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Selective autophagy helps eukaryotes to cope with endogenous dangers or foreign invaders; its initiation often involves membrane damage. By studying a Salmonella effector SopF, we recently identified the vacuolar ATPase (V-ATPase)-ATG16L1 axis that initiates bacteria-induced autophagy. Here we show that SopF is an ADP-ribosyltransferase specifically modifying Gln124 of ATP6V0C in V-ATPase. We identify GTP-bound ADP-ribosylation factor (ARF) GTPases as a cofactor required for SopF functioning. Crystal structures of SopF–ARF1 complexes not only reveal structural basis of SopF ADP-ribosyltransferase activity but also a unique effector-binding mode adopted by ARF GTPases. Further, the N terminus of ARF1, although dispensable for high-affinity binding to SopF, is critical for activating SopF to modify ATP6V0C. Moreover, lysosome or Golgi damage-induced autophagic LC3 activation is inhibited by SopF or Q124A mutation of ATP6V0C, thus also mediated by the V-ATPase-ATG16L1 axis. In this process, the V-ATPase functions to sense membrane damages, which can be uncoupled from its proton-pumping activity. The authors show that the Salmonella effector SopF is activated by ARF GTPases to ADP-ribosylate a glutamine in the V-ATPase subunit ATP6V0C, blocking xenophagy or other selective autophagy types independent of proton-pumping activity.

The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

Osteocytes are the terminally differentiated cell type of the osteoblastic lineage and have important functions in skeletal homeostasis. Although the transcriptional regulation of osteoblast differentiation has been well characterized, the factors that regulate differentiation of osteocytes from mature osteoblasts are poorly understood. Here we show that miR-23a∼27a∼24-2 (miR-23a cluster) promotes osteocyte differentiation. Osteoblast-specific miR-23a cluster gain-of-function mice have low bone mass associated with decreased osteoblast but increased osteocyte numbers. By contrast, loss-of-function transgenic mice overexpressing microRNA decoys for either miR-23a or miR-27a, but not miR24-2, show decreased osteocyte numbers. Moreover, RNA-sequencing analysis shows altered transforming growth factor-β (TGF-β) signalling. Prdm16 , a negative regulator of the TGF-β pathway, is directly repressed by miR-27a with concomitant alteration of sclerostin expression, and pharmacological inhibition of TGF-β rescues the phenotypes observed in the gain-of-function transgenic mice. Taken together, the miR-23a cluster regulates osteocyte differentiation by modulating the TGF-β signalling pathway through targeting of Prdm16 . Control of osteocyte differentiation is not well understood. Here the authors show that the miR-23 cluster represses the TGF-β signalling repressor Prdm16 in osteoblasts, thus enhancing osteocyte differentiation and a low bone mass phenotype.

Marmoset has emerged as a useful nonhuman primate species for studying brain structure and function. Previous studies on the mouse primary auditory cortex (A1) showed that neurons with preferential frequency-tuning responses are mixed within local cortical regions, despite a large-scale tonotopic organization. Here we found that frequency-tuning properties of marmoset A1 neurons are highly uniform within local cortical regions. We first defined the tonotopic map of A1 using intrinsic optical imaging and then used in vivo two-photon calcium imaging of large neuronal populations to examine the tonotopic preference at the single-cell level. We found that tuning preferences of layer 2/3 neurons were highly homogeneous over hundreds of micrometers in both horizontal and vertical directions. Thus, marmoset A1 neurons are distributed in a tonotopic manner at both macro- and microscopic levels. Such organization is likely to be important for the organization of auditory circuits in the primate brain.

Hyperlipidemia is a common metabolic disorder and one of risk factors for cardiovascular disease. Clinical studies have shown that hyperlipidemia increases the risk of non-ischemic heart failure, while decreasing serum lipids can reverse heart dysfunction. Apart from indirectly affecting the function of the heart by promoting the development of atherosclerosis, hyperlipidemia also affects the systolic function and cardiac electrophysiological response of the heart directly, which may be related to gradual accumulation of cardiac lipids and consequent systemic oxidative stress, proinflammatory state and mitochondrial dysfunction. However, the mechanism underlying direct effects of hyperlipidemia on the heart are not fully understood. In this review, we provide an updated summary of recent experimental and clinical studies that focus on elucidating the mechanisms of the action of hyperlipidemia on cardiac function, the relationship between heart failure and serum lipids, and protective effects of lipid-lowering drugs on the heart. The exciting progress in this field supports the prospect of guiding early protection of the heart to benefit the patients with chronic hyperlipidemia and familial hyperlipidemia.

