bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of agricultural production waste in relation to bio nano technology for the synthesis of functionalized selenium nanoparticles
Authors: Bityutskyy V. , Tsekhmistrenko S. , Demchenko O. , Tsekhmistrenko O. , Melnichenko O. , Melnichenko Yu. , Oleshko O.
Published: March 2023

The application of nanotechnological innovations to increase the effectiveness of the bioflavonoid quercetin is considered. The ability to functionalize with specific ligands that target specific organs or cells is very important because it is possible to increase the concentration of quercetin at the desired target level while reducing side effects. Quercetin, as a flavonoid antioxidant, is widely used to reduce oxidative stress and activate important signalling pathways in cells. However, poor solubility in water, intensive first-pass metabolism limits its use. A strategy for the development of nanocomposites is presented, which involves combining quercetin obtained from agricultural waste with selenium nanoparticles. In vitro results demonstrated that quercetin-nanoselenium has high water solubility compared to individual flavonoids. It has been proven that quercetin-nano-selenium nanoparticles are capable of reducing 1,1-dipheny l-2-picrylhydrazyl (DPPH) radicals and are characterized by high antioxidant activity. The ability to functionalize nanoparticles with specific ligands that target the modulation of specific signaling pathways (Keap1/ Nrf2/ARE, Nf-kB, mTOR) in individual cells is very important, as it allows increasing the concentration of quercetin to the desired level while reducing side effects. Considering the beneficial effects of quercetin, a strategy has been developed that involves the use of selenium nanoparticles to deliver quercetin in a specific and controlled manner. Research in this direction is promising, as it will contribute to clarifying the expediency of using such nanosystems, which have not yet been widely used. The use of onion waste and its extracts in biotechnology, biomedicine, pharmaceuticals and the agro-industrial sector can be an optimal solution for reducing environmental damage. In addition, it will provide an economically determined alternative for the production of feed additives for animals and poultry. Compounds of quercetin with nanoselenium should take a worthy place in clinical medical practice, biology and agriculture. The beneficial effects of quercetin can be further enhanced with the help of nanotechnology, which will contribute to the effective use of this compound with such great biological potential.
Key words: nanobiotechnologies, waste, onion peel, 1,1-dipheny l- 2-picrylhydrazyl, antiradical activity.
Uncovering the molecular mechanisms underlying arrhythmogenic cardiomyopathy using the CRISPR-toolbox
Authors:   , van Kampen Sebastiaan Johannes
Published: March 2023

In Chapter 1B and chapter 1C, we provide an overview of the challenges encountered within the cardiac biology research field and how the CRISPR/Cas9 toolbox can facilitate in overcoming these limitations.

Chapter 2 describes a novel heterozygous knock-in mouse model bearing a known pathogenic variant in PKP2. We demonstrate the value of matching this model with an equivalent hiPSC-derived cardiomyocyte model bearing the same heterozygous mutation, revealing that degradation of desmosomal proteins is a driving force behind ACM pathogenesis. These findings were further validated in human explanted ACM hearts.

In chapter 3 we identified a novel DSP mutation found in a patient experiencing arrhythmogenic episodes. Using CRISPR/Cas9, we created two isogenic pairs of hiPSC lines to study the clinical relevance of this mutation. In one set we corrected patient-derived cells and in the other set we introduced the mutation in the endogenous locus of commercially bought control hiPSCs. This approach underscored the advantages but also the disadvantages of hiPSC-derived cardiomyocyte models and allowed us to rigidly identify PITX2 as a novel factor involved in ACM pathology.

In chapter 4 we performed spatial transcriptomics on the left ventricular wall of an explanted heart obtained from an ACM patient bearing a nonsense mutation in DSP. The overall goal was to identify disease-driving factors by comparing relatively healthy myocardial regions with areas of active remodeling. We used a KI hiPSC-derived cardiomyocyte model, bearing a known pathogenic nonsense mutation in DSP, to assess the relevance of the identified candidates.

Chapter 5 summarizes the results obtained from two novel heterozygous KI mouse models bearing mutations in DSP, which are equivalent to the human mutations introduced in chapters 3 and 4. This study highlights the challenges and dissimilarities between a rationally designed mouse model and the clinical situation observed in patients.

Chapter 6 is an introduction to CRISPR prime editing. Not only do we show that this novel methodology has the potential to overcome limitations inherent to the basic CRISPR/Cas9 machinery, but also how we want to exploit this system to efficiently restore the PKP2 mutation introduced in chapter 2.

Chapter 7 summarizes all the studies and their contribution towards furthering our understanding of ACM pathology. Finally, a brief outlook is given with respect to CRISPR-based methodologies and ACM pathogenesis.
Laser-activated nanoparticles for ultrasound/photoacoustic imaging-guided prostate cancer treatment
Authors: Xiao Linkang , Wu Yunfang , Dai Junyong , Zhang Weili , Cao Yang
Published: March 2023

