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Trieu Tien Sang,1 Khoa Tran Van,1 Nguyen Thanh Tung,2 Phong Nguyen Van,1 Phuong Tran Hoang3 1Department of Biology and Medical Genetics, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 2Military Institute of Clinical Embryology and Histology, Vietnam Military Medical University, Hanoi, 10000, Vietnam; 3Department of Oncology, 108 Military Central Hospital, Hanoi, 10000, VietnamCorrespondence: Trieu Tien Sang, Vietnam Military Medical University, Hanoi, 10000, Vietnam, Email trieusangk83@yahoo.com.vnBackground: Androgen resistance syndrome or androgen insensitivity syndrome (AIS – Androgen Insensitivity Syndrome, OMIM 300068) is an X-linked recessive genetic syndrome causing disorders of sexual development in males. This disease is caused by mutations in the AR gene located on the X chromosome, which encodes the protein that structures the androgen receptor, with the role of receiving androgens. Mutation of the AR gene causes complete or partial loss of androgen receptor function, thereby androgen not being obtained and exerting its effect on target organs, resulting in abnormalities of the male reproductive system due to this organ system, differentiating towards feminization under the influence of estrogen. Disease prevention can be achieved by using pre-implantation genetic diagnosis, which enables couples carrying the mutation to have healthy offspring.Aim: To carry out preimplantation genetic diagnosis of androgen resistance syndrome.Methods: Sanger sequencing was used to detect the mutation in the blood samples of the couple, their son, and 01 embryo that were biopsied on the fifth day based on the findings of next-generation sequencing (NGS) of the affected son. We combined Sanger sequencing and linkage analysis using short tandem repeats (STR) to provide diagnostic results.Results: We performed preimplantation genetic diagnosis for AIS on an embryo from a couple who had previously had an affected son. Consequently, one healthy embryo was diagnosed without the variant NM_000044: c.796del (p.Asp266IlefsTer30).Conclusion: We report on a novel variant (NM_000044: c.796del (p.Asp266IlefsTer30)) in the AR gene discovered in Vietnam. The developed protocol was helpful for the preimplantation genetic diagnosis process to help families with the monogenic disease of AIS but wish to have healthy children.Keywords: androgen insensitivity syndrome, AIS, AR gene, preimplantation genetic diagnosis, short tandem repeats, STR

Ting-Yu Lin,1,2 Firdian Makrufardi,3,4 Nguyen Thanh Tung,3,5 Amja Manullang,3 Po-Jui Chang,1,2 Chun-Yu Lo,1,2 Tzu-Hsuan Chiu,1 Pi-Hung Tung,1 Chiung-Hung Lin,1 Horng-Chyuan Lin,1,2 Chun-Hua Wang,1,2 Shu-Min Lin1,2 1Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 4Department of Child Health, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada – Dr. Sardjito Hospital, Yogyakarta, Indonesia; 5Otorhinolaryngology Department, Cho Ray Hospital, Ho Chi Minh City, VietnamCorrespondence: Shu-Min Lin, Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa N. Road, Taipei, Taiwan, Fax +886 33272474, Email smlin100@gmail.comBackground: Early-onset asthma (EOA) and late-onset asthma (LOA) are two distinct phenotypes. Air pollution has been associated with an increase in poorer asthma outcomes. The objective of this study was to examine the effects of traffic-related air pollution (TRAP) on asthma outcomes in EOA and LOA patients.Methods: A cross-sectional study was conducted on 675 asthma patients (LOA: 415) recruited from a major medical center in Taiwan. The land-use regression (LUR) model was used to estimate the level of exposure to PM10, PM2.5, NO2, and O3 on an individual level. We investigated the association between TRAP and asthma outcomes in EOA and LOA patients, stratified by allergic sensitization status, using a regression approach.Results: An increase in PM10 was associated with younger age of onset, increased asthma duration, and decreased lung function in EOA patients (p< 0.05). An increase in PM10 was associated with older age of onset, and decreased asthma duration, eosinophil count, and Asthma Control Test (ACT) score in LOA patients. An increase in PM2.5 was associated with younger age of onset, increased asthma duration, decreased eosinophil count, and lung function in EOA patients (p< 0.05). An increase in PM2.5 was associated with decreased lung function and ACT score in LOA patients. An increase in NO2 was associated with increased eosinophil count and decreased lung function in EOA patients (p< 0.05). An increase in O3 was associated with decreased lung function in LOA patients (p< 0.05). In addition, associations of TRAP with age of onset and eosinophil counts were mainly observed in both EOA and LOA patients with allergic sensitization, and an association with ACT was mainly observed in LOA patients without allergic sensitization.Conclusion: The impact of TRAP on age of onset, eosinophil count, and lung function in EOA patients, and ACT in LOA patients, was affected by the status of allergic sensitization.Keywords: air pollution, allergy, early-onset asthma, late-onset asthma, respiratory disease

Discovering high-utility itemsets from a transaction database is one of the important tasks in High-Utility Itemset Mining (HUIM). The discovered high-utility itemsets (HUIs) must meet a user-defined given minimum utility threshold. Several methods have been proposed to solve the problem efficiently. However, they focused on exploring and discovering the set of HUIs. This research proposes a more generalized approach to mine HUIs using any user-specified correlated measure, named the General Method for Correlated High-utility itemset Mining (GMCHM). This proposed approach has the ability to discover HUIs that are highly correlated, based on the all_confidence and bond measures (and 38 other correlated measures). Evaluations were carried out on the standard datasets for HUIM, such as Accidents, BMS_utility and Connect. The results proved the high effectiveness of GMCHM in terms of running time, memory usage and the number of scanned candidates.

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by the proliferation of Langerhans cells, a type of dendritic cell essential for immune response. While LCH predominantly affects children, its manifestation in adults, especially within the gastrointestinal (GI) tract, is exceedingly rare. We present a unique case of a 56-year-old female with rare GI manifestations of LCH. The patient initially noticed pimple-like lesions around her anal orifice, which evolved into prominent protruding lesions over 3 months. Subsequent colonoscopy revealed multiple ulcers in the colorectal area, particularly concentrated in the sigmoid colon. Histopathological examination of biopsy samples, combined with immunohistochemical staining, confirmed the diagnosis of LCH. This case underscores the importance of a comprehensive diagnostic approach, especially when patients are present with atypical symptoms. The current literature suggests that such GI manifestations of LCH in adults are infrequent, making this case a valuable contribution to the understanding of LCH's clinical spectrum., (© The Author(s), 2024.)

Advances in Alzheimer's disease (AD) are related to the oligomerization of Amyloid β (Aβ) peptides. Therefore, alteration of the process can prevent AD. We investigated the Aβ 42 dimerization under the effects of gold nanoparticles using temperature replica-exchange molecular dynamics (REMD) simulations. The structural change of dimers in the presence and absence of the gold nanoparticle, Au 55 , was monitored over stable intervals. Physical insights into the oligomerization of Aβ were thus clarified. The computed metrics indicate that Au 55 affects the progress of oligomerization. Specifically, the presence of the gold nanoparticle significantly modifies the structure of dimeric Aβ 42 . The β-content experienced a substantial decrease with the induction of Au 55 . The turn and coil-contents are also decreased under the effects of the gold nanoparticle. However, the α-content of the dimer exhibited a rigid increase. The influence of gold nanoparticles on the dimeric Aβ 42 differs significantly from that of silver nanoparticles, which reduce β-content but increase coil-, turn-, and α-contents. The nature of inhibition will be discussed, in which the vdW interaction plays a driving force for the interaction between the Aβ 42 dimer and the gold nanoparticle.

