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Recent studies indicate that the extent of perceived motion smear is attenuated asymmetrically during smooth pursuit eye movements, based on the relative directions of the target and eye motion. We conducted two experiments to determine if the reduction of perceived smear during pursuit might be associated with an acceleration of the temporal impulse response function (TIRF). In Experiment 1, two-pulse increment sensitivity was determined during fixation and rightward pursuit for sequential flashes of a long horizontal line, presented with stimulus-onset asynchronies between 5.9 and 234 ms. In Experiment 2, temporal contrast sensitivity was measured during fixation and rightward pursuit for a vertical 1 cpd grating with retinal image velocities between 4 and 30 Hz. During pursuit, grating motion was either in the same or the opposite direction as the eye movement. TIRFs were modeled as the impulse responses of a second-order, low-pass linear system, fit to the two-pulse increment sensitivity data by an optimization procedure and to the temporal contrast sensitivity results by iterative Fourier synthesis. The results indicate that the natural temporal frequency of the fitted TIRFs was approximately 10% higher during pursuit than fixation. In Experiment 2, the increased natural frequency of the TIRF was restricted to the condition in which the grating moved spatially in the opposite direction of the pursuit eye movement. The results are consistent with the hypothesis that extra-retinal signals reduce the extent of perceived motion smear during pursuit, in part by increasing the speed of visual processing preferentially for one direction of image motion. [ABSTRACT FROM AUTHOR]

Objective: To comparing the accuracy of pedicle screw placement in posterior surgery for adult degenerative scoliosis (ADS) between robotic-assisted and traditional freehand techniques. Methods: This retrospective study included 92 patients with ADS who underwent posterior spinal surgery at the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital) between March 2019 and December 2023. There were 19 males and 73 females with a mean age of (63.6±9.8) years. The patients were divided into two groups based on the technique used for pedicle screw placement: robot-assisted group (34 cases) and manual group (58 cases). Operative duration, intraoperative blood loss, facet joint violation, postoperative complications, magnitude of curve correction, visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores preoperatively, 1 week postoperatively, and 1 month postoperatively were compared and analyzed between the two groups. The Gertzbein-Robbins classification criteria was used to assess the accuracy of screw placement. Results: Differences in baseline data, operative duration, intraoperative blood loss, magnitude of curve correction, and VAS and ODI scores preoperatively, 1 week postoperatively, and 1 month postoperatively between the two groups exhibited no statistically significant differences (all P >0.05). The accuracy of pedicle screw placement in the robot-assisted group was significantly higher than that in the manual group [90.9% (416/458) vs 80.1% (697/870), P <0.001]. In terms of surgical segments, in T 1 -T 12 and L 1 -S 1 segments, the accuracy of pedicle screw placement in the robot group were both significantly higher than those in the control group [91.5% (130/142) vs 77.8% (186/239), P =0.001; 90.3% (271/300) vs 80.8% (502/621), P <0.001]. However, no significant differences was observed in the accuracy of S 2 -alar-iliac (S 2 AI) screw placement between the two groups [90.0%(9/10) vs 93.8%(15/16), P =0.727]. Moreover, no significant differences was found in the deviation direction of the cortical screw penetration between both groups ( P =0.133). Significant differences were observed in the accuracy of screw placement between the Nash Moe 2 and 3 vertebral bodies in the robot group compared with those in the control group [88.9% (88/99) vs 71.0% (115/162), P =0.001; 89.2% (83/93) vs 60.2% (68/113), P <0.001]. Additionally, the incidence and grade of facet joint violation in the manual group were both significantly higher than those in the robot-assisted group (both P <0.001). No statistically significant differences was identified in postoperative complications between the two groups ( P =0.841). Conclusion: It suggests that robot-assisted pedicle screw placement in posterior surgery for patients with ADS can significantly improve the accuracy of screw placement and reduce the incidence of facet joint violation.

Abstract: The aim of this study was to compare the accuracies of cognitive fusion-guided targeted biopsy (TB), systematic biopsy (SB), and combined TB+SB for the detection of prostate cancer (PCa) and clinically significant PCa (csPCa) in males with lesions detected by magnetic resonance imaging (MRI). We conducted a retrospective analysis of individuals who underwent prostate biopsy at Peking University People's Hospital (Beijing, China), with an emphasis on patients with both transrectal TB and SB. The main objective was to determine the precisions of SB, TB, and TB+SB for diagnosing PCa and csPCa. We also evaluated the detection rates of TB, SB, TB+ipsilateral-SB (ipsi-SB), TB+contralateral-SB (contra-SB), and TB+SB for PCa and csPCa in patients with unilateral MRI lesions. We compared the diagnostic yields of the various biopsy schemes using the McNemar's test. A total of 180 patients were enrolled. The rates of PCa detection using TB, SB, and TB+SB were 52.8%, 62.2%, and 66.7%, respectively, and the corresponding rates for csPCa were 46.1%, 56.7%, and 58.3%, respectively. Among patients with unilateral MRI lesions, the PCa detection rates for TB, SB, TB+ipsi-SB, TB+contra-SB, and TB+SB were 53.3%, 64.8%, 65.6%, 61.5%, and 68.0%, respectively. TB+ipsi-SB detected 96.4% of PCa and 95.9% of csPCa cases. These findings suggest that the combination of TB+SB has better diagnostic accuracy compared with SB or TB alone. For patients with unilateral MRI lesions, the combination of TB+ipsi-SB may be suitable in clinical settings., (Copyright © 2024 Copyright: ©The Author(s)(2024).)

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide, the global burden of which is rising. It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults. To develop a focused screening plan and treatment for Chinese adults with prediabetes, it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age., Aim: To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China., Methods: The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008. A thorough evaluation was conducted. Individuals with prediabetes were categorized into two groups based on age. Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years. Random forest was established in both age groups. SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution., Results: In total, 6948 people were diagnosed with prediabetes in this study. In pre-diabetes, prevalences of CVD were 5 (0.29%) in the younger group and 148 (2.85%) in the older group. Overall, 11.11% of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years. In the younger age group, the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle, whereas in the older age group, resident status was more closely linked., Conclusion: The susceptibility to CVD is age-specific in newly diagnosed prediabetes. It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

