Determination and prediction of amino acid digestibility in brown rice for growing-finishing pigs.

Objective: The experiment aimed to determine the standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AA) in 10 brown rice samples fed to pigs, and to construct predictive models for SID of CP and AA based on the physical characteristics and chemical composition of brown rice. Methods: Twenty-two cannulated pigs (initial body weight: 42.0±1.2 kg) were assigned to a replicated 11×3 incomplete Latin square design, including an N-free diet and 10 brown rice diets. Each period included 5 d adaptation and 2 d ileal digesta collection. Chromic oxide was added at 0.3% to all the diets as an indigestible marker for calculating the ileal CP and AA digestibility. Results: The coefficients of variation of all detected indices for physical characteristics and chemical composition, except for bulk weight, dry matter (DM) and gross energy (GE), in 10 brown rice samples were greater than 10%. The SID of CP, lysine (Lys), methionine (Met), threonine (Thr) and tryptophan (Trp) in brown rice was 77.2% (62.6% to 85.5%), 87.5% (80.3% to 94.3%), 89.2% (78.9% to 98.9%), 55.4% (46.1% to 67.6%) and 92.5% (86.3% to 96.3%), respectively. The best prediction equations for the SID of CP, Lys, Thr and Trp were as following, SIDCP=ï¹£664.181+8.484×DM (R2=0.40), SIDLys=53.126+6.031×ether extract (EE) +0.893×thousand-kernel volume (R2=0.66), SIDThr=39.916+7.843×EE (R2=0.41) and SIDTrp=ï¹£361.588+4.891×DM+0.387×total starch (R2=0.85). Conclusion: Overall, a great variation exists among 10 sources of brown rice, and the thousand-grain volume, DM, EE, and total starch can be used as the key predictors for SID of CP and AA.

Diagnosis and management of intraspinal tuberculoma with osseous involvement: a case report.

Introduction and importance: Intraspinal tuberculoma is rare and challenging situation, which results in serious neurological dysfunctions. Case presentation: This case report shows an intraspinal tuberculoma with osseous involvement in a 31-year-old male patient with subacute progressing neurologic deficit. His medical history included tuberculosis of pulmonary and intestinal 8 years previously, at which time he had been treated with intestinal obstruction operation and antituberculosis treatment. A quadruple antituberculosis treatment was carried out after admission; however, his neurological condition was steadily worsening. He underwent debulking of mass for decompression and pathological analysis revealed intraspinal tuberculoma. The patient was prescribed a 12-month course of antituberculosis therapy, and a good clinical outcome was obtained subsequently. Clinical discussion: This case was treated by microsurgical resection and antituberculosis therapy, and the outcome was favourable. Conclusion: Intraspinal tuberculoma should be considered when an intraspinal mass is found with a history of tuberculosis, it can be effectively diagnosed by MRI and treated by the combination of medical and surgical treatments.

Design and Control of Upper Limb Rehabilitation Training Robot Based on a Magnetorheological Joint Damper.

In recent years, rehabilitation robots have been developed and used in rehabilitation training for patients with hemiplegia. In this paper, a rehabilitation training robot with variable damping is designed to train patients with hemiplegia to recover upper limb function. Firstly, a magnetorheological joint damper (MR joint damper) is designed for the rehabilitation training robot, and its structural design and dynamic model are tested theoretically and experimentally. Secondly, the rehabilitation robot is simplified into a spring-damping system, and the rehabilitation training controller for human movement is designed. The rehabilitation robot dynamically adjusts the excitation current according to the feedback speed and human-machine interaction torque, so that the rehabilitation robot always outputs a stable torque. The magnetorheological joint damper acts as a clutch to transmit torque safely and stably to the robot joint. Finally, the upper limb rehabilitation device is tested. The expected torque is set to 20 N, and the average value of the output expected torque during operation is 20.02 N, and the standard deviation is 0.635 N. The output torque has good stability. A fast (0.5 s) response can be achieved in response to a sudden motor speed change, and the average expected output torque is 20.38 N and the standard deviation is 0.645 N, which can still maintain the stability of the output torque.

Is cranioplasty the optimal treatment for contralateral subdural effusion after decompressive craniectomy?: a case report.

