Dual mutations in the whitefly nicotinic acetylcholine receptor ß1 subunit confer target-site resistance to multiple neonicotinoid insecticides.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

A novel inherited CARD9 deficiency in an otherwise healthy woman with CNS candidiasis.

Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.

F11R RNA trinucleotide over-edited by ADAR in gastric and colorectal cancers: Cross-cohort validation, gene expression regulation, and diagnostic significance.

The F11 receptor (F11R) gene encoding junctional adhesion molecule A has been associated with gastric cancer (GC) and colorectal cancer (CRC), in which its role and regulation remain to be further elucidated. Recently F11R was also identified as a potential target of adenosine-to-inosine (A-to-I) mediated by the adenosine deaminases acting on RNA (ADARs). Herein, using RNA-Seq and experimental validation, our current study revealed an F11R RNA trinucleotide over-edited by ADAR, with its regulation of gene expression and clinical significance in four GC and three CRC cohorts. Our results found an over-edited AAA trinucleotide in an AluSg located in the F11R 3'-untranslated region (3'-UTR), which showed editing levels correlated with elevated ADAR expression across all GC and CRC cohorts in our study. Overexpression and knockdown of ADAR in GC and CRC cells, followed by RNA-Seq and Sanger sequencing, confirmed the ADAR-mediated F11R 3'-UTR trinucleotide editing, which potentially disrupted an RBM45 binding site identified by crosslinking immunoprecipitation sequencing (CLIP-seq) and regulated F11R expression in luciferase reporter assays. Moreover, the F11R trinucleotide editing showed promising predictive performance for diagnosing GC and CRC across GC and CRC cohorts. Our findings thus highlight both the potential biological and clinical significance of an ADAR-edited F11R trinucleotide in GC and CRC, providing new insights into its application as a novel diagnostic biomarker for both cancers.

ADAR-mediated RNA editing regulates PVR immune checkpoint in colorectal cancer.

Recent studies have revealed that tumor immunotherapy resistance is influenced by ADAR-mediated RNA editing, but its targets remain unelucidated. Our current study identified the poliovirus receptor (PVR) oncogene, which encodes an immune checkpoint in colorectal cancer (CRC), as a potential target for RNA editing. We performed transcriptome sequencing analysis and experimental validation in two Chinese CRC cohorts. PVR and ADAR expressions significantly increased in CRC tumors and showed positive correlations in both cohorts, coupled with upregulated PVR RNA editing in CRC tumors. Manipulation of ADAR expression by over-expression or knockdown substantially changed PVR expression and RNA editing in HTC116 CRC cells. Luciferase reporter and actinomycin D assays further revealed that RNA editing in PVR 3'-UTR could upregulate PVR RNA expression, probably by increasing the RNA stability. By increasing PVR expression, ADAR-mediate RNA editing might contribute to tumor- and immune-related gene functions and pathways in CRC. Moreover, a signature combining PVR RNA editing and expression showed promising predictive performance in CRC diagnosis in both Chinese CRC cohorts. Our findings thus highlight the importance of ADAR-mediated RNA editing in PVR up-regulation in CRC tumors and provide new insight into the application of PVR RNA editing as a novel diagnostic biomarker for CRC.

Carbon Corrosion Induced by Surface Defects Accelerates Degradation of Platinum/Graphene Catalysts in Oxygen Reduction Reaction.

Graphene supported electrocatalysts have demonstrated remarkable catalytic performance for oxygen reduction reaction (ORR). However, their durability and cycling performance are greatly limited by Oswald ripening of platinum (Pt) and graphene support corrosion. Moreover, comprehensive studies on the mechanisms of catalysts degradation under 0.6-1.6 V versus RHE (Reversible Hydrogen Electrode) is still lacking. Herein, degradation mechanisms triggered by different defects on graphene supports are investigated by two cycling protocols. In the start-up/shutdown cycling (1.0-1.6 V vs. RHE), carbon oxidation reaction (COR) leads to shedding or swarm-like aggregation of Pt nanoparticles (NPs). Theoretical simulation results show that the expansion of vacancy defects promotes reaction kinetics of the decisive step in COR, reducing its reaction overpotential. While under the load cycling (0.6-1.0 V vs. RHE), oxygen containing defects lead to an elevated content of Pt in its oxidation state which intensifies Oswald ripening of Pt. The presence of vacancy defects can enhance the transfer of electrons from graphene to the Pt surface, reducing the d-band center of Pt and making it more difficult for the oxidation state of platinum to form in the cycling. This work will provide comprehensive understanding on Pt/Graphene catalysts degradation mechanisms.

