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Urogenital reconstructive malformation surgery is sometimes hampered by lack of tissue for the repair. We have previously shown that autologous micrografting allows for single-staged scaffold cellularization after surgical implantation. Here, a collagen-based scaffold reinforced with biodegradable mesh and a stent was implanted as a bladder conduit in ten full-grown female minipigs. We aimed to assess short-term regenerative outcomes, safety, and feasibility of implanting tubular urinary micrografted scaffolds versus acellular controls. Five scaffolds were embedded with autologous urothelial micrografts harvested perioperatively. After six weeks, all animals were assessed by cystoscopy, CT-urography, and microanatomical assessment of the urinary conduits. The procedure proved technically feasible within the confines of a regular surgical theater, with duration-times comparable to corresponding conventional procedures. No animals experienced postoperative complications, and all implanted conduits were patent at follow-up. Improved tissue regeneration was observed in the micrografted conduits compared with the acellular controls, including increased luminal epithelialization, increased cell proliferation, decreased cell apoptosis, and increased conduit vascularization. We concluded that single-staged on-site construction and implantation of tissue engineered urinary conduits proved feasible and safe, with improved regenerative potentials in micrografted conduits. This study presents a new approach to urinary conduits, and merits further investigations for advancement towards clinical translation., (© 2024. The Author(s).)

Vitiligo is a hypopigmented skin disease characterized by the loss of melanin. The progressive nature and widespread incidence of vitiligo necessitate timely and accurate detection. Usually, a single diagnostic test often falls short of providing definitive confirmation of the condition, necessitating the assessment by dermatologists who specialize in vitiligo. However, the current scarcity of such specialized medical professionals presents a significant challenge. To mitigate this issue and enhance diagnostic accuracy, it is essential to build deep learning models that can support and expedite the detection process. This study endeavors to establish a deep learning framework to enhance the diagnostic accuracy of vitiligo. To this end, a comparative analysis of five models including ResNet (ResNet34, ResNet50, and ResNet101 models) and Swin Transformer series (Swin Transformer Base, and Swin Transformer Large models), were conducted under the uniform condition to identify the model with superior classification capabilities. Moreover, the study sought to augment the interpretability of these models by selecting one that not only provides accurate diagnostic outcomes but also offers visual cues highlighting the regions pertinent to vitiligo. The empirical findings reveal that the Swin Transformer Large model achieved the best performance in classification, whose AUC, accuracy, sensitivity, and specificity are 0.94, 93.82%, 94.02%, and 93.5%, respectively. In terms of interpretability, the highlighted regions in the class activation map correspond to the lesion regions of the vitiligo images, which shows that it effectively indicates the specific category regions associated with the decision-making of dermatological diagnosis. Additionally, the visualization of feature maps generated in the middle layer of the deep learning model provides insights into the internal mechanisms of the model, which is valuable for improving the interpretability of the model, tuning performance, and enhancing clinical applicability. The outcomes of this study underscore the significant potential of deep learning models to revolutionize medical diagnosis by improving diagnostic accuracy and operational efficiency. The research highlights the necessity for ongoing exploration in this domain to fully leverage the capabilities of deep learning technologies in medical diagnostics., (© 2024. The Author(s).)

In Māori and Pacific adults, the CREBRF rs373863828 minor (A) allele is associated with increased body mass index (BMI) but reduced incidence of type-2 and gestational diabetes mellitus. In this prospective cohort study of Māori and Pacific infants, nested within a nutritional intervention trial for pregnant women with obesity and without pregestational diabetes, we investigated whether the rs373863828 A allele is associated with differences in growth and body composition from birth to 12-18 months' corrected age. Infants with and without the variant allele were compared using generalised linear models adjusted for potential confounding by gestation length, sex, ethnicity and parity, and in a secondary analysis, additionally adjusted for gestational diabetes. Carriage of the rs373863828 A allele was not associated with altered growth and body composition from birth to 6 months. At 12-18 months, infants with the rs373863828 A allele had lower whole-body fat mass [FM 1.4 (0.7) vs. 1.7 (0.7) kg, aMD -0.4, 95% CI -0.7, 0.0, P = 0.05; FM index 2.2 (1.1) vs. 2.6 (1.0) kg/m 2 aMD -0.6, 95% CI -1.2,0.0, P = 0.04]. However, this association was not significant after adjustment for gestational diabetes, suggesting that it may be mediated, at least in part, by the beneficial effect of CREBRF rs373863828 A allele on maternal glycemic status., (© 2024. The Author(s).)

Facing to a planar tracking problem, a multiple-interpretable improved Proximal Policy Optimization (PPO) algorithm with few-shot technique is proposed, namely F-GBQ-PPO. Compared with the normal PPO, the main improvements of F-GBQ-PPO are to increase the interpretability, and reduce the consumption for real interaction samples. Considering to increase incomprehensibility of a tracking policy, three levels of interpretabilities has been studied, including the perceptual, logical and mathematical interpretabilities. Detailly speaking, it is realized through introducing a guided policy based on Apollonius circle, a hybrid exploration policy based on biological motions, and the update of external parameters based on quantum genetic algorithm. Besides, to deal with the potential lack of real interaction samples in real applications, a few-shot technique is contained in the algorithm, which mainly generate fake samples through a multi-dimension Gaussian process. By mixing fake samples with real ones in a certain proportion, the demand for real samples can be reduced., (© 2024. The Author(s).)

