FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates

The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326–380 of p62 directly interact with the C-terminal region (CTR) of FIP200. Crystal structure determination shows that the FIP200 CTR contains a dimeric globular domain that we designated the “Claw” for its shape. The interaction of p62 with FIP200 is mediated by a positively charged pocket in the Claw, enhanced by p62 phosphorylation, mutually exclusive with the binding of p62 to LC3B, and it promotes degradation of ubiquitinated cargo by autophagy. Furthermore, the recruitment of the FIP200 CTR slows the phase separation of ubiquitinated proteins by p62 in a reconstituted system. Our data provide the molecular basis for a crosstalk between cargo condensation and autophagosome formation

Phase separation in LuFeO\u3csub\u3e3\u3c/sub\u3e films

The structural transition at about 1000°C, from the hexagonal to the orthorhombic phase of LuFeO3, has been investigated in thin films of LuFeO3. Separation of the two structural phases of LuFeO3 occurs on a length scale of micrometer, as visualized in real space using X-ray photoemission electron microscopy. The results are consistent with X-ray diffraction and atomic force microscopy obtained from LuFeO3 thin films undergoing the irreversible structural transition from the hexagonal to the orthorhombic phase of LuFeO3, at elevated temperatures. The sharp phase boundaries between the structural phases are observed to align with the crystal planes of the hexagonal LuFeO3 phase. The coexistence of different structural domains indicates that the irreversible structural transition, from the hexagonal to the orthorhombic phase in LuFeO3, is a first order transition, for epitaxial hexagonal LuFeO3 films grown on Al2O3

Chinese international students in the United States: The interplay of students’ acculturative stress, academic standing, and quality of life

Background: Acculturation could cause grave health consequences in international students. However, there is a shortage of research into how acculturative stress might affect international students’ quality of life in light of their academic standing and experience. The lack of research is particularly pronounced among Chinese international students, representing the largest body of international students studying in the United States (U.S.). Thus, to bridge the research gap, this study aims to examine the interplay between international students’ acculturative stress, academic standing, and quality of life among a nationally representative sample of Chinese international students studying in the United States. Methods: An online survey that gauges Chinese international students’ levels of acculturative stress, academic standing, and quality of life was developed. Over 350 higher education institutions across the United States were approached, including public universities, private universities, and community colleges, among which approximately 220 institutions responded positively and supported survey distribution. A total of 751 students completed the survey. Multiple regression analyses were carried out to examine the associations between students’ acculturative stress, academic standing, and quality of life. Results: Findings reveal that acculturative stress negatively affects all four domains of Chinese international students’ quality of life, irrespective of their academic standing. Data analyses also show that compared to master’s and doctoral students, undergraduates experience the highest levels of acculturative stress. Furthermore, a significant difference emerged among undergraduate and doctoral international students’ acculturative stress levels, but not among undergraduate and master’s students, or master’s and doctoral students. Conclusion: Our study found that, compared to master’s and doctoral students, undergraduates had more significant acculturative stress associated with lower levels of quality of life. This finding highlights the potentially positive role of academic experience – while acculturative stress deteriorates international students’ quality of life, students’ academic standing and experience could be the protective factor in the equation. Future research could further examine how universities and colleges can capitalize on their academic apparatuses and resources to improve international students’ academic performance and students’ acculturation experience and quality of life

Green synthesis of biogenetic Te(0) nanoparticles by high tellurite tolerance fungus Mortierella sp. AB1 with antibacterial activity

Tellurite [Te(IV)] is a high-toxicity metalloid. In this study, a fungus with high Te(IV) resistance was isolated. Strain AB1 could efficiently reduce highly toxic Te(IV) to less toxic Te(0). The reduced products formed rod-shaped biogenetic Te(0) nanoparticles (Bio-TeNPs) intracellularly. Further TEM-element mapping, FTIR, and XPS analysis showed that the extracted Bio-TeNPs ranged from 100 to 500 nm and consisted of Te(0), proteins, lipids, aromatic compounds, and carbohydrates. Moreover, Bio-TeNPs exhibited excellent antibacterial ability against Shigella dysenteriae, Escherichia coli, Enterobacter sakazakii, and Salmonella typhimurium according to inhibition zone tests. Further growth and live/dead staining experiments showed that E. coli and S. typhimurium were significantly inhibited by Bio-TeNPs, and cells were broken or shriveled after treatment with Bio-TeNPs based on SEM observation. Additionally, the antioxidant and cytotoxicity tests showed that the Bio-TeNPs exhibited excellent antioxidant capacity with no cytotoxicity. All these results suggested that strain AB1 showed great potential in bioremediation and Bio-TeNPs were excellent antibacterial nanomaterials with no cytotoxicity.Peer reviewe

