylogenetic and phylogenomic analyses based on the 16S rRNA gene and core genome indicated that this isolate belongs to the genus Campylobacter. There were low dDDH relatedness and ANI values shared within this strain and its closest species C. mucosalis below the cut-off values generally recognized for isolates of the same species. The draft genome size of PS10T is 2,240,910 bp in length with a percentage of DNA G+C contents of 37.72%. Comparing the phenotypic and phylogenetic features among this isolate and its related organisms, strain PS10T represents a novel species within the genus Campylobacter, for which the name Campylobacter gastrosuis sp. nov. (Type strain PS10T = GDMCC 1.3686T = JCM 35849T) is proposed.
The Abnormal Accumulation of Lipopolysaccharide Secreted by Enriched Gram-Negative Bacteria Increases the Risk of Rotavirus Colonization in Young Adults
Authors: Wu Yifan , Pei Shuang , Wu Jie , Tu Xinru , Ren Lingling , Ji Yanli , Yao Yuyou , Liu Yehao
Published: September 2023

Human rotavirus (HRV) is an enteric virus that causes infantile diarrhea. However, the risk factors contributing to HRV colonization in young adults have not been thoroughly investigated. Here, we compared the differences in dietary habits and composition of gut microbiota between asymptomatic HRV-infected young adults and their healthy counterparts and investigated potential risk factors contributing to HRV colonization. Our results indicated that asymptomatic HRV-infected adults had an excessive intake of milk and dairy and high levels of veterinary antibiotics (VAs) and preferred veterinary antibiotic (PVAs) residues in urine samples. Their gut microbiota is characterized by abundant Gram-negative (G−) bacteria and high concentrations of lipopolysaccharide (LPS). Several opportunistic pathogens provide discriminatory power to asymptomatic, HRV-infected adults. Finally, we observed an association between HRV colonization and disrupted gut microbiota caused by the exposure to VAs and PVAs. Our study reveals the traits of disrupted gut microbiota in asymptomatic HRV-infected adults and provides a potential avenue for gut microbiota-based prevention strategies for HRV colonization.
Effects of Hypoxemia by Acute High-Altitude Exposure on Human Intestinal Flora and Metabolism
Authors: Qi Ping , Lv Jin , Bai Liu-Hui , Yan Xiang-Dong , Zhang Lei
Published: September 2023

This study examined the effects of hypoxemia caused by acute high-altitude hypoxia (AHAH) exposure on the human intestinal flora and its metabolites. The changes in the intestinal flora, metabolism, and erythropoietin content in the AHAH population under altitude hypoxia conditions were comprehensively analyzed using 16S rRNA sequencing, metabonomics, and erythropoietin content. The results showed that compared with those in the control group (C group), the flora and metabolites in the hypoxemia group (D group) were altered. We found alterations in the flora according to the metabolic marker tyrosine through random forest and ROC analyses. Fecal and serum metabonomics analyses revealed that microbial metabolites could be absorbed into the blood and participate in human metabolism. Finally, a significant correlation between tyrosine and erythropoietin (EPO) content was found, which shows that human intestinal flora and its metabolites can help to confront altitude stress by regulating EPO levels. Our findings provide new insights into the adaptive mechanism and prevention of AHAH.
Isolation of Latilactobacillus curvatus with Enhanced Nitric Oxide Synthesis from Korean Traditional Fermented Food and Investigation of Its Probiotic Properties
Authors: Jin Hao , Park Sang-Kyu , Yun Yong-Gun , Song Nho-Eul , Baik Sang-Ho
Published: September 2023

Nitric oxide (NO) is a free radical associated with physiological functions such as blood pressure regulation, cardiovascular health, mitochondrial production, calcium transport, oxidative stress, and skeletal muscle repair. This study aimed to isolate Latilactobacillus curvatus strains with enhanced NO production from the traditional Korean fermented food, jangajji, and evaluate their probiotic properties for industrial purposes. When cells were co-cultured with various bacterial stimulants, NO production generally increased, and NO synthesis was observed in the range of 20–40 mg/mL. The selected strains of Lat. curvatus were resistant to acid and bile conditions and with variable effectiveness (1–14%) in adhering to Caco-2 cells. Most bacterial strains can inhibit the growth of various pathogens. In addition, they are capable of reducing cholesterol levels via assimilation of cholesterol at 10–50%. Among the selected NO synthases from Lat. curvatus strains, the strain JBCC38 showed the highest capacity to scavenge ABTS (30.1%) and DPPH radicals (39.4%). Moreover, these strains exhibited immunomodulatory properties. The production of TNF-α and IL-6 in the macrophages treated with various bacterial stimulants was induced in all the selected strains.
Clinical Predictors of Monkeypox Diagnosis: A Case-Control Study in a Nonendemic Region during the 2022 Outbreak
Authors: De la Herrán-Arita Alberto Kousuke , González-Galindo Cuitláhuac , Inzunza-Leyva Gerardo Kenny , Valdez-Flores Marco Antonio , Norzagaray-Valenzuela Claudia Desiree , Camacho-Zamora Alejandro , Batiz-Beltrán José Candelario , Urrea-Ramírez Francisco Javier , Romero-Utrilla Alejandra , Angulo-Rojo Carla , Guadrón-Llanos Alma Marlene , Picos-Cárdenas Verónica Judith , Camberos-Barraza Josué , Rábago-Monzón Ángel Radamés , Osuna-Ramos Juan Fidel
Published: September 2023

