Enhancing the biosynthesis of taxadien-5α-yl-acetate in Escherichia coli by combinatorial metabolic engineering approaches.

Biosynthesis of paclitaxel (Taxol™) is a hot topic with extensive and durable interests for decades. However, it is severely hindered due to the very low titers of intermediates. In this study, Escherichia coli was employed to de novo synthesize a key intermediate of paclitaxel, taxadien-5α-yl-acetate (T5OAc). Plasmid-based pathway reconstruction and optimization were conducted for T5OAc production. The endogenous methylerythritol phosphate pathway was enhanced to increase the precursor supply. Three taxadien-5α-ol O-acetyltransferases were tested to obtain the best enzyme for the acetylation step. Metabolic burden was relieved to restore cell growth and promote production through optimizing the plasmid production system. In order to achieve metabolic balance, the biosynthesis pathway was regulated precisely by multivariate-modular metabolic engineering. Finally, in a 5-L bioreactor, the T5OAc titer was enhanced to reach 10.9 mg/L. This represents an approximately 272-fold increase in production compared to the original strain, marking the highest yield of T5OAc ever documented in E. coli, which is believed to be helpful for promoting the progress of paclitaxel biosynthesis.

PemK's Arg24 is a crucial residue for PemIK toxin-antitoxin system to induce the persistence of Weissella cibaria against ciprofloxacin stress.

The toxin-antitoxin (TA) system plays a key role in bacteria escaping antibiotic stress with persistence, however, the mechanisms by which persistence is controlled remain poorly understood. Weissella cibaria, a novel probiotic, can enters a persistent state upon encountering ciprofloxacin stress. Conversely, it resumes from the persistence when ciprofloxacin stress is relieved or removed. Here, it was found that PemIK TA system played a role in transitioning between these two states. And the PemIK was consisted of PemK, an endonuclease toxic to mRNA, and antitoxin PemI which neutralized its toxicity. The PemK specifically cleaved the U↓AUU in mRNA encoding enzymes involved in glycolysis, TCA cycle and respiratory chain pathways. This cleavage event subsequently disrupted the crucial cellular processes such as hydrogen transfer, electron transfer, NADH and FADH2 synthesis, ultimately leading to a decrease in ATP levels and an increase in membrane depolarization and persister frequency. Notably, Arg24 was a critical active residue for PemK, its mutation significantly reduced the mRNA cleavage activity and the adverse effects on metabolism. These insights provided a clue to comprehensively understand the mechanism by which PemIK induced the persistence of W. cibaria to escape ciprofloxacin stress, thereby highlighting another novel aspect PemIK respond for antibiotic stress.

Nerve bypass surgery for spinal cord reconstruction.

OBJECTIVE: Spinal cord injury (SCI) is a devastating condition that significantly decreases the patient's quality of life. Therefore, treatments that can facilitate nerve regeneration, reduce complications, and increase quality of life are valuable for these patients. In this study, we aimed to assess nerve bypass surgery's feasibility and clinical outcomes by transferring the intercostal nerves (ICNs) into the spinal cord. METHODS: Eight patients with complete thoracic SCI and delayed presentation more than a year after the injury were analyzed retrospectively. All patients underwent nerve bypass surgery with the transfer of two pairs of ICNs from proximal to the injury site to the anterolateral spinal cord, followed by duraplasty with fascia grafting to close the dura. RESULTS: Six of the eight (75%) patients demonstrated motor and sensory improvements, based on the American Spinal Cord Injury Association score. Three patients demonstrated a limited recovery of motor function that could be independently triggered without ICN initiation. Five patients demonstrated evidence of cerebrospinal fluid (CSF) leakage after surgery; however, only one patient complained of a headache. CONCLUSION: Spinal cord bypass surgery is a potential reconstruction method to treat chronic complete thoracic SCI with functional improvements, and is worth further investigation.

Survival prognostic in different age groups of patients undergoing local versus radical excision for rectal cancer: a study based on the SEER database.