Prostate cancer (PCa) is the most common malignant tumor in men. Prostate-specific membrane antigen (PSMA), which is overexpressed on the surface of Prostate cancer cells, may serve as a potential therapeutic target. Recently, image-guided and targeted therapy for prostate cancers has attracted much attention by using Prostate-specific membrane antigen targeting nanoparticle. In this study, we produced PSMA-targeted light-responsive nanosystems. These nanosystems of liquid perfluorocarbon cores and polymer shells were loaded with the photosensitizer IR780 and therapeutic drugs paclitaxel. The liquid perfluorocarbon (PFP) in nanoparticles can perform ultrasound-enhanced imaging by liquid-gas transition and promote the deliver and release of paclitaxel. IR780 can perform photothermal therapy (PTT) guided by photoacoustic (PA) imaging. Combination treatment with photothermal therapy and chemotherapy exhibited excellent inhibition of cell proliferation in vitro and a significant therapeutic effect in vivo. In conclusion, we successfully formulated PSMA-targeted nanosystems with precision targeting and ultrasound/PA dual-modality imaging for anti-tumor effects.
Radical scavenging activity of Chlorophytum borivilianum L. root extract and its protective role in cauda epididymal sperm integrity in Mus musculus after gamma irradiation
Authors: Vyas Ruchi , Kesari Kavindra Kumar , Lukac Norbert , Slama Petr , Roychoudhury Shubhadeep , Sisodia Rashmi
Published: March 2023

Background:Chlorophytumborivilianum L. is a recognized herbal medicine for the management of impotency in South Asian countries. In Ayurveda, it is used for the management of multiple health conditions, including diabetes, infection, and cardiovascular diseases. Parts of the plant have been used as excellent antioxidants and scavengers of free radicals. Since oxidative stress plays an important role in spermatogenesis and fertility in male populations, this study evaluated the role of ethanolic extract of C. borivilianum roots in epididymal sperm maturation against adversities posed by ionizing gamma irradiation.

Materials and methods: Antioxidant potential of C. borivilianum root extract (CRE) was evaluated through DPPH (2,2-diphenylpicrylhydrazyl) and NO (nitric oxide) scavenging assays. Four groups of healthy Swiss albino mice were constituted, which were labeled as follows: Group I: sham control, Group II: 7-day pre-treatment with 50 mg/kg CRE, Group III: 6 Gy irradiation without pre-treatment, and Group IV: 7-day pre-treatment with 50 mg/kg CRE and 6 Gy irradiation on day 7. Swiss albino mice were observed for 30 days and later sacrificed to evaluate sperm quality parameters.

Results: CRE showed a remarkable antioxidant potential with IC50 values of 46.37 μg/ml and 98.39 μg/ml for DPPH and NO, respectively. A significant decline (p < 0.001) in cauda epididymal sperm count, motility, and viability was observed in Group III animals. Group IV also showed a substantial decline (p < 0.01) in all three parameters compared to Group I; nonetheless, these were significantly higher than Group III. Morphological alterations indicated a coiled and bent tail, with the presence of cytoplasmic droplets in Group III, which declined substantially in Group IV. The ultrastructure of sperm indicated higher curvature of hook in Group III than Group IV, indicating specific interferences in the sperm maturation process.

Conclusion: It was concluded that pre-treatment with 50 mg/kg body weight of CRE could protect sperm during epididymal maturation against oxidative stress.
The epigenetic function of androgen receptor in prostate cancer progression
Authors: Sawada Takahiro , Kanemoto Yoshiaki , Kurokawa Tomohiro , Kato Shigeaki
Published: March 2023

Androgen and androgen deprivation (castration) therapies, including androgen receptor antagonists, are clinically used to treat patients with prostate cancer. However, most hormone-dependent prostate cancer patients progress into a malignant state with loss of hormone-dependency, known as castration (drug)-resistant prostate cancer (CRPC), after prolong androgen-based treatments. Even in the CRPC state with irreversible malignancy, androgen receptor (AR) expression is detectable. An epigenetic transition to CRPC induced by the action of AR-mediated androgen could be speculated in the patients with prostate cancer. Androgen receptors belongs to the nuclear receptor superfamily with 48 members in humans, and acts as a ligand-dependent transcriptional factor, leading to local chromatin reorganization for ligand-dependent gene regulation. In this review, we discussed the transcriptional/epigenetic regulatory functions of AR, with emphasis on the clinical applications of AR ligands, AR protein co-regulators, and AR RNA coregulator (enhancer RNA), especially in chromatin reorganization, in patients with prostate cancer.
Epigenetic clocks and female fertility timeline: A new approach to an old issue?
Authors: Li Piani Letizia , Vigano' Paola , Somigliana Edgardo
Published: March 2023

