A sheep pangenome reveals the spectrum of structural variations and their effects on tail phenotypes.

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5' untranslated region (5' UTR) of HOXB13 is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep.

Ag-modified enhance the performances of ZnO@CFs based omnidirectional photoelectrochemical ultraviolet detectors.

There are several prospective applications for omnidirectional ultraviolet (UV) detectors and underwater detection detectors in optical systems and optical fields. In this work, ZnO nanorods arrays were grown on carbon fibers (CFs). An appropriate amount of Ag nanoparticles (NPs) was deposited on the surface of ZnO nanorods by photochemical deposition. This improved the performance of photoelectrochemical (PEC) based UV detectors. Under 365 nm and 10 mW cm-2UV irradiation, the photocurrent density of the 30s-Ag/ZnO@CFs based PEC UV detector can reach 1.28 mA cm-2, which is about 7 times that of the ZnO@CFs based PEC UV detector, and the rising time is shortened from 0.17 to 0.10 s. The reason is that increased absorption of ultraviolet light induced by the localized surface plasmon resonance. In addition, the detector exhibits a good flexibility and remains flexible after hundreds of bends and twists. Moreover, the detector is responsive in the range of rotation angle from 0° to 360°. It provides an insight to improve the photoelectric performance and underwater omnidirectional detection ability of the PEC UV detector.

Leading and following: Noise differently affects semantic and acoustic processing during naturalistic speech comprehension.

Despite the distortion of speech signals caused by unavoidable noise in daily life, our ability to comprehend speech in noisy environments is relatively stable. However, the neural mechanisms underlying reliable speech-in-noise comprehension remain to be elucidated. The present study investigated the neural tracking of acoustic and semantic speech information during noisy naturalistic speech comprehension. Participants listened to narrative audio recordings mixed with spectrally matched stationary noise at three signal-to-ratio (SNR) levels (no noise, 3 dB, -3 dB), and 60-channel electroencephalography (EEG) signals were recorded. A temporal response function (TRF) method was employed to derive event-related-like responses to the continuous speech stream at both the acoustic and the semantic levels. Whereas the amplitude envelope of the naturalistic speech was taken as the acoustic feature, word entropy and word surprisal were extracted via the natural language processing method as two semantic features. Theta-band frontocentral TRF responses to the acoustic feature were observed at around 400 ms following speech fluctuation onset over all three SNR levels, and the response latencies were more delayed with increasing noise. Delta-band frontal TRF responses to the semantic feature of word entropy were observed at around 200 to 600 ms leading to speech fluctuation onset over all three SNR levels. The response latencies became more leading with increasing noise and decreasing speech comprehension and intelligibility. While the following responses to speech acoustics were consistent with previous studies, our study revealed the robustness of leading responses to speech semantics, which suggests a possible predictive mechanism at the semantic level for maintaining reliable speech comprehension in noisy environments.

Manganese Local Environment Modulation via SiO4 Substitution to Boost Sodium Storage Performance of Na4 MnCr(PO4 )3.

Manganese-based Na superionic conductors (NASICONs) Na4 MnCr(PO4 )3 with three-electron reaction are attractive cathode materials for sodium-ion batteries. However, the irreversible distortion of Mn local structure leads to sluggish electrode kinetics, voltage hysteresis, and poor cycling stability. Here, SiO4 is introduced to substitute PO4 to modulate the local environment of Mn to activate the redox activity and stabilize the reversibility of Na4 MnCr(PO4 )2.9 (SiO4 )0.1 (NMCP-Si). A combined experimental and theoretical investigation have been undertaken to reveal the evolution of electronic structures and Na storage properties associated with SiO4 substitution. The NMCP-Si exhibits much-enhanced rate capability and cycling stability, being attributed to the unique Jahn-Teller distortion (Mn3+ ) that facilitates sodium de/insertion kinetics by optimizing the Na ion diffusion channels. This work addresses the challenge of stabilizing the structure of Mn-based NASICONs and represents a breakthrough in understanding how to improve the Na+ conductivity by regulating local structure.