Co n -1 TMO n -2 + ( n = 6-8), (TM = V, Cr, Mn, and Fe) clusters are investigated using density functional theory calculations. The transition metal atoms preferentially replace one Co atom at sites where the number of metal-oxygen bonds is maximized, forming more stable structures. The evaporation of a Co atom is the most fragile dissociation channel for both pure and doped species. Bare cobalt oxide clusters exhibit parallel spin ordering, whereas both parallel and antiparallel spin ordering are observed in the doped species. Notably, a ferromagnetic-to-ferrimagnetic transition occurs in the V-doped clusters, while the ferromagnetic behavior is enhanced in the Fe-doped species., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Genome editing technologies are rapidly evolving, from the early zinc-finger nucleases, transcription activator-like effector nucleases (TALENs), and CRISPR-Cas9 (Figure 1, initial genome editing technologies), which generate double-strand breaks (DSBs), to base editing, which makes precise nucleobase conversion without inducing DSBs, and prime editing, which can carry out all types of edits without DSBs or donor DNA templates. The emergence of these revolutionary technologies offers us unprecedented opportunities for biomedical research and therapy development., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Hematopoiesis is a continuous process of blood cell production driven by hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Proliferation and differentiation of HSPCs are regulated by complex transcriptional networks. In order to identify transcription factors with key roles in HSPC-mediated hematopoietic reconstitution, we developed an efficient and robust CRISPR/Cas9-based in vivo genetic screen. Using this experimental system, we identified the TFDP1 transcription factor to be essential for HSPC proliferation and post-transplant hematopoiesis. We further discovered that E2F4, an E2F transcription factor, serves as a binding partner of TFDP1 and is required for HSPC proliferation. Deletion of TFDP1 caused downregulation of genes associated with the cell cycle, with around 50% of these genes being identified as direct targets of TFDP1 and E2F4. Thus, our study expands the transcriptional network governing hematopoietic development through an in vivo CRISPR/Cas9-based genetic screen and identifies TFDP1/E2F4 as positive regulators of cell cycle genes in HSPCs., (© 2024. The Author(s).)

Virgibacillus spp. stand out as a potent starter culture for accelerating the fermention of fish sauces and shrimp pastes. However, the underlying molecular mechanisms responsible for their adaptation and biotechnological potential remain elusive. Therefore, the present study focuses on phenotypic and genomic analyses of a halophilic bacterium Virgibacillus dokdonensis T4.6, derived from Vietnamese high-salt fermented shrimp paste. The draft genome contained 4,096,868 bp with 3780 predicted coding sequences. Genome mining revealed the presence of 143 genes involved in osmotic adaptation explaining its resistant phenotype to 24% (w/v) NaCl. Among them, 37 genes making up the complete ectoine metabolism pathway, confirmed its ability to produce 4.38 ± 0.29 wt% ectoine under 12.5% NaCl stress. A significant finding was the identification of 39 genes responsible for an entire degradation pathway of the toxic biogenic amine histamine, which was in agreement with its histamine degradation rate of 42.7 ± 2.1% in the HA medium containing 5 mM histamine within 10 days at 37 °C. Furthermore, 114 proteolytic and 19 lipolytic genes were detected which might contribute to its survival as well as the nutrient quality and flavor of shrimp paste. Of note, a putative gene vdo2592 was found as a possible novel lipase/esterase due to its unique Glycine-Aspartate-Serine-Leucine (GDSL) sequence motif. This is the first report to reveal the adaptative strategies and related biotechnological potential of Virgibacillus associated with femented foods. Our findings indicated that V. dokdonensis T4.6 is a promising starter culture for the production of fermented shrimp paste products., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fermented eggplant is a traditional fermented food, however lactic acid bacteria capable of producing exopolysaccharide (EPS) have not yet been exploited. The present study focused on the production and protective effects against oxidative stress of an EPS produced by Lacticaseibacillus paracasei NC4 (NC4-EPS), in addition to deciphering its genomic features and EPS biosynthesis pathway. Among 54 isolates tested, strain NC4 showed the highest EPS yield and antioxidant activity. The maximum EPS production (2.04 ± 0.11 g/L) was achieved by culturing in MRS medium containing 60 g/L sucrose at 37 °C for 48 h. Under 2 mM H 2 O 2 stress, the survival of a yeast model Saccharomyces cerevisiae treated with 0.4 mg/mL NC4-EPS was 2.4-fold better than non-treated cells, which was in agreement with the catalase and superoxide dismutase activities measured from cell lysates. The complete genome of NC4 composed of a circular chromosome of 2,888,896 bp and 3 circular plasmids. The NC4 genome comprises more genes with annotated function in nitrogen metabolism, phosphorus metabolism, cell division and cell cycle, and iron acquisition and metabolism as compared to other reported L. paracasei. Of note, the eps gene cluster is not conserved across L. paracasei. Pathways of sugar metabolism for EPS biosynthesis were proposed for the first time, in which gdp pathway only present in few plant-derived bacteria was identified. These findings shed new light on the cell-protective activity and biosynthesis of EPS produced by L. paracasei, paving the way for future efforts to enhance yield and tailor-made EPS production for food and pharmaceutical industries., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Three unique linear oligomeric depsipeptides, designated as cavomycins A-C ( 1 - 3 ), were identified from Streptomyces cavourensis , a gut bacterium associated with the annelid Paraleonnates uschakovi . The structures of these depsipeptides were determined through a combination of spectroscopic methods and chemical derivatization techniques, including methanolysis, the modified Mosher's method, advanced Marfey's methods, and phenylglycine methyl ester derivatization. The unique dipeptidyl residue arrangements in compounds 1 - 3 indicate that they are not degradation products of valinomycin. Compound 2 and its methylation derivative 2a exhibited antiproliferative activity against PANC-1 pancreatic cancer cells with IC 50 values of 1.2 and 1.7 μM, respectively.

