Radical-Driven Crystal-Amorphous-Crystal Transition of a Metal-Organic Framework.

Self-assembly-based structural transition has been explored for various applications, including molecular machines, sensors, and drug delivery. In this study, we developed new redox-active metal-organic frameworks (MOFs) called DGIST-10 series that comprise π-acidic 1,4,5,8-naphthalenediimide (NDI)-based ligands and Ni2+ ions, aiming to boost ligand-self-assembly-driven structural transition and study the involved mechanism. Notably, during the synthesis of the MOFs, a single-crystal-amorphous-single-crystal structural transition occurred within the MOFs upon radical formation, which was ascribed to the fact that radicals prefer spin-pairing or through-space electron delocalization by π-orbital overlap. The radical-formation-induced structural transitions were further confirmed by the postsynthetic solvothermal treatment of isolated nonradical MOF crystals. Notably, the transient amorphous phase without morphological disintegration was clearly observed, contributing to the seminal structural change of the MOF. We believe that this unprecedented structural transition triggered by the ligand self-assembly magnifies the structural flexibility and diversity of MOFs, which is one of the pivotal aspects of MOFs.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

PURPOSE: To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). METHODS: This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24 and 48 weeks. Secondary outcomes included arthroscopic, histological and magnetic resonance imaging assessments at 1 year. RESULTS: Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignment and clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). CONCLUSION: hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. LEVEL OF EVIDENCE: Level II, Prospective Comparative Cohort Study.

uORF-mediated riboregulation controls transcription of whiB7/wblC antibiotic resistance gene.

WhiB7/WblC is a transcriptional factor of actinomycetes conferring intrinsic resistance to multiple translation-inhibitory antibiotics. It positively autoregulates its own transcription in response to the same antibiotics. The presence of a uORF and a potential Rho-independent transcription terminator in the 5' leader region has suggested a possibility that the whiB7/wblC gene is regulated via a uORF-mediated transcription attenuation. However, experimental evidence for the molecular mechanism to explain how antibiotic stress suppresses the attenuator, if any, and induces transcription of the whiB7/wblC gene has been lacking. Here we report that the 5' leader sequences of the whiB7/wblC genes in sub-clades of actinomycetes include conserved antiterminator RNA structures. We confirmed that the putative antiterminator in the whiB7/wblC leader sequences of both Streptomyces and Mycobacterium indeed suppresses Rho-independent transcription terminator and facilitates transcription readthrough, which is required for WhiB7/WblC-mediated antibiotic resistance. The antibiotic-mediated suppression of the attenuator can be recapitulated by amino acid starvation, indicating that translational inhibition of uORF by multiple signals is a key to induce whiB7/wblC expression. Our findings of a mechanism leading to intrinsic antibiotic resistance could provide an alternative to treat drug-resistant mycobacteria.

A myosin-7B-dependent endocytosis pathway mediates cellular entry of α-synuclein fibrils and polycation-bearing cargos.

Cell-to-cell transmission of misfolding-prone α-synuclein (α-Syn) has emerged as a key pathological event in Parkinson's disease. This process is initiated when α-Syn-bearing fibrils enter cells via clathrin-mediated endocytosis, but the underlying mechanisms are unclear. Using a CRISPR-mediated knockout screen, we identify SLC35B2 and myosin-7B (MYO7B) as critical endocytosis regulators for α-Syn preformed fibrils (PFFs). We show that SLC35B2, as a key regulator of heparan sulfate proteoglycan (HSPG) biosynthesis, is essential for recruiting α-Syn PFFs to the cell surface because this process is mediated by interactions between negatively charged sugar moieties of HSPGs and clustered K-T-K motifs in α-Syn PFFs. By contrast, MYO7B regulates α-Syn PFF cell entry by maintaining a plasma membrane-associated actin network that controls membrane dynamics. Without MYO7B or actin filaments, many clathrin-coated pits fail to be severed from the membrane, causing accumulation of large clathrin-containing "scars" on the cell surface. Intriguingly, the requirement for MYO7B in endocytosis is restricted to α-Syn PFFs and other polycation-bearing cargos that enter cells via HSPGs. Thus, our study not only defines regulatory factors for α-Syn PFF endocytosis, but also reveals a previously unknown endocytosis mechanism for HSPG-binding cargos in general, which requires forces generated by MYO7B and actin filaments.

