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ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, its mechanisms of poly-specific substrate recognition and transport remain poorly resolved. Here we present cryo-EM structures of lipid embedded human ABCB1 in its apo, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.4-3.9 Å resolution without using stabilizing antibodies or mutations and each revealing a distinct conformation. The substrate binding site is located within one half of the molecule and, in the apo state, is obstructed by transmembrane helix (TM) 4. Substrate and inhibitor binding are distinguished by major differences in TM arrangement and ligand binding chemistry, with TM4 playing a central role in all conformational transitions. Our data offer fundamental new insights into the role structural asymmetry, secondary structure breaks, and lipid interactions play in ABCB1 function and have far-reaching implications for ABCB1 inhibitor design and predicting its substrate binding profiles.
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Breaking structural symmetry in two-dimensional layered Janus materials can result in enhanced new phenomena and create additional degrees of piezoelectric responses. In this study, we theoretically design a series of Janus monolayers HfGeZ3H (Z = N, P, As) and investigate their structural characteristics, crystal stability, piezoelectric responses, electronic features, and carrier mobility using first-principles calculations. Phonon dispersion analysis confirms that HfGeZ3H monolayers are dynamically stable and their mechanical stability is also confirmed through the Born-Huang criteria. It is demonstrated that while HfGeN3H is a semiconductor with a large bandgap of 3.50 eV, HfGeP3H and HfGeAs3H monolayers have narrower bandgaps being 1.07 and 0.92 eV, respectively. When the spin-orbit coupling is included, large spin-splitting energy is found in the electronic bands of HfGeZ3H. Janus HfGeZ3H monolayers can be treated as piezoelectric semiconductors with the coexistence of both in-plane and out-of-plane piezoelectric responses. In particular, HfGeZ3H monolayers exhibit ultra-high electron mobilities up to 6.40 × 103 cm2 V-1 s-1 (HfGeAs3H), indicating that they have potential for various applications in nanoelectronics.
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Background: Critically ill patients are at high risk of multiple organ failure syndrome (MODS) and gastrointestinal (GI) injury and dysfunction, which are associated with increased mortality rates. The acute gastrointestinal injury (AGI) scale has shown promise in assessing GI dysfunction. However, the combined utility of AGI with established disease severity scores remains unclear. This study aimed to investigate the performance of AGI in conjunction with modified nutritional risk in critically ill (mNUTRIC), sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE II) scores for predicting mortality in critically ill patients. Materials and methods: A retrospective cross-sectional study was conducted in the intensive care unit (ICU) from May 2021 to December 2021. Demographic and clinical data were collected, including AGI grade, mNUTRIC score, SOFA score, APACHE II score, and mortality. Results: Among 93 critically ill patients, AGI was observed in 47.3% of cases, and the in-hospital mortality rate was 30.1%. The area under the curve (AUC) for AGI in predicting in-hospital mortality was 0.67 [95% confidence interval (CI), 0.56, 0.79; p = 0.008], similar to the AUCs of SOFA, APACHE II, and mNUTRIC scores. The combination of AGI with mNUTRIC, APACHE II, or SOFA scores improved the predictive performance compared with AGI alone. Conclusion: The AGI grade, in conjunction with disease severity scores, such as mNUTRIC, SOFA, and APACHE II scores, shows promise in predicting mortality in critically ill patients. Integrating AGI into evaluating critically ill patients can enhance prognostic accuracy. How to cite this article: Hai PD, Tot NH, Thao LT, Khoa Q, Thien DH. Prognostic Value of Acute Gastrointestinal Injury Combined with Disease Severity Scores in Critically Ill Patients. Indian J Crit Care Med 2024;28(6):575-580.
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The exploration of potential variations in fundamental physical constants is crucial for testing of Grand Unification Theories (GUTs), which aim to unify the fundamental forces of nature. This study utilizes direct observational tests to explore these variations, offering a deep-look into the universe's distant past. By analyzing high-resolution quasar spectra of HE 0515-4414* and comparing them with laboratory-calibrated Ritz wavelengths, we establish an upper limit on the possible cosmological deviation of the gravitational constant: G Ë / G = ( 0.918 ± 2.830 ) × 10 - 15 yr - 1 over cosmic timescales. Our findings provide a novel tool for probing the physical implications of GUTs, contributing to our understanding of fundamental physics.