Molecular and dissociative hydrogen adsorption of transition metal (TM)-doped [Mo 3 S 13 ] 2- atomic clusters were investigated using density functional theory calculations. The introduced TM dopants form stable bonds with S atoms, preserving the geometric structure. The S-TM-S bridging bond emerges as the most stable configuration. The preferred adsorption sites were found to be influenced by various factors, such as the relative electronegativity, coordination number, and charge of the TM atom. Notably, the presence of these TM atoms remarkably improved the hydrogen adsorption activity. The dissociation of a single hydrogen molecule on TM[Mo 3 S 13 ] 2- clusters (TM = Sc, Cr, Mn, Fe, Co, and Ni) is thermodynamically and kinetically favorable compared to their bare counterparts. The extent of favorability monotonically depends on the TM impurity, with a maximum activation barrier energy ranging from 0.62 to 1.58 eV, lower than that of the bare cluster (1.69 eV). Findings provide insights for experimental research on hydrogen adsorption using TM-doped molybdenum sulfide nanoclusters, with potential applications in the field of hydrogen energy., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

VP39, an essential 2'-O-RNA methyltransferase enzyme discovered in Monkeypox virus (MPXV), plays a vital role in viral RNA replication and transcription. Inhibition of the enzyme may prevent viral replication. In this context, using a combination of molecular docking and molecular dynamics (MDs) simulations, the inhibitory ability of NCI Diversity Set VII natural compounds to VP39 protein was investigated. It should be noted that the computed binding free energy of ligand via molecular docking and linear interaction energy (LIE) approaches are in good agreement with the corresponding experiments with coefficients of R = 0.72 and 0.75, respectively. NSC 319990, NSC 196515 and NSC 376254 compounds were demonstrated that can inhibit MPVX methyltransferase VP39 protein with the similar affinity compared to available inhibitor sinefungin. Moreover, nine residues involving Gln39 , Gly68 , Gly72 , Asp95 , Arg97 , Val116 , Asp138 , Arg140 and Asn156 may be argued that they play an important role in binding process of inhibitors to VP39.Communicated by Ramaswamy H. Sarma.

Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This research aims to develop bitter taste-masking microcapsules containing azithromycin (AZI) by a simpler and familiar method, fluid-bed coating technology, in comparison with Zithromax ® . Cores of microcapsules, AZI microparticles, were prepared by fluid-bed granulation, then taste-masking polymer was covered on by fluid-bed coating technique. Eudragit L100, Eudragit RL100, and ethyl cellulose in single and combined with Eudragit L100 and Eudragit E100 were used as taste-masking polymers. The obtained microcapsules were characterised by taste-masking ability, in vitro release, SEM, coating thickness, and coating efficiency. Combination of ethyl cellulose and Eudragit E100 (3:1) in coating thickness of 45.13 ± 2.12% w/w prevents AZI release from microcapsules below bitter taste threshold (1.78 ± 1.17 µg/ml). Bioavailability of powders containing AZI microcapsules and pH modulators (50 mg Na 3 PO 4 and 35 mg Mg(OH) 2 ) was not significantly different from the reference product (Zithromax ® , Pfizer, New York, NY) in the rabbit model ( p  > 0.05). These results support the possibility of developing a generic product containing AZI.

Plant diseases caused by phytopathogenic fungi are one of the leading factors affecting crop loss. In the present study, sixty-one Streptomyces strains were screened for their antifungal activity against relevant wide range fungal pathogens prominent in Vietnam, namely Lasiodiplodia theobromae, Fusarium fujikuroi, and Scopulariopsis gossypii. Endophytic strain RC2 was the most effective strain in the mycelial inhibition of the tested fungi. Based on phenotypic characteristics, 16S rDNA gene analysis, and genomic analysis, strain RC2 belonged to Streptomyces albus. An ethyl acetate extract of S. albus RC2 led to the strong growth inhibition of S. gossypii Co1 and F. fujikuroi L3, but not L. theobromae N13. The crude extract also suppressed the spore germination of S. gossypii Co1 and F. fujikuroi L3 to 92.4 ± 3.2% and 87.4% ± 1.9%, respectively. In addition, the RC2 extract displayed potent and broad-spectrum antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, and the phytopathogenic bacteria Ralstonia solanacearum and Xanthomonas oryzae. The genome of strain RC2 was sequenced and revealed the presence of 15 biosynthetic gene clusters (BGCs) with similarities ≥ 45% to reference BGCs available in the antiSMASH database. The UPLC-HRMS analysis led to the identification of 8 other secondary metabolites, which have not been reported in S. albus. The present study indicated that RC2 could be a potent biocontrol agent against phytopathogenic fungi. Further attention should be paid to antifungal metabolites without functional annotation, development of product prototypes, and greenhouse experiments to demonstrate effective control of the plant diseases., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Endophytic fungi are known as an alternative promising source of anticancer drug, paclitaxel, however fungi inhabiting in medicinal plant Podocarpus pilgeri and their paclitaxel production have not been reported to date. In the present study, a total of 15 culturable fungi classified into 5 genera, were successfully recovered from P. pilgeri collected in Vietnam. Screening fungal dichloromethane extracts for anticancer activity revealed that only PQF9 extract displayed potent inhibitory effects on A549 and MCF7 cancer cell lines with IC 50 values of 33.9 ± 2.3 µg/mL and 43.5 ± 1.7 µg/mL, respectively. Through PCR-based molecular screening, the isolate PQF9 was found to possess 3 key genes involved in paclitaxel biosynthesis. Importantly, high-performance liquid chromatography quantification showed that fungal isolate PQF9 was able to produce 18.2 µg/L paclitaxel. The paclitaxel-producing fungus was identified as Fusarium solani PQF9 based on morphological and molecular phylogenetic analysis. Intensive investigations by chromatographic methods and spectroscopic analyses confirmed the presence of paclitaxel along with tyrosol and uracil. The pure paclitaxel had an IC 50 value of 80.8 ± 9.4 and 67.9 ± 7.0 nM by using cell viability assay on A549 lung and MCF7 breast cancer cells. In addition, tyrosol exhibited strong antioxidant activity by scavenging 2, 2-diphenyl-picrylhydrazyl (DPPH) (IC 50 5.1 ± 0.2 mM) and hydroxyl radical (IC 50 3.6 ± 0.1 mM). In contrast, no biological activity was observed for uracil. Thus, the paclitaxel-producing fungus F. solani PQF9 could serve as a new material for large-scale production and deciphering paclitaxel biosynthesis., Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01119-z., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© Association of Microbiologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Floating treatment wetlands (FTW) are nature-based solutions for the purification of open water systems such as rivers, ponds, and lakes polluted by diffuse sources as untreated or partially treated domestic wastewater and agricultural run-off. Compared with other physicochemical and biological technologies, FTW is a technology with low-cost, simple configuration, easy to operate; has a relatively high efficiency, and is energy-saving, and aesthetic. Water remediation in FTWs is supported by plant uptake and the growth of a biofilm on the water plant roots, so the selection of the macrophyte species is critical, not only to pollutant removal but also to the local ecosystem integrity, especially for full-scale implementation. The key factors such as buoyant frame/raft, plant growth support media, water depth, seasonal variation, and temperature have a considerable role in the design, operation, maintenance, and pollutant treatment performance of FTW. Harvesting is a necessary process to maintain efficient operation by limiting the re-pollution of plants in the decay phase. Furthermore, the harvested plant biomass can serve as a green source for the recovery of energy and value-added products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The first oral drug for the treatment of COVID-19, Paxlovid, has been authorized; however, nirmatrelvir, a major component of the drug, is reported to be associated with some side effects. Moreover, the appearance of many novel variants raises concerns about drug resistance, and designing new potent inhibitors to prevent viral replication is thus urgent. In this context, using a hybrid approach combining machine learning (ML) and free energy simulations, 6 compounds obtained by modifying nirmatrelvir were proposed to bind strongly to SARS-CoV-2 Mpro. The structural modification of nirmatrelvir significantly enhances the electrostatic interaction free energy between the protein and ligand and slightly decreases the vdW term. However, the vdW term is the most important factor in controlling the ligand-binding affinity. In addition, the modified nirmatrelvir might be less toxic to the human body than the original inhibitor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this study, we evaluated the deactivating efficacy of strong basicity-based (T4-102) and hydrogen peroxide-based (DF-200) disinfectants that were past their expiration date when used to deactivate biological and chemical toxins on building material surfaces. The decontamination efficacies of DF-200 and T4-102 disinfectants against dimethyl methylphosphonate (DMMP) and 2-chloroethyl ethylsulfide (2-CEES) were studied using GC-MS analysis. The bactericidal efficacies of disinfectants against Gram-negative E. coli and P. aeruginosa , and Gram-positive B. subtilis and S. aureus , were assessed in terms of the zone of inhibition, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The results indicated that the deactivation efficacy varied significantly according to the disinfectant amount, contact time, and building material. Higher efficacy of up to 99-100% was observed for biological toxins, despite passing their expiration dates. Approximately 70-78% of deactivation efficacies were observed for disinfectants against DMMP on the tile coupon at 100 μL and 24 h contact time. Moreover, the deactivation efficacy of DF-200 was better than that of T4-102. The data presented here demonstrate that the responders may use past-expiration-date disinfectants for efficacious disinfectaion in large-scale contamination incidents., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The maximum power point tracking (MPPT) solutions improve power generation efficiency, quickly stabilizing the output waveform of photovoltaic (PV) systems under variable operating conditions. Along with new algorithms, improved and adjusted methods to exploit energy from PV systems are increasingly being researched and proposed. However, the proposed solutions based on the traditional algorithms and their improvements have poor performance, while the advanced algorithms or hybrid methods bring high performance but need to be simplified, and the response speed is higher. Moreover, a suitable PV configuration makes choosing a simple but highly efficient algorithm, especially in low-power PV system applications such as rooftop solar power, traffic lights, and moving vehicles…where the number of PV panels is insufficient to implement flexible configurations. This paper proposes a modified version of the Perturb and Observe (MPO) algorithm to improve MPPT performance and increase convergence speed in the parallel structure of PV panels. The Short-Circuit Current (I sc ) and Open-Circuit Voltage (V oc ) are calculated directly at specific operating conditions to quickly determine the potential maximum power point (MPP) that will reduce power interruptions and increase power generation efficiency compared to periodic updates. Therefore, the proposed solution converges faster, with higher efficiency, and the output signal in static and dynamic MPPT situations is more stable. The results show that the highest efficiency in simulation and experiment is 99.99% and 99.93%, respectively, while the convergence speed is 0.01 s and 0.03 s, respectively. They are better than the traditional Perturb and Observe (P&O) algorithm, the Variable Step Size Perturb and Observe (VSSP&O) method, and the Particle Swarm Optimization (PSO) technique under the same operating conditions. In addition, its performance and convergence speed are also compared with the latest introduced algorithms. The results show that it is valuable and reliable for parallel PV configuration.