Epidemiology of idiopathic sudden sensorineural hearing loss in the era of big data.

OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a medical emergency, and delayed treatment can have permanent sequelae. However, the etiology of ISSNHL is diverse and unclear; thus, it is idiopathic. To develop an insight into this condition, patients with ISSNHL must be clearly identified. We propose an operational definition for the unambiguous identification of ISSNHL patients. Patients are identified through suggested definitions, and prevalence and general information are investigated. METHODS: A retrospective study of patients with ISSNHL was performed using the Health Insurance and Review Assessment-National Patient Sample from 2009 to 2016. To present a new operational definition, a systematic review was conducted for studies on ISSNHL from January 2007 to June 2021. After constructing several operant definitions using the conditions that can specify patients with ISSNHL in big data, we compared each definition to propose an operational definition. RESULTS: The important conditions required to classify patients with ISSNHL using big data were the International Classification of Diseases (ICD)-10 code, number of pure tone audiometry (PTA) tests, and whether steroids were prescribed. Among them, those who had undergone PTA tests more than twice could be clearly identified as patients with ISSNHL. CONCLUSION: As the use of big data becomes smoother, research using national medical data is being conducted; however, the results of the studies may vary depending on how a patient with ISSNHL is classified. Clear identification of patients with ISSNHL will be beneficial for better management of this condition.

Time from Exposure to Diagnosis among Quarantined Close Contacts of SARS-CoV-2 Omicron Variant Index Case-Patients, South Korea.

To determine optimal quarantine duration, we evaluated time from exposure to diagnosis for 107 close contacts of severe acute respiratory syndrome coronavirus 2 Omicron variant case-patients. Average time from exposure to diagnosis was 3.7 days; 70% of diagnoses were made on day 5 and 99.1% by day 10, suggesting 10-day quarantine.

Community Transmission of SARS-CoV-2 Omicron Variant, South Korea, 2021.

In South Korea, a November 2021 outbreak caused by severe acute respiratory syndrome coronavirus 2 Omicron variant originated from 1 person with an imported case and spread to households, kindergartens, workplaces, restaurants, and hospitals, resulting in 11 clusters within 3 weeks. An epidemiologic curve indicated rapid community transmission of the Omicron variant.

Resilient consumers accelerate the plant decomposition in a naturally acidified seagrass ecosystem.

Anthropogenic stressors are predicted to alter biodiversity and ecosystem functioning worldwide. However, scaling up from species to ecosystem responses poses a challenge, as species and functional groups can exhibit different capacities to adapt, acclimate, and compensate under changing environments. We used a naturally acidified seagrass ecosystem (the endemic Mediterranean Posidonia oceanica) as a model system to examine how ocean acidification (OA) modifies the community structure and functioning of plant detritivores, which play vital roles in the coastal nutrient cycling and food web dynamics. In seagrass beds associated with volcanic CO2 vents (Ischia, Italy), we quantified the effects of OA on seagrass decomposition by deploying litterbags in three distinct pH zones (i.e., ambient, low, extreme low pH), which differed in the mean and variability of seawater pH. We replicated the study in two discrete vents for 117 days (litterbags sampled on day 5, 10, 28, 55, and 117). Acidification reduced seagrass detritivore richness and diversity through the loss of less abundant, pH-sensitive species but increased the abundance of the dominant detritivore (amphipod Gammarella fucicola). Such compensatory shifts in species abundance caused more than a threefold increase in the total detritivore abundance in lower pH zones. These community changes were associated with increased consumption (52%-112%) and decay of seagrass detritus (up to 67% faster decomposition rate for the slow-decaying, refractory detrital pool) under acidification. Seagrass detritus deployed in acidified zones showed increased N content and decreased C:N ratio, indicating that altered microbial activities under OA may have affected the decay process. The findings suggest that OA could restructure consumer assemblages and modify plant decomposition in blue carbon ecosystems, which may have important implications for carbon sequestration, nutrient recycling, and trophic transfer. Our study highlights the importance of within-community response variability and compensatory processes in modulating ecosystem functions under extreme global change scenarios.

SigR, a hub of multilayered regulation of redox and antibiotic stress responses.