As traditional per and polyfluoroalkyl substances (PFAS) are phased out, emerging PFAS are being developed and widely used. However, little is known about their properties, including persistence, bioaccumulation, and toxicity (PBT). Screening for emerging PFAS relies on available chemical inventory databases. Here, we compiled a database of emerging PFAS obtained from nontargeted analysis and assessed their PBT properties using machine learning models, including qualitative graph attention networks, Insubria PBT Index and quantitative EAS-E Suite, VEGA, and ProTox-II platforms. Totally 282 homologues (21.8% of emerging PFAS) were identified as PBT based on the combined qualitative and quantitative prediction, in which 140 homologues were detected in industrial and nonbiological/biological samples, belong to four categories, i.e. modifications of perfluoroalkyl carboxylic acids, perfluoroalkane sulfonamido substances, fluorotelomers and modifications of perfluoroalkyl sulfonic acids. Approximately 10.1% of prioritized emerging PFAS were matched to chemical vendors and 19.6% to patents. Aqueous film-forming foams and fluorochemical factories are the predominant sources for prioritized emerging PFAS. The database and screening results can update the assessment related to legislative bodies such as the US Toxic Substances Control Act and the Stockholm Convention. The combined qualitative and quantitative machine learning models can provide a methodological tool for prioritizing other emerging organic contaminants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Because of the unstable wastewater quantity and quality, the biological treatment efficiency of digested effluent was not as expected. A convenient and effective way was eagerly required to improve the efficiency of biological treatment. By sheet iron addition (R 1 ), the COD and TN removal efficiencies under continuous flow condition increased by 59% and 37% respectively. The bulk pH maintained at around 7.5 which benefited most bacteria, while in the control (R 0 , without sheet iron addition) the pH decreased to 5.0. Both chemical and bio-removal of COD existed in R 1 , but the chemical removal dominated (63.71%). The enhanced COD removal efficiency came from the chemical oxidation by Fe 3+ (47.43%) and Fe 0 (10.86%). For the TN removal, the enhancement mainly came from the improvement of anammox activity by Fe 3+ (14.87%), the bio-oxidation of ammonium with Fe 3+ as electron acceptor (8.78%), and the bio-reduction of nitrate/nitrite with Fe 2+ and H 2 as electron donor (35.76%). By the first-order kinetic fitting analysis, the COD and TN removal rate in R 1 was higher than that in R 0 . Thus, for a quick and high COD and TN removal from digested effluent, the addition of Fe 0 /Fe 2+ /Fe 3+ was suggested, and the best form should be Fe 0 (e.g., sheet iron). The addition of sheet iron reduces the cost of nitrogen removal and improves the efficiency of COD and TN removal. Comparing with the combined processes, this novel approach has potential advantages with simple operation and high efficiency. It endows the biological process much broader application in digested effluent treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Jiuzhuan Huangjing Pills (JHP) composed of Polygonati Rhizoma (PR) and Angelicae Sinensis Radix (ASR) remedied mitochondria to cure metabolic dysfunction-associated fatty liver disease (MAFLD). However, a comparison of the anti-MAFLD ability between JHP prescription and PR and ASR single-medicines in MAFLD has not been performed, and the action mechanisms and substances remain unknown. Our results show that JHP, PR and ASR decreased serum and liver lipid levels. The effects of JHP were stronger than those of PR and ASR. JHP, PR and ASR afforded protection to mitochondrial ultrastructure, and regulated oxidative stress and energy metabolism in mitochondria. JHP also regulated the expression of β-oxidation genes, which were not regulated by PR and ASR. JHP-, PR- and ASR-derived components in mitochondrial extracts regulated oxidative stress, energy metabolism, and β-oxidation gene expression and alleviated cellular steatosis. Four, six and eleven compounds were identified in mitochondrial extracts from PR-, ASR- and JHP-treated rats, respectively. The data suggest that JHP, PR and ASR alleviated MAFLD by remedying mitochondria, while the ability of JHP was stronger than that of PR and ASR, which was involved with the β-oxidation promotion. The compounds identified may be the main ingredients in the three extracts active in MAFLD improvement., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a severe threat to human health. Polygonum multiflorum (PM) has been proven to remedy mitochondria and relieve MAFLD, but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear., Aim: To research the active ingredients of PM adjusting mitochondria to relieve high-fat diet (HFD)-induced MAFLD in rats., Methods: Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms. The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats (mitochondrial pharmacology). PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry (mitochondrial pharmacochemistry). The abilities of PM-derived monomer and monomer groups were evaluated by the adipocyte model and MAFLD mouse model, respectively., Results: PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD. PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis. Eight chemicals were found in the liver mitochondria of PM-administrated rats. The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated., Conclusion: PM restored mitochondrial structure and function and alleviated MAFLD, which may be associated with the remedy of oxidative stress and energy production. The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD. Thus, PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction. Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease that currently lacks approved pharmacological treatment options. The mechanisms and active ingredients of Polygonum cuspidatum (PC) that regulate the mitochondria to relieve MAFLD have not been assessed. Thus, this study was designed to explore the bioactive components of PC extract in regulating mitochondria to alleviate high-fat diet-induced MAFLD using mitochondrial pharmacology and pharmacochemistry. Our results demonstrate that PC protected the mitochondrial ultrastructure and inhibited oxidative stress and energy metabolism disorder in the liver mitochondria. Furthermore, PC-derived components in the liver mitochondria attenuated oxidative stress and restored the energy metabolism of fat emulsion-induced steatosis in L02 cell. Sixteen compounds were identified in the liver-mitochondrial extracts of PC-treated rats. The antisteatotic effects of three identified monomers and anti-MAFLD ability of the monomer group were confirmed. Collectively, our data suggest that the extract of PC can alleviate lipid metabolism disorder in MAFLD by protecting the mitochondrial ultrastructure, reducing oxidative stress injury, and promoting energy metabolism. The sixteen identified compounds were potentially the main effective ingredients of PC in treating MAFLD. Thus, PC shows potential in treating MAFLD and related mitochondrial dysfunction. The proposed strategy to identify the ingredients of herbal medicines based on mitochondrial pharmacology and pharmacochemistry presents a new approach in exploring the pharmacodynamic components of herbal medicines that regulate mitochondria in preventing and treating diseases., Competing Interests: Conflict of Interest Statement The authors have no conflicts of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Prediabetes risk assessment models derived from large sample sizes are scarce., Aim: To establish a robust assessment model for prediabetes and to validate the model in different populations., Methods: The China National Diabetes and Metabolic Disorders Study (CNDMDS) collected information from 47325 participants aged at least 20 years across China from 2007 to 2008. The Thyroid Disorders, Iodine Status and Diabetes Epidemiological Survey (TIDE) study collected data from 66108 participants aged at least 18 years across China from 2015 to 2017. A logistic model with stepwise selection was performed to identify significant risk factors for prediabetes and was internally validated by bootstrapping in the CNDMDS. External validations were performed in diverse populations, including populations of Hispanic (Mexican American, other Hispanic) and non-Hispanic (White, Black and Asian) participants in the National Health and Nutrition Examination Survey (NHANES) in the United States and 66108 participants in the TIDE study in China. C statistics and calibration plots were adopted to evaluate the model's discrimination and calibration performance., Results: A set of easily measured indicators (age, education, family history of diabetes, waist circumference, body mass index, and systolic blood pressure) were selected as significant risk factors. A risk assessment model was established for prediabetes with a C statistic of 0.6998 (95%CI: 0.6933 to 0.7063) and a calibration slope of 1.0002. When externally validated in the NHANES and TIDE studies, the model showed increased C statistics in Mexican American, other Hispanic, Non-Hispanic Black, Asian and Chinese populations but a slightly decreased C statistic in non-Hispanic White individuals. Applying the risk assessment model to the TIDE population, we obtained a C statistic of 0.7308 (95%CI: 0.7260 to 0.7357) and a calibration slope of 1.1137. A risk score was derived to assess prediabetes. Individuals with scores ≥ 7 points were at high risk of prediabetes, with a sensitivity of 60.19% and specificity of 67.59%., Conclusion: An easy-to-use assessment model for prediabetes was established and was internally and externally validated in different populations. The model had a satisfactory performance and could screen individuals with a high risk of prediabetes., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Gamma-aminobutyric acid (GABA) is a nonproteinogenic amino acid that plays vital roles in plant growth and developmental processes. However, its role in regulating potato sprouting is unknown. Therefore, the physiological and molecular mechanisms underlying the sprouting process were assessed, and we found that GABA promoted sprouting after treatment for 50 d. In addition, the GABA and soluble sugar contents increased while the starch content decreased. To study the molecular mechanism by which exogenous GABA accelerates tuber sprouting, comparative proteomic analysis of tuber bud eyes was performed after GABA treatment for 48 h. Further analysis revealed 316 differentially abundant proteins (DAPs) that are mainly involved in fatty acid and sugar metabolism and cutin, suberin and wax biosyntheses. The qRT‒PCR results suggested that the GABA transaminase 2 (GABA-T2) and GABA-T3 expression levels showed the greatest decrease at 30 d of storage. Peroxidase 42 (StPOD42) expression showed the greatest increase at 30 d. Overexpression of StPOD42 in potato was found to promote tuber sprouting. Our results provide new insights into the role of GABA in regulating the sprouting process and indicate that StPOD42 is a target gene for molecular breeding to modulate potato sprouting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: As of 2022, inactivated SARS-CoV-2 vaccines had been used in more than 91 countries. However, limited real world information was available on the immune responses of the inactivated SARS-CoV-2 vaccine., Methods: We used SARS-CoV-2 pseudovirues to determine the neutralizing antibodies (NAbs) to wild type and several global variants and utilized enzyme-linked immunosorbent assay to investigate IFN-γ-secreting T-cell responses to SARS-CoV-2 among 240 vaccinated individuals after two doses of inactivated vaccine in China., Results: A majority of the vaccinated (>90%) developed robust NAbs and T-cell responses to SARS-CoV-2 in the first two months after the second dose. After six months, only 37.0% and 44.0% of vaccinees had NAbs and T-cell immunity to SARS-CoV-2, respectively. Immune serum retained most of its neutralizing potency against the Alpha and Iota variants, but lost significant neutralizing potency against the Beta, Kappa, Delta, and Omicron variants. Only 40% of vaccine-sera retained low-level neutralization activities to Omicron, with a 14.7-fold decrease compared to the wild type., Conclusion: The inactivated SARS-CoV-2 vaccine stimulated robust NAbs and T-cell immune responses in the first two months after the second dose but the immune effect dropped rapidly, highlighing that a third dose or additional booster immunizations may be required to boost immunity against SARS-CoV-2.