The classical theory of elastic critical buckling stress works well for slender columns and thin flat plates under compression; however, the situation is different for longitudinally compressed thin-walled circular cylindrical shells, and the issue has plagued us despite considerable efforts over the last 100 years. We noticed that all such buckling analyses thus far, both linear and nonlinear, in terms of the main philosophy, inherited and were confined to Euler's pioneering solution for the slender column model that focuses on the longitudinal buckling deformation mode and should be classified as the 'longitudinal open-loop' eigenmode because the deformations of the two longitudinal ends are physically independent of each other. In view of this, for an ideal linear-elastic buckling model of a thin-walled perfectly circular cylindrical shell under uniform longitudinal compression on the foundation of the longitudinal open-loop eigenmode solution, it is also necessary to consider a 'circumferential closed-loop' eigenmode simultaneously to physically avoid violating the reality of its ideal periodic deformation on the entire perimeter and to mathematically redefine the biunique and precise relationship for each distinct eigenmode by the critical circumferential wavelength. Originating from such a case study, the mathematical uniqueness issue hidden in the general solution of the Donnell equation is further discussed. The authenticity of the competing eigenmode characterized by the Koiter circle is also discussed. Furthermore, a preliminary attempt was conducted to interpret the discrepancy between theoretical and experimental buckling loads, mainly initiated by the characteristic type of longitudinally generated circumferential local inward displacement in initial geometric imperfections, using the insights herein., (© 2023. Springer Nature Limited.)

Most recent survival prediction has been based on TNM staging, which does not provide individualized information. However, clinical factors including performance status, age, sex, and smoking might influence survival. Therefore, we used artificial intelligence (AI) to analyze various clinical factors to precisely predict the survival of patients with larynx squamous cell carcinoma (LSCC). We included patients with LSCC (N = 1026) who received definitive treatment from 2002 to 2020. Age, sex, smoking, alcohol consumption, Eastern Cooperative Oncology Group (ECOG) performance status, location of tumor, TNM stage, and treatment methods were analyzed using deep neural network (DNN) with multi-classification and regression, random survival forest (RSF), and Cox proportional hazards (COX-PH) model for prediction of overall survival. Each model was confirmed with five-fold cross validation, and performance was evaluated using linear slope, y-intercept, and C-index. The DNN with multi-classification model demonstrated the highest prediction power (1.000 ± 0.047, 0.126 ± 0.762, and 0.859 ± 0.018 for slope, y-intercept, and C-index, respectively), and the prediction survival curve showed the strongest agreement with the validation survival curve, followed by DNN with regression (0.731 ± 0.048, 9.659 ± 0.964, and 0.893 ± 0.017, respectively). The DNN model produced with only T/N staging showed the poorest survival prediction. When predicting the survival of LSCC patients, various clinical factors should be considered. In the present study, DNN with multi-class was shown to be an appropriate method for survival prediction. AI analysis may predict survival more accurately and improve oncologic outcomes., (© 2023. The Author(s).)

Although opioids are necessary for the treatment of acute pain, cancer pain, and palliative care, opioid abuse is a serious threat to society. Heroin (Diacetylmorphine) is the most commonly abused opioid, and it can have a variety of effects on the body's tissues and organs, including the well-known gastrointestinal depression and respiratory depression; however, there is little known about the effects of diacetylmorphine on cardiac damage. Here, we demonstrate that diacetylmorphine induces abnormal electrocardiographic changes in rats and causes damage to cardiomyocytes in vitro by an underlying mechanism of increased autophosphorylation of CaMKII and concomitant regulation of myocardial contractile protein TPM1 and MYOM2 protein expression. The CaMKII inhibitor KN-93 was first tested to rescue the toxic effects of heroin on cardiomyocytes in vitro and the abnormal ECG changes caused by heroin in SD rats, followed by the TMT relative quantitative protein technique to analyze the proteome changes. Diacetylmorphine causes increased phosphorylation at the CaMKII Thr287 site in myocardium, resulting in increased autophosphorylation of CaMKII and subsequent alterations in myocardial contractile proteins, leading to myocardial rhythm abnormalities. These findings provide a theoretical basis for the treatment and prevention of patients with arrhythmias caused by diacetylmorphine inhalation and injection., (© 2023. The Author(s).)