Multiple myeloma (MM) is a devastating plasma cell malignancy characterized by the expansion of aberrant monoclonal plasma cells in the bone marrow, leading to severe clinical manifestations and poor prognosis, particularly in relapsed/refractory cases. Identifying novel therapeutic targets is crucial to improve treatment outcomes in these patients. In this study, we investigated the role of the protein arginine methyltransferase 1 (PRMT1) in MM pathogenesis and explored its potential as a therapeutic target. We observed that PRMT1, responsible for most asymmetric di-methylation in cells, exhibited the highest expression among PRMT family members in MM cell lines and primary MM cells. Importantly, PRMT1 expression was significantly elevated in relapsed/refractory patients compared to newly diagnosed patients. High expression of PRMT1 expression was strongly associated with poor prognosis. We found that genetic or enzymatic inhibition of PRMT1 impaired MM cell growth, induced cell cycle arrest, and triggered cell death. Treatment with MS023, a potent PRMT type I inhibitor, demonstrated a robust inhibitory effect on the viability of primary cells isolated from newly diagnosed and proteasome inhibitor-relapsed/refractory patients in a dose-dependent manner. Suppression of PRMT1 downregulated genes related to cell division and upregulated genes associated with apoptosis pathway. We also found that genes related to immune response and lymphocyte activation were significantly upregulated in PRMT1-suppressed cells. Notably, the activation status of T cells was strikingly enhanced upon co-culturing with PRMT1-KO MM cells. In vivo studies using a xenograft model revealed that targeting PRMT1 by either CRISPR/Cas9-mediated knockout or MS023 treatment significantly attenuated MM tumor growth and prolonged the survival of tumor-bearing mice. Histological analysis further confirmed increased apoptotic cell death in MS023-treated tumors. Collectively, our findings establish PRMT1 as an indispensable and novel therapeutic vulnerability in MM. The elevated expression of PRMT1 in relapsed/refractory patients underscores its potential as a target for overcoming treatment resistance. Moreover, our results highlight the efficacy of MS023 as a promising therapeutic agent against MM, offering new avenues for therapeutic approaches in relapsed/refractory MM., Competing Interests: Author BW reports unrelated grants from Bristol Myers Squibb, Genentech, and Leukemia and Lymphoma Society during the conduct of the study. Author NTT is an inventor on a patent application related to this work filed by the MDC European patent application no. 21192657.1-1111, filed 23 August 2021. The patent is not related to the works in the manuscript. Author FP is an inventor on patents related to adoptive cell therapies, held by Memorial Sloan Kettering Cancer Center some licensed to Takeda and Indiana University. Research funding from Lonza and NGMBiopharmaceuticals. Scientific advisory board for BioLegend and Orbitaltx Indiana. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nguyen, Le, Liu, Cesarano, DiMeo, Perna, Kapur, Walker and Tran.)

Developing highly efficient and durable hydrogen evolution reaction (HER) electrocatalysts is crucial for addressing the energy and environmental challenges. Among the 2D-layered chalcogenides, MoSe 2 possesses superior features for HER catalysis. The van der Waals attractions and high surface energy, however, stack the MoSe 2 layers, resulting in a loss of edge active catalytic sites. In addition, MoSe 2 suffers from low intrinsic conductivity and weak electrical contact with active sites. To overcome the issues, this work presents a novel approach, wherein the in situ incorporated diethylene glycol solvent into the interlayers of MoSe 2 during synthesis when treated thermally in an inert atmosphere at 600 °C transformed into graphene (Gr). This widened the interlayer spacing of MoSe 2 , thereby exposing more HER active edge sites with high conductivity offered by the incorporated Gr. The resulting MoSe 2 -Gr composite exhibited a significantly enhanced HER catalytic activity compared to the pristine MoSe 2 in an acidic medium and demonstrated a superior HER catalytic activity compared to the state-of-the-art Pt/C catalyst, particularly at a high current density beyond ca. 55 mA cm -2 . Additionally, the MoSe 2 -Gr catalyst demonstrated long-term electrochemical stability during HER. This work, thus, presents a facile and novel approach for obtaining an efficient MoSe 2 electrocatalyst applicable in green hydrogen production.