Synthesis of AuX (X = Ni, Ga, Mo, Zn, and Cr) Alloy Aerogels as High-Performance Electrocatalytic CO2 Reduction Reaction Catalysts.

Electrocatalytic CO2 reduction reaction (eCO2RR) into value-added chemicals is highly desirable to mitigate the global warming effect and energy crisis. Metal aerogels, as featured by a self-supporting structure, large specific surface area, outstanding conductivity, and a hierarchical porous structure, are ideal electrocatalysts in eCO2RR. Herein, we report a simple and general strategy for constructing a series of Au-based alloy aerogels which contain Au with another metal including Ga, Ni, Mo, Zn, and Cr, respectively. For the first time, the electrocatalytic activities of AuGa aerogels, AuNi aerogels, and AuMo aerogels for CO2RR were studied in detail. The resultant Au81Ga19 aerogel achieves a 95.2% Faradaic efficiency (FE) at -1.16 V versus reversible hydrogen (vs RHE) in H-cells. Impressively, a total 99.4% FE for C1 products (CO + HCOOH) with a current density of 100 mA cm-2 at -0.6 V vs RHE and a large current density of 228 mA cm-2 can be achieved at -0.9 V with a 72.3% FE for the C1 product in a flow cell. Electrochemical characterization and theoretical calculations further revealed that the outstanding performance of the Au-based aerogels was derived from the large specific surface area, abundant grain boundaries, low interfacial charge transfer resistance, and synergetic effect. Overall, this study provides a promising alternative to engineer alloy aerogel electrocatalysts for highly efficient CO2 electroreduction.

Synthesis and Biological Evaluation of Water-Soluble Esterase-Activated CO-Releasing Molecules Targeting Mitochondria.

Due to the beneficial effects of carbon monoxide as a cell-protective and anti-inflammatory agent, CO-releasing molecules (CORMs) offer some promising potential applications in medicine. In this context, we synthesized a set of acyloxy-cyclohexadiene-Fe(CO)3 complexes, all displaying a N-methyl-pyridinium triflate moiety in the ester side chain, as mitochondria-targeting esterase-triggered CORM prodrugs. Whereas the compounds in which the acyloxy substituent is attached to the 2-position of the diene-Fe(CO)3 unit (A series) spontaneously release CO upon dissolution in phosphate buffer, which remarkably is partly suppressed in the presence of porcine liver esterase (PLE), the 1-substituted isomers (B series) show the expected PLE-induced release of CO (up to 3 equiv.). The biological activity of Mito-CORMs 2/3-B and their isophorone-derived analogs 2/3-A', which also displayed PLE-induced CO release, was assessed by using human umbilical vein endothelial cells (HUVEC). Whereas Mito-CORMs 2/3-B were not cytotoxic up to 500 µM (MTT assay), Mito-CORMs 2/3-A' caused significant toxicity at concentrations above 50 µM. The anti-inflammatory potential of both Mito-CORM variants was demonstrated by concentration-dependent down-regulation of the pro-inflammatory markers VCAM-1, ICAM-1 and CXCL1 as well as induction of HO-1 in TNFα-stimulated human umbilical vein endothelial cells (HUVECs; western blotting and qPCR). Energy phenotyping by seahorse real-time cell metabolic analysis, revealed opposing shifts of metabolic potentials in cells treated either with Mito-CORMs 2/3-B (increased mitochondrial respiration and glycolytic activity) or Mito-CORMs 2/3-A' (suppressed mitochondrial respiration and increased glycolytic activity). Thus, the Mito-CORMs represent valuable tools for the safe and targeted delivery of CO to mitochondria as a subcellular compartment to induce positive anti-inflammatory effects with only minor shifts in cellular energy metabolism. Also, due to their water solubility, these compounds provide a promising starting point for further pharmacological studies.