Frequency tripled semiconductor disk laser with over 0.5 W ultraviolet output power.

Semiconductor disk lasers can produce high output power and good beam quality simultaneously. The high intracavity circulating power of about hundreds of watts, along with the flexibility of tailorable emitting wavelengths, make it an attractive light source for obtaining ultraviolet (UV) radiation from near-infrared lasers through nonlinear frequency conversion. This work reports a frequency tripled 327 nm semiconductor disk laser with record output power and wavelength tuning range by using a type-I phase-matched LiB3O5 (LBO) crystal and a type-I phase-matched ß-BaB2O4 (BBO) crystal as the frequency-doubling and -tripling crystals respectively. Thanks to the obviously larger nonlinear coefficient of the type-I phase-matched BBO compared to the commonly used type-II phase-matched LBO, as well as the small spot size specifically designed at the crystal location, the maximum output power of UV lasers reaches 538 mW, corresponding to an optical-to-optical conversion efficiency from pump to UV laser of about 1.14%. A wavelength tuning range of about 8.6 nm and good power stability with a standard deviation of about 0.94 are also achieved.

Determining fatigue threshold of elastomers through an elastic limit strain point.

Determining the fatigue threshold of elastomers is particularly important to predict their durability and lifespan. However, there has been almost no effective approach to calculate this threshold fast and accurately so far. To realize rapid fatigue performance testing, in this paper, a new method is proposed to calculate the fatigue threshold through the elastic limit strain point of elastomers that can be obtained from the continuous Mullins test. Compared with the traditional binary method to predict fatigue threshold, this method significantly reduces the time required for fatigue testing of elastomers, which can save approximately 2-3 sampling points in the fatigue test, i.e. a time savings of around 40%. Our method also proved to be effective for the elastomers at 0 °C. Additionally, a dual-network elastomer was synthesized using the interpenetrating network method, exhibiting improved elasticity (2.1 MPa and 3.1 MPa), toughness (1423 J m-2 and 2100 J m-2), and higher fatigue threshold (125 J m-2 and 385 J m-2) at 0 °C and room temperature. This material presents great application potential in marine anti-fouling.

Serum 8-Hydroxydeoxyguanosine Is a Potential Indicator for the Severity and Prognosis in Patients with Community-Acquired Pneumonia: A Prospective Cohort Study.

Previous studies have demonstrated that 8-hydroxydeoxyguanosine (8-OHdG) exerted key roles in various pulmonary diseases, but the evidence for its role in community-acquired pneumonia (CAP) was lacking. The goal of this research was to evaluate the correlations of serum 8-OHdG with the severity and prognosis among patients with CAP through a prospective cohort study. A total of 239 patients with CAP and 239 healthy participants were enrolled. Fasting blood samples were collected. 8-OHdG and inflammatory cytokines were measured by ELISA. On admission, serum 8-OHdG was significantly increased in patients with CAP compared with control subjects. Besides, serum 8-OHdG was incrementally increased in line with CAP severity scores. Pearson correlative analysis found that serum 8-OHdG was correlated with clinical characteristics and inflammatory cytokines in patients with CAP. Linear and logistic regression analysis showed that serum 8-OHdG was positively associated with CAP severity scores. Furthermore, the prognostic outcomes were tracked. Higher serum 8-OHdG on admission increased the risks for intensive care unit admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stay among patients with CAP. Serum 8-OHdG combination with confusion, respiratory rate, blood pressure, and age ≥65 y or pneumonia severity index had stronger predictive powers for death than single 8-OHdG, CAP severity scores, or several inflammatory cytokines in patients with CAP. These results indicated that serum 8-OHdG is positively associated with the severity and poor prognosis in patients with CAP, demonstrating that 8-OHdG may be involved in the pathophysiology process of CAP.

Potential of niacin skin flush response in adolescent depression identification and severity assessment: a case-control study.