Histoplasmosis is an endemic infection caused by Histoplasma capsulatum , leading to a broad spectrum of disease from asymptomatic to severe disseminated disease. To diagnose Histoplasmosis, culture remains the gold standard for the laboratory diagnosis; however, this fungus grows slowly, taking a long time 2 to 3 weeks or may take up to 8 weeks. Therefore, some other methods such as bone marrow examination play an essential role in rapid identification and early diagnosis, especially in cases of severe disseminated disease. In this case, we report a 55-year-old man with a 1-year history of gout, self-medicating (including Medrol) who was admitted to the hospital because of persistent fever and swelling of his left arm. About laboratory investigation, there was a bicytopenia (RBC and PLT), blood and pus cultures many times were negative. On the slide of the bone marrow specimen, images of yeast suspected of Histoplasma capsulatum were observed. Therefore, the patient was treated with antifungal medication, and the culture was repeated with prolonged follow-up time and positive results with H. capsulatum after 16 days. In conclusion, bone marrow test plays a significant role in the diagnosis of some fungal infections, which can contribute to an early diagnosis, especially in cases of culture and serological tests are not available or cannot be performed. Patients who present with fever and bicytopenia or pancytopenia should be performed early bone marrow test, which can support the earlier diagnosis to have appropriate treatment., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Purpose: Body composition is considered to be associated with obstructive sleep apnea (OSA) severity. This cross-sectional study aimed to examine associations of overnight body composition changes with positional OSA., Methods: The body composition of patients diagnosed with non-positional and positional OSA was measured before and after overnight polysomnography. Odds ratios (ORs) of outcome variables between the case (positional OSA) and reference (non-positional OSA) groups were examined for associations with sleep-related parameters and with changes in body composition by a logistic regression analysis., Results: Among 1584 patients with OSA, we used 1056 patients with non-positional OSA as the reference group. We found that a 1-unit increase in overnight changes of total fat percentage and total fat mass were associated with 1.076-fold increased OR (95% confidence interval (CI): 1.014, 1.142) and 1.096-fold increased OR (95% CI: 1.010, 1.189) of positional OSA, respectively (all p < 0.05). Additionally, a 1-unit increase in overnight changes of lower limb fat percentage and upper limb fat mass were associated with 1.043-fold increased OR (95% CI: 1.004, 1.084) and 2.638-fold increased OR (95% CI: 1.313, 5.302) of positional OSA, respectively (all p < 0.05). We observed that a 1-unit increase in overnight changes of trunk fat percentage and trunk fat mass were associated with 1.056-fold increased OR (95% CI: 1.008, 1.106) and 1.150-fold increased OR (95% CI: 1.016, 1.301) of positional OSA, respectively (all p < 0.05)., Conclusion: Our findings indicated that nocturnal changes in the body's composition, especially total fat mass, total fat percentage, lower limb fat percentage, upper limb fat mass, trunk fat percentage, and trunk fat mass, may be associated with increased odds ratio of positional OSA compared with non-positional OSA., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This paper presents a systematic literature review focused on the use of inductively coupled plasma mass spectrometry (ICP-MS) combined with PCA, a multivariate technique, for determining the geographical origin of plant foods. Recent studies selected and applied the ICP-MS analytical method and PCA in plant food geographical traceability. The collected results from many previous studies indicate that ICP-MS with PCA is a useful tool and is widely used for authenticating and certifying the geographic origin of plant food. The review encourages scientists and managers to discuss the possibility of introducing an international standard for plant food traceability using ICP-MS combined with PCA. The use of a standard method will reduce the time and cost of analysis and improve the efficiency of trade and circulation of goods. Furthermore, the main steps needed to establish the standard for this traceability method are reported, including the development of guidelines and quality control measures, which play a pivotal role in providing authentic product information through each stage of production, processing, and distribution for consumers and authority agencies. This might be the basis for establishing the standards for examination and controlling the quality of foods in the markets, ensuring safety for consumers.

A chemical investigation of the endophytic Streptomyces sp. HBQ95, associated with the medicinal plant Cinnamomum cassia Presl, enabled the discovery of four new piperazic acid-bearing cyclodepsipeptides, lydiamycins E-H ( 1 - 4 ), and one known compound (lydiamycin A). Their chemical structures, including absolute configurations, were defined by a combination of spectroscopic analyses and multiple chemical manipulations. Lydiamycins F-H ( 2 - 4 ) and A ( 5 ) exhibited antimetastatic activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.

The CRISPR/Cas9 system is a powerful tool for gene repair that holds great potential for gene therapy to cure monogenic diseases. Despite intensive improvement, the safety of this system remains a major clinical concern. In contrast to Cas9 nuclease, Cas9 nickases with a pair of short-distance (38-68 bp) PAM-out single-guide RNAs (sgRNAs) preserve gene repair efficiency while strongly reducing off-target effects. However, this approach still leads to efficient unwanted on-target mutations that may cause tumorigenesis or abnormal hematopoiesis. We establish a precise and safe spacer-nick gene repair approach that combines Cas9 D10A nickase with a pair of PAM-out sgRNAs at a distance of 200-350 bp. In combination with adeno-associated virus (AAV) serotype 6 donor templates, this approach leads to efficient gene repair with minimal unintended on- and off-target mutations in human hematopoietic stem and progenitor cells (HSPCs). Here, we provide detailed protocols to use the spacer-nick approach for gene repair and to assess the safety of this system in human HSPCs. The spacer-nick approach enables efficient gene correction for repair of disease-causing mutations with increased safety and suitability for gene therapy. Graphical overview., Competing Interests: Competing interestsK.R., V.T.C., N.T.T. and R.K. are inventors on a patent application related to this protocol filed by the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC) (European Patent Application Nr. 21192657.1-1111, filed 23 August 2021). All other authors declare no competing interests., (Copyright © 2023 The Authors.)