Introduction and importance: Contralateral subdural effusion (CSDE) is a rare complication secondary to decompressive craniectomy (DC), which can lead to encephalocele and neurologic deterioration. The authors report a case that confirm the existence of unidirectional membrane valve, and cranioplasty is an effective treatment for CSDE. Case presentation: The authors reported a case of 43-year-old female was diagnosed with ruptured intracranial aneurysm and treated with interventional embolization. She underwent DC because of postoperative cerebral infarction subsequently. Her conscious state deteriorated accompanied by encephalocele in postoperative 2 week. A craniocerebral computed tomography (CT) confirmed the diagnosis of CSDE with cerebral hernia. A compression bandaging of the skull defect was applicated, whereas, her conscious state progressive deteriorated. She was transferred to the author's hospital where she underwent burr-hole drainage and clinical symptom has been improved. However, a relapse of CSDE was observed after the removal of drainage tube. Continuous lumbar drainage was employed, and which was ineffective for CSDE in this case. Finally, she underwent cranioplasty, with the help of drainage of subdural effusion, CSDE was completely resolved. Clinical discussion: CSDE is occasionally observed in patients after DC. Intracranial pressure (ICP) gradient and unidirectional membrane valve are the possible mechanisms of CSDE. At present, there is no optimal therapy for CSDE. For symptomatic CSDE patients, one or more treatment measures should be applicated. Conclusion: Cranioplasty is one of the curative and optimal method to treat symptomatic CSDE patients, early cranioplasty combined with burr-hole drainage should be performed for conservative treatment failed and intractable cases.

Experimental Study on the Skyhook Control of a Magnetorheological Torsional Vibration Damper.

This study proposes a dual-coil magnetorheological torsional vibration damper (MRTVD) and verifies the effectiveness of semi-active damping control to suppress the shaft system's torsional vibration via experimental research. Firstly, the mechanical model of the designed MRTVD and its coupling mechanical model with the rotating shaft system are established. Secondly, the torsional response of the shaft system is obtained via resonance experiments, and the influence of the current on the torsional characteristics of the magnetorheological torsional damper is analyzed. Finally, the MRTVD is controlled using the skyhook control approach. The experimental results demonstrate that when the main shaft passes through the critical speed range at various accelerations, the amplitude of the shaft's torsional vibration decreases by more than 15%, and the amplitude of the shaft's torsional angular acceleration decreases by more than 22%. These conclusions validate the inhibitory effect of MRTVD on the main shaft's torsional vibrations under skyhook control.

Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease.

We aimed to investigate the role of renal pericyte pyruvate kinase M2 (PKM2) in the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). The role of PKM2 in renal pericyte-myofibroblast transdifferentiation was investigated in an AKI-CKD mouse model. Platelet growth factor receptor beta (PDGFRß)-iCreERT2; tdTomato mice were used for renal pericyte tracing. Western blotting and immunofluorescence staining were used to examine protein expression. An 5-ethynyl-2'-deoxyuridine assay was used to measure renal pericyte proliferation. A scratch cell migration assay was used to analyse cell migration. Seahorse experiments were used to examine glycolytic rates. Enzyme-linked immunoassay was used to measure pyruvate kinase enzymatic activity and lactate concentrations. The PKM2 nuclear translocation inhibitors Shikonin and TEPP-46 were used to alter pericyte transdifferentiation. In AKI-CKD, renal pericytes proliferated and transdifferentiated into myofibroblasts and PKM2 is highly expressed in renal pericytes. Shikonin and TEPP-46 inhibited pericyte proliferation, migration, and pericyte-myofibroblast transdifferentiation by reducing nuclear PKM2 entry. In the nucleus, PKM2 promoted downstream lactate dehydrogenase A (LDHA) and glucose transporter 1 (GLUT1) transcription, which are critical for glycolysis. Therefore, PKM2 regulates pericyte glycolytic and lactate production, which regulates renal pericyte-myofibroblast transdifferentiation. PKM2-regulated renal pericyte-myofibroblast transdifferentiation by regulating downstream LDHA and GLUT1 transcription and lactate production. Reducing nuclear PKM2 import can reduce renal pericytes-myofibroblasts transdifferentiation, providing new ideas for AKI-CKD treatment.

Physiological and Pathological Roles of NTSR2 in Several Organs and Diseases (Review).