Age significantly affects the prognosis of patients with rectal cancer after radical excision (RE), and local excision (LE) is an alternative surgical procedure to RE. To compare the survival prognosis in different age groups of LE versus RE for rectal cancer. Patients diagnosed with rectal adenocarcinoma treated by LE or RE from 2010 to 2017 were obtained from the SEER database. The primary outcomes are 5-year OS and CSS. A total of 11,170 patients were eventually included, and there were 490 patients in LE and RE groups, respectively, after 1:1 propensity score matching. The 5-year OS and CSS after LE were significantly better in < 50 years and 50-66 years groups than in > 66 years group (5-year OS: 95.70% vs 88.40% vs 67.00%, P < 0.001; 5-year CSS: 95.70% vs 96.30% vs 82.60%, P < 0.001). No statistical significance was found for the differences in 5-year OS and CSS between LE and RE in < 50, 50-66, and > 66 years group (P > 0.05). Multivariate analysis showed age > 66 years, poorly differentiated or undifferentiated (Grade III/IV), and tumor size 3 to 5 cm was independent risk factors for 5-year OS after LE; age > 66 years, perineural invasion, and tumor size 3 to 5 cm were the 5-year CSS independent risk factors for after LE. We found that the survival prognosis of younger rectal cancer patients treated with LE was significantly better than older (> 66 years) patients, and the survival prognosis of rectal cancer patients in the three age groups was similar between LE and RE.

The safety and feasibility assessment of overlap esophagojejunostomy with self-pulling and latter transection technique in totally laparoscopic total gastrectomy.

BACKGROUND: This study presented an innovative technique in totally laparoscopic total gastrectomy (TLTG) for overlap esophagojejunostomy (E-J), termed self-pulling and latter transection (SPLT) (overlap SPLT). It evaluated the effectiveness and short-term outcomes of this novel method through a comparative analysis with the established functional end-to-end (FETE) E-J incorporating SPLT. METHODS: From September 2018 to September 2023, this study enrolled 68 patients with gastric cancer who underwent TLTG with overlap SPLT anastomosis and 120 patients who underwent TLTG with FETE SPLT anastomosis. Clinicopathologic characteristics and surgical and postoperative outcomes data for overlap SPLT cases were gathered and retrospectively compared with those from FETE SPLT TLTG to evaluate the effectiveness and clinical safety. RESULTS: The duration of anastomosis for overlap SPLT was 25.3 ± 7.4 minutes, significantly longer than that for the FETE SPLT (18.1 ± 4.0 minutes, P = .031). Perioperatively, 1 anastomosis-related complication occurred in each group, but this did not constitute a statistically significant difference (P = .682). No statistically significant differences were found between the 2 groups in terms of operative time, postoperative hospital stay, operative cost, surgical margins, or number of lymph nodes removed. Postoperative morbidity rates were similar between the groups (4.4% vs 5.8%, P = .676). CONCLUSION: The overlap SPLT technique is regarded as a safe and feasible method for anastomosis. There were no apparent differences in complications between overlap SPLT and FETE SPLT, but overlap SPLT costed 1 additional stapler cartridge and required a longer duration.

2D Exfoliation Chemistry Towards Covalent Pseudo-Layered Phosphate Framework Derived by Radical/Strain-Synergistical Process.

2D compounds exfoliated from weakly bonded bulk materials with van der Waals (vdW) interaction are easily accessible. However, the strong internal ionic/covalent bonding of most inorganic crystal frameworks greatly hinders 2D material exfoliation. Herein, we first proposed a radical/strain-synergistic strategy to exfoliate non-vdW interacting pseudo-layered phosphate framework. Specifically, hydroxyl radicals (•OH) distort the covalent bond irreversibly, meanwhile, H2O molecules as solvents, further accelerating interlayered ionic bond breakage but mechanical expansion. The innovative 2D laminar NASICON-type Na3V2(PO4)2O2F crystal, exfoliated by •OH/H2O synergistic strategy, exhibits enhanced sodium-ion storage capacity, high-rate performance (85.7 mA h g-1 at 20 C), cyclic life (2300 cycles), and ion migration rates, compared with the bulk framework. Importantly, this chemical/physical dual driving technique realized the effective exfoliation for strongly coupled pseudo-layered frameworks, which accelerates 2D functional material development.