The prevalence of mitral valve prolapse (MVP) among middle- and older-aged individuals is estimated to be 2–4% in Western countries. However, few studies have been conducted among Asian individuals and young adults. This study included a sample of 2442 consecutive military adults aged 18–39 years in Hualien, Taiwan. MVP was defined as displacement of the anterior or posterior leaflet of the mitral valve to the mid portion of the annular hinge point > 2 mm in the parasternal long-axis view of echocardiography. Cardiac chamber size and wall thickness were measured based on the latest criteria of the American Society of Echocardiography. The clinical features of participants with MVP and those without MVP were compared using a two-sample t test, and the cardiac structures were compared using analysis of covariance with adjustment for body surface area (BSA). Eighty-two participants were diagnosed with MVP, and the prevalence was 3.36% in the overall population. Compared with those without MVP, participants with MVP had a lower body mass index (kg/m 2 ) (24.89 ± 3.70 vs. 23.91 ± 3.45, p = 0.02) and higher prevalence of somatic symptoms related to exercise (11.0% vs. 4.9%, p = 0.02) and systolic click in auscultation (18.3% vs. 0.6%, p < 0.01). In addition, participants with MVP had greater left ventricular mass (gm) and smaller right ventricular wall thickness (mm) and dimensions (mm) indexed by BSA than those without MVP (149.12 ± 35.76 vs. 155.38 ± 36.26; 4.66 ± 0.63 vs. 4.40 ± 0.68; 26.57 ± 3.99 vs. 25.41 ± 4.35, respectively, all p-values < 0.01). In conclusion, the prevalence and clinical features of MVP in military young adults in Taiwan were in line with those in Western countries. Whether the novel MVP phenotype found in this study has any pathological meaning needs further investigation.

Eclipsing Algol-type systems containing a δ Scuti (hereafter δ Sct) star enable precise determination of physical parameters and the investigation of stellar internal structure and evolution. We present the absolute parameters of CZ Aquarius (hereafter CZ Aqr) based on TESS data. CZ Aqr has an orbital period of 0.86275209 day, a mass ratio of 0.489 (6), and the secondary component nearly fills its Roche lobe. O − C analysis reveals a downward parabolic trend and a cyclical variation with a period of 88.2 yr. The downward parabola suggests a long-term decrease in the orbital period with Ṗ = −3.09 × 10−8 days yr−1. The mass loss rate is estimated to be 4.54 × 10−9 M ⊙ yr−1, which is possibly due to magnetic stellar wind or a hot spot. The cyclical variation might be caused by the light travel time effect via the presence of a third body with a minimum mass of M3min = 0.312 (21) M ⊙. Additionally, there are two possible celestial bodies in a 2:7 resonance orbit around CZ Aqr. The asymmetric light curve is explained by adding a hot spot on the surface of the primary star. After removing the binary model, 26 frequencies were extracted from TESS data. Two radial modes were newly identified among three possible independent frequencies. Our results show that the eclipsing Algol-type system is composed of a δ Sct primary star and a subgiant star in a quadruple system.

Objectives This study aims to evaluate the accuracy of intraoral scanner (IOS) in both intraoral and extraoral settings within primary dentition, as well as patient satisfaction among preschool-aged children. Methods Forty-one preschool-aged children underwent intraoral scanning with the iTero Element 2 scanner and conventional alginate impressions (CI). Resulting plaster models were digitized via both IOS and a desktop scanner. To assess precision, one plaster model was scanned ten times with the IOS. Accuracy was measured via Geomagic Control 2022, which evaluated root mean square (RMS) deviation and intra-arch linear distances. A validated questionnaire was used to access the degree of comfort and preference between IOS and CI. Statistical analyses included paired t-tests, repeated-measures ANOVA, Friedman tests and Wilcoxon signed-rank tests, with statistical significance set at P  < 0.05. Results The trueness of the intraoral scan was 0.1282 ± 0.0230 mm (maxilla) and 0.1341 ± 0.0255 mm (mandible), whereas the extraoral scan showed significantly higher trueness (0.0399 ± 0.0059 mm in the maxilla, 0.0430 ± 0.0087 mm in the mandible) ( P  < 0.001). The precision was 0.0347 ± 0.0066 mm for the maxilla and 0.0358 ± 0.0063 mm for the mandible. Most intra-arch distances showed no significant variation across scanning methods. The questionnaire responses favored IOS, with significantly greater comfort and preference ( P  = 0.014), despite some perceptions of scanner bulkiness. Conclusions The IOS delivers high accuracy for both intraoral and extraoral scans in primary dentition and is well accepted by preschool children, showing potential for wider application in pediatric dentistry.