BACKGROUND: The diagnosis of adolescent Depressive Disorder (DD) lacks specific biomarkers, posing significant challenges. This study investigates the potential of Niacin Skin Flush Response (NSFR) as a biomarker for identifying and assessing the severity of adolescent Depressive Disorder, as well as distinguishing it from Behavioral and Emotional Disorders typically emerging in childhood and adolescence(BED). METHODS: In a case-control study involving 196 adolescents, including 128 Depressive Disorder, 32 Behavioral and Emotional Disorders, and 36 healthy controls (HCs), NSFR was assessed. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and anxious symptoms with the Generalized Anxiety Disorder 7-item scale (GAD-7). Pearson correlation analysis determined the relationships between NSFR and the severity of depression in DD patients. Receiver Operating Characteristic (ROC) was used to identify DD from BED integrating NSFR data with clinical symptom measures. RESULTS: The adolescent Depressive Disorder group exhibited a higher rate of severe blunted NSFR (21.4%) compared to BED (12.5%) and HC ( 8.3%). Adolescent Depressive Disorder with psychotic symptoms showed a significant increase in blunted NSFR (p = 0.016). NSFR had negative correlations with depressive (r = -0.240, p = 0.006) and anxious (r = -0.2, p = 0.023) symptoms in adolescent Depressive Disorder. Integrating NSFR with three clinical scales improved the differentiation between adolescent Depressive Disorder and BED (AUC increased from 0.694 to 0.712). CONCLUSION: The NSFR demonstrates potential as an objective biomarker for adolescent Depressive Disorder, aiding in screening, assessing severity, and enhancing insights into its pathophysiology and diagnostic precision.

The role of miR-216a-mediated Nrf2 pathway in muscle oxidative stress of Siniperca chuatsi induced by cadmium.

Cadmium (Cd) is a toxic heavy metal pollutant in the environment. Excessive Cd in water has toxic effects on fish, endangering their healthy growth and ultimately affecting the quality and safety of aquatic products. To evaluate the toxicity of excessive Cd to fish through potential oxidative damage, Siniperca chuatsi was exposed to Cd in water for 15 days. It was found that Cd exposure significantly decreased the survival rate of S. chuatsi and Cd was detected in their muscle. Meanwhile, Cd disrupts the redox balance by reducing antioxidant enzyme activities, increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle, and promoting oxidative damage. Histomorphology showed that enlargement of muscle fiber gaps, cell swelling and vacuolar degeneration after Cd exposure. In addition, Cd toxicity induced up-regulating the expression of miR-216a, while down-regulation of Nrf2 protein and its downstream antioxidant enzyme genes expression. Further analysis revealed that miR-216a was significantly negatively correlated with the expression of Nrf2, and injection of miR-216a antagomir significantly enhanced the expression of Nrf2 and antioxidant enzyme genes, as well as the activity of antioxidant enzymes, thereby reducing the damage of Cd to fish. These results suggested that miR-216a-mediated Nrf2 signaling pathway plays an important role in Cd-induced oxidative stress of S. chuatsi muscle.

FUS-stabilized USP35 promotes growth, invasion and angiogenesis in NSCLC through deubiquitinating VEGFA.

Vascular endothelial growth factor A (VEGFA) is an important regulator for non-small cell lung cancer (NSCLC). Our study aimed to reveal its upstream pathway to provide new ideas for developing the therapeutic targets of NSCLC. The mRNA and protein levels of VEGFA, ubiquitin-specific peptidase 35 (USP35), and FUS were determined by quantitative real-time PCR and Western blot. Cell proliferation, apoptosis, invasion and angiogenesis were detected using CCK8 assay, EdU assay, flow cytometry, transwell assay and tube formation assay. The interaction between USP35 and VEGFA was assessed by Co-IP assay and ubiquitination assay. Animal experiments were performed to assess USP35 and VEGFA roles in vivo. VEGFA had elevated expression in NSCLC tissues and cells. Interferences of VEGFA inhibited NSCLC cell proliferation, invasion, angiogenesis, and increased apoptosis. USP35 could stabilize VEGFA protein level by deubiquitination, and USP35 knockdown suppressed NSCLC cell growth, invasion and angiogenesis via reducing VEGFA expression. FUS interacted with USP35 to promote its mRNA stability, thereby positively regulating VEGFA expression. Also, USP35 silencing could reduce NSCLC tumorigenesis by downregulating VEGFA. FUS-stabilized USP35 facilitated NSCLC cell growth, invasion and angiogenesis through deubiquitinating VEGFA, providing a novel idea for NSCLC treatment.