This study aimed to evaluate the removal effect of the ProTaper Next system (PTN) combined with manual nickel-titanium Hedström (MNiTiH) files or chloroform on filling materials of mandibular incisors by microcomputed tomography (micro-CT). Sixty-four extracted human mandibular incisors were finally selected and assigned to two groups (n = 32) based on root canal morphology after instrumentation. Two subgroups (n = 16) were formed based on two retreatment methods. The volume of residual filling materials (RFMs) and the surface area covered by RFMs were analyzed by micro-CT, the apical extrusion and the time taken for removing the filling materials were recorded. A smaller percentage of the volume of RFMs and less surface area covered by RFMs occurred in PTN combined with MNiTiH groups and round-shaped canal incisors (P < 0.05). The time taken for removing the filling materials was not significantly different in all groups (P > 0.05). The apical extrusion was significantly less in PTN combined with MNiTiH groups than in PTN combined with chloroform groups (P < 0.05). Neither of the two methods rendered root canals completely free from filling materials. PTN combined with MNiTiH could reduce the apical extrusion and remove filling materials more efficiently than PTN combined with chloroform., (© 2023. The Author(s).)

The Chinese medicine formula Pien Tze Huang (PZH) has been applied to the treatment of various diseases, the reported anti-tumor mechanisms included regulation of inflammation-associated cytokine secretion and cancer growth pathways. However, the potential influence of PZH on tumor metabolism remains unclear. This study aimed to investigate the global effect of PZH on hepatocellular carcinoma (HCC) compared with the anti-tumor agent sorafenib based on tandem mass tag (TMT) label proteomic and phosphoproteomic analysis in addition to parallel reaction monitoring (PRM) verification. It was observed that PZH could inhibit tumor weight by 59-69% in different concentrations. TMT proteomic studies indicated that fructose/mannose metabolism and glucagon signaling pathway in PZH group, and arachidonic acid metabolism and PPAR signaling pathway in sorafenib group, were significantly enriched, while glycolysis/gluconeogenesis pathway was found to be enriched remarkably both in PZH and sorafenib groups in TMT phosphoproteomic study. PRM verification further indicated that both PZH and sorafenib could down-regulate phosphorylations of the glycolytic enzymes phosphofructokinases 1, fructose-bisphosphate Aldolase A, phosphoglycerate mutase 2 and lactate dehydrogenase A chain, while phosphorylations of long chain fatty acid CoA ligase in fatty acid activation and acetyl-coenzyme A synthetase in glycolysis were significantly inhibited by PZH and sorafenib, respectively. This study proposed that PZH shared a similar anti-tumor mechanism of metabolic regulation to sorafenib, but differed in the regulation of some metabolic nodes. This is the first time to uncover the relationship between the anti-tumor effect of PZH and metabolic related enzymes, which distinguished from the known mechanisms of PZH. These data provided the potential molecular basis for PZH acting as a therapeutic drug for HCC, and offered cues of manipulation on Warburg effect under the treatment of PZH., (© 2023. The Author(s).)

Digging in hilly regions is an important measure to promote afforestation on difficult sites. In view of the working conditions to build fish-scale pit on slope, the auger mechanism of soil lifting and throwing was investigated in this study. This study utilized EDEM software to establish the operation model of the earth auger and conduct DEM (Discrete Element Method) virtual simulation experiments. A quadratic rotating orthogonal center combination test was implemented by setting the efficiency of conveying-soil (Y 1 ) and the distance of throwing-soil (Y 2 ) as the evaluation indices. Variance analysis and response surface optimization were performed on the virtual experimental data. The results indicated that the weight of the factors affecting the Y 1 and Y 2 , were feeding speed > helix angle > rotating speed > slope angle, and slope auger > rotating speed > feeding speed > helix angle. The optimal parameter combination of each influencing factor was obtained. Among them, when the slope preparation was required, the optimal operating parameter combination of the auger was: Slope of 26.467°, Helix angle of 21.567°, Feeding speed of 0.1 m/s, Rotating speed of 67.408 r/min. This research provides theoretical references for the design optimization of the earth auger in hilly regions., (© 2022. The Author(s).)

The aim of this study is to evaluate the antimicrobial activity of the fast-setting iRoot Fast Set Root Repair Material (iRoot FS), Mineral trioxide aggregate (MTA) and Biodentine. The materials were freshly mixed or set for 1 and 7 days to conduct the agar diffusion test, direct contact test and carry-over effect test against E. faecalis and P. gingivalis, and the pH values were also measured. The data were analyzed by an analysis of variance and one-way ANOVA or Dunnett's T3 test, and the Tukey's post hoc test for multiple comparisons (α = 0.05). In the direct contact test, all three materials showed good antibacterial activity after setting for 20 min. The antibacterial properties of the three materials decreased with the increase of setting time (p < 0.05). The suspension of all the three materials showed high pH values (11-12) and no significant difference was observed (p > 0.05). With the extension of setting time, the pH of iRoot FS and Biodentine slightly decreased (p < 0.05). Fresh iRoot FS, Biodentine, and MTA killed E. faecalis and P. gingivalis effectively, but their antimicrobial effect decreased after 24 h, and distinctly decreased after 7 days after mixing. iRoot FS, Biodentine, and MTA showed a tendency of alkalinity during this 7-day experiment., (© 2022. The Author(s).)