This study aimed to evaluate the miscibility of cellulose derivatives to improve the release rate and stability of microparticles containing the weakly basic drug itraconazole (ITZ). We also investigated the effect of some organic acids on the microenvironmental pH (pH m ) and the release rate of ITZ from the cellulose-based microparticles. The synergistic effect of cellulose-based microparticles and pH m modulators on the bioavailability of ITZ compared with the reference product was investigated in a rabbit model. Differential scanning calorimetry and Fourier-transform infrared spectroscopy (FTIR) analysis showed that ITZ, hydroxypropyl methylcellulose, and hydroxypropyl methylcellulose phthalate were miscible at a ratio of 1.5:3:1 (w/w/w), and the stability of the microparticles was maintained for 6 months under accelerated conditions. In addition, X-ray diffraction, FTIR, and scanning electron microscopy were used to characterize the properties of the microparticles. Through the titration technique and determination of pH m , the combination of fumaric acid and maleic acid (1:2, w/w) was found to be the most effective pH m modulator for microparticles. The integration of cellulose-based microparticles and pH m modulators showed a synergistic effect on the flux and relative bioavailability of ITZ and its active metabolite OH-ITZ (182.60 % and 217.67 %, respectively) when compared with the reference product., Competing Interests: Declaration of competing interest The authors do not have any personal conflict of interest that may arise from submission of our research., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Alcaligenes faecalis D334 was determined in this study as a salt-tolerant bacterium isolated from mangrove sediment. In response to 6% (w/v) NaCl, strain D334 produced the highest ectoines of 14.14 wt%. To understand adaptive features to mangrove environment, strain D334 was sequenced using Pacific BioScience platform, resulting in a circular chromosome of 4.23 Mb. Of note, D334 genome harbored 81 salt-responsive genes, among which two membrane-associated genes ompc and eric were absent in 3 selected A. faecalis genomes. Apart from that, a complete pathway for ectoine and 5-hydroxyectoine synthesis was predicted. To resist 40 mM H 2 O 2 , 46 genetic determinants contributing to oxidative stress response were employed. Moreover, two operons involved in polyhydroxyalkanoate (PHA) production were identified in the D334 genome, resulting in maximum PHA content of 5.03 ± 0.04 wt% and PHA concentration of 0.13 ± 0.001 g/L. A large flagellar biosynthesis operon contributing to swimming motility was found to be conserved in D334 and 8 other A. faecalis genomes. These findings shed light for the first time on the high versatility of A. faecalis D334 genome to adapt to mangrove lifestyle and the possibility to develop D334 as an industrial platform for PHA and 5-hydroxyectoine production., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Computational approaches, including physics- and knowledge-based methods, have commonly been used to determine the ligand-binding affinity toward SARS-CoV-2 main protease (Mpro or 3CLpro). Strong binding ligands can thus be suggested as potential inhibitors for blocking the biological activity of the protease. In this context, this paper aims to provide a short review of computational approaches that have recently been applied in the search for inhibitor candidates of Mpro. In particular, molecular docking and molecular dynamics (MD) simulations are usually combined to predict the binding affinity of thousands of compounds. Quantitative structure-activity relationship (QSAR) is the least computationally demanding and therefore can be used for large chemical collections of ligands. However, its accuracy may not be high. Moreover, the quantum mechanics/molecular mechanics (QM/MM) method is most commonly used for covalently binding inhibitors, which also play an important role in inhibiting the activity of SARS-CoV-2. Furthermore, machine learning (ML) models can significantly increase the searching space of ligands with high accuracy for binding affinity prediction. Physical insights into the binding process can then be confirmed via physics-based calculations. Integration of ML models into computational chemistry provides many more benefits and can lead to new therapies sooner.

This publisher's note corrects errors in Appl. Opt.61, 9078 (2022)APOPAI0003-693510.1364/AO.471949.

Increasing interest has been paid for hydrogen adsorption on atomically controlled nanoalloys due to their potential applications in catalytic processes and energy storage. In this work, we investigate the interaction of H 2 with small-sized Ag n Cr ( n = 1-12) using density functional theory calculations. It is found that the cluster structures are preserved during the adsorption of H 2 either molecularly or dissociatively. Ag 3 Cr-H 2 , Ag 6 Cr-H 2 , and Ag 9 Cr-H 2 clusters are identified to be relatively more stable from computed binding energies and second-order energy difference. The dissociation of adsorbed H 2 on Ag 2 Cr, Ag 3 Cr, Ag 6 Cr, and Ag 7 Cr clusters is favored both thermodynamically and kinetically. The dissociative adsorption is unlikely to occur because of a considerable energy barrier before reaching the final state for Ag 4 Cr or due to energetic preferences for n = 1, 5, and 8-12 species. Comprehensive analysis shows that the geometric structure of clusters, the relative electronegativity, and the coordination number of the Cr impurity play a decisive role in determining the preferred adsorption configuration., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: This study aims to investigate the frequencies and association of CYP3A5 polymorphism with tacrolimus concentration among renal transplant recipients in Vietnam., Methods: Sixty-eight kidney transplant recipients were included in this study from the department of nephrology and dialysis, Military Hospital 103. Blood samples were collected for monitoring of tacrolimus levels and determination of CYP3A5 genetic polymorphism., Results: A total of 68 patients studied. The CYP3A5*3*3, CYP3A5*1*3, and CYP3A5*1*1 genotypes were detected in 48 (70.6%), 16 (23.5%), and 4 (5.9%), respectively. Tacrolimus concentrations were much lower in CYP3A5 expressors than in CYP3A5 nonexpressors on the first day, month 1, 3, 6, and 12 (5.98 ± 1.05 vs 6.57 ± 1.03, P = .03; 5.79 ± 1.13 vs 6.82 ± 1.05, P < .001; 4.76 ± 1.48 vs 6.73 ± 1.09, P < .001; 4.29 ± 1.64 vs 6.46 ± 1.23, P < .001; 4.20 ± 1.36 vs 6.04 ± 1.26, P < .001), respectively. Notably, the concentration/dose ratio in the CYP3A5 expressors was lower than in CYP3A5 nonexpressors at time points of follow up (P < .001). However, there were no significant differences in the age, sex, HLA mismatch, type of donors, acute rejection, and creatinine levels at time points between group of CYP3A5 expressors and those of CYP3A5 nonexpressors., Conclusion: In conclusion, this research indicated the significant association of CYP3A5 genetic polymorphism with daily dose and tacrolimus concentrations in renal transplant recipients. This study provided a closer step to individualize the dose of tacrolimus in renal transplant patients in Vietnam., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Whole-genome sequencing and genome mining are recently considered an efficient approach to shine more light on the underlying secondary metabolites of Streptomyces . The present study unearths the biosynthetic potential of endophytic SX6 as a promising source of biologically active substances and plant-derived compounds for the first time. Out of 38 isolates associated with Aegiceras corniculatum (L.) Blanco, Streptomyces parvulus SX6 was highly active against Pseudomonas aeruginosa ATCC® 9027™ and methicillin-resistant Staphylococcus epidermidis (MRSE) ATCC® 35984™. Additionally, S. parvulus SX6 culture extract showed strong cytotoxicity against Hep3B, MCF-7, and A549 cell lines at a concentration of 30 μg/ml, but not in non-cancerous HEK-293 cells. The genome contained 7.69 Mb in size with an average G + C content of 72.8% and consisted of 6,779 protein-coding genes. AntiSMASH analysis resulted in the identification of 29 biosynthetic gene clusters (BGCs) for secondary metabolites. Among them, 4 BGCs showed low similarity (28-67% of genes show similarity) to actinomycin, streptovaricin, and polyoxypeptin gene clusters, possibly attributed to antibacterial and anticancer activities observed. In addition, the complete biosynthetic pathways of plant-derived compounds, including daidzein and genistein were identified using genome mining and HPLC-DAD-MS analysis. These findings portray an exciting avenue for future characterization of promising secondary metabolites from mangrove endophytic S. parvulus ., (© 2022 Ngoc Tung Quach et al., published by Sciendo.)