Worldwide increase in life expectancy has boosted research on aging. Overcoming the concept of chronological age, higher attention has been addressed to biological age, which reflects a person’s real health state, and which may be the resulting combination of both intrinsic and environmental factors. As epigenetics may exert a pivotal role in the biological aging, epigenetic clocks were developed. They are based on mathematical models aimed at identifying DNA methylation patterns that can define the biological age and that can be adopted for different clinical scopes (i.e., estimation of the risks of developing age-related disorders or predicting lifespan). Recently, epigenetic clocks have gained a peculiar attention in the fertility research field, in particular in the female counterpart. The insight into the possible relations between epigenetic aging and women’s infertility might glean additional information about certain conditions that are still not completely understood. Moreover, they could disclose significant implications for health promotion programs in infertile women. Of relevance here is that the impact of biological age and epigenetics may not be limited to fertility status but could translate into pregnancy issues. Indeed, epigenetic alterations of the mother may transfer into the offspring, and pregnancy itself as well as related complications could contribute to epigenetic modifications in both the mother and newborn. However, even if the growing interest has culminated in the conspicuous production of studies on these topics, a global overview and the availability of validated instruments for diagnosis is still missing. The present narrative review aims to explore the possible bonds between epigenetic aging and fertility timeline. In the “infertility” section, we will discuss the advances on epigenetic clocks focusing on the different tissues examined (endometrium, peripheral blood, ovaries). In the “pregnancy” section, we will discuss the results obtained from placenta, umbilical cord and peripheral blood. The possible role of epigenetic aging on infertility mechanisms and pregnancy outcomes represents a question that may configure epigenetic clock as a bond between two apparently opposite worlds: infertility and pregnancy.
A multi-subgroup predictive model based on clinical parameters and laboratory biomarkers to predict in-hospital outcomes of plasma exchange-centered artificial liver treatment in patients with hepatitis B virus-related acute-on-chronic liver failure
Authors: Liu Jie , Shi Xinrong , Xu Hongmin , Tian Yaqiong , Ren Chaoyi , Li Jianbiao , Shan Shigang , Liu Shuye
Published: March 2023

Background

Postoperative risk stratification is challenging in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) who undergo artificial liver treatment. This study characterizes patients’ clinical parameters and laboratory biomarkers with different in-hospital outcomes. The purpose was to establish a multi-subgroup combined predictive model and analyze its predictive capability.

Methods

We enrolled HBV-ACLF patients who received plasma exchange (PE)-centered artificial liver support system (ALSS) therapy from May 6, 2017, to April 6, 2022. There were 110 patients who died (the death group) and 110 propensity score-matched patients who achieved satisfactory outcomes (the survivor group). We compared baseline, before ALSS, after ALSS, and change ratios of laboratory biomarkers. Outcome prediction models were established by generalized estimating equations (GEE). The discrimination was assessed using receiver operating characteristic analyses. Calibration plots compared the mean predicted probability and the mean observed outcome.

Results

We built a multi-subgroup predictive model (at admission; before ALSS; after ALSS; change ratio) to predict in-hospital outcomes of HBV-ACLF patients who received PE-centered ALSS. There were 110 patients with 363 ALSS sessions who survived and 110 who did not, and 363 ALSS sessions were analyzed. The univariate GEE models revealed that several parameters were independent risk factors. Clinical parameters and laboratory biomarkers were entered into the multivariate GEE model. The discriminative power of the multivariate GEE models was excellent, and calibration showed better agreement between the predicted and observed probabilities than the univariate models.

Conclusions

The multi-subgroup combined predictive model generated accurate prognostic information for patients undergoing HBV-ACLF patients who received PE-centered ALSS.
Effect of rheological heterogeneities on the lithospheric deformation of the Tibetan Plateau and neighbouring regions
Authors: Sun Yujun , Li Hailong , Fan Taoyuan , Li Bing
Published: March 2023

The Tibetan Plateau, induced by the India-Eurasian collision, has the highest average altitude in the world. During its uplift vertically, the Tibetan Plateau has been considered to expand laterally. However, there are several strong and almost non-deformable cratons on its periphery, such as the Tarim, North China craton, and South China block. The present landform features show that these cratons limit the expansion of the Tibetan Plateau. However, there is still much controversy over whether the deformation can be transmitted to periphery orogens or reactivate ancient orogens in the cratons. This study used numerical models to investigate the effect of rheological heterogeneities on the lithospheric deformation of the Tibetan Plateau and its neighbouring regions. The results show that the lateral heterogeneities of the lithosphere have an important influence on the deformation or strain partitioning. Generally, during the lateral expansion of the Tibetan Plateau, its peripheral cratons can transmit the deformation or high strain to neighbouring weak orogens. This case can be used to understand the Tian Shan orogen, which was reactivated by the India-Eurasian collision. However, when the orogens inside the cratons have high lithospheric strength, high strain is difficult to distribute on them and the expanding Tibetan Plateau is constrained by its peripheral cratons. These results can be used to explain the ancient orogens that are not strongly deformed, such as the Jiangnan orogen in the South China block. Because these orogens formed at the same time as the cratons and have relatively high lithospheric strength. In addition, the large lithospheric thickness difference and low crustal rheological contrast favor high strain rates localized on the lithosphere of the ancient orogen in the craton, such as the Trans-North China orogen in the North China craton.
Proteomic analysis reveals semaglutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice
Authors: Zhu Ruiyi , Chen Shuchun
Published: March 2023

Background and objectives

Obesity is a global health problem with few pharmacologic options. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that induces weight loss. Yet, the role of semaglutide in adipose tissue has not yet been examined. The following study investigated the mechanism of semaglutide on lipid metabolism by analyzing proteomics of epididymal white adipose tissue (eWAT) in obese mice.

Methods

A total of 36 C57BL/6JC mice were randomly divided into a normal-chow diet group (NCD, n = 12), high-fat diet (HFD, n = 12), and HFD+semaglutide group (Sema, n = 12). Mice in the Sema group were intraperitoneally administered semaglutide, and the HFD group and the NCD group were intraperitoneally administered an equal volume of normal saline. Serum samples were collected to detect fasting blood glucose and blood lipids. The Intraperitoneal glucose tolerance test (IPGTT) was used to measure the blood glucose value at each time point and calculate the area under the glucose curve. Tandem Mass Tag (TMT) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to study the expression of eWAT, while cellular processes, biological processes, corresponding molecular functions, and related network molecular mechanisms were analyzed by bioinformatics.