Ordered Perovskite Structure with Functional Units for High Performance and Stable Solar Cells.

Ion migration is one of the most critical challenges that affects the stability of metal-halide perovskite solar cells (PSCs). However, the current arsenal of available strategies for solving this issue is limited. Here, novel perovskite active layers following the concept of ordered structures with functional units (OSFU) to intrinsically suppress ion migration, in which a three-dimensional (3D) perovskite layer is deposited by vapor deposition for light absorption and a 2D layer is deposited by solution process for ion inhibition, are constructed. As a promising result, the activation energy of ion migration increases from 0.36 eV for the conventional perovskite to 0.54 eV for the OSFU perovskite. These devices exhibit substantially enhanced operational stability in comparison with the conventional ones, retaining >85% of their initial efficiencies after 1200 h under ISOS-L-1. Moreover, the OSFU devices show negligible fatigue behavior with a robust performance under light/dark cycling aging test (ISOS-LC-1 protocol), which demonstrates the promising application of functional motif theory in this field.

Dual roles of α1,4-galactosyltransferase 1 in spermatogenesis of Drosophila melanogaster.

Spermatogenesis is critical for insect reproduction and the process is regulated by multiple genes. Glycosyltransferases have been shown to participate in the development of Drosophila melanogaster; however, their role in spermatogenesis is still unclear. In this study, we found that α1,4-galactosyltransferase 1 (α4GT1) was expressed at a significantly higher level in the testis than in the ovary of Drosophila. Importantly, the hatching rate was significantly decreased when α4GT1 RNA interference (RNAi) males were crossed with w1118 females, with only a few mature sperm being present in the seminal vesicle of α4GT1 RNAi flies. Immunofluorescence staining further revealed that the individualization complex (IC) in the testes from α4GT1 RNAi flies was scattered and did not move synchronically, compared with the clustered IC observed in the control flies. Terminal deoxyribonucleotide transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay showed that apoptosis signals in the sperm bundles of α4GT1 RNAi flies were significantly increased. Moreover, the expression of several individualization-related genes, such as Shrub, Obp44a and Hanabi, was significantly decreased, whereas the expression of several apoptosis-related genes, including Dronc and Drice, was significantly increased in the testes of α4GT1 RNAi flies. Together, these results suggest that α4GT1 may play dual roles in Drosophila spermatogenesis by regulating the sperm individualization process and maintaining the survival of sperm bundles.

Impaired topology and connectivity of grey matter structural networks in major depressive disorder: evidence from a multi-site neuroimaging data-set.

BACKGROUND: Major depressive disorder (MDD) has been increasingly understood as a disruption of brain connectome. Investigating grey matter structural networks with a large sample size can provide valuable insights into the structural basis of network-level neuropathological underpinnings of MDD. AIMS: Using a multisite MRI data-set including nearly 2000 individuals, this study aimed to identify robust topology and connectivity abnormalities of grey matter structural network linked to MDD and relevant clinical phenotypes. METHOD: A total of 955 MDD patients and 1009 healthy controls were included from 23 sites. Individualised structural covariance networks (SCN) were established based on grey matter volume maps. Following data harmonisation, network topological metrics and focal connectivity were examined for group-level comparisons, individual-level classification performance and association with clinical ratings. Various validation strategies were applied to confirm the reliability of findings. RESULTS: Compared with healthy controls, MDD individuals exhibited increased global efficiency, abnormal regional centralities (i.e. thalamus, precentral gyrus, middle cingulate cortex and default mode network) and altered circuit connectivity (i.e. ventral attention network and frontoparietal network). First-episode drug-naive and recurrent patients exhibited different patterns of deficits in network topology and connectivity. In addition, the individual-level classification of topological metrics outperforms that of structural connectivity. The thalamus-insula connectivity was positively associated with the severity of depressive symptoms. CONCLUSIONS: Based on this high-powered data-set, we identified reliable patterns of impaired topology and connectivity of individualised SCN in MDD and relevant subtypes, which adds to the current understanding of neuropathology of MDD and might guide future development of diagnostic and therapeutic markers.