Anti-IL-17 Antibody Improves Hepatic Steatosis by Suppressing Interleukin-17-Related Fatty Acid Synthesis and Metabolism

To investigate the relationship between interleukin-17 and proteins involved in fatty acid metabolism with respect to alcoholic liver disease, male ICR mice were randomized into five groups: control, alcoholic liver disease (ALD) at 4 weeks, 8 weeks, and 12 weeks, and anti-IL-17 antibody treated ALD. A proteomic approach was adopted to investigate changes in liver proteins between control and ALD groups. The proteomic analysis was performed by two-dimensional difference gel electrophoresis. Spots of interest were subsequently subjected to nanospray ionization tandem mass spectrometry (MS/MS) for protein identification. Additionally, expression levels of selected proteins were confirmed by western blot. Transcriptional levels of some selected proteins were determined by RT-PCR. Expression levels of 95 protein spots changed significantly (ratio >1.5, P<0.05) during the development of ALD. Sterol regulatory element-binding protein-lc (SREBP-1c), carbohydrate response element binding protein (ChREBP), enoyl-coenzyme A hydratase (ECHS1), and peroxisome proliferator-activated receptor alpha (PPAR-α) were identified by MS/MS among the proteins shown to vary the most; increased IL-17 elevated the transcription of SREBP-1c and ChREBP but suppressed ECHS1 and PPAR-α. The interleukin-17 signaling pathway is involved in ALD development; anti-IL-17 antibody improved hepatic steatosis by suppressing interleukin-17-related fatty acid metabolism

On the Structural Origin of the Single-ion Magnetic Anisotropy in LuFeO3

Electronic structures for the conduction bands of both hexagonal and orthorhombic LuFeO3 thin films have been measured using x-ray absorption spectroscopy at oxygen K (O K) edge. Dramatic differences in both the spectra shape and the linear dichroism are observed. These differences in the spectra can be explained using the differences in crystal field splitting of the metal (Fe and Lu) electronic states and the differences in O 2p-Fe 3d and O 2p-Lu 5d hybridizations. While the oxidation states has not changed, the spectra are sensitive to the changes in the local environments of the Fe3+ and Lu3+ sites in the hexagonal and orthorhombic structures. Using the crystal-field splitting and the hybridizations that are extracted from the measured electronic structures and the structural distortion information, we derived the occupancies of the spin minority states in Fe3+, which are non-zero and uneven. The single ion anisotropy on Fe3+ sites is found to originate from these uneven occupancies of the spin minority states via spin-orbit coupling in LuFeO3

Electronic structure and direct observation of ferrimagnetism in multiferroic hexagonal YbFeO3

The magnetic interactions between rare-earth and Fe ions in hexagonal rare-earth ferrites (h-RFeO3), may amplify the weak ferromagnetic moment on Fe, making these materials more appealing as multiferroics. To elucidate the interaction strength between the rare-earth and Fe ions as well as the magnetic moment of the rare-earth ions, element-specific magnetic characterization is needed. Using x-ray magnetic circular dichroism, we have studied the ferrimagnetism in h-YbFeO3 by measuring the magnetization of Fe and Yb separately. The results directly show antialignment of magnetization of Yb and Fe ions in h-YbFeO3 at low temperature, with an exchange field on Yb of about 17 kOe. The magnetic moment of Yb is about 1.6μB at low temperature, significantly reduced compared with the 4.5 μB moment of a free Yb3+. In addition, the saturation magnetization of Fe in h-YbFeO3 has a sizable enhancement compared with that in h-LuFeO3. These findings directly demonstrate that ferrimagnetic order exists in h-YbFeO3; they also account for the enhancement of magnetization and the reduction of coercivity in h-YbFeO3 compared with those in h-LuFeO3 at low temperature, suggesting an important role for the rare-earth ions in tuning the multiferroic properties of h-RFeO3

