Correlation between sarcopenia index and cognitive function in older adult women: A cross-sectional study using NHANES data.

OBJECTIVES: The Sarcopenia Index (SI) has the potential as a biomarker for sarcopenia, which is characterized by muscle loss. There is a clear association between sarcopenia and cognitive impairment. However, the relationship between SI and cognitive impairment is yet to be fully understood. METHODS: We employed data extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2002. Our study encompassed individuals aged 65 to 80 who possessed accessible information regarding both SI and cognitive evaluations with a GFR ≥ 90. Cognitive function was assessed using the digit symbol substitution test (DSST). SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L)*100. Employing multivariate modeling, we estimated the connection between SI and cognitive performance. Furthermore, to enhance the reliability of our data analysis, we categorized SI using tertiles and subsequently calculated the P-value for trend. RESULTS: After adjustment for potential confounders, we found SI was significantly and positively correlated with cognitive function scores both in older female in the American population [ß = 0.160, 95 % confidence interval (CI) 0.050 to 0.271, P = 0.00461]. Similarly, when the total cognitive function score was treated as a categorical variable according to tertiles, higher SI was related to better total cognitive function scores in females [odds ratio (OR) = 3.968, 95 % CI 1.863 to 6.073, P = 0.00025] following adjustment for confounders. CONCLUSIONS: Higher SI was correlated with a lower prevalence of cognitive impairment among older adult women with normal kidney function.

Deletion of speA and aroC genes impacts the pathogenicity of Vibrio anguillarum in spotted sea bass.

Vibrio anguillarum is one of the major pathogens responsible for bacterial infections in marine environments, causing significant impacts on the aquaculture industry. The misuse of antibiotics leads to bacteria developing multiple drug resistances, which is detrimental to the development of the fisheries industry. In contrast, live attenuated vaccines are gradually gaining acceptance and widespread recognition. In this study, we constructed a double-knockout attenuated strain, V. anguillarum ΔspeA-aroC, to assess its potential for preparing a live attenuated vaccine. The research results indicate a significant downregulation of virulence-related genes, including Type VI secretion system, Type II secretion system, biofilm synthesis, iron uptake system, and other related genes, in the mutant strain. Furthermore, the strain lacking the genes exhibited a 67.47% reduction in biofilm formation ability and increased sensitivity to antibiotics. The mutant strain exhibited significantly reduced capability in evading host immune system defenses and causing in vivo infections in spotted sea bass (Lateolabrax maculatus), with an LD50 that was 13.93 times higher than that of the wild-type V. anguillarum. Additionally, RT-qPCR analysis of immune-related gene expression in spotted sea bass head kidney and spleen showed a weakened immune response triggered by the knockout strain. Compared to the wild-type V. anguillarum, the mutant strain caused reduced levels of tissue damage. The results demonstrate that the deletion of speA and aroC significantly reduces the biosynthesis of biofilms in V. anguillarum, leading to a decrease in its pathogenicity. This suggests a crucial role of biofilms in the survival and invasive capabilities of V. anguillarum.

The Characterization of Subcutaneous Adipose Tissue in Sunit Sheep at Different Growth Stages: A Comprehensive Analysis of the Morphology, Fatty Acid Profile, and Metabolite Profile.

Adipose tissue is a crucial economically significant trait that significantly influences the meat quality and growth performance of domestic animals. To reveal the changes in adipose tissue metabolism during the growth of naturally grazing sheep, we evaluated the thickness, adipocyte morphology, fatty acid profile, and metabolite profile of subcutaneous adipose tissue (SAT) from naturally grazing Sunit sheep at 6, 18, and 30 months of age (referred to as Mth-6, Mth-18, and Mth-30, respectively). The fat thickness and adipocyte number were significantly increased with the growth of the sheep (p < 0.05), and the increase of which from Mth-18 to Mth-30 was less than that from Mth-6 to Mth-18. Additionally, the alpha-linolenic acid metabolism was enhanced and fatty acid (FA) elongation increased with growth. The metabolomic analysis revealed 76 differentially expressed metabolites (DEMs) in the SAT in different growth stages. Interestingly, we observed elongation of FAs in lipids correlated with sheep growth. Furthermore, the expression of acylcarnitines was downregulated, and fatty acid amides, aspartic acid, acetic acid and phosphocholine were upregulated in Mth-18 and Mth-30 compared to Mth-6. Altogether, the study found that the difference in SAT in Mth-6 was great compared to Mth-18 and Mth-30. An increase in fat deposition via adipocyte proliferation with the growth of the sheep in naturally grazing. The DEMs of acylcarnitines, fatty acid amides, aspartic acid, acetic acid, and phosphocholine emerged as potential key regulators of adipose tissue metabolism. These findings illustrate the variation in and metabolic mechanism of sheep adipose tissue development under natural grazing, thus providing valuable insights into improving the edible quality of sheep meat and developing the mutton sheep industry.