Mesenchymal Stem Cell Therapy: Therapeutic Opportunities and Challenges for Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD), which severely affects the quality of patients' lives. However, the current therapeutic approaches can only postpone its progression to ESRD. It is therefore imperative to develop a novel therapeutic strategy for renal injury in DKD, with the objective of restoring renal function and reversing the process of ESRD. In recent years, the potential of mesenchymal stem cell (MSC) therapy for DKD has garnered increasing attention within the scientific community. Preclinical research on MSC therapy has yielded promising results, and the safety of MSC treatment in vivo has been substantiated in clinical studies. An increasing body of evidence suggests that MSC therapy has significant potential for the treatment of DKD. This article reviews the existing research on MSCs and their derived exosomes in treating DKD and analyzes the underlying mechanism of MSC-based therapy for DKD. Additionally, we discuss the potential of combining MSC therapy with conventional pharmacological treatments, along with the constraints and prospects of MSC therapy for DKD. We hope this review can provide a precise and comprehensive understanding of MSCs for the treatment of DKD.

Baicalin Inhibits FIPV Infection In Vitro by Modulating the PI3K-AKT Pathway and Apoptosis Pathway.

Feline infectious peritonitis (FIP), a serious infectious disease in cats, has become a challenging problem for pet owners and the industry due to the lack of effective vaccinations and medications for prevention and treatment. Currently, most natural compounds have been proven to have good antiviral activity. Hence, it is essential to develop efficacious novel natural compounds that inhibit FIPV infection. Our study aimed to screen compounds with in vitro anti-FIPV effects from nine natural compounds that have been proven to have antiviral activity and preliminarily investigate their mechanisms of action. In this study, the CCK-8 method was used to determine the maximum noncytotoxic concentration (MNTC), 50% cytotoxic concentration (CC50), and 50% effective concentration (EC50) of natural compounds on CRFK cells and the maximum inhibition ratio (MIR) of the compounds inhibit FIPV. The effect of natural compounds on FIPV-induced apoptosis was detected via Annexin V-FITC/PI assay. Network pharmacology (NP), molecular docking (MD), and 4D label-free quantitative (4D-LFQ) proteomic techniques were used in the joint analysis the mechanism of action of the screened natural compounds against FIPV infection. Finally, Western blotting was used to validate the analysis results. Among the nine natural compounds, baicalin had good antiviral effects, with an MIR > 50% and an SI > 3. Baicalin inhibited FIPV-induced apoptosis. NP and MD analyses showed that AKT1 was the best target of baicalin for inhibiting FIPV infection. 4D-LFQ proteomics analysis showed that baicalin might inhibit FIPV infection by modulating the PI3K-AKT pathway and the apoptosis pathway. The WB results showed that baicalin promoted the expression of EGFR, PI3K, and Bcl-2 and inhibited the expression of cleaved caspase 9 and Bax. This study found that baicalin regulated the PI3K-AKT pathway and the apoptosis pathway in vitro and inhibited FIPV-induced apoptosis, thus exerting anti-FIPV effects.

Obesity and atrial fibrillation: a narrative review from arrhythmogenic mechanisms to clinical significance.

The prevalence of obesity and atrial fibrillation (AF), which are inextricably linked, is rapidly increasing worldwide. Obesity rates are higher among patients with AF than healthy individuals. Some epidemiological data indicated that obese patients were more likely to develop AF, but others reported no significant correlation. Obesity-related hypertension, diabetes, and obstructive sleep apnea are all associated with AF. Additionally, increased epicardial fat, systemic inflammation, and oxidative stress caused by obesity can induce atrial enlargement, inflammatory activation, local myocardial fibrosis, and electrical conduction abnormalities, all of which led to AF and promoted its persistence. Weight loss reduced the risk and reversed natural progression of AF, which may be due to its anti-fibrosis and inflammation effect. However, fluctuations in weight offset the benefits of weight loss. Therefore, the importance of steady weight loss urges clinicians to incorporate weight management interventions in the treatment of patients with AF. In this review, we discuss the epidemiology of obesity and AF, summarize the mechanisms by which obesity triggers AF, and explain how weight loss improves the prognosis of AF.

Midterm Outcomes of Kissing Covered Self-Expanding Stents for Reconstruction of Complex Aortoiliac Occlusive Disease.