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This study addresses the effect of electron-phonon coupling (EPC) on the electro-optical properties of gated ß12-borophene. The focus is on how EPC influences the orbital hybridization of boron atoms, particularly within the Barisic-Labbe-Friedel-Su-Schrieffer-Heeger framework, and considers the role of gate electrodes in this process. The results reveal a redshift in the optical spectrum only when there is positive feedback from one electrode on EPC. In other configurations, except for the y-direction, a blueshift spectrum is observed. The study emphasizes the importance of tuning these spectral shifts for maximizing the performance of solar cells in converting sunlight into usable energy.
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Alcohol consumption remains a significant global health challenge, causing millions of direct and indirect deaths annually. Intriguingly, recent work has highlighted the prefrontal cortex, a major brain area that regulates inhibitory control of behaviors, whose activity becomes dysregulated upon alcohol abuse. However, whether an endogenous mechanism exists within this brain area that limits alcohol consumption is unknown. Here we identify a discrete GABAergic neuronal ensemble in the medial orbitofrontal cortex (mOFC) that is selectively recruited during binge alcohol-drinking and intoxication. Upon alcohol intoxication, this neuronal ensemble suppresses binge drinking behavior. Optogenetically silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. We find that this neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. We further show, using brain-wide analysis, that this neuronal ensemble projects widely, and that its projections specifically to the mediodorsal thalamus are responsible for regulating binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by halting alcohol intake. These results provide valuable insights into the complex nature of alcohol abuse and offers potential avenues for the development of mOFC neuronal ensemble-targeted interventions.
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In a recent call to action, we described pressing issues in the health-service-psychology (HSP) internship from the perspective of interns. In our article, we sought to initiate a dialogue that would include trainees and bring about concrete changes. The commentaries on our article are a testament to the readiness of the field to engage in such a dialogue, and we applaud the actionable recommendations that they make. In our response to these commentaries, we seek to move the conversation further forward. We observe two themes that cut across these responses: the impetus to gather novel data on training (the "need to know") and the importance of taking action (the "need to act"). We emphasize that in new efforts to gather data and take policy-level action, the inclusion of trainee stakeholders (as well as others involved in and affected by HSP training) is a crucial ingredient for sustainable and equitable change.
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Background: Birch pollen-related food allergy (BPFA) is the most common type of food allergy in birch-endemic areas such as Western and Central Europe. Currently, there is no treatment available for BPFA. Due to the cross-reactivity between birch pollen and a range of implicated plant foods, birch pollen allergen immunotherapy (AIT) may be effective in the treatment of BPFA. In this study, we systematically evaluate the effectiveness of birch pollen-specific subcutaneous or sublingual immunotherapy in treating BPFA. Methods: A search was performed in the PubMed, Embase, and Cochrane libraries. Studies were independently screened by two reviewers against predefined eligibility criteria. The outcomes of interest were changes in (1) severity of symptoms during food challenge, (2) eliciting dose (ED), and (3) food allergy quality of life (FA-QoL). The validity of the selected articles was assessed using the revised Cochrane risk of bias tool. We focused on studies with the lowest risk of bias and considered studies with a high risk of bias as supportive. Data were descriptively summarized. Results: Ten studies were selected that included 475 patients in total. Seven studies were categorized into "high risk of bias" and three into "moderate risk of bias." The three moderate risk of bias studies, with a total of 98 patients, reported on severity of symptoms during challenge and on the ED. All three studies had a control group. Compared to the control group, improvement in severity of symptoms was observed during challenge in two out of the three studies and on the eliciting dose in one out of three. Only one study investigated the effect of birch pollen AIT on FA-QoL, showing that there was no significant difference between patients receiving subcutaneous immunotherapy or a placebo. Of the seven supportive studies, four had a control group and of those, three showed improvement on both severity of symptoms and ED. None of the supportive studies investigated the effect of the therapy on FA-QoL. Conclusion: This systematic review shows that there is not enough evidence to draw firm conclusions about the effect of AIT on BPFA. Future research is warranted that uses robust clinical studies that include long-term effects, QoL, and multiple BPFA-related foods.