Intraperitoneal vancomycin plus levofloxacin for the treatment of peritoneal dialysis-related peritonitis in patients with no response to cefazolin plus ceftazidime.

INTRODUCTION: Peritoneal dialysis-related peritonitis (PDRP) should be treated as soon as possible by an empirical regimen without waiting for effluent bacterial culture results. We retrospectively investigated patients treated with vancomycin plus levofloxacin as a treatment regimen if there was no response to cefazolin plus ceftazidime. MATERIALS AND METHODS: We collected records of adult patients with PDRP from January 1, 2013, to November 30, 2020. The characteristics of episodes of PDRP with no response to cefazolin plus ceftazidime treated by intraperitoneal (IP) injection of vancomycin plus levofloxacin were analyzed. RESULTS: 118 episodes of PDRP were recorded, among which 115 episodes were treated with IP antibiotics. 93 episodes were treated with cefazolin plus ceftazidime. In 38 episodes, treatment was switched to IP injection of vancomycin plus levofloxacin if there was no response to cefazolin plus ceftazidime. 26/38 (68.4%) episodes were cured by vancomycin plus levofloxacin. Fever, diabetes, fasting glucose, a decrease in effluent leukocytes on day 3 and day 5, and Charlson Comorbidity Index (CCI) scores were significantly different between uncured and cured episodes. No variable was associated with treatment failure after multiple logistic regression. Fever, diabetes, a decrease in effluent leukocytes on day 3, and CCI score were associated with treatment failure after univariable logistic regression. CONCLUSION: Vancomycin plus levofloxacin may be effective if patients are not responsive to cefazolin plus ceftazidime.

Curcumin-Loaded Bamboo Shoot Cellulose Nanofibers: Characterization and In Vitro Studies.

Given its high biological and pharmacological activities, curcumin (CUR) offers promising applications in functional foods. However, its low stability and bioavailability have greatly hindered its application in the food industry. The present study prepared cellulose nanofiber (CNF) from bamboo shoot processing byproducts and investigated its potential as a low-cost carrier. Our results showed that CUR was immobilized on CNF surfaces mainly through hydrogen bonding and eventually encapsulated in CNF matrices, forming a CNF-CUR complex with an encapsulation efficiency of 88.34% and a loading capacity of 67.95%. The CUR encapsulated in the complex showed improved stability after thermal and UV light treatments. Moreover, a slow and extended release pattern of CUR in a simulated gastrointestinal tract was observed, which could be appropriately described using the Korsmeyer-Peppas model. These results revealed that CNF is a promising protective carrier for the slow release of CUR, making it a better candidate for functional foods.

OCMR: A comprehensive framework for optical chemical molecular recognition.

Artificial intelligence (AI) has achieved significant progress in the field of drug discovery. AI-based tools have been used in all aspects of drug discovery, including chemical structure recognition. We propose a chemical structure recognition framework, Optical Chemical Molecular Recognition (OCMR), to improve the data extraction capability in practical scenarios compared with the rule-based and end-to-end deep learning models. The proposed OCMR framework enhances the recognition performances via the integration of local information in the topology of molecular graphs. OCMR handles complex tasks like non-canonical drawing and atomic group abbreviation and substantially improves the current state-of-the-art results on multiple public benchmark datasets and one internally curated dataset.

Higher D-dimer and activated partial thromboplastin time are poor prognostic factors in patients with peritoneal dialysis-related peritonitis.