Objective: To analyze the risk factors of persistent hypertension in patients who underwent adrenalectomy for primary aldosteronism and to evaluate the predictive value of the aldosteronoma resolution score (ARS) scoring system for surgical outcomes of adrenalectomy for primary aldosteronism., Methods: We reviewed the clinical characteristics of patients who underwent adrenalectomy for primary aldosteronism from 2018 to 2021 at Peking University People' s Hospital to recognize risk factors of uncured hypertension after surgery. Based on the patient' s clinical outcomes, the patients were divided into complete success group and partial/absent success group. Risk factors for persistent hypertension were analyzed. The value of the ARS scoring system was assessed by the area under the curve ( AUC )., Results: In this study, 112 patients were included. Most of the patients benefited from the surgery for 94.6% were a complete or partial clinical success after follow-up for at least 6 months. According to postoperative hypertension status, the patients were divided into complete success group (51 cases) and partial/absent success group (61 cases). There were statistical differences between the two groups in age, body mass index (BMI), waist circumference, duration of hypertension, number of preoperative antihypertension medications, preoperative systolic blood pressure, history of diabetes, history of cardiovascular and cerebrovascular diseases, serum creatinine, estimated glomerular filtration rate(eGFR), high-density lipoprotein cholesterol and triglyceride. Logistic regression analysis showed that age ( OR =1.111, 95% CI : 1.029-1.199), waist circumference ( OR =1.073, 95% CI: 1.013-1.137), pre-operative systolic blood pressure ( OR =1.033, 95% CI : 1.008-1.060) and history of cardiovascular and cerebrovascular diseases ( OR =16.061, 95% CI : 1.312-196.612) were the risk factors for uncured hypertension in primary aldosteronism patients after surgery, but female gender not. The median ARS in the complete success group was 4 and in the partial/absent success group, it was 2. Among the patients with ARS of 4-5, the cure rate of hypertension was 76.5%. The area under the curve of ARS was 0.743., Conclusion: The history of cardiovascular and cerebrovascular diseases is a significant risk factor for persistent hypertension after surgery in primary aldosteronism patients. ARS scoring system has a certain value in predicting the postoperative hypertension status of primary aldosteronism patients. However, further research is still needed on a prediction model for surgical outcomes of primary aldosteronism which is more suitable for the Chinese population is still needed.

Objective: To investigate the effects of MetS on the prognosis of patients with clear cell renal cell carcinoma (ccRCC)., Methods: Clinical and pathological data and the laboratory test of ccRCC 342 patients with diverticular stones who underwent ccRCC who underwent radical or partial nephrectomy were retrospectively collected and analyzed.The patients were divided into MetS group and non-MetS group, and the subgroups were defined according to the tumor size. The overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) of the two groups were analyzed by univariate Cox analysis, and the subgroup analyses were also performed. Kaplan-Meier survival curve and survival analysis for OS, CSS, and PFS of the two groups and the subgroups were conducted., Results: Univariate Cox analysis showed that MetS was a protective factor of postoperative OS [hazard ratio ( HR )=0.551, 95% CI : 0.321-0.949, P =0.031], CSS ( HR =0.460, 95% CI : 0.234-0.905, P =0.025), and PFS (HR 0.585, 95% CI : 0.343-0.998, P =0.049) in the patients with ccRCC. In the subgroup with tumor size≤4 cm, MetS was not associated with postoperative OS ( HR =0.857, 95% CI : 0.389-1.890, P =0.702), CSS ( HR =1.129, 95% CI : 0.364-3.502, P =0.833), and PFS ( HR =1.554, 95% CI : 0.625-3.864, P =0.343). In the subgroup with tumor size>4 cm, Mets was a protective factor of postoperative OS (HR=0.377, 95% CI : 0.175-0.812, P= 0.013), CSS ( HR =0.280, 95% CI : 0.113-0.690, P =0.006), and PFS ( HR =0.332, 95% CI : 0.157-0.659, P =0.002); Obesity was a protective factor of postoperative CSS ( HR =0.464, 95% CI : 0.219-0.981, P =0.044), and PFS ( HR =0.445, 95% CI : 0.238-0.833, P =0.011). Kaplan-Meier survival analysis showed that the long-term survival of patients with MetS was better than those without MetS in OS ( P =0.029), CSS ( P =0.021), and PFS ( P= 0.046); for the subgroup with tumor size≤4 cm, there was no significant difference in postoperative OS ( P =0.702), CSS ( P =0.833), and PFS ( P =0.339) between patients with and without MetS; For the subgroup with tumor size>4 cm, the OS ( P =0.010), CSS ( P= 0.003), and PFS ( P =0.001) of patients with MetS were better than those without MetS., Conclusion: MetS was a protective factor of postoperative OS, CSS, and PFS in the patients with ccRCC, which was more obvious in subgroup with tumor size>4 cm. And obesity, the component of MetS, was correlated with postoperative OS and CSS.