Monkeypox (Mpox) is an emerging zoonotic disease with the potential for severe complications. Early identification and diagnosis are essential to prompt treatment, control its spread, and reduce the risk of human-to-human transmission. This study aimed to develop a clinical diagnostic tool and describe the clinical and sociodemographic features of 19 PCR-confirmed Mpox cases during an outbreak in a nonendemic region of northwestern Mexico. The median age of patients was 35 years, and most were male. Mpox-positive patients commonly reported symptoms such as fever, lumbago, and asthenia, in addition to experiencing painful ulcers and a high frequency of HIV infection among people living with HIV (PLWH). Two diagnostic models using logistic regression were devised, with the best model exhibiting a prediction accuracy of 0.92 (95% CI: 0.8–1), a sensitivity of 0.86, and a specificity of 0.93. The high predictive values and accuracy of the top-performing model highlight its potential to significantly improve early Mpox diagnosis and treatment in clinical settings, aiding in the control of future outbreaks.
Development, Validation, and Two-Year Application of Rapid and Simple LC-MS/MS-Based Method for the Determination of K2MK-7 in Blood Samples
Authors: Paprotny Łukasz , Szewczak Dorota , Bryshten Iryna , Wianowska Dorota
Published: September 2023

Biological properties of menaquinone-7, one of the vitamin K2 vitamers (K2MK-7), both those proven and those that remain to be investigated, arouse extensive interest that goes beyond the strictly scientific framework. The most important of them is the prevention of age-related diseases, considering that we live in the times identified as the era of aging societies and many people are exposed to the vitamin K2MK-7 deficiency. Therefore, an effective analytical protocol that can be adopted as a diagnostic and preventive analytics tool is needed. Herein, a simple sample preparation method followed by the liquid chromatography-tandem mass spectrometry-based method (LC-MS/MS), was used for the selective and sensitive determination of K2MK-7 in serum samples. Under the optimized conditions, using 500 µL of serum and the same amount of n-hexane, the reproducibility and the accuracy were obtained in the ranges of 89–97% and 86–110%, respectively, and the limit of detection value was 0.01 ng/mL. This method was used for the routine analysis. Statistical interpretation of the data from 518 samples obtained during 2 years of practice allowed for obtaining information on the content and distribution of K2MK-7 in the Polish population, broken down by the sex and age groups.
A Review of Theoretical Studies on Carbon Monoxide Hydrogenation via Fischer–Tropsch Synthesis over Transition Metals
Authors: Jamaati Maryam , Torkashvand Mostafa , Sarabadani Tafreshi Saeedeh , de Leeuw Nora H.
Published: September 2023

The increasing demand for clean fuels and sustainable products has attracted much interest in the development of active and selective catalysts for CO conversion to desirable products. This review maps the theoretical progress of the different facets of most commercial catalysts, including Co, Fe, Ni, Rh, and Ru. All relevant elementary steps involving CO dissociation and hydrogenation and their dependence on surface structure, surface coverage, temperature, and pressure are considered. The dominant Fischer–Tropsch synthesis mechanism is also explored, including the sensitivity to the structure of H-assisted CO dissociation and direct CO dissociation. Low-coordinated step sites are shown to enhance catalytic activity and suppress methane formation. The hydrogen adsorption and CO dissociation mechanisms are highly dependent on the surface coverage, in which hydrogen adsorption increases, and the CO insertion mechanism becomes more favorable at high coverages. It is revealed that the chain-growth probability and product selectivity are affected by the type of catalyst and its structure as well as the applied temperature and pressure.
Advances and Challenges in Plant Sterol Research: Fundamentals, Analysis, Applications and Production
Authors: Evtyugin Dmitry D. , Evtuguin Dmitry V. , Casal Susana , Domingues Maria Rosário
Published: September 2023