INTRODUCTION: Coagulation system dysfunction is associated with adverse outcomes of peritoneal dialysis (PD) and bacterial infection. We investigated the association between coagulation system and treatment failure of peritoneal dialysis-related peritonitis (PDRP). METHODS: We collected records of patients aged ≥18 years with PDRP. PDRP episodes were divided into: shortened activated partial thromboplastin time (APTT) group and prolonged APTT group, low D-dimer (DD) group and high DD group. The baseline characteristics of the groups were collected and compared. The association between APTT, DD and treatment failure of PDRP was analyzed using logistic regression analysis. RESULTS: Thirty episodes of treatment failure were observed in 110 episodes of PDRP in our study. After adjusting for variables, prolonged APTT (OR = 1.166 [1.049-1.296], p = 0.004) or high level of DD (OR = 1.374 [1.057-1.787], p = 0.017) was associated with treatment failure of PDRP. CONCLUSION: Prolonged baseline APTT or high level of DD increased the risk of treatment failure of PDRP.

Characterization of Type I and Type III Collagen in the Intramuscular Connective Tissue of Wuzhumuqin Sheep.

Intramuscular connective tissue (IMCT) collagen is an important factor in meat quality. This study analyzed the characteristics of type I and III collagen in the IMCT of the semitendinosus (SD) and longissimus dorsi (LD) of Wuzhumuqin sheep at different growth stages (6, 9, 12, and 18 months). Utilizing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Fourier transform infrared spectroscopy (FTIR), collagen types I and III were successfully isolated and shown to contain an intact triple helix structure. Immunofluorescence revealed that these collagens were located in the endomysium and perimysium. Collagen-related genes were significantly expressed in sheep aged 9 and 12 months. The amino acid content increased with age in type I collagen whereas it decreased in type III collagen. Furthermore, type III collagen contained more hydroxyproline (Hyd) than type I collagen. Differential scanning calorimetry (DSC) revealed that the thermal stability of collagen increased with age, accompanied by a decrease in solubility. Semitendinosus muscle had more collagen cross-linkages than LD muscle due to the high pyridinoline (Pyr) content in the endomysium. Finally, a correlation analysis highlighted the multiple correlations between characteristics in different types of collagen during sheep growth. In summary, the collagen characteristics in the IMCT of sheep were impacted by collagen type, muscle type, and age. Furthermore, the various correlations between these characteristics may play an important role in the development of IMCT.

A Low Prognostic Nutritional Index Is a Risk Factor for High Peritoneal Transport Status in Patients Undergoing Peritoneal Dialysis.

OBJECTIVES: A high peritoneal transport status is a risk factor for mortality and causes technical failure in patients on peritoneal dialysis (PD). High peritoneal transport status is associated with malnutrition and inflammation in patients with PD. The prognostic nutritional index (PNI) is a marker determined by the serum albumin level and lymphocyte count in the peripheral blood. The aim of this study is to investigate the association between PNI and high peritoneal transport status in patients with PD. METHODS: We retrospectively investigated patients with PD from January 1, 2013 to May 31, 2020, in 4 PD centers. Patients with PD were divided into 2 groups according to PNI quartiles: the low PNI group (PNI ≤ 36.6) and the high PNI group (PNI > 36.6). The demographics and clinical and laboratory baseline data of the 2 groups were collected and compared. The association between PNI and high peritoneal transport status was analyzed by multivariate logistic regression analysis. RESULTS: A total of 404 patients with PD were enrolled in our study. A total of 77 (19.06%) patients had high peritoneal transport status. After adjusting for age, sex, body mass index, hypertension, diabetes mellitus, residual urine volume, current smoking status, pre-existing cardiovascular disease, hemoglobin, white blood cell count, triglycerides, and intact parathyroid hormone, low PNI levels were significantly associated with high peritoneal transport status (odds ratio 3.42, 95% confidence interval 1.82-5.18, P = .0056). Subgroup analysis showed that there was no interaction among PNI and age, sex, diabetes, body mass index, pre-existing cardiovascular disease, or current smoking. CONCLUSION: As a marker for malnutrition and inflammation, a low level of PNI is an independent risk factor for high peritoneal transport status in patients with PD.

Insulin sensitivity, ß cell function, and adverse pregnancy outcomes in women with gestational diabetes.