Signal-specific activation of alternative sigma factors redirects RNA polymerase to induce transcription of distinct sets of genes conferring protection against the damage the signal and the related stresses incur. In Streptomyces coelicolor, σR (SigR), a member of ECF12 subfamily of Group IV sigma factors, responds to thiol-perturbing signals such as oxidants and electrophiles, as well as to translation-blocking antibiotics. Oxidants and electrophiles interact with and inactivate the zinc-containing anti-sigma factor, RsrA, via disulfide bond formation or alkylation of reactive cysteines, subsequently releasing σR for target gene induction. Translation-blocking antibiotics induce the synthesis of σR , via the WhiB-like transcription factor, WblC/WhiB7. Signal transduction via RsrA produces a dramatic transient response that involves positive feedback to produce more SigR as an unstable isoform σ R ' and negative feedbacks to degrade σ R ' , and reduce oxidized RsrA that subsequently sequester σR and σ R ' . Antibiotic stress brings about a prolonged response by increasing stable σR levels. The third negative feedback, which occurs via IF3, lowers the translation efficiency of the sigRp1 transcript that utilizes a non-canonical start codon. σR is a global regulator that directly activates > 100 transcription units in S. coelicolor, including genes for thiol homeostasis, protein quality control, sulfur metabolism, ribosome modulation and DNA repair. Close homologues in Actinobacteria, such as σH in Mycobacteria and Corynebacteria, show high conservation of the signal transduction pathways and target genes, thus reflecting the robustness of this type of regulation in response to redox and antibiotic stresses.

Risk of cerebro- and cardiovascular disease in patients with scrub typhus.

We analyzed the National Health Insurance Service-National Sample Cohort (NHIS-NSC) data to evaluate whether scrub typhus infection is associated with increased risk of subsequent cardio- and cerebrovascular disease. Compared with the control group, the scrub typhus group showed a greater incidence rate of cardiovascular disease (14.5 vs. 9.0 cases per 1000 person-years). In contrast, the scrub typhus group showed no difference in incidence rate of cerebrovascular disease (12.0 vs. 13.3 cases per 1000 person-years). Based on the NHIS-NSC data, patients with scrub typhus are at greater risk of developing cardiovascular disease long term compared with that of the general population.

Nanometer-Scale Vibration Measurement Using an Optical Quadrature Interferometer based on 3 × 3 Fiber-Optic Coupler.

We propose a nanometer-scale displacement or vibration measurement system, using an optical quadrature interferometer and the post-processing technique that extracts the parameters necessary for characterizing the interferometric system. Using a 3 × 3 fiber-optic coupler, the entire complex interference signal could be reconstructed with two interference signals measured at two return ports of the coupler. The intrinsic phase difference between the return ports was utilized to obtain the quadratic part of the interference signal, which allowed one to reconstruct the entire complex interference signal. However, the two measured signals were appreciably affected by the unequal detector gains and non-uniform intrinsic phases of the coupler. Fortunately, we could find that the Lissajous curve plotted by the two signals of the interferometric system would form an ellipse. Therefore, by fitting the measured Lissajous curve to an ellipse, we could extract the parameters characterizing the actual system, which allowed the nanometer-scale measurement. Experimental results showed that a 20 kHz sinusoidal vibration with an amplitude of 1.5 nm could be measured with a standard deviation of 0.4 nm.

Secretion of misfolded cytosolic proteins from mammalian cells is independent of chaperone-mediated autophagy.

In eukaryotic cells, elimination of misfolded proteins is essential for maintaining protein homeostasis and cell viability. Misfolding-associated protein secretion (MAPS) is a protein quality-control mechanism that exports misfolded cytosolic proteins via a compartment characteristic of late endosomes, but how cytosolic proteins enter this compartment is unclear. Because chaperone-mediated autophagy (CMA) is a known mechanism that imports cytosolic proteins bearing a specific CMA motif to lysosomes for degradation and because late endosomes and lysosomes overlap significantly in mammalian cells, we determined here whether CMA is involved in targeting protein cargoes to the lumen of late endosomes in MAPS. Using HEK293T and COS-7 cells and immunoblotting and -staining and coimmunoprecipitation methods, we show that, unlike CMA, the secretion of misfolded proteins in MAPS does not require cargo unfolding, is inhibited by serum starvation, and is not dependent on the CMA motif in cargo. Intriguingly, knockdown of lysosome-associated membrane protein 2 (LAMP2), which consists of three isoforms, including a variant proposed to form a protein channel on lysosomes for CMA, attenuated MAPS. However, this could not be attributed to the proposed channel function of the LAMP2a isoform because overexpression of a cytosolic MAPS stimulator, DnaJ heat shock protein family (Hsp40) member C5 (DNAJC5), fully rescued the secretion defect associated with LAMP2 deficiency. We conclude that, in MAPS, cargoes use a CMA-independent mechanism to enter a nondegradative prelysosomal compartment.