Functional characterization of melanocortin-3 receptor in rainbow trout (Oncorhynchus mykiss).

The melanocortin-3 receptor (MC3R) is an important regulator of energy homeostasis and inflammation in mammals. However, its function in teleost fish needs to be further explored. In this study, we characterized rainbow trout MC3R (rtMC3R), which encoded a putative protein of 331 amino acids. Phylogenetic and chromosomal synteny analyses showed that rtMC3R was closely related to bony fishes. Quantitative PCR (qPCR) revealed that the transcripts of rtMC3R were highly expressed in the brain and muscle. The cellular function of rtMC3R was further verified by the signal-pathway-specific luciferase reporter assays. Four agonists such as α-MSH, ß-MSH, ACTH (1-24), and NDP-MSH can active rtMC3R, increasing the production of intracellular cAMP and upregulating MAPK/ERK signals. Moreover, we found that rtMC3R stimulated with α-MSH and NDP-MSH can significantly inhibit the NF-κB signaling pathway. This research will be helpful for further studies on the function of MC3R in rainbow trout, especially the role of energy metabolism and immune regulation.

Synergistic hepatoprotective effect of combined administration of Lachnum polysaccharide with silymarin.

In recent years, combination therapy has gradually become one of the hot spots. As a new therapy strategy, we investigated the combination treatment of polysaccharide from Lachnum sp. (LEP-2b) with silymarin and compared the effects with mono-therapy. In this study, combining high-dose LEP-2b with silymarin (CH) significantly reduced serum biochemistry indexes (ALT, AST, AKP, LDH), hepatic inflammation (TNF-α, IL-6 and IL-1ß) and improved the antioxidant status (SOD, CAT, GSH-Px, GSH, MDA and T-AOC), in which its effect on TNF-α was very significant (P < 0.001). Therefore, the expressions of related proteins in the JNK/p38 signaling pathway associated with TNF-α were examined. The result showed that CH treatment markedly increased the expression of p-p38 and inhibited the JNK phosphorylation. TUNEL staining, immunohistochemical staining and western blot assays demonstrated that the hepatoprotective effect of CH treatment was probably related with inhibiting hepatocyte apoptosis. In summary, combination of high dose LEP-2b with silymarin would be a more effective method to protect liver injury than mono-therapy.

Tunable magnetic and half-metallic properties of the two-dimensional electron gas in LaAlO3/SrTiO3(111) heterostructures.

Half-metallic materials have gained a lot of attention because of their unique properties and applications in spintronic devices. Despite the fact that these materials have been studied by several research groups there are very limited studies on their heterostructure (HS) systems. In the current study we have investigated the electronic and magnetic properties of (LaAlO3)6.5/(SrTiO3)2.5(111) HS using density functional theory (DFT) calculations. We demonstrate that the system exhibits a 100% spin-polarized two-dimensional electron gas (2DEG) which is extremely confined to the Ti 3d orbitals of the SrTiO3 layers. In particular, this system can keep its half-metallic properties under different in-plane strains from -3 to 2%. This property proves that this material has relatively stable half-metallic properties. In addition, the conducting and magnetic ground states of the system can also be tailored by changing in-plane strain and interfacial cation intermixing of La and Sr (Sr ⇔ La intermixing). By increasing the in-plane lattice parameters, this system has the ability to evolve from a nonmagnetic to a ferromagnetic metal and then to a half-metal and by further increasing the in-plane lattice parameter it becomes a ferromagnetic insulator. Sr ⇔ La intermixing can destroy the original half-metallic properties and the system exhibits an AFM Mott-type insulator phase. Our results demonstrate that the system has high potential for application in the field of spintronics, and opens the prospect of using LaAlO3/SrTiO3(111) HSs to explore quantum phase transitions.

Electron localization in niobium doped CaMnO3 due to the energy difference of electronic states of Mn and Nb.