BACKGROUND: We sought to investigate the midterm results of kissing self-expanding covered stents (SECSs) for the reconstruction of aortic bifurcation in complex aortoiliac occlusive disease. METHODS: Data of consecutive patients who had undergone endovascular treatment for aortoiliac occlusive disease were screened. Only patients with TransAtlantic Inter-Society Consensus (TASC) class C and D lesions treated by bilateral iliac kissing stents (KSs) were included. Midterm primary patency, risk factors, and limb salvage rates were analyzed. Follow-up results were analyzed using the Kaplan-Meier curves. Cox proportional hazards models were used to identify the predictors of primary patency. RESULTS: A total of 48 patients (95.8% men; mean age, 65.3 ± 10.2 years) were treated with kissing SECSs. Of them, 17 patients had TASC-II class C lesions and 31 had class D lesions. There were 38 total occlusive lesions, with a mean occlusive lesion length of 108.2 ± 57.3 mm. The overall mean lesion length was 140.3 ± 60.5 mm, and the mean length of implanted stents in the aortoiliac arteries was 141.9 ± 59.9 mm. The mean diameter of the deployed SECSs was 7.8 ± 0.5 mm. The mean follow-up time was 36.5 ± 15.8 months, and the follow-up rate was 95.8%. At 36 months, the overall primary patency, assisted primary patency, secondary patency, and limb salvage rates were 92.2%, 95.7%, 97.8%, and 100%, respectively. Univariate Cox regression analysis revealed that stent diameter ≤7 mm (hazard ratio [HR]: 9.53; 95% confidence interval [CI] 1.56-57.94, P = 0.014) and severe calcification (HR: 12.66; 95% CI 2.04-78.45, P = 0.006) were significantly associated with restenosis. Multivariate analysis showed severe calcification to be the only significant determinant of restenosis (HR: 12.66; 95% CI 2.04-78.45, P = 0.006). CONCLUSIONS: Kissing SECSs provide good midterm results for the treatment of aortoiliac occlusive disease. A stent diameter >7 mm is a potent protective factor against restenosis. Because severe calcification appears to be the only significant determinant of restenosis, patients with severe calcification require close follow-up.

Induction therapy with high-dose fluconazole plus flucytosine for human immunodeficiency virus-uninfected cryptococcal meningitis patients: Feasible or not?

BACKGROUND: Cryptococcal meningitis (CM) is increasingly recognised in human immunodeficiency virus (HIV)-uninfected patients with high mortality. The efficacy and safety profiles of induction therapy with high-dose fluconazole plus flucytosine remain unclear. METHODS: HIV-uninfected CM patients who received high-dose fluconazole (800 mg/d) for initial therapy in Huashan Hospital were included in this retrospective study from January 2013 to December 2018. Efficacy and safety of initial therapy, clinical outcomes and risk factors were evaluated. RESULTS: Twenty-seven (71.1%) patients who received high-dose fluconazole with flucytosine combination therapy and 11 (28.9%) having fluconazole alone for induction therapy were included. With a median duration of 42 days (IQR, 28-86), the successful response rate of initial therapy was 76.3% (29/38), while adverse drug reactions occurred in 14 patients (36.8%). The rate of persistently positive cerebrospinal fluid (CSF) culture results was 30.6% at 2 weeks, which was significantly associated with CSF CrAg titre >1:1280 (OR 9.56; 95% CI 1.40-103.65; p = .010) and CSF culture of Cryptococcus >3.9 log10 CFU/ml (OR 19.20; 95% CI 1.60-920.54; p = .011), and decreased to 8.6% at 4 weeks. One-year mortality was 15.8% (6/38), and low serum albumin (35 g/L) was found as an independent risk factor for 1-year mortality (HR 6.31; 95% CI 1.150-34.632; p = .034). CONCLUSIONS: Induction therapy with high-dose fluconazole (800 mg/d), combined with flucytosine, effectively treated HIV-uninfected CM and was well tolerated. Long-term fluconazole treatment with continued monitoring is beneficial for patients with persistent infection.

Diagnostic performance of noncultural methods for central nervous system aspergillosis.

BACKGROUND: Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult. OBJECTIVES: We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis. METHODS: In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next-generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut-off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis. RESULTS: Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively. CONCLUSIONS: In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients.

HSPA6, a novel prognostic and therapeutic biomarker, associated with Ming classification in gastric cancer.