Tear resistance is of vital importance in the fabrication and application of synthetic soft materials. However, the paradox of simultaneously improving the tearing energy and elasticity remains a huge challenge for conventional approaches. Here, inspired by the skin, we successfully constructed an extraordinary tear-resistant, superelastic elastomer by the introduction of nanosized polycyclodextrin into the elastomer network to form a slidable interpenetrate double network structure. The tearing energy of the SDEP elastomer is up to 274 KJ/m 2 , which is comparable to metals and alloys and increased more than 100 times compared with the chemically cross-linked elastomer. The fracture strain exceeded 3300%, which is hardly achieved by other materials with high tearing energy. This comprehensive improvement of antitearing and super elasticity property was achieved by (i) a slide ring effect to dissipate energy and blunt a crack tip; (ii) straightening and reorientation of the slidable double network to deflect the advancing of a crack tip; (iii) a double network sharing the load. These results provide a novel strategy to fabricate elastic, tear-resistant soft material, which may contribute to the practical application as tear-resistant flexible electronics and irregular-shaped stretchable devices.

Polyhydroxyalkanoates (PHA) are a family of biodegradable and biocompatible plastics with potential to replace petroleum based plastics. Diversity of PHA monomer structures provides flexibility in material properties to suit more applications. In this study, 5-hydroxyvalerate (5HV) synthesis pathway was established based on intrinsic alcohol/aldehyde dehydrogenases. The PHA polymerase cloned from Cupriavidus necator functions to polymerize 5HV into its copolymers in ratios ranging from 8% to 32%. Elastic copolymer P(85% 3HB-co-15% 5HV) was generated with an elongation at break and a Young's modulus of 1283% and 73.1 MPa, respectively. The recombinant H. bluephagenesis was able to convert various diols including 1, 3-propanediol, 1, 4-butanediol and 1, 5-pentanediol into PHA, leading to 13 PHA polymers including transparent P(53% 3HB-co-20% 4HB-co-27% 5HV) and sticky P(3HB-co-3HP-co-4HB-co-5HV). The engineered H. bluephagenesis was successfully grown in a 7-L bioreactor to produce the highly elastic P(85% 3HB-co-15% 5HV) and the sticky P(3HB-co-3HP-co-4HB-co-5HV), demonstrating their potential for industrial scale-up., (Copyright © 2022 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

The nonunion following a fracture is associated with severe patient morbidity and economic consequences. Currently, accumulating studies are focusing on the importance of macrophages during fracture repair. However, details regarding the process by which macrophages facilitate endochondral ossification (EO) are largely unknown. In this study, we present evidence that apoptotic chondrocytes (ACs) are not inert corpses awaiting removal, but positively modulate the osteoinductive ability of macrophages. In vivo experiments revealed that fatty acid (FA) metabolic processes up-regulated following EO. In vitro studies further uncovered that FAs derived from ACs are taken up by macrophages mainly through macrophage scavenger receptor 1 (MSR1). Then, our functional experiments confirmed that these exogenous FAs subsequently activate peroxisome proliferator-activated receptor α (PPARα), which further facilitates lipid droplets generation and fatty acid oxidation (FAO). Mechanistically, elevated FAO is involved in up-regulating the osteoinductive effect by generating BMP7 and NAD + /SIRT1/EZH2 axis epigenetically controls BMP7 expression in macrophages cultured with ACs culture medium. Our findings advanced the concept that ACs could promote bone regeneration by regulating metabolic and function reprogram in macrophages and identified macrophage MSR1 represents a valuable target for fracture treatments., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Many patients with ocular myasthenia gravis (OMG) progress to generalized disease within the first 2 years of the onset of ocular symptoms. Several retrospective studies have identified risk factors associated with generalization, however these studies included patients on immunosuppression therapy or those undergoing thymectomy, which may reduce the generalization risk. In this study we explored the risk factors for generalization in non-immunosuppressed and non-thymectomized patients with OMG., Methods: Data from patients with OMG treated at seven tertiary hospitals in China were retrospectively reviewed. Clinical characteristics, including sex, age at onset, symptoms at onset, comorbid autoimmune diseases, neostigmine test response, repetitive nerve stimulation (RNS) findings, presence of serum anti-acetylcholine receptor antibody (AChR-Ab), and thymic status based on radiological and pathological studies, were collected. The main outcome measure was disease generalization. The follow-up period was defined as the date of ocular symptom onset to the date of confirmation of generalization or immunotherapy initiation, or last follow-up (defined as 60 months). The Cox proportional hazards model was used to assess the risk factors for generalization., Results: Overall, 572 patients (269 women) were eligible for inclusion in the analysis, of whom 144 developed generalization. The mean (standard deviation) onset age was 45.5 (19.8) years, and the median (interquartile range) follow-up period was 14.5 (7.0-47.3) months. Multivariable Cox regression analysis demonstrated that both early-onset (adjusted hazard ratio [aHR] 5.34; 95% confidence interval [CI] 1.64-17.36; p = 0.005) and late-onset (aHR 7.18; 95% CI 2.22-23.27; p = 0.001) in adulthood, abnormal RNS findings (aHR 3.01; 95% CI 1.97-4.61; p < 0.001), seropositivity for AChR-Ab (aHR 2.58; 95% CI 1.26-5.26; p = 0.01), and thymoma (aHR 1.62; 95% CI 1.05-2.49; p = 0.03) were independently associated with increased risk of generalization., Conclusion: The risk of generalization increased significantly in patients with adult-onset OMG, abnormal RNS findings, seropositivity for AChR-Ab, and thymoma, suggesting that these risk factors may predict OMG generalization., (© 2021. The Author(s).)