Bidirectional association between eating disorder and temporomandibular joint disorder: A retrospective longitudinal nationwide population-based cohort study.

Background/purpose: An increasing body of evidence indicates correlations between the symptoms of temporomandibular disorder and those of eating disorder (ED). However, further investigation is required to elucidate the temporal and causal relationships between the aforementioned disorders. Materials and methods: This retrospective cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Temporomandibular joint disorder (TMJD) was analyzed both as the cause and consequence of ED. We collected the data (from January 1, 1998, to December 31, 2011) of patients with antecedent TMJD (N = 15,059) or ED (N = 1219) and their respective controls (1:10), matched by age, sex, income level, residential location, and comorbidities. This study included patients who had received a new diagnosis of an ED or a TMJD between January 1, 1998, and December 31, 2013. Cox regression models were used to assess the risk of ED or TMJD development in patients with antecedent TMJD or ED. Results: TMJD patients had an approximately 3.70-fold (95 % confidence interval [CI]: 1.93-7.10) risk of ED development. Similarly, patients with ED had an approximately 4.78-fold (95 % CI: 2.52-9.09) risk of TMJD development. Subgroup analyses based on ED subtypes indicated antecedent TMJD and bulimia nervosa as the predictors of increased bulimia nervosa and TMJD risks (hazard ratios: 6.41 [95 % CI: 2.91 to 14.11] and 5.84 [95 % CI: 2.75 to 12.41]), respectively. Conclusion: Previous TMJD and ED are associated with increased risks of subsequent ED and TMJD; these findings suggest the presence of a bidirectional temporal association between TMJD and ED.

The alteration of fecal microbial and metabolic profile of gallstone patients in Taiwan: Single-center study.

BACKGROUND: Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls. METHODS: We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics. RESULT: Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium , Prevotella 9 , and Bacteroides plebeius DSM 17135 . The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella . In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group ( p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness. CONCLUSION: Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort.

SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl- concentration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupts the epithelial barrier and triggers airway inflammation. The envelope (E) protein, a core virulence structural component of coronaviruses, may play a role in this process. Pathogens could interfere with transepithelial Cl- transport via impairment of the cystic fibrosis transmembrane conductance regulator (CFTR), which modulates nuclear factor κB (NF-κB) signaling. However, the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function, Cl- transport and the robust inflammatory response remain to be elucidated. Here, we have demonstrated that E protein down-regulated the expression of tight junctional proteins, leading to the disruption of the airway epithelial barrier. In addition, E protein triggered the activation of Toll-like receptor (TLR) 2/4 and downstream c-Jun N-terminal kinase (JNK) signaling, resulting in an increased intracellular Cl- concentration ([Cl-]i) via up-regulating phosphodiesterase 4D (PDE4D) expression in airway epithelial cells. This elevated [Cl-]i contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1 (SGK1). Moreover, blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E protein. Overall, these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

Identification of a novel Scn3b mutation in a Chinese Brugada syndrome pedigree: implications for Nav1.5 electrophysiological properties and intracellular distribution of Nav1.5 and Navß3.