Perioperative cardiac arrest (POCA) is associated with a high mortality rate. This work aimed to study its prognostic factors for risk mitigation by means of care management and planning. A database of 380,919 surgeries was reviewed, and 150 POCAs were curated. The main outcome was mortality prior to hospital discharge. Patient demographic, medical history, and clinical characteristics (anesthesia and surgery) were the main features. Six machine learning (ML) algorithms, including LR, SVC, RF, GBM, AdaBoost, and VotingClassifier, were explored. The last algorithm was an ensemble of the first five algorithms. k-fold cross-validation and bootstrapping minimized the prediction bias and variance, respectively. Explainers (SHAP and LIME) were used to interpret the predictions. The ensemble provided the most accurate and robust predictions (AUC = 0.90 [95% CI, 0.78-0.98]) across various age groups. The risk factors were identified by order of importance. Surprisingly, the comorbidity of hypertension was found to have a protective effect on survival, which was reported by a recent study for the first time to our knowledge. The validated ensemble classifier in aid of the explainers improved the predictive differentiation, thereby deepening our understanding of POCA prognostication. It offers a holistic model-based approach for personalized anesthesia and surgical treatment., (© 2022. The Author(s).)

Terpenoids from natural plant sources are valuable for their diverse biological activities that have important roles in the medical and agrochemical industries. In this study, we assessed the antioxidant, antifungal, and aphicidal activities of a mixture of spinasterol and 22,23-dihydrospinasterol from the leaves of Citrullus colocynthis. We used 1,1-diphenyl-2-picrylhydrazyl (DPPH) to assess antioxidant activity, and we measured antifungal activity using mycelium growth inhibition assays with three pathogenic fungi, Magnaporthe grisea, Rhizoctonia solani, and Phytophthora infestans. Aphicidal activity against adults of Myzus persicae was determined using in vitro and in vivo assays. Spinasterol and 22,23-dihydrospinasterol exhibited moderate antioxidant activity, even at lower concentrations: 19.98% at 0.78 µg mL -1 , 31.52% at 3.0 µg mL -1 , 36.61% at 12.5 µg mL -1 , and 49.76% at 50 µg mL -1 . Spinasterol and 22,23-dihydrospinasterol showed reasonable levels of fungicidal activity toward R. solani and M. grisea, with EC 50 values of 129.5 and 206.1 µg mL -1 , respectively. The positive controls boscalid and carbendazim were highly effective against all fungi except boscalid for M. grisea (EC 50  = 868 µg mL -1 ) and carbendazim for P. infestans (EC 50  = 8721 µg mL -1 ). Significant insecticidal activity was observed in both residual and greenhouse assays, with LC 50 values of 42.46, 54.86, and 180.9 µg mL -1 and 32.71, 42.46, and 173.8 µg mL -1 at 72, 48, and 24 h, respectively. The antioxidant activity of spinasterol and 22,23-dihydrospinasterol was strongly positively correlated with their antifungal and insecticidal activity. Spinasterol and 22,23-dihydrospinasterol therefore show good antioxidant and aphicidal activity with moderate fungicidal activity, making them suitable candidates for an alternative to synthetic agents., (© 2022. The Author(s).)

Flour whiteness and colour are important factors that influence the quality of wheat flour and end-use products. In this study, a genome wide association study focusing on flour and dough sheet colour using a high density genetic map constructed with 90K single nucleotide polymorphism arrays in a panel of 205 elite winter wheat accessions was conducted in two different locations in 2 years. Eighty-six significant marker-trait associations (MTAs) were detected for flour whiteness and the brightness index (L* value), the redness index (a* value), and the yellowness index (b* value) of flour and dough sheets (P < 10 -4 ) on homologous group 1, 2, 5 and 7, and chromosomes 3A, 3B, 4A, 6A and 6B. Four, three, eleven, eleven MTAs for the flour whiteness, L* value, a* value, b* value, and one MTA for the dough sheet L* value were identified in more than one environment. Based on MATs, some important new candidate genes were identified. Of these, two candidate genes, TraesCS5D01G004300 and Gsp-1D, for BS00000020&#95;51 were found in wheat, relating to grain hardness. Other candidate genes were associated with proteins, the fatty acid biosynthetic process, the ketone body biosynthetic process, etc.

To construct a machine learning algorithm model of lymph node metastasis (LNM) in patients with poorly differentiated-type intramucosal gastric cancer. 1169 patients with postoperative gastric cancer were divided into a training group and a test group at a ratio of 7:3. The model for lymph node metastasis was established with python machine learning. The Gbdt algorithm in the machine learning results finds that number of resected nodes, lymphovascular invasion and tumor size are the primary 3 factors that account for the weight of LNM. Effect of the LNM model of PDC gastric cancer patients in the training group: Among the 7 algorithm models, the highest accuracy rate was that of GBDT (0.955); The AUC values for the 7 algorithms were, from high to low, XGB (0.881), RF (0.802), GBDT (0.798), LR (0.778), XGB + LR (0.739), RF + LR (0.691) and GBDT + LR (0.626). Results of the LNM model of PDC gastric cancer patients in test group : Among the 7 algorithmic models, XGB had the highest accuracy rate (0.952); Among the 7 algorithms, the AUC values, from high to low, were GBDT (0.788), RF (0.765), XGB (0.762), LR (0.750), RF + LR (0.678), GBDT + LR (0.650) and XGB + LR (0.619). Single machine learning algorithm can predict LNM in poorly differentiated-type intramucosal gastric cancer, but fusion algorithm can not improve the effect of machine learning in predicting LNM.