BACKGROUND: The potential impact of ß cell function and insulin sensitivity on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM) remains uncertain. We aimed to investigate the association between ß cell dysfunction, insulin resistance, and the composite adverse pregnancy outcomes. METHODS: This observational study included 482 women diagnosed with GDM during pregnancy. Quantitative metrics on ß cell function and insulin sensitivity during pregnancy were calculated using traditional equations. The association of ß cell dysfunction and insulin resistance with the risk of the composite adverse pregnancy outcomes was investigated using multivariable-adjusted logistic regression models. RESULTS: Multivariable-adjusted odds ratios (ORs) of adverse pregnancy outcomes across quartiles of homeostatic model assessment for insulin resistance (HOMA-IR) were 1.00, 0.95, 1.34, and 2.25, respectively (P for trend = 0.011). When HOMA-IR was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 1.34 (95% confidence interval 1.16-1.56) for each 1-unit increase in HOMA-IR. Multivariable-adjusted ORs of adverse pregnancy outcomes across quartiles of homeostatic model assessment for ß cell function (HOMA-ß) were 1.00, 0.51, 0.60, and 0.53, respectively (P for trend = 0.068). When HOMA-ß was considered as a continuous variable, the multivariable-adjusted OR of adverse pregnancy outcomes was 0.57 (95% CI 0.24-0.90) for each 1-unit increase in HOMA-ß. However, other quantitative metrics were not associated with the composite adverse pregnancy outcomes. CONCLUSIONS: We demonstrated a significant association of ß cell function and insulin sensitivity with the risk of adverse pregnancy outcomes. We have provided additional evidence on the early identification of adverse pregnancy outcomes besides the glycemic values.

MicroRNA and circular RNA profiling in the deposited fat tissue of Sunite sheep.

As the most typical deposited fat, tail fat is an important energy reservoir for sheep adapted to harsh environments and plays an important role as a raw material in daily life. However, the regulatory mechanisms of microRNA (miRNA) and circular RNA (circRNA) in tail fat development remain unclear. In this study, we characterized the miRNA and circRNA expression profiles in the tail fat of sheep at the ages of 6, 18, and 30 months. We identified 219 differentially expressed (DE) miRNAs (including 12 novel miRNAs), which exhibited a major tendency to be downregulated, and 198 DE circRNAs, which exhibited a tendency to be upregulated. Target gene prediction analysis was performed for the DE miRNAs. Functional analysis revealed that their target genes were mainly involved in cellular interactions, while the host genes of DE circRNAs were implicated in lipid and fatty acid metabolism. Subsequently, we established a competing endogenous RNA (ceRNA) network based on the negative regulatory relationship between miRNAs and target genes. The network revealed that upregulated miRNAs play a leading role in the development of tail fat. Finally, the ceRNA relationship network with oar-miR-27a_R-1 and oar-miR-29a as the core was validated, suggesting possible involvement of these interactions in tail fat development. In summary, DE miRNAs were negatively correlated with DE circRNAs during sheep tail fat development. The multiple ceRNA regulatory network dominated by upregulated DE miRNAs may play a key role in this developmental process.

The relationship between the prognostic nutritional index and new-onset pneumonia in peritoneal dialysis patients.

PURPOSE: As an indicator of nutrition and immunity, the prognostic value of the prognostic nutritional index (PNI) has been confirmed in various diseases. However, the relationship between PNI and the incidence of pneumonia in peritoneal dialysis (PD) patients remains unknown. The purpose of this study was to investigate the relationship between PNI and new-onset pneumonia in patients undergoing PD. METHODS: Thousand two hundred and nighty eight patients were enrolled in this multicenter retrospective study from February 1, 2010, to February 28, 2020. A total of 899 patients were included in the final statistical analysis. The patients were stratified into two groups by PNI quartiles. The primary endpoint was a new-onset pneumonia event. Cox regression model analysis was used to explore the association between PNI and the first occurrence of pneumonia. RESULTS: During a mean follow-up of 41.43 months, 147 patients developed new-onset pneumonia. Kaplan-Meier survival curves showed a significant difference in the incidence of the first presentation of pneumonia between the two groups, that patients in the low PNI group had a higher risk of pneumonia (P = 0.016). By adjusting for demographic parameters, comorbidities, and laboratory indicators, the Cox regression model showed that the high PNI group had less risk compared to the low PNI group (HR 0.479 95% CI 0.297-0.772, P = 0.003). There were no interactions in the subgroups as follows: diabetes, hypertension, age, and sex. CONCLUSIONS: Low PNI levels were independently associated with the first occurrence of pneumonia in PD patients. PNI was an independent predictor of new-onset pneumonia in PD patients.