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It is essential that communities at risk from TB are involved in TB research. Community advisory groups (CAGs) are one mechanism for involving communities in research and creating platforms for discussions between researchers and community members. We organised a CAG meeting with community members and people with lived experience in Ho Chi Minh City, Vietnam, to explore the community's knowledge about TB and their perspectives on different diagnostic tests in Vietnam, a low-middle-income country with a high TB burden. Researchers shared basic information and addressed questions about TB. CAG members commented on preference of TB screening tests, and suggested that chest X-rays and blood tests were more acceptable than sputum tests because of the difficulty in sputum expectoration. In addition, clinical studies that required fewer visits to the hospitals would be preferred, even if this meant a greater reliance on blood sampling.
Il est essentiel que les communautés exposées au risque de TB soient impliquées dans la recherche sur la TB. Les groupes consultatifs communautaires (CAG, pour l'anglais « community advisory groups ¼) constituent un mécanisme permettant d'impliquer les communautés dans la recherche et de créer des plateformes de discussion entre les chercheurs et les membres de la communauté. Nous avons organisé une réunion du CAG avec des membres de la communauté et des personnes ayant une expérience vécue à Ho Chi Minh Ville, au Viêt Nam, afin d'explorer les connaissances de la communauté sur la TB et leurs perspectives sur les différents tests de diagnostic au Viêt Nam, un pays à revenu faible et moyen où la charge de la TB est élevée. Les chercheurs ont partagé des informations de base et répondu à des questions sur la TB. Les membres du CAG ont fait part de leur préférence pour les tests de dépistage de la TB et ont suggéré que les radiographies pulmonaires et les analyses de sang étaient plus acceptables que les tests d'expectoration en raison de la difficulté d'expectoration des crachats. En outre, les études cliniques qui nécessitent moins de visites dans les hôpitaux seraient préférées, même si cela implique une plus grande dépendance à l'égard des prélèvements sanguins.
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This study investigates the optical absorption of monolayer phosphorene, focusing on its response to the electron-phonon coupling (EPC) and an electric field. Using a tight-binding Hamiltonian model based on the Barisic-Labbe-Friedel-Su-Schrieffer-Heeger model and the Kubo formula, we calculate the electronic band structure and optical absorption characteristics. The anisotropic dispersion of carriers along armchair and zigzag directions leads to distinct optical responses. Positive and negative EPC effects increase and decrease hopping parameters, respectively, enlarging and reducing/closing the band gap. Moreover, both EPCs cause an admixture of blue and red shift spectrum along the armchair direction, while a red (blue) shift spectrum is observed for positive (negative) EPC along the zigzag direction. Incorporating electric field effects in the EPC increases band gaps for both positive and negative EPC activities, resulting in shifted optical peaks along both directions.
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Tuberculosis, caused by infection with Mycobacterium tuberculosis (MTB), remains a global public health challenge. Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains make tuberculosis more difficult to control. New tools to study the biology of MTB can identify novel targets for drug discovery. Recently, the Clustered Regularly Interspaced Short Palindromic Repeats interference (CRISPRi) combined with next-generation sequencing has provided many novel insights into the physiology and genetics of MTB. This review summarizes the application and optimization of CRISPRi in MTB biology.