We conducted a cross-sectional study to investigate associations of particulate matter (PM) of less than 2.5 μm in aerodynamic diameter (PM 2.5 ) and PM deposition with nocturnal changes in body composition in obstructive sleep apnea (OSA) patients. A bioelectric impedance analysis was used to measure the pre- and postsleep body composition of 185 OSA patients. Annual exposure to PM 2.5 was estimated by the hybrid kriging/land-use regression model. A multiple-path particle dosimetry model was employed to estimate PM deposition in lung regions. We observed that an increase in the interquartile range (IQR) (1 μg/m 3 ) of PM 2.5 was associated with a 20.1% increase in right arm fat percentage and a 0.012 kg increase in right arm fat mass in OSA ( p < 0.05). We observed that a 1 μg/m 3 increase in PM deposition in lung regions (i.e., total lung region, head and nasal region, tracheobronchial region, and alveolar region) was associated with increases in changes of fat percentage and fat mass of the right arm (β coefficient) ( p < 0.05). The β coefficients decreased as follows: alveolar region > head and nasal region > tracheobronchial region > total lung region ( p < 0.05). Our findings demonstrated that an increase in PM deposition in lung regions, especially in the alveolar region, could be associated with nocturnal changes in the fat percentage and fat mass of the right arm. PM deposition in the alveolar region could accelerate the body fat accumulation in OSA., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Poly-γ‑glutamic acid (γ‑PGA) produced by Bacillus species is a natural biopolymer, which is widely used in various fields including food, pharmaceuticals, and cosmetics. In this study, the screening of 19 Bacillus isolates derived from traditionally fermented foods revealed that Bacillus velezensis VCN56 was the most potent γ‑PGA producer. The maximum concentration of crude γ‑PGA was 32.9 ± 1.5 g/L in the PGA-3 medium containing glycerol, citric acid, sodium glutamate, NH 4 Cl, and starch. The resulting γ-PGA was purified and then characterized by HPLC, FTIR, and 1 H-NMR analyses. Molecular weight of purified γ‑PGA was estimated to be 98 kDa with a polydisperse index of 2.04. Notably, the pure γ‑PGA showed significant in vitro antioxidant scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (72.0 ± 1.5%), hydroxyl (81.0 ± 0.6%), and superoxide (43.9 ± 0.8%) radicals at the concentration of 4 mg/mL. Using whole-genome sequencing, the genetic organization of pgs operon responsible for γ‑PGA biosynthesis in B. velezensis VCN56 differs from those in other Bacillus genomes. Further genome analysis revealed metabolic pathways for γ-PGA production and degradation. For the first time, the present study provides a better understanding of γ-PGA with a promising antioxidant activity produced by B. velezensis at the phenotypic, biochemical, and genomic levels, which hold potential applications in the foods, cosmetics, and pharmaceutical industries., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Glass biodeterioration by fungi has caused irreversible damage to valuable glass materials such as cultural heritages and optical devices. To date, knowledge about metabolic potential and genomic profile of biodeteriorative fungi is still scarce. Here, we report for the first time the whole genome sequence of Curvularia eragrostidis C52 that strongly degraded silica-based glasses coated with fluorine and hafnium, as expressed by the hyphal surface coverage of 46.16 ± 3.3% and reduced light transmission of 50.93 ± 1.45%. The genome of C. eragrostidis C52 is 36.9 Mb long with a GC content of 52.1% and contains 14,913 protein-coding genes, which is the largest genome ever recorded in the genus Curvularia. Phylogenomic analysis revealed C. eragrostidis C52 formed a distinct cluster with Curvularia sp. IFB-Z10 and was not evolved from compared genomes. Genome-wide comparison showed that strain C52 harbored significantly higher proportion of proteins involved in carbohydrate-active enzymes, peptidases, secreted proteins, and transcriptional factors, which may be potentially attributed to a lifestyle adaptation. Furthermore, 72 genes involved in the biosynthesis of 6 different organic acids were identified and expected to be crucial for the fungal survival in the glass environment. To form biofilm against stress, the fungal strain utilized 32 genes responsible for exopolysaccharide production. These findings will foster a better understanding of the biology of C. eragrostidis and the mechanisms behind fungal biodeterioration in the future., (© 2022. The Author(s).)

Graphene has been extensively considered an ideal additive to improve the mechanical properties of many composite materials, including rubbers, because of its novel strength, high surface area, and remarkable thermal and electron conductivity. However, the pristine graphene shows low dispersibility in the rubber matrix resulting in only slightly enhanced mechanical properties of the rubber composite. In this work, graphene nanoplatelets (GNPs) were modified with dioctyl phthalate (DOP) to improve the dispersibility of the graphene in the natural rubber (NR). The distribution of the DOP-modified GNPs in the NR matrix was investigated using scanning electron microscopy, X-ray diffraction, and Raman spectroscopy. The effect of the modified GNPs' contents on the mechanical properties of the GNPs/NR composite was studied in detail. The results showed that the abrasion resistance of the graphene-reinforced rubber composite significantly improved by 10 times compared to that of the rubber without graphene (from 0.3 to 0.03 g/cycle without and with addition of the 0.3 phr modified GNPs). The addition of the modified GNPs also improved the shear and tensile strength of the rubber composite. The tensile strength and shear strength of the NR/GNPs composite with a GNPs loading of 0.3 phr were determined to be 23.63 MPa and 42.69 N/mm, respectively. Even the presence of the graphene reduced the other mechanical properties such as Shore hardness, elongation at break, and residual elongation; however, these reductions were negligible, which still makes the modified GNPs significant as an effective additive for the natural rubber in applications requiring high abrasion resistance.

This paper presents for the first time the systematic synthesis of AgInS 2 (AIS) nanocrystals (NCs) with different sizes of 2.6-6.8 nm just by controlling only the reaction temperature. The synthesis of AIS core NCs was carried out in 2 steps: (i) synthesis of Ag 2 S NCs and then (ii) partial exchange of Ag + with In 3+ in the template Ag 2 S NCs. For step (i), Ag 2 S NCs of different sizes were synthesized by reaction of the Ag and S precursors at different temperatures of 30 °C to 130 °C, for the same reaction time of 30 min. For step (ii), AIS NCs were created by the exchange of Ag + with In 3+ at 120 °C for 60 min. Finally, GaS x was shelled on AIS core NCs to produce the AgInS 2 /GaS x core/shell structures. The synthesized AIS/GaS x NCs demonstrate the clear excitonic absorptions and strong, narrow excitonic luminescence peaking at 530-606 nm depending on the size of AIS core NCs., (© 2022 IOP Publishing Ltd.)

While CRISPR-Cas9 is key for the development of gene therapy, its potential off-target mutations are still a major concern. Here, we establish a "spacer-nick" gene correction approach that combines the Cas9 D10A nickase with a pair of PAM-out sgRNAs at a distance of 200 to 350 bp. In combination with adeno-associated virus (AAV) serotype 6 template delivery, our approach led to efficient HDR in human hematopoietic stem and progenitor cells (HSPCs including long-term HSCs) and T cells, with minimal NHEJ-mediated on-target mutations. Using spacer-nick, we developed an approach to repair disease-causing mutations occurring in the HBB , ELANE , IL7R , and PRF1 genes. We achieved gene correction efficiencies of 20 to 50% with minimal NHEJ-mediated on-target mutations. On the basis of in-depth off-target assessment, frequent unintended genetic alterations induced by classical CRISPR-Cas9 were significantly reduced or absent in the HSPCs treated with spacer-nick. Thus, the spacer-nick gene correction approach provides improved safety and suitability for gene therapy.