The association between diabetes coexisting with low levels of high-density lipoprotein cholesterol and peritoneal dialysis-related peritonitis.

BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDL-C) and diabetes are common in patients undergoing peritoneal dialysis (PD). The aim of this study was to investigate the association between the coexistence of diabetes with a low level of HDL-C and the first episode of peritoneal dialysis-related peritonitis (PDRP) in patients with PD. METHODS: We retrospectively investigated patients with PD from January 1, 2003, to May 31, 2020, in four PD centers. Patients with PD were divided into four groups: no comorbidities, low HDL-C only, diabetes only, and diabetes plus low HDL-C. The clinical and laboratory baseline data of the four groups were collected and compared. The association between diabetes coexisting with low HDL-C levels and the first episode of PDRP was analyzed by multivariate Cox regression analysis. RESULTS: A total of 1013 patients with PD were included in our study. The mean age was 49.94 ± 14.32 years, and 597 (58.99%) patients were males. A total of 301 (29.7%) patients had their first episodes of PDRP, and low HDL-C levels coexisted with diabetes in 72 patients with PD. After adjusting for confounding factors, a low level of HDL-C coexisting with diabetes was significantly associated with the first episode of PDRP in our study (hazard ratio: 2.81, 95% CI 1.32 ~ 4.73, p = 0.005). The associations among HDL-C, diabetes and PDRP were consistent in the following subgroups: sex, age, and pre-existing CVD (all P interaction > 0.05). CONCLUSIONS: Patients with both diabetes and low HDL-C levels were at higher risk for PDRP in patients with PD.

Erratum: RNF6 promotes the migration and invasion of breast cancer by promoting the ubiquitination and degradation of MST1.

[This corrects the article DOI: 10.3892/etm.2021.11041.].

Protective Effect of Extended Laminectomy on Spinal Cord Injury Induced by Spinal Shortening.

This study investigates the effect of extended laminectomy (EL) on spinal cord injury (SCI) caused by spinal shortening, and further, the timing and the optimal length of removal. Dogs received spinal column shortening at T13 segment, following which the control group underwent regular laminectomy while other groups underwent laminectomy with an additional 1-lamina length removed 6h after shortening ("1-lamina EL 6 h"), an extra 1.5-lamina length resected at 6 h or 12 h after shortening ("1.5-lamina EL 6 h" and "1.5-lamina EL 12 h"), and an extra 2-lamina length removed at 6 or 12 h after shortening ("2-lamina EL 6 h" and 2-lamina EL 12 h"), respectively. Somatosensory evoked potential (SSEP) and neurological function were recorded periodically; spinal cord blood flow (SCBF) and nerve cell apoptosis were detected. The results showed that resection of an additional 1-lamina length appeared inadequate to relieve the sharp kinking of the spinal cord, whereas the kinking disappeared with an additional 2-lamina length resection. The "1-lamina EL 6 h" and "1.5-lamina EL 12 h" groups showed no significant differences from the control in latency of SSEP, SCBF, hindlimb function and apoptosis. By contrast, significant recovery of SSEP, SCBF and hindlimb function as well as reduction of apoptosis were presented in other three groups. The "2-lamina EL 6 h" group, in particular, showed the most prominent recovery. In conclusion, an additional resection of two laminae at 6 h after shortening showed the best effect in alleviating SCI. Timely and adequately extended laminectomy could be a potential therapeutic strategy for SCI attributable to spinal shortening.

The effectiveness and safety of corticosteroid therapy for IgA nephropathy with crescents: a prospective, randomized, controlled study.