Plant sterols (PS) are cholesterol-like terpenoids widely spread in the kingdom Plantae. Being the target of extensive research for more than a century, PS have topped with evidence of having beneficial effects in healthy subjects and applications in food, cosmetic and pharmaceutical industries. However, many gaps in several fields of PS’s research still hinder their widespread practical applications. In fact, many of the mechanisms associated with PS supplementation and their health benefits are still not fully elucidated. Furthermore, compared to cholesterol data, many complex PS chemical structures still need to be fully characterized, especially in oxidized PS. On the other hand, PS molecules have also been the focus of structural modifications for applications in diverse areas, including not only the above-mentioned but also in e.g., drug delivery systems or alternative matrixes for functional foods and fats. All the identified drawbacks are also superimposed by the need of new PS sources and technologies for their isolation and purification, taking into account increased environmental and sustainability concerns. Accordingly, current and future trends in PS research warrant discussion.
Distribution, Typical Structure and Self-Assembly Properties of Collagen from Fish Skin and Bone
Authors: Zhang Xuening , Wang Jie , Zhang Qian , Fan Yan , Zhang Hongwei , Ahmad Khurshid , Hou Hu
Published: September 2023

The source and type of collagen are crucial to its application, and both play a decisive role. Collagen was prepared from both tilapia skin and bone and skate skin and cartilage, named as CI-TI-s, CI-TI-b, CI-SK-s, and CII-SK-c, respectively. Types, distributions, structures, and self-assembly of collagen were studied. It showed that yellow collagen fibers from skin arranged longitudinally, while collagen fibers from skate cartilages displayed varying colors. CI-TI-s, CI-TI-b, CI-SK-s, and CII-SK-c showed the typical amide A (3316–3336 cm−1) and amide B (2929–2948 cm−1) in FTIR spectra. CI-TI-b and CII-SK-c showed 218–229 nm of UV absorption, 11.56–12.20 Å of d values in XRD, and 0.12–0.14 of Rpn values in CD. The thermal denaturation temperatures of CI-TI-s and CI-SK-s were 30.7 and 20.6 °C, respectively. The self-assembly of CI-TI-s and CII-SK-c were maximum at pH 7.2 and 7.4–7.6, respectively. The unique collagen peptides of tilapia and skate were GPSGPQGAVGATGPK, PAMPVPGPMGPMGPR, SPAMPVPGPMGPMGPR, GESGPSGPAGPAGPAGVR, SSGPPVPGPIGPMGPR, GLTGPIGVPGPPGAQGEK, GLAGPQGPR, and GLSGDPGVQGIK, respectively. The unique peptides of type I and type II collagen were GPTGEIGATGLAGAR, GVLGLTGMR, LGLTGMR, GEPGAAGPAGPSGPMGPR, SSGPPVPGPIGPMGPR, and GLSGDPGVQGIK, respectively.
Polydentate N,O-Ligands Possessing Unsymmetrical Urea Fragments Attached to a p-Cresol Scaffold
Authors: Todorova Stanislava E. , Rusew Rusi I. , Shivachev Boris L. , Kurteva Vanya B.
Published: September 2023

In this study, three series of polydentate N,O-ligands possessing unsymmetrical urea fragments attached to a p-cresol scaffold are obtained, namely mono- and bi-substituted open-chain aromatics, synthesised using a common experiment, as well as fused aryloxazinones. Separate protocols for the preparation of each series are developed. It is found that in the case of open-chain compounds, the reaction output is strongly dependent on both bis-amine and carbamoyl chloride substituents, while oxazinones can be effectively obtained via a common protocol. The products are characterized via 1D and 2D NMR spectra in solution and using single-crystal XRD. A preliminary study on the coordination abilities of the products performed via ITC shows that there are no substantial interactions in the pH range of 5.0–8.5 in general.
Fine-Tuning of the Optical and Electrochemical Properties of Ruthenium(II) Complexes with 2-Arylbenzimidazoles and 4,4′-Dimethoxycarbonyl-2,2′-bipyridine
Authors: Lavrova Maria A. , Verzun Stepan A. , Mishurinskiy Sergey A. , Sirotin Maxim A. , Bykova Sofya K. , Gontcharenko Victoria E. , Mariasina Sofia S. , Korshunov Vladislav M. , Taydakov Ilya V. , Belousov Yury A. , Dolzhenko Vladimir D.
Published: September 2023