In the multi-effect evaporation salt making process, the smooth operation of the salt making process is crucial. As the salt production process continues, many unstable factors will cause the salt production process not to proceed smoothly. These factors can be discovered in advance by predicting the salt production data, thus, it is of great significance to predict the multi-effect evaporation salt production data. In the process of multi-effect evaporation and salt production, the multiple salt-making devices make the influence between the parameters closer, and the influence of a single parameter on itself is sometimes ductile. Therefore, the data of multi-effect evaporation and salt production have the characteristics of high dimensions, high complexity and temporal information. If the historical salt production data is used for data prediction directly, the prediction model will take a long time and the prediction effect is not good. Thus, how to predict the multi-effect evaporation salt production data is the main research problem of this paper. In view of the above problems, according to the characteristics of multi-effect evaporation salt production data, this paper analyzes and improves the self encoder for feature extraction of multi effect-evaporation salt production data, so as to solve the problem of high dimensions and high complexity of salt production data. On this basis, combined with the time-series information contained in the salt production data, a multi-effect evaporation salt production data prediction model is proposed based on long-term and short-term memory cycle neural network to solve the prediction problem of time-series salt production data. Experiments show that the prediction model can predict and prevent the problems in salt production line in advance. It has a certain theoretical research value and application value in the intelligent production process and production line optimization of salt chemical industry.

Co-deletion of 1p/19q is a hallmark of oligodendroglioma and predicts better survival. However, little is understood about its metabolic characteristics. In this study, we aimed to explore the extracellular acidity of WHO grade II and III gliomas associated with 1p/19q co-deletion. We included 76 glioma patients who received amine chemical exchange saturation transfer (CEST) imaging at 3 T. Magnetic transfer ratio asymmetry (MTR asym ) at 3.0 ppm was used as the pH-sensitive CEST biomarker, with higher MTR asym indicating lower pH. To control for the confounder factors, T 2 relaxometry and L-6- 18 F-fluoro-3,4-dihydroxyphenylalnine ( 18 F-FDOPA) PET data were collected in a subset of patients. We found a significantly lower MTR asym in 1p/19q co-deleted gliomas (co-deleted, 1.17% ± 0.32%; non-co-deleted, 1.72% ± 0.41%, P = 1.13 × 10 -7 ), while FDOPA (P = 0.92) and T 2 (P = 0.61) were not significantly affected. Receiver operating characteristic analysis confirmed that MTR asym could discriminate co-deletion status with an area under the curve of 0.85. In analysis of covariance, 1p/19q co-deletion status was the only significant contributor to the variability in MTR asym when controlling for age and FDOPA (P = 2.91 × 10 -3 ) or T 2 (P = 8.03 × 10 -6 ). In conclusion, 1p/19q co-deleted gliomas were less acidic, which may be related to better prognosis. Amine CEST-MRI may serve as a non-invasive biomarker for identifying 1p/19q co-deletion status.

Plant extracts contain many active compounds, which are tremendously fruitful for plant defence against several insect pests. The prime objectives of the present study were to calculate the extraction yield and to evaluate the leaf extracts of Citrullus colocynthis (L.), Cannabis indica (L.) and Artemisia argyi (L.) against Brevicoryne brassicae and to conduct biochemical analysis by gas chromatography-mass spectrometry (GC-MS). The results suggested that when using ethanol, C. colocynthis produced a high dry yield (12.45%), followed by that of C. indica and A. argyi, which were 12.37% and 10.95%, respectively. The toxicity results showed that A. argyi was toxic to B. brassicae with an LC 50 of 3.91 mg mL -1 , followed by the toxicity of C. colocynthis and C. indica, exhibiting LC 50 values of 6.26 and 10.04 mg mL -1 , respectively, which were obtained via a residual assay; with a contact assay, the LC 50 values of C. colocynthis, C. indica and A. argyi were 0.22 mg mL -1 , 1.96 and 2.87 mg mL -1 , respectively. The interaction of plant extracts, concentration and time revealed that the maximum mortality based on a concentration of 20 mg L -1 was 55.50%, the time-based mortality was 55% at 72 h of exposure, and the treatment-based mortality was 44.13% for A. argyi via the residual assay. On the other hand, the maximum concentration-based mortality was 74.44% at 20 mg mL -1 , the time-based mortality was 66.38% after 72 h of exposure, and 57.30% treatment-based mortality was afforded by A. argyi via the contact assay. The biochemical analysis presented ten constituents in both the A. argyi and C. colocynthis extracts and twenty in that of C. indica, corresponding to 99.80%, 99.99% and 97% of the total extracts, respectively. Moreover, the detected caryophylleneonides (sesquiterpenes), α-bisabolol and dronabinol (Δ 9 -THC) from C. indica and erucylamide and octasiloxane hexamethyl from C. colocynthis exhibited insecticidal properties, which might be responsible for aphid mortality. However, A. argyi was evaluated for the first time against B. brassicae. It was concluded that all the plant extracts possessed significant insecticidal properties and could be introduced as botanical insecticides after field evaluations.