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Tuberculose Extensivamente Resistente a Medicamentos , Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Mycobacterium tuberculosis/genética , Antituberculosos/uso terapêutico , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Biologia , Testes de Sensibilidade MicrobianaRESUMO
Pratylenchus coffeae, belonging to the root-lesion nematode group, is a highly prevalent and destructive plant-parasitic nematode that is able to infest a wide range of host plants. Although this species' devastating impacts on coffee plantations across the world are widely known on other host plants, its association with Ming aralia has never been reported. Our study characterized two popu lations of P. coffeae (associated with Ming aralia and coffee) and compared them with other popu lations from previous studies in Vietnam and other countries in the world. The identification of P. coffeae in our study was confirmed by the comprehensive analysis encompassing morphological examination, morphometric data, and molecular characterizations of the COI mtDNA and D2D3 of 28S rRNA regions. The cluster and MDS analyses revealed that the two populations of P. coffeae from Vietnam are closely related to those from Japan and Indonesia. The D2-D3 sequences of 28S rRNA and COI mtDNA regions exhibited high similarity among these populations, indicating a stable genetic profile. Our research contributes to a better understanding of the distribution and genetic characterizations of P. coffeae by offering new morphological and molecular insights into the presence of this nematode in Vietnam. Additionally, this nematode species was found to be associated with host plant's symptoms such as chlorotic leaves, stunted growth and root lesion in both hosts. Given the economic significance of both Ming aralia and coffee crops in Vietnam, as well as the damaging potential of P. coffeae, this study emphasizes the need of proactive nematode management measures to control this destructive pest.
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Radioactive seed localization (RSL) provides a precise and efficient method for removing non-palpable breast lesions. It has proven to be a valuable addition to breast surgery, improving perioperative logistics and patient satisfaction. This retrospective review examines the lessons learned from a high-volume cancer center's RSL program after 10 years of practice and over 25 000 cases. We provide an updated model for assessing the patient's radiation dose from RSL seed implantation and demonstrate the safety of RSL to staff members. Additionally, we emphasize the importance of various aspects of presurgical evaluation, surgical techniques, post-surgical management, and regulatory compliance for a successful RSL program. Notably, the program has reduced radiation exposure for patients and medical staff.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Mastectomia Segmentar/métodos , Radioisótopos do Iodo , Mama , Estudos RetrospectivosRESUMO
Element doping has been widely employed to modify the ground state properties of two-dimensional (2D) materials. In this work, the effects of doping with alkaline earth metals (AEMs) on the structural, electronic, and magnetic properties of indium nitride (InN) monolayers are investigated using first-principles calculations based on density functional theory. In a graphene-like honeycomb structure, the InN monolayer possesses good dynamical and thermal stability, and exhibits an indirect gap semiconductor character with a band gap of 0.37 (1.48) eV as determined by using the PBE(HSE06) functional. A single In vacancy leads to the emergence of a magnetic semiconductor character, where magnetic properties with a large total magnetic moment of 3.00 µB are produced mainly by the N atoms closest to the defect site. The incorporation of AEMs impurities causes local structural distortion due to the difference in atomic size, where Mg and Ca doping processes are energetically most favorable. Half-metallicity is induced by the partial occupancy of the N-2p orbital, which is a consequence of having one valence electron less. In these cases, the total magnetic moment of 1.00 µB mainly originates from N atoms neighboring the dopants. Further increasing the doping level preserves the half-metallic character, where N atoms play a key role on the magnetism of the highly doped systems. Results presented herein suggest the In replacement by AEMs impurities is an effective approach to make prospective spintronic 2D materials from InN monolayers.
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Surveillance of pathogen richness in wildlife is needed to identify host species with a high risk of zoonotic disease spillover. While several predictors of pathogen richness in wildlife hosts have been proposed, their relative importance has not been formally examined. This hampers our ability to identify potential disease reservoirs, particularly in remote areas with limited surveillance efforts. Here we analyzed 14 proposed predictors of pathogen richness using ensemble modeling and a dataset of 1040 host species to identify the most important predictors of pathogen richness in wild mammal species. After controlling for research effort, larger species geographic range area was identified to be associated with higher pathogen richness. We found evidence of duality in the relationship between the fast-slow continuum of life-history traits and pathogen richness, where pathogen richness increases near the extremities. Taxonomic orders Carnivora, Proboscidea, Artiodactyla, and Perissodactyla were predicted to host high pathogen richness. The top three species with the highest pathogen richness predicted by our ensemble model were Canis lupus, Sus scrofa, and Alces alces. Our results can help support evidence-informed pathogen surveillance and disease reservoir management to prevent the emergence of future zoonotic diseases.