A series of cyclometalated complexes of ruthenium (II) with four different substituents in the aryl fragment of benzimidazole was synthesized in order to study the effect of substituent donation on the electronic structure of the substances. The resulting complexes were studied using X-ray diffraction, NMR spectroscopy, MALDI mass spectrometry, electron absorption spectroscopy, luminescence spectroscopy, and cyclic voltammetry as well as DFT/TDDFT was also used to interpret the results. All the complexes have intense absorption in the range of up to 700 nm, the triplet nature of the excited state was confirmed by measurement of luminescence decay. With an increase in substituent donation, a red shift of the absorption and emission bands occurs, and the lifetime of the excited state and the redox potential of the complex decrease. The combination of these properties shows that the complexes are excellent dyes and can be used as photosensitizers.
Thermal Investigations of Annelated Triazinones—Potential Analgesic and Anticancer Agents
Authors: Sztanke Małgorzata , Sztanke Krzysztof , Ostasz Agnieszka , Głuchowska Halina , Łyszczek Renata
Published: September 2023

In this article, for the first time, TG-DSC and TG-FTIR investigations of potential pharmaceutics, i.e., analgesic and anticancer active annelated triazinones (1–9) have been presented. The thermal behaviour of these molecules was established in oxidative and inert conditions. The solid–liquid phase transition for each compound (1–9) was documented by one sharp DSC peak confirming the high purity of each sample studied. All the molecules were characterised in terms of calorimetric changes and mass changes during their heating. They revealed high thermal stability in oxidative and inert conditions. The observed tendency in thermal stability changes in relation to a substituent present at the phenyl moiety was found to be similar in air and nitrogen. It was confirmed that annelated triazinones 1–9 were stable up to a temperature range of 241–296 °C in air, and their decomposition process proceeded in two stages under oxidative conditions. In addition, it was established that their thermal stability in air decreased in the following order of R at the phenyl moiety: 4-Cl > 3,4-Cl2 > H > 3-Cl > 4-CH3 > 2-CH3 > 3-CH3 > 2-Cl > 2-OCH3. The volatile decomposition products of the investigated molecules were proposed by comparing the FTIR spectra collected during their thermogravimetric analysis in nitrogen with the spectra from the database of reference compounds. None of annelated triazinones 1–9 underwent any polymorphic transformation during thermal studies. All the compounds proved to be safe for erythrocytes. In turn, molecules 3, 6, and 9 protected red blood cells from oxidative damage, and therefore may be helpful in the prevention of free radical-mediated diseases.
Electrophysical Properties and Heat Capacity of Activated Carbon Obtained from Coke Fines
Authors: Ordabaeva Aigul T. , Muldakhmetov Zainulla M. , Kim Sergey V. , Kasenova Shuga B. , Sagintaeva Zhenisgul I. , Gazaliev Arstan M.
Published: September 2023

This paper studies the dependence of the specific heat capacity (Cp) of activated carbon obtained by the activation of coke fines on temperature (T, K) and the dependence of electrical resistance (R, Om) on temperature (T, K). In the course of the work, it was found that in the temperature range of 298.15–448 K on the curve of dependence Cp − f(T) at 323 K there is a jump in heat capacity, associated with a phase transition of the second kind. Measurements of the temperature dependence of electrical resistance on temperature were also carried out, which showed that activated carbon in the temperature range of 293–343 K exhibits metallic conductivity, turning into a semiconductor in the temperature range of 343–463 K. The calculation of the band gap showed that the resulting activated carbon is a semiconductor with a moderately narrow band gap. The satisfactory agreement of the phase transition temperatures on the curves of the temperature dependences of the heat capacity on temperature (323 K) and on the curves of the dependences of electrical resistance and the relative permittivity on temperature (343 K) indicates the nature of this phase transition, i.e., at a temperature of 323 K, the change in heat capacity is associated with the transition from semiconductor conductivity to metallic.
Bioactivity-Guided Synthesis: In Silico and In Vitro Studies of β-Glucosidase Inhibitors to Cope with Hepatic Cytotoxicity
Authors: Khushal Aneela , Farooq Umar , Khan Sara , Rasul Azhar , Wani Tanveer A. , Zargar Seema , Shahzad Sohail Anjum , Bukhari Syed Majid , Khan Nazeer Ahmad
Published: September 2023