Background: The Scn3b gene encodes for Navß3, a pivotal regulatory subunit of the fast sodium channel in cardiomyocytes. However, its mutation status in the Chinese population suffering from Brugada Syndrome (BrS) has not been characterized, and the contributory pathophysiological mechanisms to disease pathology remain undefined. Methods and Results: A Scn3b (c.260C>T, p.P87l) mutation was identified in a patient with BrS of Chinese descent. Functional analyses demonstrated that sodium channel activation for the wild type, mutant samples, and co-expression of both commenced at -55 mv and peaked at -25 mv. The mutant group exhibited a notable reduction, approximately 60%, in peak sodium channel activation current (INa) at -25 mv. The parameters for half-maximal activation voltages (V1/2) and slope factors (k) showed no significant differences when comparing wild type, mutant, and combined expression groups (P = 0.98 and P = 0.65, respectively). Additionally, no significant disparities were evident in terms of the steady-state sodium channel inactivation parameters V1/2 and k (with P-values of 0.85 and 0.25, respectively), nor were there significant differences in the activation time constant τ (P = 0.59) and late sodium current density (P = 0.23) across the wild-type, mutant, and co-expressed groups. Confocal imaging and Western blot analysis demonstrated decreased plasma membrane localization of SCN3B and SCN5A in the P87l group. Computational simulations of cardiac action potentials suggested that SCN3B P87l can alter the morphology of the action potentials within the endocardium and epicardium while reducing the peak of depolarization. Conclusions: The pathogenic impact of the Scn3b P87l mutation predominantly originates from a reduction in peak INa activation current coupled with decreased cell surface expression of Nav1.5 and Navß3. These alterations may influence cardiac action potential configurations and contribute to the risk of ventricular arrhythmias in individuals with BrS.

Predictive factors for lung metastasis in pediatric differentiated thyroid cancer: a clinical prediction study.

OBJECTIVES: The objective of this study was to develop and evaluate the efficacy of a nomogram for predicting lung metastasis in pediatric differentiated thyroid cancer. METHODS: The SEER database was utilized to collect a dataset consisting of 1,590 patients who were diagnosed between January 2000 and December 2019. This dataset was subsequently utilized for the purpose of constructing a predictive model. The model was constructed utilizing a multivariate logistic regression analysis, incorporating a combination of least absolute shrinkage feature selection and selection operator regression models. The differentiation and calibration of the model were assessed using the C-index, calibration plot, and ROC curve analysis, respectively. Internal validation was performed using a bootstrap validation technique. RESULTS: The results of the study revealed that the nomogram incorporated several predictive variables, namely age, T staging, and positive nodes. The C-index had an excellent calibration value of 0.911 (95 % confidence interval: 0.876-0.946), and a notable C-index value of 0.884 was achieved during interval validation. The area under the ROC curve was determined to be 0.890, indicating its practicality and usefulness in this context. CONCLUSIONS: This study has successfully developed a novel nomogram for predicting lung metastasis in children and adolescent patients diagnosed with thyroid cancer. Clinical decision-making can be enhanced by assessing clinicopathological variables that have a significant predictive value for the probability of lung metastasis in this particular population.

Characterization of a germline variant TNS1 c.2999-1G > C in a hereditary cancer syndrome family.

Hereditary cancer syndromes result from the presence of inherited pathogenic variants within susceptibility genes. However, the susceptibility genes associated with hereditary cancer syndrome remain predominantly unidentified. Here, we reported a case of hereditary cancer syndrome observed in a Chinese family harboring a germline mutation in Tensin1 (TNS1). We described a 59-year-old female patient presented with Multiple myeloma and Thyroid carcinoma. The proband and her family members exhibited suspected tumor syndrome due to occurrences of other cancer cases. After oncogenetic counseling, whole-exome sequencing and Sanger sequencing were conducted and a primary driver mutation of TNS1 (NM_022648.7:c.2999-1G > C) was detected. Gene Expression Profiling Interactive Analysis revealed that TNS1 was expressed lower in different tumors when compared to normal, including Pancreatic adenocarcinoma, Breast invasive carcinoma, Thyroid carcinoma andColon adenocarcinoma cells. Despite the well-established role of TNS1 as a tumor suppressor in breast cancer and colorectal cancer, its potential utility as a marker gene for diagnosis and treatment of pancreatic cancer remains uncertain. Here, our data demonstrated that knockdown of TNS1 could promote cell proliferation and migration in Pancreatic adenocarcinoma (PDAC) cells. In addition, TNS1 regulated migration through EMT signaling pathway in PDAC cells. Our findings proposed that this variant was likely involved in cancer predisposition by disrupting the normal splicing process. In summary, we presented a genetic disease by linking an intronic mutation inTNS1. We aim to provide early detection of cancers by identifying germline variants in susceptibility genes.