Microbial conversion of methane to electricity, fuels, and liquid chemicals has attracted much attention. However, due to the low solubility of methane, it is not considered a suitable substrate for microbial fuel cells (MFCs). In this study, a conductive fiber membrane (CFM) module was constructed as the bioanode of methane-driven MFCs, directly delivering methane. After biofilm formation on the CFM surface, a steady voltage output of 0.6 to 0.7 V was recorded, and the CFM-MFCs obtained a maximum power density of 64 ± 2 mW/m 2 . Moreover, methane oxidation produced a high concentration of intermediate acetate (up to 7.1 mM). High-throughput 16S rRNA gene sequencing suggests that the microbial community was significantly changed after electricity generation. Methane-related archaea formed a symbiotic consortium with characterized electroactive bacteria and fermentative bacteria, suggesting a combination of three types of microorganisms for methane conversion into acetate and electricity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Cerebral palsy (CP) is a neurodevelopmental disorder caused by a brain injury resulting in poor coordination and motor control deficits, which is one of the most common physical disabilities in children. CP brings a heavy burden on families and society and becomes a significant public health issue. In recent years, hydrotherapy, and transcranial direct current stimulation (tDCS) as a physical therapy for CP is developing rapidly. When hydrotherapy and tDCS are used to treat separately, it has positive therapeutic effect in children with CP. The development of new therapies in combination with physical rehabilitation approaches is critical to optimize functional outcomes. tDCS has attracted interest in this context, because of significant functional improvements have been demonstrated in individuals with brain injuries after a short period of cerebral stimulation. Since the onset of this work, tDCS has been used in combination with constraint-induced therapy, virtual reality therapy to potentiate the treatment effect. Up to now, there are no studies on the effect of a combined application of hydrotherapy and tDCS in children with CP. We will conduct a 2-arm parallel clinical trial to investigate the effect of a combined application of tDCS and hydrotherapy., Methods and Analysis: This study is an outcome assessor and data analyst-blinded, randomized, controlled superiority trial during the period from October 2021 to December 2023. CP patients meeting the inclusion criteria will be allocated in a 1:1 ratio into the treatment group (hydrotherapy plus tDCS), or the control group (treatment as usual). All participants will receive 30 sessions of treatment over 10 weeks. The primary outcomes will be the difference in the Gross Motor Function Assessment and Pediatric Balance Scale during rest and activity. The secondary outcomes will be the difference in adverse effects between the control and treatment groups., Conclusions: This study aims to estimate the efficacy of a combined application of tDCS and hydrotherapy in patients with CP., Trial Registration: This study protocol was registered in Chinese ClinicalTrials.gov, ID: ChiCTR2100047946., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Since the successful preparation of few-layer transition metal carbides from three-dimensional MAX phases in 2011, MXenes (known as a family of layered transition metal carbides, nitrides, and carbonitrides) have been intensively studied. Though MXenes have been adopted as active materials in many applications, issues including aggregation and restacking are likely to hamper their potential applications. In order to address these prevailing challenges, the concept of MXene/carbon nanotube (CNT) hybrids was proposed initially in 2015, where CNTs were incorporated as the spacers and conductive additives. Ever since, MXene/CNT hybrids with different architectures have been synthesized by a number of methods and applied in numerous fields. Herein, after the discussion about general synthesis approaches, architectures, and properties of the hybrids, this Review summarized the recent advances in the application of MXene/CNT hybrids in energy storage devices, sensors, electrocatalysis, electromagnetic interference shielding, and water treatment, in which the function of individual components was clarified. In the end, the current research trend in this field were discussed and several technical issues were highlighted along with some suggestions on future research directions., (© 2021 Wiley-VCH GmbH.)

PINK1 , also known as PARK6 , is a PTEN -induced putative kinase 1 that is encoded by nuclear genes. PINK1 is ubiquitously expressed and regulates mitochondrial function and mitophagy in a range of cell types. The dysregulation of PINK1 is associated with the pathogenesis and development of mitochondrial-associated disorders. Many natural products could regulate PINK1 to relieve PINK1-associated diseases. Here, we review the structure and function of PINK1, its relationship to human diseases, and the regulation of natural products to PINK1. We further highlight that the discovery of natural PINK1 regulators represents an attractive strategy for the treatment of PINK1-related diseases, including liver and heart diseases, cancer, and Parkinson's disease. Moreover, investigating PINK1 regulation of natural products can enhance the in-depth comprehension of the mechanism of action of natural products., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Yan-Qin Li et al.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common global chronic liver disease. Jiuzhuan Huangjing Pills (JHP) have been used for the treatment of human disease for over a thousand years, but their efficacy and underlying mechanism(s) of action against MAFLD are unknown. We investigated the alleviating effects of JHP on high-fat diet (HFD)-induced MAFLD., Methods: In vitro and in vivo methods were used to evaluate the effects of JHP on MAFLD. L02 adipocyte models were induced by fat emulsion and adipocytes were treated with JHP for 24 h. MAFLD rat models were induced by HFD-feeding and were intragastrically administered JHP for 12 weeks. Changes in fat accumulation, L02 cell damage, body weight, food intake, histological parameters, organ indexes, biochemical parameters, and mitochondrial indicators including ultrastructure, oxidative stress, energy metabolism, and fatty acid metabolism were investigated., Results: JHP attenuated the increase in levels of total cholesterol, triglyceride, low density lipoprotein cholesterol, alanine transaminase, and aspartate transaminase levels, and significantly increased high density lipoprotein cholesterol. JHP up-regulated levels of glutathione (GSH) and superoxide dismutase (SOD), and down-regulated malondialdehyde (MDA). JHP afforded protection to the mitochondrial ultrastructure, and inhibited the HFD-induced increase in MDA and the reduction of SOD, GSH, ATP synthase, and complex I and II, in liver mitochondria. JHP regulated the expression of β-oxidation genes, including acyl-CoA dehydrogenase, cyl-CoA dehydrogenase long chain, carnitine palmitoyltransferase 1A, carnitine palmitoyltransferase 1B, peroxisomal proliferator-activated receptor-gamma coactivator-1α and peroxide proliferator activated receptor α., Conclusion: JHP alleviates HFD-induced MAFLD through the protection of mitochondrial function., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production. Halomonas bluephagenesis shows the potential as a chassis for competitive bioproduction of various chemicals due to its ability to grow under an open, unsterile and continuous process. Here, we report the strategy for producing 3HP and its copolymer poly(3-hydroxybutyrate-co-3-hydroxypropionate) (P3HB3HP) by the development of H. bluephagenesis. The transcriptome analysis reveals its 3HP degradation and synthesis pathways involving endogenous synthetic enzymes from 1,3-propanediol. Combing the optimized expression of aldehyde dehydrogenase (AldD Hb ), an engineered H. bluephagenesis strain of whose 3HP degradation pathway is deleted and that overexpresses alcohol dehydrogenases (AdhP) on its genome under a balanced redox state, is constructed with an enhanced 1.3-propanediol-dependent 3HP biosynthetic pathway to produce 154 g L -1 of 3HP with a yield and productivity of 0.93 g g -1 1,3-propanediol and 2.4 g L -1 h -1 , respectively. Moreover, the strain could also accumulate 60% poly(3-hydroxybutyrate-co-32-45% 3-hydroxypropionate) in the dry cell mass, demonstrating to be a suitable chassis for hyperproduction of 3HP and P3HB3HP.