The major cause of hyperglycemia can generally be attributed to β-glucosidase as per its involvement in non-alcoholic fatty liver disease. This clinical condition leads to liver carcinoma (HepG2 cancer). The phthalimides and phthalamic acid classes possess inhibitory potential against glucosidase, forming the basis for designing new phthalimide and phthalamic acid analogs to test their ability as potent inhibitors of β-glucosidase. The study also covers in silico (molecular docking and MD simulations) and in vitro (β-glucosidase and HepG2 cancer cell line assays) analyses. The phthalimide and phthalamic acid derivatives were synthesized, followed by spectroscopic characterization. The mechanistic complexities associated with β-glucosidase inhibition were identified via the docking of the synthesized compounds inside the active site of the protein, and the results were analyzed in terms of the best binding energy and appropriate docking pose. The top-ranked compounds were subjected to extensive MD simulation studies to understand the mode of interaction of the synthesized compounds and binding energies, as well as the contribution of individual residues towards binding affinities. Lower RMSD/RMSF values were observed for 2c and 3c, respectively, in the active site, confirming more stabilized, ligand-bound complexes when compared to the free state. An anisotropic network model was used to unravel the role of loop fluctuation in the context of ligand binding and the dynamics that are distinct to the bound and free states, supported by a 3D surface plot. An in vitro study revealed that 1c (IC50 = 1.26 µM) is far better than standard acarbose (2.15 µM), confirming the potential of this compound against the target protein. Given the appreciable potential of the candidate compounds against β-glucosidase, the synthesized compounds were further tested for their cytotoxic activity against hepatic carcinoma on HepG2 cancer cell lines. The cytotoxicity profile of the synthesized compounds was performed against HepG2 cancer cell lines. The resultant IC50 value (0.048 µM) for 3c is better than the standard (thalidomide: IC50 0.053 µM). The results promise the hypothesis that the synthesized compounds might become potential drug candidates, given the fact that the β-glucosidase inhibition of 1c is 40% better than the standard, whereas compound 3c holds more anti-tumor activity (greater than 9%) against the HepG2 cell line than the known drug.
Investigation of the Impact of L-Phenylalanine and L-Tyrosine Pre-Treatment on the Uptake of 4-Borono-L-Phenylalanine in Cancerous and Normal Cells Using an Analytical Approach Based on SC-ICP-MS
Authors: Balcer Emilia , Giebułtowicz Joanna , Sochacka Małgorzata , Ruszczyńska Anna , Muszyńska Magdalena , Bulska Ewa
Published: September 2023

Boron has gained significant attention in medical research due to its B-10 isotope’s high cross section for the reaction with thermal neutrons, generating ionizing particles that can eliminate cancer cells, propelling the development of boron neutron capture therapy (BNCT) for cancer treatment. The compound 4-borono-L-phenylalanine (BPA) has exhibited potential in BNCT clinical trials. Enhancing BPA uptake in cells involves proposing L-amino acid preloading. This study introduces a novel analytical strategy utilizing ICP-MS and single cell ICP-MS (SC-ICP-MS) to assess the effectiveness of L-tyrosine and L-phenylalanine preloading on human non-small cell lung carcinoma (A549) and normal Chinese hamster lung fibroblast (V79-4) models, an unexplored context. ICP-MS outcomes indicated that L-tyrosine and L-phenylalanine pre-treatment increased BPA uptake in V79-4 cells by 2.04 ± 0.74-fold (p = 0.000066) and 1.46 ± 0.06-fold (p = 0.000016), respectively. Conversely, A549 cells manifested heightened BPA uptake solely with L-tyrosine preloading, with a factor of 1.24 ± 0.47 (p = 0.028). BPA uptake remained higher in A549 compared to V79-4 regardless of preloading. SC-ICP-MS measurements showcased noteworthy boron content heterogeneity within A549 cells, signifying diverse responses to BPA exposure, including a subset with notably high BPA uptake. This study underscores SC-ICP-MS’s utility in precise cellular boron quantification, validating cellular BPA uptake’s heterogeneity.
Fibrillization Process of Human Amyloid-Beta Protein (1–40) under a Molecular Crowding Environment Mimicking the Interior of Living Cells Using Cell Debris
Authors: Hirai Mitsuhiro , Arai Shigeki , Iwase Hiroki
Published: September 2023

Molecular crowding environments play a crucial role in understanding the mechanisms of biological reactions. Inside living cells, a diverse array of molecules coexists within a volume fraction ranging from 10% to 30% v/v. However, conventional spectroscopic methods often face difficulties in selectively observing the structures of particular proteins or membranes within such molecularly crowded environments due to the presence of high background signals. Therefore, it is crucial to establish in vitro measurement conditions that closely resemble the intracellular environment. Meanwhile, the neutron scattering method offers a significant advantage in selectively observing target biological components, even within crowded environments. Recently, we have demonstrated a novel scattering method capable of selectively detecting the structures of targeted proteins or membranes in a closely mimicking intracellular milieu achieved utilizing whole-cell contents (deuterated-cell debris). This method relies on the inverse contrast matching technique in neutron scattering. By employing this method, we successfully observed the fibrillization process of human amyloid beta-protein (Aβ 1–40) under a molecular crowding environment (13.1% w/v cell debris, Aβ/cell debris = ~1/25 w/w) that closely mimics the interior of living cells. Aβ protein is well known as a major pathogenic component of Alzheimer’s disease. The present results combining model simulation analyses clearly show that the intracellular environment facilitates the potential formation of even more intricate higher-order aggregates of Aβ proteins than those previously reported.
A Novel Antimicrobial Peptide, Dermaseptin-SS1, with Anti-Proliferative Activity, Isolated from the Skin Secretion of Phyllomedusa tarsius
Authors: Ma Xiaonan , Chen Yuping , Shu Anmei , Jiang Yangyang , Chen Xiaoling , Ma Chengbang , Zhou Mei , Wang Tao , Chen Tianbao , Shaw Chris , Wang Lei
Published: September 2023