Unmet needs and related factors of Korean breast cancer survivors: a multicenter, cross-sectional study.

BACKGROUND: Identification of specific needs in patients with cancer is very important for the provision of patient-centered medical service. The aim of this study was to investigate the unmet needs and related factors of Korean breast cancer survivors. METHODS: A multicenter, cross-sectional, interview survey was performed among 332 Korean breast cancer survivors. The Comprehensive Needs Assessment Tool for cancer patients was administered to survivors who gave written informed consent to participate. Data were analyzed using t-test, ANOVA and multiple regression analysis. RESULTS: The level of unmet needs was highest in the domain 'Information and education' (mean ± SD; 1.70 ± 1.14) and the item with the highest level of unmet needs was 'Needed help in coping with fear of recurrence' (2.04 ± 1.09). Unmet needs were correlated with age, stage, multiplicity, HER2, treatment state, marital status, employment, psychosocial status, and problems in EQ-5D dimensions. In multiple regression analysis, the 50-59 age group showed a higher level of recognition for physical symptom needs and the unemployed group expressed greater needs for information and education. Survivors with multiplicity had greater needs in the domains of healthcare staff and physical symptom. The stress group showed high levels of needs in all domains except religious support. The group with thoughts of suicide showed higher levels of unmet needs for physical symptom. CONCLUSION: Most prevalent unmet needs in Korean breast cancer survivors were found in the 'information and education' domain. The 50-59 age group, unemployment, multiplicity, stress and suicidal thoughts were associated with higher levels of unmet needs among Korean breast cancer survivors. Our findings revealed more vulnerable breast cancer survivors with unmet needs and physicians should take a precision approach to satisfy unmet needs of these survivors.

Recent Increase of Human Granulocytic Anaplasmosis and Co-Infection with Scrub Typhus or Korean Hemorrhagic Fever with Renal Syndrome in Korea.

We report 17 patients with human granulocytic anaplasmosis between January 2015 and September 2018 at two tertiary university hospitals in Korea. Monthly incidence peaked in May and June. Among these patients, we identified three who were co-infected with scrub typhus, and one patient with hemorrhagic fever with renal syndrome.

Identifying labile DOM components in a coastal ocean through depleted bacterial transcripts and chemical signals.

Understanding which compounds comprising the complex and dynamic marine dissolved organic matter (DOM) pool are important in supporting heterotrophic bacterial production remains a major challenge. We eliminated sources of labile phytoplankton products, advected terrestrial material and photodegradation products to coastal microbial communities by enclosing water samples in situ for 24 h in the dark. Bacterial genes for which expression decreased between the beginning and end of the incubation and chemical formulae that were depleted over this same time frame were used as indicators of bioavailable compounds, an approach that avoids augmenting or modifying the natural DOM pool. Transport- and metabolism-related genes whose relative expression decreased implicated osmolytes, carboxylic acids, fatty acids, sugars and organic sulfur compounds as candidate bioreactive molecules. FT-ICR MS analysis of depleted molecular formulae implicated functional groups ~ 30-40 Da in size cleaved from semi-polar components of DOM as bioreactive components. Both gene expression and FT-ICR MS analyses indicated higher lability of compounds with sulfur and nitrogen heteroatoms. Untargeted methodologies able to integrate biological and chemical perspectives can be effective strategies for characterizing the labile microbial metabolites participating in carbon flux.

Comparison of transient severe motion in gadoxetate disodium and gadopentetate dimeglumine-enhanced MRI: effect of modified breath-holding method.