Results

Compared with the model group, the semaglutide-treated mice presented 640 differentially expressed proteins (DEPs), including 292 up-regulated and 348 down-regulated proteins. Bioinformatics analysis showed a reduction of CD36, FABP5, ACSL, ACOX3, PLIN2, ANGPTL4, LPL, MGLL, AQP7, and PDK4 involved in the lipid metabolism in the Sema group accompanied by a decrease in visceral fat accumulation, blood lipids, and improvement in glucose intolerance.

Conclusion

Semaglutide can effectively reduce visceral fat and blood lipids and improve glucose metabolism in obese mice. Semaglutide treatment might have beneficial effects on adipose tissues through the regulation of lipid uptake, lipid storage, and lipolysis in white adipose tissue.
Comprehensive review of carbon quantification by improved forest management offset protocols
Authors: Haya Barbara K. , Evans Samuel , Brown Letty , Bukoski Jacob , Butsic Van , Cabiyo Bodie , Jacobson Rory , Kerr Amber , Potts Matthew , Sanchez Daniel L.
Published: March 2023

Improved forest management (IFM) has the potential to remove and store large quantities of carbon from the atmosphere. Around the world, 293 IFM offset projects have produced 11% of offset credits by voluntary offset registries to date, channeling substantial climate mitigation funds into forest management projects. This paper summarizes the state of the scientific literature for key carbon offset quality criteria—additionality, baselines, leakage, durability, and forest carbon accounting—and discusses how well currently used IFM protocols align with this literature. Our analysis identifies important areas where the protocols deviate from scientific understanding related to baselines, leakage, risk of reversal, and the accounting of carbon in forests and harvested wood products, risking significant over-estimation of carbon offset credits. We recommend specific improvements to the protocols that would likely result in more accurate estimates of program impact, and identify areas in need of more research. Most importantly, more conservative baselines can substantially reduce, but not resolve, over-crediting risk from multiple factors.
Distribution of a novel CYP2C haplotype in Native American populations
Authors: Fernandes Vanessa Câmara , Pretti Marco Antônio M. , Tsuneto Luiza Tamie , Petzl-Erler Maria Luiza , Suarez-Kurtz Guilherme
Published: March 2023

The CYP2C19 gene, located in the CYP2C cluster, encodes the major drug metabolism enzyme CYP2C19. This gene is highly polymorphic and no-function (CYP2C19*2 and CYP2C19*3), reduced function (CYP2C19*9) and increased function (CYP2C19*17) star alleles (haplotypes) are commonly used to predict CYP2C19 metabolic phenotypes. CYP2C19*17 and the genotype-predicted rapid (RM) and ultrarapid (UM) CYP2C19 metabolic phenotypes are absent or rare in several Native American populations. However, discordance between genotype-predicted and pharmacokinetically determined CYP2C19 phenotypes in Native American cohorts have been reported. Recently, a haplotype defined by rs2860840T and rs11188059G alleles in the CYP2C cluster has been shown to encode increased rate of metabolism of the CYP2C19 substrate escitalopram, to a similar extent as CYP2C19*17. We investigated the distribution of the CYP2C:TG haplotype and explored its potential impact on CYP2C19 metabolic activity in Native American populations. The study cohorts included individuals from the One Thousand Genomes Project AMR superpopulation (1 KG_AMR), the Human Genome Diversity Project (HGDP), and from indigenous populations living in Brazil (Kaingang and Guarani). The frequency range of the CYP2C:TG haplotype in the study cohorts, 0.469 to 0.598, is considerably higher than in all 1 KG superpopulations (range: 0.014—to 0.340). We suggest that the high frequency of the CYP2C:TG haplotype might contribute to the reported discordance between CYP2C19-predicted and pharmacokinetically verified CYP2C19 metabolic phenotypes in Native American cohorts. However, functional studies involving genotypic correlations with pharmacokinetic parameters are warranted to ascertain the importance of the CYP2C:TG haplotype.
Molecular tracking of insulin resistance and inflammation development on visceral adipose tissue
Authors: Bensussen Antonio , Torres-Magallanes José Antonio , Roces de Álvarez-Buylla Elena
Published: March 2023

Background

Visceral adipose tissue (VAT) is one of the most important sources of proinflammatory molecules in obese people and it conditions the appearance of insulin resistance and diabetes. Thus, understanding the synergies between adipocytes and VAT-resident immune cells is essential for the treatment of insulin resistance and diabetes.

Methods

We collected information available on databases and specialized literature to construct regulatory networks of VAT resident cells, such as adipocytes, CD4+ T lymphocytes and macrophages. These networks were used to build stochastic models based on Markov chains to visualize phenotypic changes on VAT resident cells under several physiological contexts, including obesity and diabetes mellitus.

Results

Stochastic models showed that in lean people, insulin produces inflammation in adipocytes as a homeostatic mechanism to downregulate glucose intake. However, when the VAT tolerance to inflammation is exceeded, adipocytes lose insulin sensitivity according to severity of the inflammatory condition. Molecularly, insulin resistance is initiated by inflammatory pathways and sustained by intracellular ceramide signaling. Furthermore, our data show that insulin resistance potentiates the effector response of immune cells, which suggests its role in the mechanism of nutrient redirection. Finally, our models show that insulin resistance cannot be inhibited by anti-inflammatory therapies alone.