The emergence of multidrug-resistant bacteria has severely increased the burden on the global health system, and such pathogenic infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly attracting great interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin-secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a ‘shotgun’ cloning strategy. The chemically synthesized peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed lower salt sensitivity and more rapid bacteria killing compared to SS1. Both peptides employed a membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues against lung cancer cell lines was found to be significant.
Adsorption of Methyl Orange from Water Using Chitosan Bead-like Materials
Authors: Alyasi Haya , Mackey Hamish , McKay Gordon
Published: September 2023

Natural product waste treatment and the removal of harmful dyes from water by adsorption are two of the crucial environmental issues at present. Traditional adsorbents are often not capable in removing detrimental dyes from wastewater due to their hydrophilic nature and because they form strong bonds with water molecules, and therefore they remain in the dissolved state in water. Consequently, new and effective sorbents are required to reduce the cost of wastewater treatment as well as to mitigate the health problems caused by water pollution contaminants. In this study, the adsorption behaviour of methyl orange, MO, dye on chitosan bead-like materials was investigated as a function of shaking time, contact time, adsorbent dosage, initial MO concentration, temperature and solution pH. The structural and chemical properties of chitosan bead-like materials were studied using several techniques including SEM, BET, XRD and FTIR. The adsorption process of methyl orange by chitosan bead materials was well described by the Langmuir isotherm model for the uptake capacity and followed by the pseudo-second-order kinetic model to describe the rate processes. Under the optimal conditions, the maximum removal rate (98.9%) and adsorption capacity (12.46 mg/g) of chitosan bead-like materials were higher than those of other previous reports; their removal rate for methyl orange was still up to 87.2% after three regenerative cycles. Hence, this chitosan bead-like materials are very promising materials for wastewater treatment.
Identification of Antioxidative Hydrolyzable Tannins in Water Chestnut
Authors: Uchikura Takashi , Miura Yuka , Yoshimura Morio , Ito Hideyuki , Amakura Yoshiaki
Published: September 2023

Despite the various biological activities exhibited by water chestnut (the fruit of the Trapa genus), the phenolic compounds present in its extract require comprehensive characterization. Accordingly, we analyzed a 80% methanol extract of commercially available water chestnut and identified a new hydrolyzable tannin dimer termed trapadin A. Additionally, 22 known compounds, including 10 hydrolyzable tannin monomers and 2 dimers, were also detected in the extract. Spectroscopic and chemical methods were used to elucidate the structure of trapadin A, revealing it to be a hydrolyzable tannin dimer formed from units of tellimagrandin II and 1,2,3,6-tetra-O-galloyl-β-d-glucose. Moreover, the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity assay used to determine the half-maximal effective concentration values for the 23 compounds isolated from water chestnut indicated significant radical scavenging activity associated with hydrolyzable tannins. Notably, trapadin A, the new hydrolyzable tannin dimer, exhibited the highest activity value among the tested compounds.
Overview on the Development of Alkaline-Phosphatase-Linked Optical Immunoassays
Authors: Liu Lin , Chang Yong , Lou Jiaxin , Zhang Shuo , Yi Xinyao
Published: September 2023