BACKGROUND: Pozzi protocol (methylprednisolone intravenous infusion in 1st-3rd-5th months and oral steroid for 6 months) has been thought to be the classic therapy for IgA nephropathy (IgAN) patients with proteinuria> 1.0 g/24 h. There is no consensus on the treatments for IgAN with active pathological changes, especially for IgAN patients with crescents proportion < 50%. This study aimed to evaluate the effectiveness and safety of the treatment protocol of methylprednisolone intravenous infusion at the 1st-2nd-3rd months for IgAN patients with crescents. METHODS: In this prospective, randomized, controlled, non-blind study, 68 IgAN patients with crescents proportion < 50% were divided into the 1-2-3 group receiving 0.25 g/d methylprednisolone intravenously for 3 consecutive days in the 1st-2nd-3rd months, and oral prednisone 0.5 mg/kg/d on consecutive days for 6 months and the 1-3-5 group with the same intravenous methylprednisolone treatment in the 1st-3rd-5th months, and the same oral prednisone. The primary outcome measure was remission of proteinuria (complete or partial); while the secondary outcome measures were deterioration of renal function (evidenced by a 50% rise from baseline serum creatinine levels, or a 25% decline from baseline eGFR levels). RESULTS: There was no significant difference in incidence of crescents (median 14.66% vs. 11.45%, p = 0.143) between the 1-2-3 and 1-3-5 groups. From month 1 to month 6, there was a decreasing trend in the levels of urine protein and serum creatinine and an increasing trend in eGFR in both groups. The mean period of remission in the 1-2-3 group seemed shorter. Overall, there were 55 (80.89%) patients meeting remission. The rates of remission in the 1-2-3 group and 1-3-5 group were 85.3 and 76.47%, respectively (P = 0.644). The 1-2-3 group had lower creatinine and higher eGFR than the 1-3-5 group, but the difference was not significant. The complication rate was 11.11 and 15.79% in the two groups, respectively. There was no significant difference in the complications between groups. CONCLUSIONS: Both the 1st-3rd-5th and 1st-2nd-3rd protocols can effectively alleviate proteinuria and protect renal function in IgAN patients with crescents but the 1st-2nd-3rd protocol seemed to have better effectiveness. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02160132 , Registered June 10, 2014.

Hypertriglyceridemia is a risk factor for treatment failure in patients with peritoneal dialysis-related peritonitis.

OBJECTIVE: Disorders of triglycerides (TG) are common in patients with peritoneal dialysis (PD). Hypertriglyceridemia has been demonstrated in various infections. The association between triglycerides and the outcomes of peritoneal dialysis-related peritonitis (PDRP) was investigated in this study. METHODS: We retrospectively investigated patients with PDRP from January 1, 2013 to October 31, 2020. Hypertriglyceridemia was defined as triglycerides ≥ 1.7 mmol/L. PDRP episodes were divided into two groups: hypertriglyceridemia and normal levels of triglycerides. The clinical and laboratory baseline data of the two groups were collected and compared. The association between triglycerides and treatment failure was analyzed by logistic regression analysis. RESULTS: Ninety episodes in 66 patients were recorded in our center. Hypertriglyceridemia occurred in 38% (34/90) of episodes. Twenty-five episodes were not cured in 90 episodes (27.8%, 25/90). The levels of thrombocytes, high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C) and glycated hemoglobin, were higher in hypertriglyceridemia episodes of PDRP at baseline. The bacterial classification was different between elevated triglyceride group and normal triglyceride group. Adjusted for age, duration of dialysis, residual renal function, diabetes, thrombocytes, hs-CRP, serum albumin, cholesterol, HDL-C, LDL-C, intact parathyroid hormone (iPTH), glycated hemoglobin and spectrum of bacteria, hypertriglyceridemia were associated significantly with treatment failure of PDRP in our study (OR 3.416, 95% CI 1.223-9.540 p < 0.05). CONCLUSION: Hypertriglyceridemia at baseline was an independent risk factor for treatment failure of PDRP.

The role of autophagy on eye migration during the metamorphosis of Paralichthys olivaceus.