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Carnívoros , Cervos , Características de História de Vida , Animais , Mamíferos , Zoonoses/epidemiologia , Animais Selvagens , Reservatórios de DoençasRESUMO
Tomato (Solanum lycopersicum L.) is an important grown vegetable in Vietnam. Bacterial wilt caused by Pseudomonas solanacearum has been considered to be an important disease resulting in a harvest loss up to 90% and significant economic loss to farmers. In this study, two bacteriophages DLDT_So2 and BHDT_So9 specific to P. solanacearum were isolated. Morphological analysis indicated that DLDT_So2 and BHDT_So9 had podovirus morphology and were classified into Autographiviridae family. The latent period and burst size of DLDT_So2 was found to be approximately 120 min and 20.0 ± 2.4 virions per infected cell. Meanwhile, the latent period of BHDT_So9 was 140 min with a burst size of 11.5 ± 2.8 virions per infected cell. Of the 23 bacterial strains tested, the phages infected 7/11 strains of P. solanacearum and none of the other bacteria tested were susceptible to the phages. Stability of the phages at different temperatures, pHs, solvents was also investigated. The genomes of DLDT_So2 and BHDT_So9 are 41,341 bp and 41,296 bp and long with a total GC content of 63%, contains 48 and 46 predicted protein-encoding CDSs. No virulence or antibiotic resistance genes were found in the genomes, suggesting they would be useful biocontrol agents against P. solanacearum. Classification of the phage using average nucleotide identity, phylogenetic analysis was also carried out. The two phages represented new species when they had overall average nucleotide identity of < 95%. This is first report of the isolation and characterization of P. solanacearum-specific phages from tomato farms in Vietnam. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01090-9.
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The objective of the present study is to synthesize g-C3N4-Ni nanocomposites composed of graphitic carbon nitride and magnetic nickel nanoparticles for benzopyrene degradation, which is one of the most potent polycyclic aromatic hydrocarbons (PAH) molecules. The concocted g-C3N4-Ni nanocomposites contained confined nanospheres with a mean particle dimension of 22 nm. Batch adsorption studies revealed that a rise in adsorbent dosage elevates benzopyrene degradation percentage in both water and soil samples with respect to time. The increase in the benzopyrene concentration did not have much influence on the degradation efficiency, and hence, the minimal concentration of PAH molecule is essential for the effective adsorption by g-C3N4-Ni nanocomposites. The rise in pH tends to increase the degradation of Benzopyrene till 3 h of the incubation period, and beyond 3 h, the degradation percentage declines. With regard to the effect of light source, UV light has been shown to accelerate the degradation of benzopyrene by g-C3N4-Ni nanocomposites than sunlight. The adsorption kinetic and isotherm investigations have proven that the Pseudo-second order kinetic model and Freundlich isotherm model were appropriate for our study. Thus, the g-C3N4-Ni nanocomposites were found to be efficient as a photocatalyst for the adsorption of benzopyrene from environmental samples.