Neurotensin (NTS) and its receptors (NTSRs) have long been the subject of study and have shown to have a vital function in a variety of systems. They are specifically implicated in the development of tumors and have both oncogenic and anti-apoptotic effects. Neurotensin receptor 2 (NTSR2), like NTSR1, belongs to the G protein-coupled receptor family and has been linked to analgesia, mental disorders, and hematological cancers. However, several research reports have revealed that it exists in numerous different systems. As a result, it seems to be an extremely promising therapeutic target for a variety of diseases. As NTSR2 is particularly prevalent in the brain and has different distribution and developmental characteristics from NTSR1, it may play a specific role in the nervous system. The present review summarizes the expression and function of NTSR2 in different systems, to highlight its potential as a diagnostic tool or therapeutic target.

Impact of Visceral Fat Area on Intraoperative Complexity and Surgical Approach Decision for Robot-Assisted Partial Nephrectomy: A Comparative Analysis with BMI.

BACKGROUND Optimizing surgical approaches for robot-assisted partial nephrectomy (RAPN) is vital for better patient outcomes. This retrospective study aimed to examine how visceral fat area (VFA) and body mass index (BMI) correlate with intraoperative complexities, thereby guiding the selection of surgical techniques for RAPN. MATERIAL AND METHODS The study analyzed the medical records of 213 Chinese patients diagnosed with a range of benign and malignant renal neoplasms and treated with RAPN in 2020. Visceral fat area was quantified using computed tomography (CT) scans taken at the umbilical level. Various perioperative indicators, such as demographic details, clinicopathological parameters, operation time, estimated blood loss (EBL), warm ischemic time (WIT), and intraoperative complications, were assessed. RESULTS For the retroperitoneal approach, patients with either visceral obesity or general obesity had longer operation times (P<0.001 and P=0.004) and had a tendency for higher EBL (P=0.003 and P=0.001) compared to non-obese patients. In the transperitoneal approach, those with visceral obesity had significantly longer operation times (P=0.008) than their non-viscerally obese counterparts; however, general obesity showed no impact on operation time (P=0.251). Estimated blood loss was higher for patients with visceral obesity (P=0.004), but no significant difference was noted among those with general obesity (P=0.980). CONCLUSIONS VFA appears to offer predictive advantages over BMI in assessing intraoperative complexities for transperitoneal RAPN. When used in conjunction with BMI, it could serve as a valuable tool in selecting the most appropriate surgical approach for RAPN.

GGA1 interacts with the endosomal Na+/H+ Exchanger NHE6 governing localization to the endosome compartment.

Mutations in the endosomal Na+/H+ exchanger (NHE6) cause Christianson syndrome (CS), an X-linked neurological disorder. Previous studies have shown that NHE6 functions in regulation of endosome acidification and maturation in neurons. Using yeast two-hybrid screening with the NHE6 carboxyl-terminus as bait, we identify Golgi-associated, Gamma adaptin ear containing, ARF binding protein 1 (GGA1) as an interacting partner for NHE6. We corroborated the NHE6-GGA1 interaction using co-immunoprecipitation (co-IP): using over-expressed constructs in mammalian cells; and co-IP of endogenously-expressed GGA1 and NHE6 from neuroblastoma cells, as well as from mouse brain. We demonstrate that GGA1 interacts with organellar NHEs (NHE6, NHE7 and NHE9) but not with cell-surface localized NHEs (NHE1 and NHE5). By constructing hybrid NHE1/NHE6 exchangers, we demonstrate that the cytoplasmic tail of NHE6 is necessary and sufficient for interactions with GGA1. We demonstrate the co-localization of NHE6 and GGA1 in cultured, primary hippocampal neurons, using super-resolution microscopy. We test the hypothesis that the interaction of NHE6 and GGA1 functions in the localization of NHE6 to the endosome compartment. Using subcellular fractionation experiments, we show that NHE6 is mis-localized in GGA1 knockout cells wherein we find less NHE6 in endosomes but more NHE6 transport to lysosomes, and more Golgi retention of NHE6 with increased exocytosis to the surface plasma membrane. Consistent with NHE6 mis-localization, and Golgi retention, we find the intra-luminal pH in Golgi to be alkalinized. Our study demonstrates a new interaction between NHE6 and GGA1 which functions in the localization of this intra-cellular NHE to the endosome compartment.