The Copper-Responsive RicR Regulon Contributes to Mycobacterium tuberculosis Virulence

ABSTRACT As with most life on Earth, the transition metal copper (Cu) is essential for the viability of the human pathogen Mycobacterium tuberculosis. However, infected hosts can also use Cu to control microbial growth. Several Cu-responsive pathways are present in M. tuberculosis, including the regulated in copper repressor (RicR) regulon, which is unique to pathogenic mycobacteria. In this work, we describe the contribution of each RicR-regulated gene to Cu resistance in vitro and to virulence in animals. We found that the deletion or disruption of individual RicR-regulated genes had no impact on virulence in mice, although several mutants had Cu hypersensitivity. In contrast, a mutant unable to activate the RicR regulon was not only highly susceptible to Cu but also attenuated in mice. Thus, these data suggest that several genes of the RicR regulon are required simultaneously to combat Cu toxicity in vivo or that this regulon is also important for resistance against Cu-independent mechanisms of host defense. IMPORTANCE Mycobacterium tuberculosis is the causative agent of tuberculosis, killing millions of people every year. Therefore, understanding the biology of M. tuberculosis is crucial for the development of new therapies to treat this devastating disease. Our studies reveal that although host-supplied Cu can suppress bacterial growth, M. tuberculosis has a unique pathway, the RicR regulon, to defend against Cu toxicity. These findings suggest that Cu homeostasis pathways in both the host and the pathogen could be exploited for the treatment of tuberculosis

Transmitted drug resistance and transmission clusters among ART-naïve HIV-1-infected individuals from 2019 to 2021 in Nanjing, China

BackgroundTransmitted drug resistance (TDR) is an increasingly prevalent problem worldwide, which will significantly compromise the effectiveness of HIV treatments. However, in Nanjing, China, there is still a dearth of research on the prevalence and transmission of TDR among ART-naïve HIV-1-infected individuals. This study aimed to understand the prevalence and transmission of TDR in Nanjing.MethodsA total of 1,393 participants who were newly diagnosed with HIV-1 and had not received ART between January 2019 and December 2021 were enrolled in this study. HIV-1 pol gene sequence was obtained by viral RNA extraction and nested PCR amplification. Genotypes, TDR and transmission cluster analyses were conducted using phylogenetic tree, Stanford HIV database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with TDR.ResultsA total of 1,161 sequences were successfully sequenced, of which CRF07_BC (40.6%), CRF01_AE (38.4%) and CRF105_0107 (6.3%) were the main HIV-1 genotypes. The overall prevalence of TDR was 7.8%, with 2.0% to PIs, 1.0% to NRTIs, and 4.8% to NNRTIs. No sequence showed double-class resistance. Multivariate logistic regression analysis revealed that compared with CRF01_AE, subtype B (OR = 2.869, 95%CI: 1.093–7.420) and female (OR = 2.359, 95%CI: 1.182–4.707) were risk factors for TDR. Q58E was the most prevalent detected protease inhibitor (PI) -associated mutation, and V179E was the most frequently detected non-nucleoside reverse transcriptase inhibitor (NNRTI) -associated mutation. A total of 613 (52.8%) sequences were segregated into 137 clusters, ranging from 2 to 74 sequences. Among 44 individuals with TDR (48.4%) within 21 clusters, K103N/KN was the most frequent TDR-associated mutation (31.8%), followed by Q58E/QE (20.5%) and G190A (15.9%). Individuals with the same TDR-associated mutations were usually cross-linked in transmission clusters. Moreover, we identified 9 clusters in which there was a transmission relationship between drug-resistant individuals, and 4 clusters in which drug-resistant cases increased during the study period.ConclusionThe overall prevalence of TDR in Nanjing was at a moderate level during the past 3 years. However, nearly half of TDR individuals were included in the transmission clusters, and some drug-resistant individuals have transmitted in the clusters. Therefore, HIV drug-resistance prevention, monitoring and response efforts should be sustained and expanded to reduce the prevalence and transmission of TDR in Nanjing