Ferrous ion can be used as electron donor for denitrification in the ferrous ion-dependent nitrate removal (FeNiR). To prevent the FeNiR performance decrease caused by iron encrustation, a modified FeNiR process with batch sludge replacement was developed. Based on the decay kinetics of sludge mass and sludge activity, the sludge retention time (SRT) was determined as 40 days in the modified FeNiR process. To keep the FeNiR rate at 0.70 kg-N/(m 3 ·d), the sludge replacement amount was 25% of total sludge every 10 days. The FeNiR efficiency stabilized around 70%. The batch sludge replacement could be an effective method to offset the active sludge decay caused by iron encrustation, and therefore led to the good FeNiR performance. The wasted FeNiR sludge was found to adsorb phosphate at a rate of 0.9 mg-P/(g VS min). The modified FeNiR process was proposed to be coupled with phosphate removal, achieving the co-removal of nitrate and phosphate. The coupled technology is promising due to the less consumption of resources and energy, as well as the less production of excessive sludge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mitochondria are the 'engine' of cells. Mitochondrial dysfunction is an important mechanism in many human diseases. Many natural products could remedy the mitochondria to alleviate mitochondria-involved diseases. In this review, we summarized the current knowledge of the relationship between the mitochondria and human diseases and the regulation of natural products to the mitochondria. We proposed that the development of mitochondrial regulators/nutrients from natural products to remedy mitochondrial dysfunction represents an attractive strategy for a mitochondria-involved disorder therapy. Moreover, investigating the mitochondrial regulation of natural products can potentiate the in-depth comprehension of the mechanism of action of natural products., Competing Interests: The authors declare that there is no duality of interest associated with this manuscript., (Copyright © 2020 Jian-Kang Mu et al.)

Long-term muscle fatigue is a major cause of injury. Drugs/nutrients from herbal medicines that prevent fatigue remain a major research focus. In China, a prescription composed of Polygonati Rhizoma and Notoginseng Radix et Rhizoma has been commonly used as a herb and food nutrient, providing protection against fatigue in the clinic. To date, the mechanisms through which this prescription prevented fatigue are unknown. Here, we identified the effects of this prescription on muscle fatigue based on energy and oxidation regulation. Fatigue mouse models were produced through weight-bearing exhaustive swimming. Mice were intragastrically administered prescription extracts (1 and 2 g/kg) for four weeks. Changes in exhaustive swimming times, antifatigue biochemical indicators, oxidative status, and energy metabolism were investigated. The prescription prolonged the exhaustive swimming time of the mice. The content of lactic acid and blood urea nitrogen in the serum was also markedly reduced by the prescription. The content of liver glycogen and lactate dehydrogenase in the serum increased. The prescription also significantly reduced malondialdehyde levels and increased the levels of superoxide dismutase and glutathione peroxidase. The levels of ATPase, complexes I and II in the mitochondria of hind-leg skeletal muscle, and serum creatine kinase also increased in response to the prescription. Our results indicated that the prescription could effectively alleviate muscle fatigue status by promoting energy metabolism and antioxidation ability. The prescription therefore represents a useful drug/nutrient strategy to alleviate muscle fatigue., Competing Interests: The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2020 Ya-Qin Yang et al.)

Polyhydroxyalkanoates (PHA) have found widespread medical applications due to their biocompatibility and biodegradability, while further chemical modification requires functional groups on PHA. Halomonas bluephagenesis, a non-model halophilic bacterium serving as a chassis for the Next Generation Industrial Biotechnology (NGIB), was successfully engineered to express heterologous PHA synthase (PhaC) and enoyl coenzyme-A hydratase (PhaJ) from Aeromonas hydrophila 4AK4, along with a deletion of its native phaC gene to synthesize the short chain-co-medium chain-length PHA copolymers, namely poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), poly(3-hydroxybutyrate-co-3-hydroxyhex-5-enoate) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate-co-3-hydroxyhex-5-enoate). After optimizations of the expression cassette and ribosomal binding site combined with introduction of endogenous acyl-CoA synthetase (fadD), the resulting recombinant strain H. bluephagenesis TDR4 achieved a remarkably high 3-hydroxyhexenoate (3HHxE) molar ratio of 35% when grown on glucose and 5-hexenoic acid as co-substrates. The total ratio of side chain consisting of 3HHx and 3HHxE monomers in the terpolymer can approach 44 mol%. H. bluephagenesis TDR4 was grown to a cell dry mass (CDM) of 30 g/L containing approximately 20% poly(3-hydroxybutyrate-co-22.75 mol% 3-hydroxy-5-hexenoate) in a 48-h of open and unsterile fermentation with a 5-hexenoic acid conversion efficiency of 91%. The resulted functional PHA containing 12.5 mol% 3-hydroxy-5-hexenoate exhibits more than 1000% elongation at break. The engineered H. bluephagenesis TDR4 can be used as an experimental platform to produce functional PHA., Competing Interests: Declaration of competing interest The authors declare no competing financial interests. A patent related to this study has been applied., (Copyright © 2020 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Alligator weed is reported to have a strong ability to adapt to potassium deficiency (LK) stress. Leaves are the primary organs responsible for photosynthesis of plants. However, quantitative proteomic changes in alligator weed leaves in response to LK stress are largely unknown. In this study, we investigated the physiological and proteomic changes in leaves of alligator weed under LK stress. We found that chloroplast and mesophyll cell contents in palisade tissue increased, and that the total chlorophyll content, superoxide dismutase (SOD) activity and net photosynthetic rate (PN) increased after 15 day of LK treatment, but the soluble protein content decreased. Quantitative proteomic analysis suggested that a total of 119 proteins were differentially abundant proteins (DAPs). KEGG analysis suggested that most represented DAPs were associated with secondary metabolism, the stress response, photosynthesis, protein synthesis, and degradation pathway. The proteomic results were verified using parallel reaction monitoring mass spectrometry (PRM-MS) analysis and quantitative real-time PCR (qRT-PCR)assays. Additional research suggested that overexpression of cationic peroxidase 1 of alligator weed (ApCPX1) in tobacco increased LK tolerance. The seed germination rate, peroxidase (POD) activity, and K + content increased, and the hydrogen peroxide (H 2 O 2 ) content decreased in the three transgenic tobacco lines after LK stress. The number of root hairs of the transgenic line was significantly higher than that of WT, and net K efflux rates were severely decreased in the transgenic line under LK stress. These results confirmed that ApCPX1 played positive roles in low-K + signal sensing. These results provide valuable information on the adaptive mechanisms in leaves of alligator weed under LK stress and will help identify vital functional genes to apply to the molecular breeding of LK-tolerant plants in the future.