Conclusion

Insulin resistance controls adipocyte glucose intake under homeostatic conditions. However, metabolic alterations such as obesity, enhances insulin resistance in adipocytes, redirecting nutrients to immune cells, permanently sustaining local inflammation in the VAT.
Orf virus DNA prime-protein boost strategy is superior to adenovirus-based vaccination in mice and sheep
Authors: Wang Yan , Sun Shihui , Zhao Kui , Du Le , Wang Xinyue , He Wenqi , Gao Feng , Song Deguang , Guan Jiyu
Published: March 2023

Contagious ecthyma (Orf), an acute and highly contagious zoonosis, is prevalent worldwide. Orf is caused by Orf virus (ORFV), which mainly infects sheep/goats and humans. Therefore, effective and safe vaccination strategies for Orf prevention are needed. Although immunization with single-type Orf vaccines has been tested, heterologous prime-boost strategies still need to be studied. In the present study, ORFV B2L and F1L were selected as immunogens, based on which DNA, subunit and adenovirus vaccine candidates were generated. Of note, heterologous immunization strategies using DNA prime-protein boost and DNA prime-adenovirus boost in mice were performed, with single-type vaccines as controls. We have found that the DNA prime-protein boost strategy induces stronger humoral and cellular immune responses than DNA prime-adenovirus boost strategy in mice, which was confirmed by the changes in specific antibodies, lymphocyte proliferation and cytokine expression. Importantly, this observation was also confirmed when these heterologous immunization strategies were performed in sheep. In summary, by comparing the two immune strategies, we found that DNA prime-protein boost strategy can induce a better immune response, which provides a new attempt for exploring Orf immunization strategy.
Identification of key genes and imbalance of immune cell infiltration in immunoglobulin A associated vasculitis nephritis by integrated bioinformatic analysis
Authors: Jia Xianxian , Zhu Hua , Jiang Qinglian , Gu Jia , Yu Shihan , Chi Xuyang , Wang Rui , Shan Yu , Jiang Hong , Ma Xiaoxue
Published: March 2023

Background

IgAV, the most common systemic vasculitis in childhood, is an immunoglobulin A-associated immune complex-mediated disease and its underlying molecular mechanisms are not fully understood. This study attempted to identify differentially expressed genes (DEGs) and find dysregulated immune cell types in IgAV to find the underlying pathogenesis for IgAVN.

Methods

GSE102114 datasets were obtained from the Gene Expression Omnibus (GEO) database to identify DEGs. Then, the protein-protein interaction (PPI) network of the DEGs was constructed using the STRING database. And key hub genes were identified by cytoHubba plug-in, performed functional enrichment analyses and followed by verification using PCR based on patient samples. Finally, the abundance of 24 immune cells were detected by Immune Cell Abundance Identifier (ImmuCellAI) to estimate the proportions and dysregulation of immune cell types within IgAVN.

Result

A total of 4200 DEGs were screened in IgAVN patients compared to Health Donor, including 2004 upregulated and 2196 downregulated genes. Of the top 10 hub genes from PPI network, STAT1, TLR4, PTEN, UBB, HSPA8, ATP5B, UBA52, and CDC42 were verified significantly upregulated in more patients. Enrichment analyses indicated that hub genes were primarily enriched in Toll-like receptor (TLR) signaling pathway, nucleotide oligomerization domain (NOD)-like receptor signaling pathway, and Th17 signaling pathways. Moreover, we found a diversity of immune cells in IgAVN, consisting mainly of T cells. Finally, this study suggests that the overdifferentiation of Th2 cells, Th17 cells and Tfh cells may be involved in the occurrence and development of IgAVN.

Conclusion

We screened out the key genes, pathways and maladjusted immune cells and associated with the pathogenesis of IgAVN. The unique characteristics of IgAV-infiltrating immune cell subsets were confirmed, providing new insights for future molecular targeted therapy and a direction for immunological research on IgAVN.
Insights into monkeypox pathophysiology, global prevalence, clinical manifestation and treatments
Authors: Niu Liyan , Liang Dingfa , Ling Qin , Zhang Jing , Li Ziwen , Zhang Deju , Xia Panpan , Zhu Zicheng , Lin Jitao , Shi Ao , Ma Jianyong , Yu Peng , Liu Xiao
Published: March 2023

On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent of monkeypox, is a zoonotic, linear, double-stranded DNA virus. In 1970, the Democratic Republic of the Congo reported the first case of MPV infection. Human-to-human transmission can happen through sexual contact, inhaled droplets, or skin-to-skin contact. Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs, including the skin, gastrointestinal tract, genitals, lungs, and liver. By September 9, 2022, more than 57,000 cases had been reported in 103 locations, especially in Europe and the United States. Infected patients are characterized by physical symptoms such as red rash, fatigue, backache, muscle aches, headache, and fever. A variety of medical strategies are available for orthopoxviruses, including monkeypox. Monkeypox prevention following the smallpox vaccine has shown up to 85% efficacy, and several antiviral drugs, such as Cidofovir and Brincidofovir, may slow the viral spread. In this article, we review the origin, pathophysiology, global epidemiology, clinical manifestation, and possible treatments of MPV to prevent the propagation of the virus and provide cues to generate specific drugs.
Case report: Rapid development of amyloid A amyloidosis in temporal arteritis with SAA1.3 allele; An unusual case of intestinal amyloidosis secondary to temporal arteritis
Authors: Yoshida Shuhei , Matsumoto Haruki , Temmoku Jumpei , Shakespear Norshalena , Kiko Yuichiro , Kikuchi Kentaro , Sumichika Yuya , Saito Kenji , Fujita Yuya , Matsuoka Naoki , Asano Tomoyuki , Sato Shuzo , Suzuki Eiji , Watanabe Hiroshi , Ohira Hiromasa , Migita Kiyoshi
Published: March 2023