Christianson Syndrome across the Lifespan: An International Longitudinal Study in Children, Adolescents, and Adults.

Mutations in the X-linked endosomal Na+/H+ Exchanger 6 (NHE6) causes Christianson Syndrome (CS). In the largest study to date, we examine genetic diversity and clinical progression, including cerebellar degeneration, in CS into adulthood. Data were collected as part of the International Christianson Syndrome and NHE6 (SLC9A6) Gene Network Study. Forty-four individuals with 31 unique NHE6 mutations, age 2 to 32 years, were followed prospectively, herein reporting baseline, 1-year follow-up, and retrospective natural history. We present data on the CS phenotype with regard to physical growth, adaptive and motor regression, and across the lifespan, including information on mortality. Longitudinal data on body weight and height were examined using a linear mixed model: the rate of growth across development was slow and resulted in prominently decreased age-normed height and weight by adulthood. Adaptive functioning was longitudinally examined: a majority of adult (18+ years) participants lost gross and fine motor skills over a 1-year follow-up. Previously defined core diagnostic criteria for CS (present in >85%) - namely nonverbal status, intellectual disability, epilepsy, postnatal microcephaly, ataxia, hyperkinesia - were universally present in age 6 to 16; however, an additional core feature of high pain tolerance was added (present in 91%), and furthermore, evolution of symptoms were noted across the lifespan, such that postnatal microcephaly, ataxia and high pain threshold were often not apparent prior to age 6, and hyperkinesis decreased after age 16. While neurologic exams were consistent with cerebellar dysfunction, importantly, a majority of individuals (>50% older than 10) also had corticospinal tract abnormalities. Three participants died during the period of the study. In this large and longitudinal study of CS, we begin to define the trajectory of symptoms and the adult phenotype, thereby identifying critical targets for treatment.

Elevated serum uric acid is associated with cognitive impairment in acute minor ischemic stroke patients.

Background: Acute minor ischemic stroke (AMIS) has been proven to be strongly associated with post-stroke cognitive impairment (PSCI). Few studies have reported that uric acid (UA) levels are linked to PSCI in patients with AMIS, and those results are debatable. We investigated the relationship between serum UA levels and cognitive impairment in patients with AMIS. Methods: A total of 318 patients who were diagnosed with AMIS were recruited from Suining Central Hospital. Fasting serum samples were collected the day after admission for UA measurement. Cognitive function was evaluated at admission and 3 months after stroke using the Montreal Cognitive Assessment (MoCA). The relationship between UA and PSCI was examined using a multivariate binary logistic regression model. The optimal cut-off point for UA levels to predict PSCI was determined using the receiver operating characteristic (ROC) curve. Results: A total of 197 (61.9 %) of the 318 participants in this study exhibited cognitive impairment at 3 months. Serum UA was strongly linked with PSCI after adjusting for confounding factors (OR = 1.82, 95 % CI: 1.56 to 2.11, P < 0.0001). The ROC curve revealed a cut-off of 363.58 µmol/L serum UA, and the predicted sensitivity and specificity for PSCI were 67.5 % and 83.5 %, respectively. Subgroup analysis showed that confounding factors had no impact on the association between serum UA and PSCI risk. Conclusions: Higher baseline serum UA levels might be an independent risk factor for cognitive impairment in AMIS patients. Serum UA levels above 363.58 µmol/L may have clinical implications in predicting PSCI.

Advances in Cardiac Organoids.

Cardiovascular diseases rank as the leading cause of death worldwide and are a major contributor to disability, posing a significant threat to human health. Organoids offer a partial simulation of the structure and function of the tissue of origin. It is a promising model that can supplement the disadvantages of two-dimensional culture and animal models. Due to the complexity of heart development, the research of cardiac organoids is still maturing. The advancement of technology has helped address certain challenges, but it has also unveiled new issues and complexities. This paper summarizes the application of organoids technology in the cardiovascular field, the common construction methods of cardiac organoids, and the latest progress of cardiac organoids in the fields of disease model construction, cardiac development research, drug research, and regenerative medicine. The future development and challenges of cardiac organoids are also addressed.

[Effects of Chlorine-based and Sulfur-based Fertilizers on Rice Bioavailability of Cd in Soils].