The study aims to (a) enhance the solubility of a poorly soluble drug by optimization of nanocrystal formulation using the top-down approach and (b) modify the release profile of this drug, which exhibits a short elimination half-life, by the integration of a fast-release phase containing the optimized nanocrystals and a sustained-release phase in a compression-coated tablet. Nanocrystals of the model drug (lornoxicam; LNX) was prepared by simultaneous application of jet-milling and ball-milling techniques. Investigation of the precipitation inhibition capacity, thermal property, and interaction of different polymers with the drug revealed polyvinyl pyrrolidone K30 (PVP) as the most effective stabilizer for nanocrystals. The immediate-release layer containing the optimized nanocrystals (size of 279.5 ± 11.25 nm and polydispersity index of 0.204 ± 0.01) was then compressed on a zero-order sustained-release matrix core using different derivatives of hydroxypropyl methylcellulose (HPMC). Application of the Design of Experiment approach (DoE) was applied to optimize the formulation of tablet. Analysis of drug concentration in dog plasma by liquid chromatography-tandem mass spectrometry demonstrated an improvement in the release behavior of LNX from the optimal compression-coated tablet integrating a HPMC-based sustained release matrix core and a PVP-stabilized lornoxicam nanocrystals coating layer compared to the reference product., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Janus kinase 2 (JAK2) inhibitors are potential anticancer drugs in the treatment of lymphoma, leukemia, thrombocytosis and particularly myeloproliferative diseases. However, the resemblance among JAK family members has challenged the identification of highly selective inhibitors for JAK2 to reduce undesired side effects. As a result, a robust search for promising JAK2 inhibitors using a computational approach that can effectively nominate new potential candidates to be further analyzed through laborious experimental operations has become necessary. In this study, the binding affinities of JAK2 inhibitors were rapidly and precisely estimated using the fast pulling of ligand (FPL) simulations combined with a modified linear interaction energy (LIE) method. The approach correlates with the experimental binding affinities of JAK2 inhibitors with a correlation coefficient of R = 0.82 and a root-mean-square error of 0.67 kcal•mol -1 . The data reveal that the FPL/LIE method is highly approximate in anticipating the relative binding free energies of known JAK2 inhibitors with an affordable consumption of computational resources, and thus, it is very promising to be applied in in silico screening for new potential JAK2 inhibitors from a large number of molecules available., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A theoretical study of geometric and electronic structures, stability and magnetic properties of both neutral and anionic Ge 16 M 0/- clusters with M being a first-row 3d transition metal atom, is performed using quantum chemical approaches. Both the isoelectronic Ge 16 Sc - anion and neutral Ge 16 Ti that have a perfect Frank-Kasper tetrahedral T d shape and an electron shell filled with 68 valence electrons, emerge as magic clusters with an enhanced thermodynamic stability. The latter can be rationalized by the simple Jellium model. Geometric distortions from the Frank-Kasper tetrahedron of Ge 16 M having more or less than 68 valence electrons can be understood by a Jahn-Teller effect. Remarkably, DFT calculations reveal that both neutral Ge 16 Sc and Ge 16 Cu can be considered as superhalogens as their electron affinities (≥3.6 eV) exceed the value of the halogen atoms and even that of icosahedral Al 13 . A detailed view of the magnetic behavior of Ge 16 M 0/- clusters shows that the magnetic moments of the atomic metals remain large even when they are quenched upon doping. When M goes from Sc to Zn, the total spin magnetic moment of Ge 16 M 0/- increases steadily and reaches the maximum value of 3 μ B with M = Mn before decreasing towards the end of the first-row 3d block metals. Furthermore, the IR spectra of some tetrahedral Ge 16 M are also predicted., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

The present study reported the synthesis and utilization of a graphene-based hybrid nanocomposite (MnFe 2 O 4 /G) to mitigate several synthetic dyes, including methylene blue, malachite green, crystal violet, and Rhodamine B. This adsorbent was structurally analyzed by several physicochemical techniques such as X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, Raman spectroscopy, N 2 adsorption-desorption isotherm measurement, point of zero charge, and Boehm titrations. BET surface area of MnFe 2 O 4 /G was measured at 382.98 m 2 /g, which was substantially higher than that of MnFe 2 O 4 . MnFe 2 O 4 /G possessed diverse surface chemistry properties with the presence of many functional groups such as carboxylic acid, phenolic, lactone, and basic groups. MnFe 2 O 4 /G was used to remove synthetic dyes in the aqueous media. The effect of many factors, e.g., concentration (5-50 mg/L), pH (4-10), dose (5-20 mg), and temperature (25-45 °C) on adsorption performance of MnFe 2 O 4 /G was conducted. Kinetic, isotherm, intraparticle, and thermodynamic models were adopted for investigating adsorption phenomenon of dyes on MnFe 2 O 4 /G. The maximum adsorption capacity of dyes over MnFe 2 O 4 /G was found as Rhodamine B (67.8 mg/g) < crystal violet (81.3 mg/g) < methylene blue (137.7 mg/g) < malachite green (394.5 mg/g). Some tests were performed to remove mixed dyes, and mixed dyes in the presence of antibiotics with total efficiencies of 65.8-87.9% after 120 min. Moreover, the major role of π-π stacking interaction was clarified to gain insight into the adsorption mechanism. MnFe 2 O 4 /G could recycle up to 4 cycles, which may be beneficial for further practical water treatment., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ossification of the posterior longitudinal ligament (OPLL), characterized by ectopic new bone formation in the spinal ligament, causes neurological impairment due to narrowing of the spinal canal. However, the etiology has not been fully elucidated yet. Several biomarkers may be related to the pathogenesis of OPLL. The present study focused on the serum level of periostin, which is recognized as an important bone formation regulator., Methods: This study included 92 patients with OPLL and 54 control patients without OPLL. For the case-control analysis, 54 age and sex-matched patients were randomly included in the OPLL group. The serum fibroblast growth factor-23 (FGF-23), creatinine, inorganic phosphate, calcium, alkaline phosphatase, and periostin levels were assessed. Furthermore, the calcium, creatinine, and inorganic phosphate levels in urine and the percentage of tubular reabsorption of phosphate were also analyzed. Moreover, the relationship between the biomarkers and the extent of OPLL was analyzed. The data were compared between patients with OPLL progression (the progression group) and without OPLL progression (the non-progression group)., Results: The mean serum FGF-23 and periostin levels in the OPLL group were higher than that in the control group. The serum inorganic phosphate level in the OPLL group was lower than that in the control group. No correlation was found between any of the biomarkers and the extent of ossification. The serum periostin level in the progression group was higher than that in the non-progression group. No significant difference in the serum FGF-23 level was noted between the progression and non-progression groups. Moreover, no correlation was found between serum periostin and FGF-23 levels., Conclusions: The serum periostin level is related to OPLL progression., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSOA/A354)., (Copyright © 2022 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)