The metamorphosis of flatfish is unique, especially its eye migration. Autophagy has been found to be involved in a variety of organisms' metamorphosis. In order to explore the relationship between autophagy and flatfish metamorphosis, we investigated the expression of autophagy marker gene lc3b during the metamorphosis using real-time quantitative polymerase chain reaction and in situ RNA hybridization. Besides, we inhibited cell division, which was reported as the force source of eye migration, and autophagy around the mobile eye by microinjecting the inhibitors to explore the effects on autophagy expression and eye migration. We found that autophagy taking place during the metamorphosis, particularly in the areas around the eyes. In addition, the eye migration could be blocked by inhibiting the autophagy in the supraorbital area of the blind side, and after we blocked the eye migration by inhibiting cell proliferation in the infraorbital area of the blind side, the autophagy around the eye was partially inhibited. These findings indicate that the autophagy around the eyes caused by eye migration. Moreover, the cell death caused by autophagy loosen the orbital tissue to create space for the eye migration.

RNF6 promotes the migration and invasion of breast cancer by promoting the ubiquitination and degradation of MST1.

Ring finger protein 6 (RNF6), a member of E3 ubiquitin ligases, plays a potential role as a tumour promoter in numerous carcinomas. However, the role and expression of RNF6 in breast cancer (BC) remains to be elucidated. The present study showed that RNF6 upregulation was detected in BC tissues and was associated with short survival in patients with BC. Multivariate analysis also revealed that RNF6 overexpression is an independent predictor for poor outcome of patients with BC. Furthermore, migration and metastasis assay indicated that RNF6 silencing significantly inhibited the invasion and migration of BC cells in vivo and in vitro, and RNF6 suppression decreased YES-associated protein (YAP) expression. RNF6 promoted the metastatic ability of BC cells via YAP. Mechanistically, RNF6 interacts with mammalian STE20-like protein kinase 1 (MST1), a key factor that regulates YAP, and promoted its ubiquitination and degradation. Additionally, RNF6 regulated YAP signalling by promoting ubiquitination and degradation of MST1 in BC. Taken together, these data may highlight a role of RNF6 in BC, which could serve as a valuable prognostic indicator and potential therapeutic target for patients with BC.

Single-nucleotide polymorphisms responsible for pseudo-albinism and hypermelanosis in Japanese flounder (Paralichthys olivaceus) and reveal two genes related to malpigmentation.

Paralichthys olivaceus is the kind of cold-water benthic marine fish. In the early stages of development, the symmetrical juveniles transform into an asymmetrical body shape through metamorphosis for adapting benthic life. After that, one side of the fish body is attached to the ground, and the eyes turn to the opposite side which is called ocular side. The body color also appears asymmetry. The skin on the ocular side is dark brown, and the skin on the blind side is white without pigmentation. Pseudo-albinism and hypermelanosis have been considered distinct body color disorders in flatfish. Pseudo-albinism and hypermelanosis in Paralichthys olivaceus are due to abnormal or uneven pigment distribution, due to the interaction of hereditary and environmental factors, rather than a single-nucleotide mutation of a specific gene. Here, we report three single-nucleotide polymorphisms (SNPs) responsible for both pseudo-albinism and hypermelanosis, which are located on two body color-related genes involved in melanogenesis-related pathways. c.2440C>A (P. V605I) and c.2271-96T>C are located on the Inositol 1,4,5-trisphosphate receptor type 2-like (ITPR2) (Gene ID: 109624047), they are located in exon 16 and the non-coding region, respectively, and c.2406C>A (P.H798N) is located in exon 13 of the adenylate cyclase type 6-like (AC6) gene(Gene ID: 109630770). ITPR2 and AC6 expression, which both participate in the thyroid hormone synthesis pathway associated with pseudo-albinism and hypermelanosis in P. olivaceus, were also investigated using qRT-PCR. In hypermelanotic fish, there were relatively higher levels of expression in ITPR2 and AC6 mRNA of hyper-pigmented skin of blind side than that of non-pigmented skin on the blind side and pigmented skin on the ocular side, while in pseudo-albino fish, expression level of ITPR2 and AC6 mRNA in pigmented skin of ocular side was significantly higher than that in non-pigmented skin both ocular and blind side. The results indicated that the expression of the two genes in abnormal parts of body color is positively correlated with pigmentation, suggesting that the influence of abnormal expression of two genes on the pigmentation in abnormal parts of body color deserves further study.