Prognostic impact of tumor budding in rectal cancer after neoadjuvant therapy: a systematic review and meta-analysis.

BACKGROUND: Tumor budding (TB) is a negative prognostic factor in colorectal cancer; however, its prognostic impact following neoadjuvant therapy for patients with rectal cancer remains unclear. This study aims to assess the prognostic impact of TB and the correlation between TB and other pathological features in patients with rectal cancer after neoadjuvant therapy. METHODS: A comprehensive search of PubMed, Embase, Cochrane, Scopus, CNKI, Wanfang, and ClinicalKey databases was conducted for studies on the prognosis of TB in rectal cancer after neoadjuvant therapy from the inception of the databases to January 2023, and the final literature included was determined using predefined criteria. Quality assessment of the studies included, extraction of general and prognostic information from them, and meta-analyses were carried out progressively. RESULTS: A total of 11 studies were included, and the results of the meta-analysis showed that high-grade tumor budding (TB-1) increased the risk of poor 5-year disease-free survival (HR = 1.75, 95% CI 1.38-2.22, P < 0.00001), 5-year overall survival (HR = 1.77, 95% CI 1.21-2.59, P = 0.003), local recurrence (OR = 4.15, 95% CI 1.47-11.75, P = 0.007), and distant metastasis (OR = 5.36, 95% CI 2.51-11.44, P < 0.0001) in patients with rectal cancer after neoadjuvant therapy. TB-1 was significantly associated with poor differentiation and lymphatic, perineural, and venous invasion. CONCLUSION: Tumor budding is significantly correlated with unfavorable prognosis and poor pathological characteristics following neoadjuvant therapy for rectal cancer. We anticipate more high-quality, prospective studies in the future to confirm our findings. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377564.

THE IMPACT OF BILATERAL VISION STATUS ON VISION-RELATED QUALITY OF LIFE IN PEOPLE WITH DIABETES MELLITUS.

PURPOSE: To assess the impact of bilateral vision status on vision-related quality of life (VR-QOL) in patients with Type 2 diabetes in a Chinese cohort. METHODS: Patients with presenting visual acuity (PVA) and VR-QOL data from the Fushun Diabetic Retinopathy Cohort Study were included. Vision-related quality of life was assessed using the National Eye Institute Visual Function Questionnaire-25. Monocular PVA (Snellen) was categorized into three levels for both the better-seeing eye and worse-seeing eye: 1) high PVA (H, > 6/18); 2) moderate PVA (M, 6/18-6/60); and 3) low PVA (L, < 6/60). Based on the monocular PVAs, six categories of bilateral vision status were defined (H-H, H-M, H-L, M-M, M-L, and L-L). The parameters of VR-QOL were analyzed between the groups. RESULTS: A total of 1,717 patients were enrolled. For better-seeing eyes in the same PVA level, the Visual Function Questionnaire-25 composite score decreased significantly with declining PVA in the worse-seeing eye (H-M vs. H-L: 80.5 ± 17.9 vs. 73.6 ± 22.5, P = 0.01; M-M vs. M-L: 78.7 ± 19.6 vs. 69.1 ± 26.4, P = 0.01). Conversely, for worse-seeing eyes in the same PVA level, there was no significant difference in the Visual Function Questionnaire-25 composite score as PVA changed in the better-seeing eye (H-M vs. M-M, 80.5 ± 17.9 vs. 78.7 ± 19.6, P = 0.30; H-L vs. M-L: 73.6 ± 22.5 vs. 69.1 ± 26.4, P = 0.25). CONCLUSION: The PVA of the worse-seeing eye in bilateral vision has a greater impact on VR-QOL in diabetic patients. Priority treatment may be considered for the worse-seeing eye for diabetic patients with different bilateral vision statuses, to better improve VR-QOL.