Retinal hypoperfusion injury is the pathophysiologic basis of ocular ischemic syndrome (OIS) which often leads to severe visual loss. In this study, we aimed to establish a rat model of retinal chronic hypoperfusion by bilateral common carotid artery occlusion (BCCAO) and observe changes in the retinal function and morphology. We found that model rats showed retinal arteriosclerosis, slight dilated retinal vein, small hemangiomas, hemorrhages, vascular segmental filling, and nonperfused areas after 2 weeks of BCCAO. In the model rats, the retinal circulation time was significantly prolonged by fluorescein fundus angiography (FFA), the latency of a and b waves was delayed and the amplitude was decreased significantly at each time point by electroretinogram (ERG), and the perfusion of the eyes continued to reduced. Morphologic and ultrastructural changes covered that the retinal ganglion cells (RGCs) presented obvious apoptosis and the thickness in the retinal layers were significantly thinner. Collectively, these findings suggested that BCCAO induced retinal hypoperfusion injury in the model rats, thus providing an ideal animal model for the study of OIS.

Few studies focused on the residue of thiamethoxam and its metabolite clothianidin on strawberry where it is widely used, despite this is essential to assess the potential food risk of thiamethoxam and its main metabolite clothianidin. In this study, the dissipation of thiamethoxam and its metabolite clothianidin during strawberry growth and jam-making process were assessed. The strawberry was sprayed with thiamethoxam based on the field application to investigate the dissipation of thiamethoxam as well as clothianidin formation. The half-life of thiamethoxam in strawberry was 9.0 days and the concentration of clothianidin in strawberry gradually increased from 0.55 to 11 μg/kg within 30 days. In addition, the amount of thiamethoxam decreased by 51.7% and clothianidin decreased by 40.2% during the homogenization process. The processing factor values of whole processing all less than 1 except simmering. This results from this study will not only help to understand the dissipation kinetics of thiamethoxam and clothianidin in the strawberry, but also facilitate to make more accurate risk assessments of them during strawberry jam making process.

Orthostatic lightheadedness in healthy young adults often leads to syncope in severe cases. One suggested underlying mechanism of orthostatic lightheadedness is a drop in transient blood pressure (BP); however, a decrease in BP does not always lead to a drop in cerebral blood flow (CBF) due to cerebral autoregulation (CA). We present a direct assessment method of CA using a multichannel continuous-wave near-infrared spectroscopy (CW-NIRS) device that measures the temporal changes in oxy- and deoxy-hemoglobin concentrations in the prefrontal cortex. Twenty healthy young adults were recruited. During the experiment, continuous beat-to-beat BP and heart rate were simultaneously measured during repetitive squat-stand maneuvers. We introduce a new metric termed 'time-derivative hemodynamic model (DHbT)', which is the time-derivative of total-hemoglobin concentration change that reflects the changes of cerebral blood volume and CBF. Although the absolute levels and the variations of systolic and diastolic BPs and mean arterial pressure showed no significant difference between the two groups, the proposed model showed a distinct difference in slope variation and response time of DHbT between the subjects with frequent symptom of orthostatic intolerance and the healthy control subjects. Thus, these results clearly demonstrate the feasibility of using CW-NIRS devices as a CA performance assessment tool.

Current Chinese national guidelines recommend routine screening for liver cancer in patients positive for HBsAg, irrespective of fibrosis status, age, or family history of liver cancer. We aim to evaluate whether the recommended screening strategy could reduce liver-cancer-specific mortality. We conducted a liver cancer mass screening trial in Xiaolan Town, Zhongshan City, China, among residents aged 35-64 years in 2012. All volunteers were offered serological testing for hepatitis B virus surface antigen (HBsAg). We proposed biannual screening using serum alpha-fetoprotein (AFP) and ultrasonography examination for subjects positive for HBsAg. Among 17,966 participants (26.2% of 68,510 eligible residents) who were free of liver cancer at baseline in 2012, we identified 57 incident cases of liver cancer within the first 4 years of follow-up (i.e., 43 among 2,848 HBsAg-positive participants and 14 among 15,118 HBsAg-negative participants), compared with 104 cases identified in non-participants (N = 50,544). A total of 207 participants had the recommended number of ultrasonography examinations (every 6 months) during the screening period. Compared with cases identified from non-participants, the cases arising among participants were more likely to be at early stage and had better survival than those among non-participants. However, we did not observe a reduction in liver cancer-specific mortality rate among participants (relative risk = 1.04, 95% confidence interval = 0.68, 1.58, P = 0.856). Our demonstration screening study does not show a reduction in liver cancer mortality within the first 4 years of follow-up according to current guidance in China, although long-term efficacy remains to be evaluated. Targeted surveillance among high-risk individuals as recommended by international guidelines, along with measures to improve compliance, should be evaluated in the Chinese population.