The drive to achieve ultrasensitive target detection with exceptional efficiency and accuracy requires the advancement of immunoassays. Optical immunoassays have demonstrated significant potential in clinical diagnosis, food safety, environmental protection, and other fields. Through the innovative and feasible combination of enzyme catalysis and optical immunoassays, notable progress has been made in enhancing analytical performances. Among the kinds of reporter enzymes, alkaline phosphatase (ALP) stands out due to its high catalytic activity, elevated turnover number, and broad substrate specificity, rendering it an excellent candidate for the development of various immunoassays. This review provides a systematic evaluation of the advancements in optical immunoassays by employing ALP as the signal label, encompassing fluorescence, colorimetry, chemiluminescence, and surface-enhanced Raman scattering. Particular emphasis is placed on the fundamental signal amplification strategies employed in ALP-linked immunoassays. Furthermore, this work briefly discusses the proposed solutions and challenges that need to be addressed to further enhance the performances of ALP-linked immunoassays.
Bioactive Properties, Bioavailability Profiles, and Clinical Evidence of the Potential Benefits of Black Pepper (Piper nigrum) and Red Pepper (Capsicum annum) against Diverse Metabolic Complications
Authors: Dludla Phiwayinkosi V. , Cirilli Ilenia , Marcheggiani Fabio , Silvestri Sonia , Orlando Patrick , Muvhulawa Ndivhuwo , Moetlediwa Marakiya T. , Nkambule Bongani B. , Mazibuko-Mbeje Sithandiwe E. , Hlengwa Nokulunga , Hanser Sidney , Ndwandwe Duduzile , Marnewick Jeanine L. , Basson Albertus K. , Tiano Luca
Published: September 2023

The consumption of food-derived products, including the regular intake of pepper, is increasingly evaluated for its potential benefits in protecting against diverse metabolic complications. The current study made use of prominent electronic databases including PubMed, Google Scholar, and Scopus to retrieve clinical evidence linking the intake of black and red pepper with the amelioration of metabolic complications. The findings summarize evidence supporting the beneficial effects of black pepper (Piper nigrum L.), including its active ingredient, piperine, in improving blood lipid profiles, including reducing circulating levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in overweight and obese individuals. The intake of piperine was also linked with enhanced antioxidant and anti-inflammatory properties by increasing serum levels of superoxide dismutase while reducing those of malonaldehyde and C-reactive protein in individuals with metabolic syndrome. Evidence summarized in the current review also indicates that red pepper (Capsicum annum), together with its active ingredient, capsaicin, could promote energy expenditure, including limiting energy intake, which is likely to contribute to reduced fat mass in overweight and obese individuals. Emerging clinical evidence also indicates that pepper may be beneficial in alleviating complications linked with other chronic conditions, including osteoarthritis, oropharyngeal dysphagia, digestion, hemodialysis, and neuromuscular fatigue. Notably, the beneficial effects of pepper or its active ingredients appear to be more pronounced when used in combination with other bioactive compounds. The current review also covers essential information on the metabolism and bioavailability profiles of both pepper species and their main active ingredients, which are all necessary to understand their potential beneficial effects against metabolic diseases.
Effect of Dietary Fiber Supplementation on Metabolic Endotoxemia: A Protocol for Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Ranneh Yazan , Fadel Abdulmannan , Md Akim Abdah , Idris Iskandar , Ilesanmi-Oyelere Bolaji Lilian , Ismail Leila Cheikh
Published: September 2023

Introduction: Metabolic endotoxemia (ME) is the main cause of sub-clinical chronic inflammation, which subsequently triggers the onset of several chronic diseases. However, recent reports have indicated that dietary fiber (DF) contributes significantly to ameliorating ME and inflammation. This protocol aims to provide an outline of all procedures in synthesizing the available data on the effect of DF against ME. Methods: Following the PRISMA 2020 guidelines for preparing protocols, this protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) with registration number (CRD42023417833). In this review, we specifically focused on the inclusion of clinical trials that met the following criteria: they were published or available as preprints, employed random, quasi-random, or cross-over designs, and were exclusively documented in the English language. Clinical medical subject headings (MeSH) as search terms were used on prominent databases such as MEDLINE, COCHRANE library, PubMed, World Health Organization International Clinical Trials Registry Platforms, and US National Institutes of Health Ongoing Trials Register Clinicaltrials.gov. Results and discussion: This protocol will guide the exploration of articles that report changes in ME biomarkers in subjects supplemented with DF. The findings of this protocol will ensure a comprehensive evaluation of available evidence, provide a quantitative summary, identify patterns and trends, enhance statistical power, and address heterogeneity, which collectively will clarify the optimal types, doses, and duration of DF interventions for managing ME and low-grade inflammation. Ethics and dissemination: The quantitative data of clinical trials will be collected, and a meta-analysis will be performed using RevMan V.5.3 software. Therefore, no ethical approval is required.
Prevalence and Associated Factors of Cigarette Smoking among South African Adolescents and Young Adults: A Systematic Review and Meta-Analysis Protocol
Authors: Londani Mukhethwa , Oladimeji Olanrewaju
Published: September 2023