Health literacy is an important determinant of health, and is one of the key indicators of a healthy city. Developing and improving methods to measure health literacy is prudent and necessary. This review summarizes the findings of published tools for assessing health literacy among the general population to provide a reference for establishing health literacy assessment tools in the future. In this systematic review, PubMed, Embase, and Web of Science were used to search articles regarding tools for assessing health literacy among the general population published up to 10 January 2018. Two researchers independently conducted literature screening, quality assessment of methodology, and data extraction according to preset inclusion and exclusion criteria. The quality assessment of the research was examined with the use of the specifications of the reporting guidelines for survey research (SURGE). Eleven articles met the inclusion criteria. All included instruments in monitoring the health literacy of the general population were presented through the form of questionnaires. The multistage process of making all the scales generally involved the following steps: item development, pre-testing, and evaluation of readability. However, the specific methods were different. Internal consistency for all the instruments was acceptable but with weak consistency among the subscales for some instruments. Most of the identified instruments derived from the definition of health literacy or were based on existing health literacy theory. Approximately 30% of the performed studies provided no description of the important features specified in the SURGE. This review indicates a trend in the increasing tools for assessing the health literacy of the general population by using multidimensional structures and comprehensive measurement approaches. However, no clear “consensus” was observed in the dimensions of health literacy tools.

Background Sepsis is a life-threatening complication in patients with pyogenic liver abscess (PLA). Early identification of at-risk individuals is critical for improving outcomes but remains challenging. Our objective was to evaluate the prognostic value of integrating the National Early Warning Score 2 (NEWS2) with the procalcitonin-to-albumin ratio (PAR) for predicting sepsis in this population. Methods This retrospective cohort study enrolled 341 patients with PLA admitted to a tertiary hospital between 2011 and 2021. Patients were stratified based on Sepsis-3 criteria. Multivariate logistic regression identified independent predictors. Predictive performance was assessed via the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Results Among the 341 patients, 50 patients (14.7%) developed sepsis. These patients had significantly higher NEWS2 scores [4.00 (IQR 2.00–6.25) vs. 2.00 (IQR 1.00–3.00), p  < 0.001], SOFA scores [2 (IQR 1.00–4.25) vs. 1 (IQR 0.00–2.00), p  < 0.001], and PAR levels [0.47 (IQR 0.10–1.66) vs. 0.06 (IQR 0.01–0.40), p  < 0.001]. The PAR was positively correlated with both the NEWS2 score ( r  = 0.309, p  < 0.001) and the SOFA score ( r  = 0.254, p  < 0.001). Multivariate analysis confirmed both the NEWS2 score (OR 1.369, 95% CI 1.143–1.639, p  < 0.001) and the PAR (OR 1.004, 95% CI 1.000–1.008, p  = 0.048) were independent predictors. The combined model (NEWS2 + PAR) achieved superior discrimination (AUC 0.798, 95% CI 0.726–0.871) compared with NEWS2 (AUC 0.724, 95% CI 0.635–0.813) or PAR (AUC 0.727, 95% CI 0.648–0.805) alone, with significant reclassification improvement (NRI = 0.324, p  = 0.012; IDI = 0.045, p  = 0.008), and provided the highest net benefit across decision thresholds. Conclusions The integration of NEWS2 and PAR at admission may improve early sepsis prediction in PLA patients compared with either marker alone. This readily applicable integrative model could facilitate rapid risk stratification and may support earlier clinical decision‑making, potentially improving patient outcomes.