Temporal arteritis (TA) is a large-vessel vasculitis mostly seen in older patients. Amyloid A (AA) amyloidosis secondary to a chronic inflammation induces multiple organ dysfunctions, including a dysfunction of the gastrointestinal tract. Herein, we present a case of TA complicated by AA amyloidosis that was resistant to oral and intravenous steroids. An 80-year-old man with a history of new-onset headache, jaw claudication, and distended temporal arteries was referred to our department. On admission, the patient presented with tenderness and a subcutaneous temporal nodule in both temple arteries. Ultrasonography of the nodule revealed an anechoic perivascular halo surrounding the right temporal artery. Following the diagnosis of TA, high-dose prednisolone therapy was initiated. However, the patient presented with recurrent abdominal pain and refractory diarrhea. Due to the unclear origin of refractory diarrhea, an extensive workup, including biopsy of the duodenal mucosa, was performed. Endoscopy revealed chronic inflammation in the duodenum. Immunohistochemical analysis of duodenal mucosal biopsy samples revealed AA amyloid deposition resulting in the diagnosis of AA amyloidosis. After tocilizumab (TCZ) administration, refractory diarrhea reduced; however, the patient died of intestinal perforation 1 month after the start of TCZ administration. Gastrointestinal involvement was the main clinical manifestation of AA amyloidosis in the present case. This case highlights the importance of bowel biopsy screening for amyloid deposition in patients with unexplained gastrointestinal tract symptoms, even in a recent onset of large-vessel vasculitis. In the present case, the carriage of the SAA1.3 allele likely contributed to the rare association of AA amyloidosis with TA.
Laboratory evaluation of broflanilide (TENEBENAL™) against Anopheles gambiae in Moshi, Tanzania – delayed mortality, cross-resistance, and residual efficacy
Authors: Snetselaar Janneke , Rowland Mark W. , Azizi Salum , Mawa Benson , Malone David J. , Kirby Matthew J.
Published: March 2023

Introduction

Broflanilide is a novel meta-diamide insecticide, which has a distinct mode of action compared to other active ingredients used for Indoor Residual Spraying (IRS). This study details a laboratory evaluation of broflanilide, of putative discriminating concentrations, potential cross-resistance, and residual efficacy on two substrates.

Methods

Mosquitoes were exposed to broflanilide in bottle bioassays to determine lethal concentrations (LC50 and LC95). These were used to calculate resistance ratios between the susceptible Kisumu and the pyrethroid-resistant Muleba-Kis strains of Anopheles gambiae s.s. Prototype wettable powder formulations of broflanilide were applied to mud and concrete to determine the optimal observation period for determining delayed mortality, and a Cox proportional hazards model was fitted to determine a potential dose response effect. Subsequently, residual efficacy of application rates ranging between 25 mg/m2 and 300 mg/m2 were monitored monthly.

Results

LC values of tested strains were not significantly different; therefore, the polyfactorial resistance mechanisms possessed by the resistant strain did not confer resistance to broflanilide. A significant effect of concentration and time since spraying was found on mosquito survival, indicating that higher broflanilide concentrations are more effective and that this effect was strongest immediately after spraying. Knockdown at 60min post exposure was negligible, with on average only 1% of all mosquitoes knocked down. On the mud surface, but not on concrete, there was a delayed killing effect, with mortality increasing until 72 hours after exposure. The residual efficacy test indicated that on concrete the 100 mg/m2 and 200 mg/m2 concentrations of both broflanilide 50WP formulations remained efficacious for 9 months post spraying. On mud, there were large variations in mosquito mortality from month to month. Generally, higher concentrations resulted in higher mortality, despite variation over time.

Discussion

Cross-resistance to broflanilide was not detected in mosquitoes with multiple resistance mechanisms. This opens up the possibility for wide-scale use of broflanilide, especially in areas with established pyrethroid resistance. Like some other insecticide classes, delayed mortality up to 72 hours post exposure was found for broflanilide. Promising residual efficacy was found with broflanilide 50WP formulations on concrete. On mud, efficacy varied and further testing with a refined formulation is recommended.
Hybrid dynamic modeling and receding horizon speed optimization for liner shipping operations from schedule reliability and energy efficiency perspectives
Authors: Zheng Jian , Mao Chuanshuo , Zhang Qiang
Published: March 2023