The electron localization in Nb-doped CaMnO3 is analyzed in terms of the space and energy distribution of electronic states employing first-principles calculations. The energy difference of Mn 3d states and Nb 4d states makes NbO6 octahedra impede electrical conduction, so the random distribution of Nb in lattices leads to the localization of electrons near the bottom of the conduction bands. Therefore, although more carriers are introduced when Nb-doping content increases, both the electrical conductivity and absolute thermopower decrease in Nb heavy doped CaMnO3. The calculated transport properties agree well with the experimental data, supporting the analysis of localization.

Statin Use during Hospitalization and Short-Term Mortality in Acute Ischaemic Stroke with Chronic Kidney Disease.

OBJECTIVES: Statin use during hospitalization improves prognosis in patients with ischaemic stroke. However, it remains uncertain whether acute ischaemic stroke patients with chronic kidney disease (CKD) benefit from statin therapy. We investigated the effect of statin use during hospitalization in reducing short-term mortality of patients with ischaemic stroke and CKD. METHODS: Data of first-ever ischaemic stroke patients without a history of pre-stroke statin treatment was derived from the China National Stroke Registry. Patients were stratified according to estimated glomerular filtration rate (eGFR): normal renal function (eGFR ≥90 mL/min/1.73 m2), mild CKD (eGFR 60-90 mL/min/1.73 m2) and moderate CKD (eGFR < 60 mL/min/1.73 m2). Multivariate logistic regression analysis was used to evaluate the association between statin use during hospitalization and all-cause mortality with different renal functions at 3-month follow-up. RESULTS: Among 5,951 patients included, 2,595 (43.6%) patients were on statin use during hospitalization after stroke (45.7% in patients with normal renal function, 42.0% in patients with mild CKD, and 39.0% in patients with moderate CKD). Compared with the non-statin group, statin use during hospitalization was associated with decreased all-cause mortality in patients with normal renal function (OR 0.65, 95% CI 0.43-0.97, p = 0.04), mild CKD (OR 0.59, 95% CI 0.38-0.91, p = 0.02) and moderate CKD (OR 0.41, 95% CI 0.23-0.75, p = 0.004) at 3-month follow-up. CONCLUSIONS: Statin use during hospitalization was associated with decreased 3-month mortality of ischaemic stroke patients with mild and moderate CKD. However, the conclusion should be confirmed in further studies with larger population, especially with moderate CKD.

Low- versus Standard-Dose Intravenous Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: An Updated Meta-Analysis.

BACKGROUND: We performed a meta-analysis to compare the efficacy and safety between low- and standard-dose intravenous (IV) tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset. METHODS: We searched PubMed and EMBASE for relevant studies from inception to June1, 2017. Cohort or randomized controlled studies for AIS within 4.5 hours of symptom onset with comparison between low-dose and standard-dose tPA were included. The primary efficacy end point was favorable functional outcome (modified Rankin scale scores [mRS] of 0-1) at 90 days. The primary safety end point was the incidence rate of symptomatic intracerebral hemorrhage (sICH). The secondary end points were independent functional outcome (mRS scores of 0-2) and mortality. RESULTS: A total of 11 studies were pooled in this meta-analysis. The low-dose strategy appeared to be as effective as standard-dose tPA (43.4% versus 45.4%; odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.78-1.10; P = .38) in primary efficacy outcome. The secondary efficacy outcome produced similar results (57.3% versus 57.0%; OR = 0.95, 95% CI: 0.86-1.05; P= .33). There was no evidence of statistical difference for sICH (4.2% versus 4.9%; OR = 1.02 [0.66-1.55]; P = .94) and mortality (9.0% versus 10.6%; OR = 0.99 [0.74-1.31]; P = .92) at 90 days between low- and standard-dose therapy. In a subgroup analysis by ethnicity, there was no significant difference between patients of Asian and non-Asian descent for any of the end points. CONCLUSIONS: This study showed that AIS patients receiving low-dose IV-tPA had comparably efficacy and safety to those receiving standard-dose IV-tPA. However, the effect is especially pronounced within the Asian population, which limits the generalizability of these results.