To investigate the value of hip circumference related indexes for identifying childhood hypertension. In 2011, 1,352 Han children aged 7-12 years were recruited in our study. Hypertension was defined as systolic blood pressure or diastolic blood pressure ≥95th percentile for all three screenings. We set the power value of the hip circumference/height x ratio (x = 0, 0.8, 1 and 1.5) and studied the association with blood pressure. Hip circumference, hip circumference/height 0.8 , hip circumference/height and hip circumference/height 1.5 all showed a positive correlation with systolic blood pressure and diastolic blood pressure(P < 0.05). Area under the curve (AUC) was used to evaluate the abilities of hip circumference related indexes. Hip circumference/height 0.8 , hip circumference/height and hip circumference/height1.5 were not superior to hip circumference. The present study demonstrates that hip circumference measurement is a helpful tool to detect the presence of hypertension in Han children 7-12 years old.

We developed a sensitive and rapid analytical method to determine the level of Ochratoxin A contamination in grapes, processed grape products and in foods of animal origin (a total of 11 different food matrices). A pretreatment that followed a "quick, easy, cheap, effective, rugged, and safe" protocol was optimized to extract Ochratoxin A from the matrices, and the extracted Ochratoxin A was then detected with the use of a highly sensitive ultra-performance liquid chromatography-tandem mass spectrometry system. Good linearities of Ochratoxin A were obtained in the range of 0.1-500 µg L -1 (correlation coefficient (R 2 ) > 0.9994 in each case). Mean recovery from the 11 matrices ranged from 70.3 to 114.7%, with a relative standard deviation ≤19.2%. The method is easy to use and yields reliable results for routine determination of Ochratoxin A in food products of grape and animal origin. In store-purchased foods and foods obtained from the field and wholesale suppliers, the Ochratoxin A concentration ranged from undetectable to 10.14 µg kg -1 , with the more contaminated samples being mainly those of processed grape products. Our results indicate that the necessity for regulation of and supervision during the processing of grape products.

Conventional far-field microscopy cannot directly resolve the sub-diffraction spatial distribution of localized surface plasmons in metal nanostructures. Using BaTiO 3 microspheres as far-field superlenses by collecting the near-field signal, we can map the origin of enhanced two-photon photoluminescence signal from the gap region of gold nanosphere dimers and gold nanorod dimers beyond the diffraction limit, on a conventional far-field microscope. As the angle θ between dimer's structural axis and laser polarisation changes, photoluminescence intensity varies with a cos 4 θ function, which agrees quantitatively with numerical simulations. An optical resolution of about λ/7 (λ: two-photon luminescence central wavelength) is demonstrated at dimer's gap region.

This study aimed to provide insights into the relationship between lipid levels and new-onset diabetes (NOD) in 14,864 Chinese hypertensive patients without diabetes (6056 men and 8808 women) aged 45-75 years from the China Stroke Primary Prevention Trial (CSPPT, led by Nanfang Hospital, Guangzhou, China). NOD (defined as fasting plasma glucose (FPG) ≥ 7.0 mmol/L at the end of study or self-reported physician diagnosis of diabetes or self-reported use of hypoglycemic agents during follow-up) was analyzed using multivariate analysis. Follow-up was censored on August 24, 2014. Among the 14,864 subjects, 1615 developed NOD (10.9%, men = 10.8% and women = 10.9%). Increased triglycerides (TG) [odds ratio (OR) = 1.18; 95% confidence interval (CI): 1.13-1.25, P < 0.001], TG/HDL (OR = 1.12; 95%CI: 1.08-1.17, P < 0.001), and decreased high density lipoprotein (HDL) (OR = 0.79; 95%CI: 0.67-0.93, P = 0.005) were associated with NOD, independently from age, gender, body mass index, clinical center, systolic blood pressure, diastolic blood pressure, FPG, smoking, and drinking. Compared to subjects with the methylenetetrahydrofolate reductase (MTHFR) 677 CC and TT genotypes, those with the CT genotype had a higher risk of NOD (OR = 1.54; 95%CI: 1.30-1.81, P for interaction = 0.044) in subjects with high TG. These results suggested that TG and TG/HDL were independent risk factors for NOD in this Chinese hypertensive population. HDL was a protective factor for NOD.