To explore the effects of single or combined application of chlorine-and sulfur-based fertilizers on rice bioavailability of Cd in soils, pot experiments with reddish clayey soil (developed from quaternary red clay parent materials) under three exogenous Cd levels (0, 0.5, and 2.0 mg·kg-1) were conducted. Meanwhile, chlorine-based fertilizers (KCl, NH4Cl) and sulfur-based fertilizers[K2SO4, (NH4)2SO4] were added in different proportions. The soil pH, Cd morphology, and Cd accumulation in rice at different growth stages were analyzed. The results revealed that both chlorine-and sulfur-based fertilizers could acidify the soil; however, the effect of chlorine-based fertilizers was more significant. During the filling stage of rice, the soil pH value of the treatment of applying single chlorine-based fertilizer decreased by 0.28 on average compared with that of applying single sulfur-based fertilizer. At the maturity stage of rice, chlorine-based fertilizer could activate the residual Cd, whereas sulfur-based fertilizer passivated the acid-extracted Cd to its residual state. Compared with the single application of the same fertilizer, the combined application of chlorine-and sulfur-based fertilizers was more likely to promote the accumulation of Cd in rice plants. The highest Cd accumulation of brown rice was 0.21 mg·kg-1 (2.0 mg·kg-1 exogenous Cd level) in the 1:1 (mole ratios of Cl:S) treatment of chlorine-and sulfur-based fertilizers, which was 16.4% higher than that of single chlorine-based fertilizer and 113.3% higher than that of single sulfur-based fertilizer. Therefore, the combined application of chlorine-fertilizers and sulfur-based fertilizers will increase the concentration of Cd in brown rice. To ensure food quality and safety, it is more advisable to apply single sulfur-based fertilizer for rice planting.

Prediction of available energy and amino acid digestibility of Chinese sorghum fed to growing-finishing pigs.

Two experiments were conducted to determine digestible energy (DE), metabolizable energy (ME), as well as the standardized ileal digestibility (SID) of crude protein (CP) and amino acids (AA) in 10 sorghum samples fed to pigs. In experiment 1, 22 crossbred barrows (Duroc × Yorkshire × Landrace, Initial body weight [BW]: 70.0 ±â€…1.8 kg) were selected and allotted to a replicated 11 × 3 incomplete Latin square design, including a basal diet and 10 sorghum energy diets and three consecutive periods. Each period had 7 d adaptation and 5 d total feces and urine collection. The DE and ME were determined by the total collection and the difference method. In experiment 2, 22 crossbred barrows (Duroc × Yorkshire × Landrace, Initial BW: 41.3 ±â€…1.2 kg) that had a T-cannula installed in the distal ileum were assigned to a replicated 11 × 3 incomplete Latin square design, including an N-free diet and 10 sorghum diets. Each period had 5 d adaptation and 2 d ileal digesta collection. The basal endogenous N losses were measured by the N-free diet method. All diets in experiment 2 were added 0.30% titanium dioxide as an indigestible marker for calculating the ileal CP and AA digestibility. On an as-fed basis, the DE and ME contents in sorghum were 3,410 kcal/kg (2,826 to 3,794 kcal/kg) and 3,379 kcal/kg (2,785 to 3,709 kcal/kg), respectively. The best-fit prediction equation for DE and ME were DE = 6,267.945 - (1,271.154 × % tannin) - (1,109.720 × % ash) (R2 = 0.803) and ME = 51.263 + (0.976 × DE) (R2 = 0.994), respectively. The SID of CP, Lys, Met, Thr, and Trp (SIDCP, SIDLys, SIDMet, SIDThr, and SIDTrp) in 10 sorghum samples were 78.48% (69.56% to 84.23%), 74.27% (61.11% to 90.60%), 92.07% (85.16% to 95.40%), 75.46% (66.39% to 80.80%) and 87.99% (84.21% to 92.37%), respectively. The best prediction equations for SID of CP and the first four limiting AAs were as following: SIDCP = 93.404 - (21.026 × % tannin) (R2 = 0.593), SIDCP = 42.922 - (4.011 × % EE) + (151.774 × % Met) (R2 = 0.696), SIDLys = 129.947 - (670.760 × % Trp) (R2 = 0.821), SIDMet = 111.347 - (232.298 × % Trp) (R2 = 0.647), SIDThr = 55.187 + (3.851 × % ADF) (R2 = 0.609) and SIDTrp = 95.676 - (10.824 × % tannin) (R2 = 0.523), respectively. Overall, tannin and ash are the first and second predictors of DE and ME values of sorghum, respectively, and the tannin, EE, Trp, ash, CF, and ADF can be used as the key predictors for SID of CP and first four limiting AAs.