Uncertainties in port handling efficiency can cause port delays in the liner shipping system. Furthermore, policies on carbon emission reduction, such as EEXI standards, restrict the potential for speed optimization in liner shipping operations. Traditional tactical planning speed optimization is unsuitable for operational-level decision making, leading to unreliable schedules. From a schedule-reliability and energy-efficiency perspective, we propose a real-time speed optimization method based on discrete hybrid automaton (DHA) and decentered model predictive control (DMPC). We use a dynamic adjustment of sailing speed to offset the disturbance caused by port handling efficiency uncertainties. First, we establish a DHA model that describes each ship’s hybrid dynamics of state switching between sailing and berthing; then, we develop a prediction model for the DMPC controller, which is analogous to the DHA model. The schedule is transferred into time–position coordinates as controller reference trajectories in the receding horizon speed optimization framework. We consider determining tracking errors, carbon emissions, and fuel consumption as our objectives, and we carry out engine power limitation (EPL) analysis for the sample ship, which turns the EEXI standards into constraints. We attain the recommended speed by solving a mixed-integer optimization. We carry out a case study, and our results indicate the effectiveness of our proposed DHA-DMPC scheme in lowering port delays and achieving the best trade-off between schedule reliability and energy efficiency. Additionally, we conduct further experiments to analyze the impacts of various carbon reduction policies on the performance levels of liner shipping operations.
Biologically Important Areas for bowhead whales (Balaena mysticetus): Optimal site selection with integer programming
Authors: Ferguson Megan C. , Tóth Sándor F. , Clarke Janet T. , Willoughby Amy L. , Brower Amelia A. , White Timothy P.
Published: March 2023

Place-based approaches to marine conservation identify areas that are crucial to the success of populations, species, communities, or ecosystems, and that may be candidates for special management actions. In the United States, the National Oceanic and Atmospheric Administration defined Biologically Important Areas (BIAs) for cetaceans (whales, dolphins, and porpoises) as areas and periods that individual populations or species are known to preferentially use for certain activities or where small resident populations occur. The activities considered to be biologically important are feeding, migrating, and activities associated with reproduction. We present an approach using spatial optimization to refine the BIA delineation process to be more objective and reproducible for conservation planners and decision makers who wish to use various spatial criteria to address conservation or management objectives. We present a case study concerning feeding bowhead whales (Balaena mysticetus) and bowhead whale calves in the western Beaufort Sea to illustrate the mechanics and benefits of our optimization model. In the case study, we incorporate spatial information about whales’ relative density and optimally delineate BIAs under different thresholds for minimum patch (cluster) size and total area encompassed within the BIA network. Results from our case study showed three consistent patterns related to minimum cluster size (contiguity) and maximum area threshold for both BIA types and all months: (1) cells with the highest whale density were selected when contiguity or maximum area thresholds were small; (2) for a given area threshold, the number of whales inside BIAs was inversely proportional to cluster size; and (3) the number of whales inside BIAs initially increased rapidly as the area threshold increased, but eventually approached an asymptote. Additionally, information on temporal variability in a BIA may influence the development of conservation, management, monitoring, or mitigation methods. To provide additional insight into the ecological characteristics of the BIAs selected during the optimization step, we quantified inter-annual variability in whale occurrence and density within individual BIAs using statistical techniques. The bowhead whale BIAs and associated information that we present can be incorporated with other relevant information (e.g., objectives, stressors, costs, acceptable risk, legal constraints) into conservation and management decision-making processes.
Case report: Osteosarcomatous differentiation in the lung metastasis of a malignant phyllodes tumor
Authors: Liu Ruijing , Xue Jingli , Liu Wen , Jiang Beibei , Shi Fuyun , Wang Zhenzheng , Li Peifeng
Published: March 2023

Malignant phyllodes tumor is a rare breast tumor, with distant metastases and heterologous differentiation in a few cases. We report a case of malignant phyllodes tumor with liposarcomatous differentiation in the primary tumor and osteosarcomatous differentiation in the lung metastatic tumor. A middle-aged female presented with a well-defined mass in the upper lobe of the right lung measuring 5.0 × 5.0 × 3.0 cm. The patient had a history of malignant phyllodes tumor in the breast. The patient underwent a right superior lobectomy. Histologically, the primary tumor was a typical malignant phyllodes tumor with pleomorphic liposarcomatous differentiation, while the lung metastasis showed osteosarcomatous differentiation without original biphasic features. The phyllodes tumor and heterologous components showed CD10 and p53 expression, and were negative for ER, PR, and CD34. Exome sequencing revealed TP53, TERT, EGFR, RARA, RB1, and GNAS mutations in all three components. Although the lung metastasis were morphologically different from the primary breast tumor, their common origin was demonstrated through immunohistochemical and molecular characterization. Cancer stem cells give rise to tumor heterogeneous cells, and heterologous components in malignant phyllodes tumors may indicate unfavorable prognosis and a greater risk of early recurrence and metastasis.
iTRAQ-based proteomics analysis of Bacillus pumilus responses to acid stress and quorum sensing in a vitamin C fermentation system
Authors: Zhang Qian , Lyu Shuxia
Published: March 2023