MiR-2b-3p Downregulated PxTrypsin-9 Expression in the Larval Midgut to Decrease Cry1Ac Susceptibility of the Diamondback Moth, Plutella xylostella (L.).

Crystal (Cry) toxins, produced by Bacillus thuringiensis, are widely used as effective biological pesticides in agricultural production. However, insects always quickly evolve adaptations against Cry toxins within a few generations. In this study, we focused on the Cry1Ac protoxin activated by protease. Our results identified PxTrypsin-9 as a trypsin gene that plays a key role in Cry1Ac virulence in Plutella xylostella larvae. In addition, P. xylostella miR-2b-3p, a member of the micoRNA-2 (miR-2) family, was significantly upregulated by Cry1Ac protoxin and targeted to PxTrypsin-9 downregulated its expression. The mRNA level of PxTrypsin-9, regulated by miR-2b-3p, revealed an increased tolerance of P. xylostella larvae to Cry1Ac at the post-transcriptional level. Considering that miR-2b and trypsin genes are widely distributed in various pest species, our study provides the basis for further investigation of the roles of miRNAs in the regulation of the resistance to Cry1Ac and other insecticides.

Aspirin intake is not associated with diabetic retinopathy and diabetic macular edema: A report from the Fushun diabetic retinopathy cohort study.

PURPOSE: We aimed to study the effects of aspirin intake for diabetic retinopathy (DR) and diabetic macular edema (DME) in a cohort from northeastern China. METHODS: Participants in the Fushun Diabetic Retinopathy Cohort Study were enrolled between July 2012 and May 2013. Fundus photographs of six fields were graded according to the modified Airlie House Classification system. The prevalence, incidence, progression, and regression of DR, as well as the prevalence/incidence of DME, were evaluated at baseline and during follow-up examinations after at least 1 year. RESULTS: In total, 1370 patients were enrolled in the study, and 270 (19.7%) were taking aspirin. The prevalence of any DR in participants with and without aspirin intake was 47.4% and 44.9%, respectively (P = 0.46). The incidence of any DR in patients with and without aspirin intake was 9.2% and 8.3%, respectively (P = 0.74). In univariate regression, there was no association between aspirin intake and the prevalence of any DR and DME (odds ratios (OR), 95% confidence intervals (CI): 0.93, 0.68-1.27 and 1.22, 0.79-1.88, respectively). Aspirin intake was not significantly associated with the prevalence and incidence of DME (OR, 95% CI: 1.22, 0.79-1.88 and 1.79, 0.62-5.17, respectively). Furthermore, aspirin intake was not significantly associated with DR progression or regression (OR, 95% CI: 1.04, 0.66-1.66 and 0.75, 0.52-1.09, respectively). CONCLUSION: Aspirin intake was not associated with the prevalence and incidence of any DR or DME in a northeastern Chinese population. Neither progression nor regression of DR revealed a significant association with aspirin intake.

Maintaining Toll signaling in Drosophila brain is required to sustain autophagy for dopamine neuron survival.

Macroautophagy/autophagy is a conserved process in eukaryotic cells to degrade and recycle damaged intracellular components. Higher level of autophagy in the brain has been observed, and autophagy dysfunction has an impact on neuronal health, but the molecular mechanism is unclear. In this study, we showed that overexpression of Toll-1 and Toll-7 receptors, as well as active Spätzle proteins in Drosophila S2 cells enhanced autophagy, and Toll-1/Toll-7 activated autophagy was dependent on Tube-Pelle-PP2A. Interestingly, Toll-1 but not Toll-7 mediated autophagy was dMyd88 dependent. Importantly, we observed that loss of functions in Toll-1 and Toll-7 receptors and PP2A activity in flies decreased autophagy level, resulting in the loss of dopamine (DA) neurons and reduced fly motion. Our results indicated that proper activation of Toll-1 and Toll-7 pathways and PP2A activity in the brain are necessary to sustain autophagy level for DA neuron survival.