Tobacco use, particularly the initiation of smoking during adolescence and young adulthood, represents a significant public health concern in South Africa. The influence of socio-cultural factors, marketing strategies of the tobacco industry, and accessibility of tobacco products have all been implicated in this context. This systematic review and meta-analysis protocol aims to scrutinise the body of literature on this issue, providing a comprehensive understanding of the patterns and determinants of tobacco use among South African adolescents and young adults, with an eye towards informing more effective policy interventions. The available literature for studies on tobacco use will be systematically searched and reviewed. Five international scholarly databases, namely PubMed, MEDLINE, EMBASE, Global Health, and Scopus, will be searched. Peer-reviewed studies will be included if they are conducted in South Africa or South African provinces and if they include the prevalence of tobacco use among adolescents and young adults aged between 12 and 24 years. The results of such an analysis can guide future policy designs, enabling them to be more targeted and thus more effective. The findings can also have implications for shaping global tobacco control strategies, given the transferability of successful interventions across different populations and cultural contexts. This protocol has been registered in the PROSPERO database (ID: CRD42023428369).
A Novel Method for Reducing the Lift-Off Effect in Coercivity Measurement through Auxiliary Inductance Data
Authors: Lyu Ruilin , Meng Tian , Shao Yuchun , Salas Avila Jorge Ricardo , Yin Wuliang
Published: September 2023

Coercivity is the strength of the reverse magnetic field required to demagnetize a material after saturation, and it is an indication of the hardness of magnetic materials. Air gaps cause errors in coercivity measurement referred to as the lift-off effect. This paper proposes a new method to address this issue by incorporating additional inductance measurements and formulating a calibration method. The calibration principle is based on the fact that both the coercivity and the inductance measurements change with the variation of air gaps. This paper starts by finding how coercivity changes with air gaps between the sensor and the sample, then derives the coefficients for the coercivity–inductance relationship for different samples. A correction method is then proposed to predict the base coercivity (i.e., the coercivity when the air gap = 0) using the inductance and coercivity measurement results at an unknown lift-off. The measurement system was implemented, and experimental results suggest the error caused by air gaps can be reduced from 40% to less than 10%.
Exploring the Impact of Training Methods on Repeated Sprints in Hypoxia Training Effects
Authors: Rojas-Valverde Daniel , Vasquez-Bonilla Aldo A. , Timón Rafael , Feliu-Ilvonen Joan M. , Martínez-Guardado Ismael , Olcina Guillermo
Published: September 2023

Background: Emerging evidence suggests that the outcomes of hypoxia training may be influenced by various factors, contingent upon the chosen method, such as chamber, tent, or mask. This study aimed to examine how different training methods influence the effects of Repeated Sprints in Hypoxia (RSH) training. Methods: Sixteen well-trained cyclists were divided into two groups, experimental (tent; n = 8) and control (mask; n = 8), and carried out eight RSH sessions for four weeks. Training sessions consisted of three bouts of high-intensity sprints using a cycle ergometer. The indoor ambient conditions (CO2, temperature, and humidity), performance variables (power and relative power output), arterial oxygen saturation, local muscle oxygen of vastus lateralis, heart rate, core temperature, and physiological variables (perception of effort) were measured in each training session. Results: The experimental group reported significantly higher CO2 (p < 0.001 ES = 0.784), humidity levels (p < 0.001 ES = 0.750), thermal discomfort (p = 0.003 ES = 0.266), dehydration (p 0.025 ES = 0.097), heart rate (p = 0.017 ES = 0.113), and lower muscle oxygen amplification (p = 0.002 ES = 0.181) than the control group. Conclusion: According to the responses observed, interval training performed under hypoxic conditions inside a chamber induces a more severe physiological response.
Chronic Diarrhea Due to Aeromonas hydrophila in an Immunosuppressed Patient with a Pancreas–Kidney Transplant
Authors: Solís-Sánchez Pablo , Fernández-Martínez Marta , Rodrigo-Calabia Emilio , de Alegría-Puig Carlos Ruiz
Published: September 2023

The genus Aeromonas belongs to the Aeromonadaceae family. A patient with a pancreas–kidney transplant had multiple episodes of abdominal sepsis after surgery. Aeromonas hydrophila was isolated in the ascitic and biliary fluid drains. After discharge, the patient had several diarrhea episodes, and A. hydrophila was isolated in four stool samples. We decided to test whether the one strain that we initially isolated in ascitic fluid was the same that appeared in the successive stool samples. Five isolates of A. hydrophila were found in the patient. Identification was performed using the MALDI-TOF system and confirmed via multiplex PCR. The analysis of the REP-PCR fingerprint patterns showed one cluster and confirmed that all isolates were related. We also demonstrated the virulent character of this species associated with genes encoding different toxins (act, alt, ast, hlyA, and aerA). The virulence of this species is associated with the expression of genes that encode different toxins, structural proteins, and metal-associated proteins. This case report highlights the severity of this disease, especially in immunocompromised patients, and its adequate treatment.