Microbial consortia play a key role in human health, bioenergy, and food manufacturing due to their strong stability, robustness and versatility. One of the microbial consortia consisting of Ketogulonicigenium vulgare and Bacillus megaterium for the production of the vitamin C precursor, 2-keto-L-gulonic acid (2-KLG), has been widely used for large-scale industrial production. To further investigate the cell–cell communication in microbial consortia, a microbial consortium consisting of Ketogulonicigenium vulgare and Bacillus pumilus was constructed and the differences in protein expression at different fermentation time points (18 h and 40 h) were analyzed by iTRAQ-based proteomics. The results indicated that B. pumilus was subjected to acid shocks in the coculture fermentation system and responded to it. In addition, the quorum sensing system existed in the coculture fermentation system, and B. pumilus could secrete quorum-quenching lactonase (YtnP) to inhibit the signaling pathway of K. vulgare. This study offers valuable guidance for further studies of synthetic microbial consortia.
Molecular characterization of Paenibacillus antarcticus IPAC21, a bioemulsifier producer isolated from Antarctic soil
Authors: de Lemos Ericka Arregue , Procópio Luciano , da Mota Fabio Faria , Jurelevicius Diogo , Rosado Alexandre Soares , Seldin Lucy
Published: March 2023

Paenibacillus antarcticus IPAC21, an endospore-forming and bioemulsifier-producing strain, was isolated from King George Island, Antarctica. As psychrotolerant/psychrophilic bacteria can be considered promising sources for novel products such as bioactive compounds and other industrially relevant substances/compounds, the IPAC21 genome was sequenced using Illumina Hi-seq, and a search for genes related to the production of bioemulsifiers and other metabolic pathways was performed. The IPAC21 strain has a genome of 5,505,124 bp and a G + C content of 40.5%. Genes related to the biosynthesis of exopolysaccharides, such as the gene that encodes the extracellular enzyme levansucrase responsible for the synthesis of levan, the 2,3-butanediol pathway, PTS sugar transporters, cold-shock proteins, and chaperones were found in its genome. IPAC21 cell-free supernatants obtained after cell growth in trypticase soy broth at different temperatures were evaluated for bioemulsifier production by the emulsification index (EI) using hexadecane, kerosene and diesel. EI values higher than 50% were obtained using the three oil derivatives when IPAC21 was grown at 28°C. The bioemulsifier produced by P. antarcticus IPAC21 was stable at different NaCl concentrations, low temperatures and pH values, suggesting its potential use in lower and moderate temperature processes in the petroleum industry.
A study on L-threonine and L-serine uptake in Escherichia coli K-12
Authors: Khozov Andrey A. , Bubnov Dmitrii M. , Plisov Eugeny D. , Vybornaya Tatiana V. , Yuzbashev Tigran V. , Agrimi Gennaro , Messina Eugenia , Stepanova Agnessa A. , Kudina Maxim D. , Alekseeva Natalia V. , Netrusov Alexander I. , Sineoky Sergey P.
Published: March 2023

In the current study, we report the identification and characterization of the yifK gene product as a novel amino acid carrier in E. coli K-12 cells. Both phenotypic and biochemical analyses showed that YifK acts as a permease specific to L-threonine and, to a lesser extent, L-serine. An assay of the effect of uncouplers and composition of the reaction medium on the transport activity indicates that YifK utilizes a proton motive force to energize substrate uptake. To identify the remaining threonine carriers, we screened a genomic library prepared from the yifK-mutant strain and found that brnQ acts as a multicopy suppressor of the threonine transport defect caused by yifK disruption. Our results indicate that BrnQ is directly involved in threonine uptake as a low-affinity but high-flux transporter, which forms the main entry point when the threonine concentration in the external environment reaches a toxic level. By abolishing YifK and BrnQ activity, we unmasked and quantified the threonine transport activity of the LIV-I branched chain amino acid transport system and demonstrated that LIV-I contributes significantly to total threonine uptake. However, this contribution is likely smaller than that of YifK. We also observed the serine transport activity of LIV-I, which was much lower compared with that of the dedicated SdaC carrier, indicating that LIV-I plays a minor role in the serine uptake. Overall, these findings allow us to propose a comprehensive model of the threonine/serine uptake subsystem in E. coli cells.
One-pot biosynthesis of N-acetylneuraminic acid from chitin via combination of chitin-degrading enzymes, N-acetylglucosamine-2-epimerase, and N-neuraminic acid aldolase
Authors: Liu Quanzhen , Wei Guoguang , Yang Pengfan , Wang Chengyong , Chen Kequan , Ouyang Pingkai , Zhang Alei
Published: March 2023

N-acetylneuraminic acid (Neu5Ac) possesses the ability to promote mental health and enhance immunity and is widely used in both medicine and food fields as a supplement. Enzymatic production of Neu5Ac using N-acetyl-D-glucosamine (GlcNAc) as substrate was significant. However, the high-cost GlcNAc limited its development. In this study, an in vitro multi-enzyme catalysis was built to produce Neu5Ac using affordable chitin as substrate. Firstly, exochitinase SmChiA from Serratia proteamaculans and N-acetylglucosaminosidase CmNAGase from Chitinolyticbacter meiyuanensis SYBC-H1 were screened and combined to produce GlcNAc, effectively. Then, the chitinase was cascaded with N-acetylglucosamine-2-epimerase (AGE) and N-neuraminic acid aldolase (NanA) to produce Neu5Ac; the optimal conditions of the multi-enzyme catalysis system were 37°C and pH 8.5, the ratio of AGE to NanA (1:4) and addition of pyruvate (70 mM), respectively. Finally, 9.2 g/L Neu5Ac could be obtained from 20 g/L chitin within 24 h along with two supplementations with pyruvate. This work will lay a good foundation for the production of Neu5Ac from cheap chitin resources.