Prognosis of Intracerebral Hemorrhage with Newly Diagnosed Diabetes Mellitus According to Hemoglobin A1c Criteria.

OBJECTIVES: Hemoglobin A1c (HbA1c) has been recommended for diagnosing diabetes mellitus (DM). We aimed to assess the prevalence of newly diagnosed diabetes mellitus (NDDM) in patients with intracerebral hemorrhage (ICH) using HbA1c criteria and to investigate the long-term prognosis of patients with ICH with NDDM. MATERIALS AND METHODS: Data of patients with ICH without a DM history were derived from the Abnormal Glucose Regulation in Patients with Acute Stroke across China. NDDM was defined as a fasting plasma glucose (FPG) level of 7.0 mmol/L or higher, a 2-hour oral glucose tolerance test (OGTT) result of 11.1 mmol/L or higher, or an HbA1c level of 6.5% or higher. The prevalence of NDDM with different screening methods was assessed. The association between NDDM and 1-year prognosis (mortality, stroke recurrence, and poor functional outcome [modified Rankin scale score of 3-6]) was estimated. RESULTS: There were 357 patients with ICH included in the analysis, and 131 (36.7%) were diagnosed as NDDM using the new criteria. NDDM was present in 31 (8.7%), 98 (27.5%), and 68 (19.0%) patients with ICH, based on FPG, 2-hour OGTT, and HbA1c criteria, respectively. NDDM was independently associated with 1-year poor functional outcome (odds ratio 1.93; 95% confidence interval, 1.10-3.38, P = .02). Nevertheless, NDDM showed no significant association with 1-year death and stroke recurrence (P > .05 for both). CONCLUSIONS: More than one third of patients with ICH without a history of DM were diagnosed NDDM using the new criteria. NDDM by the new criteria was an independent risk factor of poor functional outcome, but not of death and stroke recurrence at 1 year after ICH onset.

Validation of the DRAGON Score in a Chinese Population to Predict Functional Outcome of Intravenous Thrombolysis-Treated Stroke Patients.

BACKGROUND: The DRAGON score predicts functional outcome of ischemic stroke patients treated with intravenous thrombolysis. Our aim was to evaluate its utility in a Chinese stroke population. METHODS: Patients with acute ischemic stroke treated with intravenous thrombolysis were prospectively registered in the Thrombolysis Implementation and Monitor of acute ischemic Stroke in China. We excluded patients with basilar artery occlusion and missing data, leaving 970 eligible patients. We calculated the DRAGON score, and the clinical outcome was measured by the modified Rankin Scale at 3 months. Model discrimination was quantified by calculating the C statistic. Calibration was assessed using Pearson correlation coefficient. RESULTS: The C statistic was .73 (.70-.76) for good outcome and .75 (.70-.79) for miserable outcome. Proportions of patients with good outcome were 94%, 83%, 70%, and 0% for 0 to 1, 2, 3, and 8 to 10 score points, respectively. Proportions of patients with miserable outcome were 0%, 3%, 9%, and 50% for 0 to 1, 2, 3, and 8 to 10 points, respectively. There was high correlation between predicted and observed probability of 3-month favorable and miserable outcome in the external validation cohort (Pearson correlation coefficient, .98 and .98, respectively, both P < .0001). CONCLUSIONS: The DRAGON score showed good performance to predict functional outcome after tissue-type plasminogen activator treatment in the Chinese population. This study demonstrated the accuracy and usability of the DRAGON score in the Chinese population in daily practice.

Application and management of continuous glucose monitoring in diabetic kidney disease.