OBJECTIVES: To compare the occurrence of transient severe motion (TSM) between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI and between gadoxetate disodium-enhanced MRI scans obtained with and without the application of a modified breath-holding technique. METHODS: We reviewed 80 patients who underwent two magnetic resonance examinations (gadoxetate disodium-enhanced MRI and gadopentetate dimeglumine-enhanced MRI) with the application of a modified breath-holding technique (dual group). This group was compared with 100 patients who underwent gadoxetate disodium-enhanced MRI without the application of the modified breath-holding technique (single group). Patient risk factors and motion scores (1 [none] to 5 [non-diagnostic]) for each dynamic-phase imaging were analysed. RESULTS: In the dual group, mean motion scores did not differ significantly between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI (p=0.096-0.807) in any phase. However, in all phases except the late dynamic phase, mean motion scores of the dual group were significantly lower than those in the single group. TSM incidence did not differ significantly between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI in the dual group (3.8% vs. 1.3%, p=0.620). CONCLUSION: With proper application of the modified breath-holding technique, TSM occurrence with gadoxetate disodium-enhanced MRI was comparable to that associated with gadopentetate dimeglumine-enhanced MRI. KEY POINTS: • The modified breath-holding method significantly reduced the incidence of TSM. • Gadoxetate disodium and gadopentetate dimeglumine showed comparable motion scores. • TSM incidence was comparable between gadoxetate disodium- and gadopentetate dimeglumine-enhanced MRI.

Factors associated with abnormal pulmonary function test among subjects with normal chest radiography: The Korean National Health and Nutrition Examination Survey.

Determinants of abnormal lung function among subjects with normal chest radiography have not been widely evaluated. We investigated 12 109 participants with normal chest radiographs from the Korean National Health and Nutrition Examination Survey. Factors associated with abnormal pulmonary function were male gender, age ≥50, smoking history and a clinical history of cough or sputum production. Pulmonary function tests should be considered in population-based screening, especially in men over 50 years old with a smoking history.

Acute Cholecystitis in Patients with Scrub Typhus.

Acute cholecystitis is a rare complication of scrub typhus. Although a few such cases have been reported in patients with scrub typhus, the clinical course is not well described. Of 12 patients, acute cholecystitis developed in 66.7% (8/12) of patients older than 60 yr. The scrub typhus group with acute cholecystitis had marginal significant longer hospital stay and higher cost than the group without cholecystitis according to propensity score matching. Scrub typhus should be kept in mind as a rare etiology of acute cholecystitis in endemic areas because the typical signs of scrub typhus such as skin rash and eschar can present after the abdominal pain.

Comparison of Arbekacin and Vancomycin in Treatment of Chronic Suppurative Otitis Media by Methicillin Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of ear infections. We attempted to evaluate the clinical usefulness of arbekacin in treating chronic suppurative otitis media (CSOM) by comparing its clinical efficacy and toxicity with those of vancomycin. Efficacy was classified according to bacterial elimination or bacteriologic failure and improved or failed clinical efficacy response. Ninety-five subjects were diagnosed with CSOM caused by MRSA. Twenty of these subjects were treated with arbekacin, and 36 with vancomycin. The bacteriological efficacy (bacterial elimination, arbekacin vs. vancomycin: 85.0% vs. 97.2%) and improved clinical efficacy (arbekacin vs. vancomycin; 90.0% vs. 97.2%) were not different between the two groups. However, the rate of complications was higher in the vancomycin group (33.3%) than in the arbekacin group (5.0%) (P=0.020). In addition, a total of 12 adverse reactions were observed in the vancomycin group; two for hepatotoxicity, one for nephrotoxicity, eight for leukopenia, two for skin rash, and one for drug fever. It is suggested that arbekacin be a good alternative drug to vancomycin in treatment of CSOM caused by MRSA.

Acetylation of cyclin-dependent kinase 5 is mediated by GCN5.

Cyclin-dependent kinase 5 (CDK5), a member of atypical serine/threonine cyclin-dependent kinase family, plays a crucial role in pathophysiology of neurodegenerative disorders. Its kinase activity and substrate specificity are regulated by several independent pathways including binding with its activator, phosphorylation and S-nitrosylation. In the present study, we report that acetylation of CDK5 comprises an additional posttranslational modification within the cells. Among many candidates, we confirmed that its acetylation is enhanced by GCN5, a member of the GCN5-related N-acetyl-transferase family of histone acetyltransferase. Co-immunoprecipitation assay and fluorescent localization study indicated that GCN5 physically interacts with CDK5 and they are co-localized at the specific nuclear foci. Furthermore, liquid chromatography in conjunction with a mass spectrometry indicated that CDK5 is acetylated at Lys33 residue of ATP binding domain. Considering this lysine site is conserved among a wide range of species and other related cyclin-dependent kinases, therefore, we speculate that acetylation may alter the kinase activity of CDK5 via affecting efficacy of ATP coordination.