Caspofungin is the first echinocandin antifungal agent that licented for pediatric use in invasive candidiasis and aspergillosis. In this study, we evaluated the population pharmacokinetics of caspofungin and investigate appropriate dosing optimization against Candida spp. in children with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in order to improve therapeutic efficacy. All participants received a recommended caspofungin 70 mg/m 2 loading dose followed by 50 mg/m 2 maintenance dose. A one-compartment model with first-order elimination was best fitted the data from 48 pediatric patients. Body surface area and aspartate aminotransferase had significant influence on caspofungin clearance from covariate analysis. Our results reviewed that dose adjustment is not necessary in patients with mild liver dysfunction. Monte Carlo simulations were performed using pharmacokinetic data from our study to evaluate the probability of target attainment (PTA) of caspofungin regimen in terms of AUC 24 /MIC targets against Candida spp. The results of simulations predicted that a caspofungin 70 mg/m 2 at first dose, 50 mg/m 2 of daily dose may have a high probability of successful outcome against C. albicans and C. glabrata whilst 60 mg/m 2 maintenance dose was required for fungistatic target against C. parapsilosis but may be not sufficient to achieve optimal fungicidal activity. Caspofungin standard regimen had high probability of successful outcome against C. albicans (MIC ⩽ 0.25 mg/L) and C. glabrata (MIC ⩽ 0.5 mg/L) but insufficient for C. parapsilosis with MIC > 0.25 mg/L. That may provide an evidence based support to caspofungin individualized administration and decrease the risk of therapeutic failure in allo-HSCT pediatric patients., (Copyright © 2020 Niu, Xu, Gao, Nie, Xing, Yu, Wu and Wang.)

Objective: To identify a multi-gene prognostic factor in patients with lung adenocarcinoma (LUAD). Materials and methods Prognosis-related genes were screened in the TCGA-LUAD cohort. Then, patients in this cohort were randomly separated into training set and test set. Least absolute shrinkage and selection operator (LASSO) regression was performed to the penalized the Cox proportional hazards regression (CPH) model on the training set, and a prognostication combination based on the result of LASSO analysis was developed. By performing Kaplan-Meier curve analysis, univariate and multivariable CPH model on the overall survival (OS) as well as recurrence free survival (RFS), the prognostication performance of the multigene combination were evaluated. Moreover, we constructed a nomogram and performed decision curve analysis to evaluate the clinical application of the multigene combination. Results We obtained 99 prognosis-related genes and screened out a 4-gene combination (including CIDEC, ZFP3, DKK1, and USP4) according to the LASSO analysis. The results of survival analyses suggested that patients in the 4-gene combination low-risk group had better OS and RFS than those in the 4-gene combination high-risk group. The 4-gene mentioned was demonstrated to be independent prognostic factor of patients with LUAD in the training set(OS, HR=11.962, P<0.001; RFS, HR=9.281, P<0.001) and test set (OS, HR=5.377, P=0.003; RFS, HR=2.949, P=0.104). More importantly, its prognosis performance was well in the validation set (OS, HR=0.955, P=0.002; RFS, HR=1.042, P<0.001). Conclusions We introduced a 4-gene combination which could predict the survival of LUAD patients and might be an independent prognostic factor in LUAD., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Fluorescent materials play an important role in biomedical fields. However, the main types of fluorescent materials suffer from several disadvantages especially the biotoxicity, which largely restrict its wider applications in biological fields. In this study, a highly efficient rare-earth-modified fluorescent material was successfully designed and fabricated based on polyhydroxyalkanoates, which are known as biodegradable and biocompatible materials. A new Functional-PHA polymer was microbially synthesized by engineered Halomonas bluephagenesis and was used as a basal matrix to generate the rare-earth-modified PHA. N -Acetyl-l-cysteine-grafted PHA (NAL-grafted-PHA) was first produced via a UV-initiated thiol-ene click reaction and the rare earth metal ions (Eu 3+ and Tb 3+ ) were subsequently chelated onto the NAL-grafted-PHA through the coordination effect. The composite material exhibited intense photoluminescence properties under UV laser excitation, indicating the excellent features as fluorescent material. The enhanced hydrophilicity and superior biocompatibility of rare-earth-chelated PHA were confirmed, suggesting its great potential application value in biomedical fields.

The chemical industry has made a contribution to modern society by providing cost-competitive products for our daily use. However, it now faces a serious challenge regarding environmental pollutions and greenhouse gas emission. With the rapid development of molecular biology, biochemistry, and synthetic biology, industrial biotechnology has evolved to become more efficient for production of chemicals and materials. However, in contrast to chemical industries, current industrial biotechnology (CIB) is still not competitive for production of chemicals, materials, and biofuels due to their low efficiency and complicated sterilization processes as well as high-energy consumption. It must be further developed into "next-generation industrial biotechnology" (NGIB), which is low-cost mixed substrates based on less freshwater consumption, energy-saving, and long-lasting open continuous intelligent processing, overcoming the shortcomings of CIB and transforming the CIB into competitive processes. Contamination-resistant microorganism as chassis is the key to a successful NGIB, which requires resistance to microbial or phage contaminations, and available tools and methods for metabolic or synthetic biology engineering. This review proposes a list of contamination-resistant bacteria and takes Halomonas spp. as an example for the production of a variety of products, including polyhydroxyalkanoates under open- and continuous-processing conditions proposed for NGIB., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To analyze the clinical and pathological features of small renal cell carcinoma (RCC), especially of those with diameter less than 4 cm and to understand the characteristics and factors related to recurrence and progression., Methods: A total of 200 patients with RCC were stratifiedly selected for retrospective analysis. Their baseline demographic features, tumor-specific clinical features, pathological features of renal lesions, especially microscopic features were collected. The patients were divided according to the largest diameter of renal tumor lesions. Univariate analysis was used to compare the differences between tumor staging and microscopic pathological features between the groups. Binary multivariate Logistic regression was used to investigate factors related to tumor progression and prognosis in the patients with small RCC., Results: The tumor diameters of 127 RCC patients were less than 4 cm and most of them had clear cell renal cell carcinoma (ccRCC). The increase in tumor diameter resulted in significantly higher T stage (P<0.01), higher WHO/International Society of Urological Pathology (ISUP) grade (P<0.05) and increasing chance of lymph node metastasis (P<0.01). Even when the tumor diameter was less than 4 cm, the patients might still have perirenal fat invasion, renal sinus invasion and greater elevated tumor grade (greater than grade 3) and synchronous lung metastasis. The incidences of intravascular thrombus (9.3% vs. 0) and tumor necrosis (27.8% vs. 5.5%) in the patients with RCC between 4-7 cm were significantly higher than those with RCC less than 4 cm (P<0.01). Sub-group analysis of small RCC (less than 4 cm) indicated that the patients with RCC between 2-4 cm were more likely to have intratumoral hemorrhage (44.7% vs. 23%, P<0.05) and necrosis than those with RCC less than 2 cm (8.2% vs. 0, P=0.095). Logistic regression analysis of small RCC showed that the incidence of tumor invasion to renal capsule was higher in ccRCC (OR=5.15, 95%CI: 1.36-19.52). Necrosis was closely related to the formation of peritumor pseudocapsule in small RCC (OR=14.90, 95%CI: 1.41-157.50). Increase in the tumor diameter was related to higher tumor grade (greater than grade 3) (OR=3.49, 95%CI: 1.11- 10.93)., Conclusion: The tumor stage and grade of small RCC (less than 4 cm) are low, but extra-renal invasion and synchronous distant metastasis may occur. Internal hemorrhage and necrosis in tumor, ccRCC subtype, along with microscopic features, such as the renal capsule invasion and perirenal pseudocapsule formation are relevant factors of malignant behavior of small RCC and could be considered in prognosis evaluation.