Diabetic kidney disease (DKD) is a common complication of diabetes mellitus that contributes to the risk of end-stage kidney disease (ESKD). Wide glycemic var-iations, such as hypoglycemia and hyperglycemia, are broadly found in diabetic patients with DKD and especially ESKD, as a result of impaired renal metabolism. It is essential to monitor glycemia for effective management of DKD. Hemoglobin A1c (HbA1c) has long been considered as the gold standard for monitoring glycemia for > 3 months. However, assessment of HbA1c has some bias as it is susceptible to factors such as anemia and liver or kidney dysfunction. Continuous glucose monitoring (CGM) has provided new insights on glycemic assessment and management. CGM directly measures glucose level in interstitial fluid, reports real-time or retrospective glucose concentration, and provides multiple glycemic metrics. It avoids the pitfalls of HbA1c in some contexts, and may serve as a precise alternative to estimation of mean glucose and glycemic variability. Emerging studies have demonstrated the merits of CGM for precise monitoring, which allows fine-tuning of glycemic management in diabetic patients. Therefore, CGM technology has the potential for better glycemic monitoring in DKD patients. More research is needed to explore its application and management in different stages of DKD, including hemodialysis, peritoneal dialysis and kidney transplantation.

Tinnitus-associated cognitive and psychological impairments: a comprehensive review meta-analysis.

Background: Tinnitus is strongly associated with an increased risk of cognitive disabilities. The findings of this research will provide valuable support for future investigations aimed at determining the correlation between tinnitus and the risk of cognitive impairments. Objectives: We investigated the potential correlation between tinnitus and the risk of various cognitive impairments, such as dementia, compromised learning attention, anxiety, depression, and insomnia. The study examined this relationship collectively and by categorizing the data based on different age groups. Methods: We compiled data from case-control studies and cohort studies obtained from reputable databases such as PubMed, Cochrane Library, and Embase. To minimize potential bias, two reviewers independently assessed the selected articles. After extracting the data, we calculated the pooled odds ratios (ORs) using a random-effects model. Results: Seventeen relevant studies, comprising an adult population, were included in this analysis. Pooled estimated outcomes revealed a strong association between tinnitus and an elevated risk of dementia-compromised learning, auditory attention, anxiety, depression, and poor sleep quality (P<0.05). Furthermore, the pooled analysis stratified by age demonstrated that patients aged above 60 years, in comparison to those aged 18 to 60 years, exhibited more significant outcomes in relation to the progression of cognitive impairments. Conclusion: Tinnitus has the potential to increase the risk of cognitive impairments. Moreover, geriatric patients aged above 60 shows a higher susceptibility to developing cognitive disabilities compared to their younger counterparts.

Exploring how health-related advertising interference contributes to the development of cyberchondria: A stressor-strain-outcome approach.

Objectives: Cyberchondria is increasingly recognized as the dark side of digital health, given the pervasive use of the internet as a main source of health information in people's daily lives. While previous studies have identified many factors contributing to cyberchondria, there is a dearth of research on the impact of health-related advertisements. Therefore, this study adopts the stressor-strain-outcome (SSO) model to investigate how health-related advertising interference is directly and indirectly related to cyberchondria. Methods: To empirically validate the proposed research model, we conducted an online survey with 437 internet users with medical information seeking experience in China. Structural equation modeling (SEM) was employed to analyze the survey data. Results: Our findings revealed a positive, direct association between health-related advertising interference and cyberchondria. Meanwhile, advertising interference was positively related to both information overload and information irrelevance, with the former further predicting cyberchondria. Moreover, doctor-patient communication weakened the positive effect of information overload on cyberchondria. Conclusions: The study not only theoretically contributes to the literature by theorizing the relationship between health-related advertising interference and cyberchondria but also practically underlines the pivotal role of effective doctor-patient communication in reducing the development of cyberchondria.

Wearable electrochemical glucose sensor of high flexibility and sensitivity using novel mushroom-like gold nanowires decorated bendable stainless steel wire sieve.