OBJECTIVE: This study aimed to explore the clinical relevance of heat shock protein family A member 6 (HSPA6) in gastric cancer (GC) and its effect on GC cell proliferation. METHODS: HSPA6 mRNA and protein levels were analyzed by bioinformatics, RT-qPCR, western blot and immunohistochemistry. HSPA6 was correlated with clinicopathological variables by the Chi-square test. Kaplan-Meier survival analysis and the univariate and multivariate Cox models were used to assess the prognostic value of HSPA6. Nomogram was used to predict overall survival in patients with GC. Knockdown or over-expression of HSPA6 in GC cell lines was constructed by lentiviral transduction. EdU and CCK-8 assay were used to detect cell proliferation. In vivo mouse tumor models were performed to evaluate the effects of HSPA6 on GC growth. RESULTS: HSPA6 were significantly upregulated in the GC tissues compared to the normal stomach epithelium and were associated with Ming classification (p < 0.001) and tumor size (p = 0.002). Patients with high expression of HSPA6 showed worse survival compared to the low expression group. HSPA6 was identified to be an independent prognostic biomarker for GC. HSPA6 was functionally annotated with the cell cycle, G2M checkpoint and Hippo pathway. Knockdown of HSPA6 suppressed XGC-1 cell proliferation both in vitro and in vivo. Overexpression of HSPA6 in AGS cells increased proliferation rates, increased the levels of cyclinB1 and YAP and decreased that of phosphorylated YAP. HSPA6 knockdown in the NUGC2 cells had the opposite effect. CONCLUSIONS: HSPA6 promotes GC proliferation by the Hippo pathway, as a novel prognostic biomarker and potential therapeutic target.

Transcriptomic analysis of thigh muscle of Lueyang black-bone chicken in free-range and caged feeding.

Lueyang black-bone chicken is free-range in hilly areas and has unique genetic characteristics and excellent muscle quality. However, the molecular mechanisms of breeding mode influence growth and meat quality in Lueyang black-bone chicken are still unclear. Here we analyzed the meat quality and transcriptome data of thigh muscle by comparing free-range and caged modes at the age of 60 and 120 days in Lueyang black-boned chicken. The results demonstrated that the free-range mode could improve the pH value, tenderness, and reducing the hardness of the thigh muscle. Intramuscular fat (IMF) content of the thigh muscle was markedly higher in the caged chickens compared with free-range animals at the age of 60 days. Functional pathway analysis illustrated that tight junction signaling was associated with the formation of slow-twitch fibers in free-range chickens at age of 120 days. All research data proved that the free-range mode could improve muscle quality by promoting the formation of slow-twitch fibers and IMF in thigh muscle in Lueyang black-bone chicken. Based on the animal benefit and healthy, the free-range feeding should be considered during the breeding process of broiler chicken. The results provide good knowledge of the functional molecular mechanisms associated with muscle quality in Lueyang black-bone chicken.

Relationships between sensory integration and the core symptoms of attention-deficit/hyperactivity disorder: the mediating effect of executive function.

Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by executive function deficits and functional alterations in sensory integration. The present study aimed to investigate the relationship between ADHD core symptoms, executive function, and sensory integration in children with ADHD. A total of 228 children with ADHD were recruited for our study. The Sensory Organization Test (SOT) and Child Sensory Integration Scale (CSIS) evaluated the sensory integration ability from lab-based and scaled-based perspectives, respectively. Three core components of executive functions (inhibition, working memory, and set-shifting) were assessed using both lab-based tests and the relevant factors from the behavior rating inventory of executive function (BRIEF). Partial correlation analysis was performed to explore the correlation of sensory integration with EF and ADHD core symptoms. Based on the observed significant correlation, bootstrap analyses were further conducted to explore the potential mediating effect of EF on the relationship between sensory integration and ADHD core symptoms. ADHD symptoms and EF were significantly correlated with CSIS scores; no factors were significantly correlated with SOT performance. In detail, the vestibular-balance score was negatively correlated with both inattention and hyperactivity/impulsivity symptoms, while the hyper-sensory and proprioception scores were negatively correlated with only inattention symptoms. For the scaled-based EF, vestibular-balance was negatively correlated with inhibition and working memory, and the hyper-sensory score was negatively correlated with shift factor. No correlation was found for the lab-based EF tests. The subsequent mediation analysis found that inhibition partially mediated the relationship between vestibular balance and hyperactivity/impulsivity symptoms. Working memory completely mediated the relationship between vestibular-balance, hyper-sensory, proprioception, and inattention symptoms. These results were well validated in an independent sample. Our present findings demonstrated that the functional alteration in basic sensory integration might be associated with impairments of executive functions and then lead to the behavioral expression of ADHD. The present findings might provide a new perspective to understand the occurrence of ADHD symptoms and potential precise intervention methods.