In this manuscript, we selected and analyzed the chemical composition of 10 different varieties of Chinese sorghum. Two digestion and metabolism experiments were conducted to measure the concentrations of available energy (digestible energy and metabolizable energy) and ileal amino acid digestibility (apparent or standardized ileal amino acid digestibility) in sorghums fed to pigs. The results showed as following: 1) The available energy values of 10 sorghum samples varied greatly, and the ileal digestibility of some amino acids also differed. 2) The available energy value and the ileal digestibility of crude protein and amino acids can be predicted by the contents of chemical components in sorghum, such as tannin (a substance in sorghum that can bind to biological macromolecules like proteins), ash, tryptophan, and fiber composition, etc. The above findings enrich the ingredient database and assist for feed enterprises to make precise formulations when using the Chinese sorghum.

Structural Design and Controllability of Magnetorheological Grease Buffers under Impact Loading.

Shock loads can pose a great threat to personnel or instruments, and efficient control of the buffering process is an effective means of reducing damage from shock energy. In this paper, magneto-rheological grease was used as the internal controllable material of the buffer to address the turbulence and settling problems of conventional magneto-rheological fluid. A bending and folding back magnetic circuit is proposed, and the magnetic circuit simulation was verified. The corresponding dynamic mechanical model was established, and the mechanical response characteristics of the buffer under impact load were also simulated dynamically. The mechanical properties of the designed and processed device were tested, and a variable current control method was used to improve the performance of the shock resistance of the buffer. The response of the magnetorheological grease buffer under different drop hammer impacts was investigated. The buffering effect and controllability of the buffer were analyzed by comparing the acceleration, velocity, and top-end cap displacement at the same drop hammer height for different current magnitudes. The results show that the buffer performance of the buffer gradually improved as the current increased. The response time of the designed new magnetorheological buffer was determined by the jump time of the peak damping force to be 9 ms. Lastly, the controllability was verified by manually and automatically adjusting the current magnitude, and the results were compared with those at 300 mm drop hammer height and 0.5 A current magnitude, and the continuous variable current control was found to be effective. This provides a feasible reference for scholars to study optimal buffer control.

Dynamic Measurement of Endosome-Lysosome Fusion in Neurons Using High-Content Imaging.

Endocytosis is a dynamic cellular process that actively transports particles into a cell. Late endosome fusion with the lysosome is a crucial step in the delivery of newly synthesized lysosomal proteins and endocytosed cargo for degradation. Disturbing this step in neurons is associated with neurological disorders. Thus, studying endosome-lysosome fusion in neurons will provide new insight into the mechanisms of these diseases and open new possibilities for therapeutic treatment. However, measuring endosome-lysosome fusion is challenging and time consuming, which limits the research in this area. Here we developed a high throughput method using pH-insensitive dye-conjugated dextrans and the Opera Phenix® High Content Screening System. By using this method, we successfully separated endosomes and lysosomes in neurons, and time-lapse images were collected to capture endosome-lysosome fusion events in hundreds of cells. Both assay set-up and analysis can be completed in an expeditious and efficient manner.

Live-Imaging Detection of Multivesicular Body-Plasma Membrane Fusion and Exosome Release in Cultured Primary Neurons.

Exosomes represent a class of extracellular vesicles (EVs) derived from the endocytic pathway that is important for cell-cell communication and implicated in the spread of pathogenic protein aggregates associated with neurological diseases. Exosomes are released extracellularly when multivesicular bodies (also known as late endosomes) fuse with the plasma membrane (PM). An important breakthrough in exosome research is the ability to capture MVB-PM fusion and exosome release simultaneously in individual cells using live-imaging microscopy techniques. Specifically, researchers have created a construct fusing CD63, a tetraspanin enriched in exosomes, with the pH-sensitive reporter pHluorin whereby CD63-pHluorin fluorescence is quenched in the acidic MVB lumen and only fluoresces when released into the less acidic extracellular environment. Here, we describe a method using this CD63-pHluorin construct to visualize MVB-PM fusion/exosome secretion in primary neurons using total internal reflection fluorescence (TIRF) microscopy.