Long-term high blood glucose levels brings extremely detrimental effect on diabetic patients, such as blindness, renal failure, and cardiovascular diseases. Therefore, there is an urgent need to develop highly flexible and sensitive sensors for precisely non-invasive and continuous monitoring glucose levels. Herein, we present a highly flexible and sensitive wearable sensor for non-enzymatic electrochemical glucose analysis with vertically aligned mushroom-like gold nanowires (v-AuNWs) chemically grown on stainless steel wire sieve (SSWS) as integrated electrode. Owing to the unique nanostructures and excellent catalysis of the v-AuNWs, the as-fabricated glucose sensors exhibit superior flexibility and excellent electro-catalytic capability. In detail, these sensors display rapid response towards glucose within 5 s, and the sensor constructed with v-AuNWs for growth time of 15 min shows the highest sensitivity of 180.1 µA mM-1 cm-2 within a wide linear range of 6.5 × 10-4 mM-12.0 mM and the lowest detection limit of 0.65 µM (S/N = 3). It is noteworthy that due to the good ductility of the v-AuNWs and their strong contact with the SSWS substrate, these glucose sensors exhibit no obvious response variation after repeated bending for 100 times at bending angle of 180°. Additionally, the glucose sensors display superior anti-interfering capability as well as desirable repeatability. More importantly, these glucose sensors can be attached on human skin to determine sweat glucose reliably and analyze glucose concentration in human serum in vitro.

LOXL1-AS1 inhibits JAK2 ubiquitination and promotes cholangiocarcinoma progression through JAK2/STAT3 signaling.

This study thoroughly investigated the role of the long non-coding RNA LOXL1-AS1 in the pathogenesis of cholangiocarcinoma (CCA). Through bioinformatics analysis and tissue samples validation, the study found that LOXL1-AS1 was significantly elevated in CCA, with its high expression closely tied to clinical pathological features and prognosis. In vitro and in vivo experiments revealed that LOXL1-AS1 was crucial in regulating CCA cell apoptosis, proliferation, migration, and invasion. Further investigations using FISH, subcellular localization experiments, RNA pull down, and RIP uncovered that LOXL1-AS1 primarily resided in the cytoplasm and influenced CCA progression by modulating the JAK2/STAT3 signaling pathway. Notably, LOXL1-AS1 might regulate the activity of JAK2 through modulating its ubiquitination and degradation. YY1 had also been found to act as an upstream transcription factor of LOXL1-AS1 to impact CCA cell malignancy. These findings shed light on the pivotal role of LOXL1-AS1 in CCA and offered potential directions for novel therapeutic strategies, providing a fresh perspective on tumor pathogenesis.

Circ_0007534 promotes cholangiocarcinoma stemness and resistance to anoikis through DDX3X-mediated positive feedback regulation of parental gene DDX42.

Cholangiocarcinoma (CCA) is a malignancy with an extremely poor prognosis, and much remains unknown about its pathogenesis and treatment modalities. Circular RNA (circRNA) has been proven to play regulatory roles in various tumorigenesis, yet its potential function and mechanism in cholangiocarcinoma require further investigation. This study is the first to identify the aberrant expression and functional role of a novel circRNA, circ_0007534, derived from the DDX42 gene, in cholangiocarcinoma. Compared to the normal control group, the expression of circ_0007534 was significantly elevated in the tissues and cells with CCA and that high expression correlated with lymph node invasion and poor prognosis. Functional experiments indicated that downregulating circ_0007534 markedly inhibited the proliferation, migration, invasion, stemness, and anti-anoikis ability of CCA cells, as well as the tumor growth and liver and lung metastasis in nude mice. Mechanistic studies revealed that DDX42, as the parent gene of circ_0007534, can mutually regulate each other's expression. Predominantly located in the cytoplasm, circ_0007534 can form a complex with the RNA-binding protein DDX3X, which enhances the stability of DDX42 mRNA, thereby upregulating the expression of DDX42. This creates a positive feedback loop among the three, collectively promoting the progression of cholangiocarcinoma. In conclusion, this study sheds light on the pivotal role and molecular mechanism of circ_0007534 in the development of CCA, offering potential new targets for early diagnosis and treatment.