Gastric duplication is a rare congenital anomaly accounting to 4% of all gastrointestinal tract duplications. It is usually diagnosed pre-natally or during infancy. Retroperitoneal gastric duplication is very rare in adult patients. It is generally asymptomatic or presents with non-specific symptoms. The sensitivity of classical imaging modalities for retroperitoneal gastric duplication is weak. Retroperitoneal gastric duplication could be misdiagnosed as other retroperitoneal cystic lesions and it could be definitely diagnosed by typical findings of abdominal enhanced computed tomography (CT) and endoscopic ultrasonography (EUS) plus EUS:guided fine needle aspiration biopsy in gastric duplicated cyst. A female adult patient was diagnosed by an exceptional hospital CT as retroperitoneal cystic lesion and was admitted in our hospital in March 2019. The abdominal enhanced CT in our hospital preoperatively indicated a cystic lesion above the left kidney and the maximum cross section was 9.0 cm×5.2 cm. Lymphocysts and others should be identified and the lesion might be from the stomach. The retroperitoneal gastric duplication was not diagnosed before operation. In the operation laparoscopy revealed the cystic lesion in the retroperitoneum. The pancreas, left adrenal gland, and left kidney were compressed by the cystic lesion. The top of the lesion was connected with the small curvature of the stomach, but it was not communicated with the stomach. The retroperitoneal cystic lesion was completely excised and the surrounding organs were not damaged. The retroperitoneal gastric duplication was clearly diagnosed by the findings in the operation and the pathology of the lesion. The patient was discharged a week after surgery without gastrointestinal and pancreatic injuries. Therefore, the differential diagnosis of retroperitoneal cysts should consider the possibility of retroperitoneal gastric duplication. For patients with typical CT findings or unclear boundaries between the tumor and the stomach wall, gastric duplication could be diagnosed by EUS plus EUS:guided fine needle aspiration biopsy in the cyst. Retroperitoneal gastric duplication cyst could be completely excised by laparoscopy through abdominal cavity and the stomach wall could be completely repaired.

The aim of this study was to determine the effect of varying excipient content on the formation and physical properties of 3 D printed tablets. Fifteen different excipient preparations were formed into tablets with radii of 5 mm and thickness of 2 mm, using binder jetting (BJ). The tablets were analyzed by assessing visual and microstructural appearance, friability, hardness, and disintegration time. We found that filling agents with high water solubility (e.g. D-sucrose), binding agents with a high viscosity in solution (e.g. polyethylene glycol 4000) and moistening agent with higher water content can increase the bonding strength and hardness of the 3 D printed tablets and prolonged their disintegration time. This work has demonstrated that the type of excipient and its concentration affects the properties of the 3 D printed tablet. This article may be used as a guide for elucidation of the effects of using conventional tablet excipients in the field of 3 D printed pharmaceuticals. The present work should enable the identification of excipients that satisfy requirements, reduce analysis time, and improve efficiency.

As a new concept in clinical research,the real world research(RWR) has attracted the attention of researchers in the world with its unique advantages. This research mainly analyzed it through visual methods,the specific steps were as follows. Firstly,the Chinese Biomedical Literature Database,China National Knowledge Infrastructure,Wan Fang Database,Medline and EMbase were searched and RWS were included,414 articles in Chinese and 2 158 articles in English were included in this research after layer-bylayer screening; secondly,the main information was extracted and sorted by BICOMS 2 software and generated its co-occurrence matrix; the network relationship diagram was drawn by Net Draw software; the cluster analysis was carried out by using g CLUTO software;finally,this research results show that the numbers of domestic and foreign literatures have shown an overall growth trend,but compared with foreign countries,China's research on the real world started late,the overall strength of research was not as good as abroad;and the domestic and foreign research on the real world was uneven in the region,the research in China was mainly distributed in developed provinces and cities,such as Beijing,Guangdong,Shanghai,etc,and there was a lack of close cooperation between provinces and cities; the foreign research are mainly distributed in developed countries such as the United States,the United Kingdom,Germany,et al; the cooperation between countries was relatively close. And the hotspots and core directions of domestic and foreign research were also different. This research was intended to provide reference for the further research of Chinese researchers through the current description of the themes and capability of the real world research in the world.

Individualized medicine is a new direction in the field of modern pharmacy. In this study, we assessed the feasibility and accuracy of 3D printing techniques for the preparation of individualized doses of mouth-disintegrating tablets of warfarin. Warfarin sodium, D-sucrose, pregelatinized starch, povidone K30, microcrystalline cellulose, and silicon dioxide (at a ratio of 1:42.45:46.15:5.1:4.9:0.4) were mixed and used as the printing powder in the 3D printer; preset parameters were used. The dosage of the tablet was controlled by the number of printing layers. The content, dose uniformity, dose accuracy, hardness, friability, disintegration time, dissolution, and the microstructural and overall appearance were determined to evaluate the printed tablets. For the doses of 3, 2, and 1 mg that were produced in the experiment, the disintegration times were 50.0 ± 5.2, 35.7 ± 4.3, and 11.0 ± 2.2 s, respectively, and the relative errors of the dose were -2.33, -1.50, and 0%, respectively. The other indicators were consistent with the preparation requirements of pharmaceutical tablets. It is possible to prepare tablets with excellent properties and controlled drug doses by using 3D printing techniques. This technology will be an important means to achieve individualized medicine.

In the present work, polyethylenimine-capped CdS quantum dots (PEI-CdS QDs) with bright green fluorescence were synthesized and applied for sensitively and selectively detecting the nitrite in vegetable and water samples. Highly fluorescent and environment-friendly PEI-CdS QDs (quantum yield about 8%) with diameters of ca. 5 nm were easily synthesized by using hyperbranched PEI as functional polymer. Formation of the PEI-CdS QDs was verified by transmission electron microscopy and UV-vis spectroscopy. The fluorescence intensity of the as-synthesized PEI-CdS QDs was enhanced pronouncedly by the increasing amount of PEI and was stable when the pH ranged from 5.0 to 9.0. Our results demonstrated that the fluorescence of the PEI-CdS QDs was effectively quenched by the nitrite in a rather wide linear range of 1.0 × 10 -7 -1.0 × 10 -4 M while efficiently avoiding the interferences from nitrate ions and other commonly coexisting anions of nitrite in the vegetable samples. The detection limit of the present method was lower than the maximum limit of nitrite in drinking water (6.5 × 10 -5 M) ruled by the World Health Organization, which is significant to the application of the method.