Multi-Objective Optimization Design and Performance Comparison of Magnetorheological Torsional Vibration Absorbers of Different Configurations.

The purpose of this study is to provide a convenient optimization design method for magnetorheological torsional vibration absorbers (MR-TVA) suitable for automotive engines, which is a damper matching design method that takes into account the needs of the engine operating conditions. In this study, three kinds of MR-TVA with certain characteristics and applicability are proposed: axial single-coil configuration, axial multi-coil configuration and circumferential configuration. The magnetic circuit model, damping torque model and response time model of MR-TVA are established. Then, under the constraints of weight, size and inertia ratio, according to different torsional vibration conditions, the MR-TVA mass, damping torque and response time are multi-objective optimized in two directions. The optimal configurations of the three configurations are obtained from the intersection of the two optimal solutions, and the performance of the optimized MR-TVA is compared and analyzed. The results show that the axial multi-coil structure has large damping torque and the shortest response time (140 ms), which is suitable for complex working conditions. The damping torque of the axial single coil structure is generally large (207.05 N.m), which is suitable for heavy load conditions. The circumferential structure has a minimum mass (11.03 kg) and is suitable for light load conditions.

Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma.

Background: Germline pathogenic variants are estimated to affect 3-5% of patients with renal cell carcinoma (RCC). The identification of patients with hereditary RCC is important for cancer screening and treatment guidance. Methods: Whole-exome sequencing (WES) (n=69) or gene panel sequencing containing 139 genes (n=54) related to germline cancer predisposition was used to analyze germline mutations in 123 patients with RCC admitted to Department of Urology, The Third Medical Center of Chinese PLA General Hospital. Chi-square test (χ2) was used to analyze relationship between clinicopathologic parameters and germline mutations. Results: A total of 13 (10.57%) patients carried pathogenic or likely pathogenic germline mutations in 10 cancer predisposition genes, including VHL, FH, FLCN, SDHB, MUTYH, RAD51C, NBN, RAD50, FANCI, and FANCM. A total of 6 of these 10 cancer predisposition genes were associated with maintenance of genomic stability and DNA repair. Patients harboring pathogenic germline mutations tended to have an earlier RCC onset. The prevalence of deleterious mutations was higher in patients with bilateral or multifocal RCC compared to patients without bilateral or multifocal RCC. Patients with non-clear cell RCC (nccRCC) were significantly more likely to have RCC-associated gene mutations. Conclusions: To our knowledge, this is the first report of pathogenic germline mutations in the FANCI and FANCM genes and heterozygous germline missense mutation in exon 5 of the FH gene c.563A>T:p.N188I in RCC. Young RCC patients, patients with bilateral or multifocal RCC, or patients with nccRCC are more likely to have pathogenic/potentially pathogenic germline mutations.

A Model Based on Artificial Intelligence Algorithm for Monitoring Recurrence of HCC after Hepatectomy.

BACKGROUND: There is no satisfactory indicator for monitoring recurrence after resection of hepatocellular carcinoma (HCC). This retrospective study aimed to design and validate an HCC monitor recurrence (HMR) model for patients without metastasis after hepatectomy. METHODS: A training cohort was recruited from 1179 patients with HCC without metastasis after hepatectomy between February 2012 and December 2015. An HMR model was developed using an AdaBoost classifier algorithm. The factors included patient age, TNM staging, tumor size, and pre/postoperative dynamic variations of alpha-fetoprotein (AFP). The diagnostic efficacy of the model was evaluated based on the area under the receiver operating characteristic curves (AUCs). The model was validated using a cohort of 695 patients. RESULTS: In preoperative patients with positive or negative AFP, the AUC of the validation cohort in the HMR model was .8877, which indicated better diagnostic efficacy than that of serum AFP (AUC, .7348). The HMR model predicted recurrence earlier than computed tomography/magnetic resonance imaging did by 191.58 ± 165 days. In addition, the HMR model can predict the prognosis of patients with HCC after resection. CONCLUSIONS: The HMR model established in this study is more accurate than serum AFP for monitoring recurrence after hepatectomy for HCC and can be used for real-time monitoring of the postoperative status in patients with HCC without metastasis.