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Nanocompostos , Hidrocarbonetos Policíclicos Aromáticos , Níquel/química , Nanocompostos/química , Água/química , Benzopirenos , CatáliseRESUMO
BACKGROUND: Adjunctive glucocorticoids are widely used to treat human immunodeficiency virus (HIV)-associated tuberculous meningitis despite limited data supporting their safety and efficacy. METHODS: We conducted a double-blind, randomized, placebo-controlled trial involving HIV-positive adults (≥18 years of age) with tuberculous meningitis in Vietnam and Indonesia. Participants were randomly assigned to receive a 6-to-8-week tapering course of either dexamethasone or placebo in addition to 12 months of antituberculosis chemotherapy. The primary end point was death from any cause during the 12 months after randomization. RESULTS: A total of 520 adults were randomly assigned to receive either dexamethasone (263 participants) or placebo (257 participants). The median age was 36 years; 255 of 520 participants (49.0%) had never received antiretroviral therapy, and 251 of 484 participants (51.9%) with available data had a baseline CD4 count of 50 cells per cubic millimeter or less. Six participants withdrew from the trial, and five were lost to follow-up. During the 12 months of follow-up, death occurred in 116 of 263 participants (44.1%) in the dexamethasone group and in 126 of 257 participants (49.0%) in the placebo group (hazard ratio, 0.85; 95% confidence interval, 0.66 to 1.10; P = 0.22). Prespecified analyses did not reveal a subgroup that clearly benefited from dexamethasone. The incidence of secondary end-point events, including cases of immune reconstitution inflammatory syndrome during the first 6 months, was similar in the two trial groups. The numbers of participants with at least one serious adverse event were similar in the dexamethasone group (192 of 263 participants [73.0%]) and the placebo group (194 of 257 participants [75.5%]) (P = 0.52). CONCLUSIONS: Among HIV-positive adults with tuberculous meningitis, adjunctive dexamethasone, as compared with placebo, did not confer a benefit with respect to survival or any secondary end point. (Funded by the Wellcome Trust; ACT HIV ClinicalTrials.gov number, NCT03092817.).
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Antirretrovirais , Antituberculosos , Dexametasona , Glucocorticoides , Infecções por HIV , Tuberculose Meníngea , Adulto , Humanos , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Método Duplo-Cego , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , HIV , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/complicações , Soropositividade para HIV/tratamento farmacológico , Tuberculose Meníngea/complicações , Tuberculose Meníngea/tratamento farmacológico , Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Antirretrovirais/efeitos adversos , Antirretrovirais/uso terapêuticoRESUMO
Bacillary necrosis of pangasius (BNP) is a disease caused by Edwardsiella ictaluri bacteria in striped catfish Pangasianodon hypophthalmus that results in high mortality rates. To control this disease, bacteriophages have been considered as alternatives to antibiotics. In this study, we applied the lytic bacteriophage PVN06 in striped catfish fingerlings to prevent E. ictaluri infection. In an experimental trial, the phage was administered to fish by feeding phage-coated feed with doses of 7.17±0.09, 8.17±0.09 and 9.17±0.09 log PFU/g feed per day before bacterial infection. Fish were infected by bacteria once with concentrations ranging from 3.01 to 7.01 log CFU/ml tank water. A day after infection, phage treatment resumed at a rate of once per day until the end of the trial. The results of the trial show that bacterial infection caused typical symptoms of BNP in fish with the cumulative fish death rate of 36.7±2.9 to 75.0±5.0%, depending on the bacterial concentration used for infection. Phage treatment with 9.17±0.09 log PFU/g significantly reduced the mortality rate, while treatments with 8.17±0.09 and 7.17±0.09 log PFU/g did not. This phage dose resulted in a 61.7-fold reduction in the toxicity of the bacterial pathogen and the survival rate of 15-23.3% in fish. Our study has demonstrated that the bacteriophage PVN06 protected striped catfish from BNP.
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Bacteriófagos , Peixes-Gato , Infecções por Enterobacteriaceae , Animais , Infecções por Enterobacteriaceae/prevenção & controle , Edwardsiella ictaluriRESUMO
We study the transport properties of monolayers MoSi2N4, WSi2N4, and MoSi2As4in a perpendicular magnetic field. The Landau level (LL) band structures including spin and exchange field effects are derived and discussed using a low-energy effective model. We show that the LLs band structures of these materials are similar to those of phosphorene and transition-metal dichalcogenides rather than graphene or silicene. The combination of strong spin-orbit coupling and exchange fields reduces the degradation of the LLs, leading to new plateaus in the Hall conductivity and Hall resistivity and new peaks in the longitudinal conductivity and longitudinal resistivity. The effect of the exchange field, carrier density, and LLs band structure on the conductivities and resistivities have been investigated. At high temperatures, the steps in Hall conductivity and resistivity plateaus disappear and reduce to their corresponding classical forms.