This study aimed to quantify the different effect of external cuff pressure on arterial volume distensibility between peripheral arteries with different compliance. 30 healthy subjects were studied with the arm at two positions (0° and 45° from the horizontal level) to introduce different compliance of arteries. The electrocardiogram and finger and ear photoplethysmograms were recorded simultaneously under five external cuff pressures (0, 10, 20, 30 and 40 mmHg) on the whole arm to obtain arterial volume distensibility. With the applied external cuff pressures of 10, 20, 30 and 40 mmHg, the overall changes in arterial volume distensibility referred to those without external pressure were 0.010, 0.029, 0.054 and 0.108% per mmHg for the arm at the horizontal level, and 0.026, 0.071, 0.170 and 0.389% per mmHg for the arm at 45° from the horizontal level, confirming the non-linearity between arterial volume distensibility and external pressure. More interestingly, the significant differences in arterial volume distensibility changes were observed between the two arm positions, which were 0.016, 0.043, 0.116 and 0.281% per mmHg (all P < 0.01). Our findings demonstrated that arterial volume distensibility of peripheral arm arteries increased with external pressure, with a greater effect for more compliant arteries.

Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage.

The functionality and viability of stored human red blood cells (RBCs) is an important clinical issue in transfusions. To systematically investigate changes in stored whole blood, the hematological properties of individual RBCs were quantified in blood samples stored for various periods with and without a preservation solution called citrate phosphate dextrose adenine-1 (CPDA-1). With 3-D quantitative phase imaging techniques, the optical measurements for 3-D refractive index (RI) distributions and membrane fluctuations were done at the individual cell level. From the optical measurements, the morphological (volume, surface area and sphericity), biochemical (hemoglobin content and concentration), and mechanical parameters (dynamic membrane fluctuation) were simultaneously quantified to investigate the functionalities and progressive alterations of stored RBCs. Our results show that stored RBCs without CPDA-1 had a dramatic morphological transformation from discocytes to spherocytes within two weeks which was accompanied by significant decreases in cell deformability and cell surface area, and increases in sphericity. However, the stored RBCs with CPDA-1 maintained their morphology and deformability for up to 6 weeks.

Cytochrome P450 3A (CYP3A) is the most abundant CYP450 enzyme in the liver and is involved in the metabolism of over 50% of xenobiotics. Our previous studies revealed that 2,2',4,4'-tetrabromodiphenyl ether (BDE47) could induce rat CYP3A1 expression, but the molecular basis remains unclear. Using in silico analysis, we identified a potential miR-23b recognition element (MRE23b) in the 3'-UTR region of CYP3A1 mRNA, which was verified by the luciferase assay. The miR-23b mimic and inhibitor significantly down- and up-regulated the expression of CYP3A1, respectively. Additionally, BDE47 significantly down-regulated the expression of miR-23b in rats and in hepatic H4IIE cells. Induction or blockage of CYP3A1 by a miR-23b inhibitor or mimic could correspondingly alter BDE47-induced expression of CYP3A1 and cytotoxicity in H4IIE cells. Furthermore, LV-anti-miR-23b significantly decreased endogenous levels of miR-23b and increased the expression and activity of CYP3A1 in rat liver. LV-anti-miR-23b also significantly increased the hydroxylated metabolites of BDE47 (3-OH-BDE47, 4-OH-BDE42, and 4'-OH-BDE49) in rat serum. In conclusion, we first found that BDE47 induced rat CYP3A1 expression by targeting the transcriptional regulation of miR-23b. This study helps provide a better understanding of CYP3A regulation and offers novel clues for the role of miRNAs in the metabolism and distribution of environmental pollutants.

BitterX is an open-access tool aimed at providing a platform for identifying human bitter taste receptors, TAS2Rs, for small molecules. It predicts TAS2Rs from the molecular structures of arbitrary chemicals by integrating two individual functionalities: bitterant verification and TAS2R recognition. Using BitterX, several novel bitterants and their receptors were predicted and experimentally validated in the study. Therefore, BitterX may be an effective method for deciphering bitter taste coding and could be a useful tool for both basic bitter research in academia and new bitterant discoveries in the industry.

The phylum candidatus Saccharibacteria formerly known as Candidate Division TM7 is a highly ubiquitous phylum with 16S rRNA gene sequences reported in soils, sediments, wastewater and animals, as well as a host of clinical environments. Here, the application of two taxon-specific primers on environmental and human-associated samples using bar-coded tag pyrosequencing revealed two new clades for this phylum to exist and we propose that the division consists of 2 monophyletic and 2 polyphyletic clades. Investigation into TM7 ecology revealed that a high proportion (58%) of phylotypes were sample specific, few were widely distributed and of those most widely distributed all belonged to subdivision 3. Additionally, 50% of the most relatively abundant phylotypes observed were also subdivision 3 members. Community analysis showed that despite the presence of a high proportion of unique phylotypes, specific groups of samples still harbor similar TM7 communities with samples clustering together. The lack of relatively abundant phylotypes from subdivisions 1, 2 and 4 and the presence of very few cosmopolitan members' highlights not only the site specific nature of this phylum but provides insight into why the majority of studies into TM7 have been biased towards subdivision 3.