The ubiquitin E3 ligase BFAR promotes degradation of PNPLA3.

A missense variant in patatin-like phospholipase domain-containing protein 3 [PNPLA3(I148M)] is the most impactful genetic risk factor for fatty liver disease (FLD). We previously showed that PNPLA3 is ubiquitylated and subsequently degraded by proteasomes and autophagosomes and that the PNPLA3(148M) variant interferes with this process. To define the machinery responsible for PNPLA3 turnover, we used small interfering (si)RNAs to inactivate components of the ubiquitin proteasome system. Inactivation of bifunctional apoptosis regulator (BFAR), a membrane-bound E3 ubiquitin ligase, reproducibly increased PNPLA3 levels in two lines of cultured hepatocytes. Conversely, overexpression of BFAR decreased levels of endogenous PNPLA3 in HuH7 cells. BFAR and PNPLA3 co-immunoprecipitated when co-expressed in cells. BFAR promoted ubiquitylation of PNPLA3 in vitro in a reconstitution assay using purified, epitope-tagged recombinant proteins. To confirm that BFAR targets PNPLA3, we inactivated Bfar in mice. Levels of PNPLA3 protein were increased twofold in hepatic lipid droplets of Bfar-/- mice with no associated increase in PNPLA3 mRNA levels. Taken together these data are consistent with a model in which BFAR plays a role in the post-translational degradation of PNPLA3. The identification of BFAR provides a potential target to enhance PNPLA3 turnover and prevent FLD.

The role of microbiome: a novel insight into urolithiasis.

Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.

Sharp angular and unidirectional filter based on accidental degeneracy between two twisted Weyl semimetal-based defect modes in a one-dimensional photonic crystal.

To address the challenges associated with the realization of optical non-reciprocity and enhance the efficiency of GaAs solar cells, among other systems, in this study, we investigated defect-mode interactions in a one-dimensional photonic crystal containing two Weyl semimetal-based defect layers. Moreover, two non-reciprocal defect modes were observed, namely, when defects are identical and nearby. Increasing the defect distance weakened the defect-mode interactions, thus causing the modes to gradually move closer and then degenerate into one mode. It should be noted that by changing the optical thickness of one of the defect layers, the mode was found to degrade to two non-reciprocal dots with different frequencies and angles. This phenomenon can be attributed to an accidental degeneracy of two defect modes with dispersion curves that intersect in the forward and backward directions, respectively. Moreover, by twisting Weyl semimetal layers, the accidental degeneracy occurred only in the backward direction, thus resulting in a sharp angular and unidirectional filter.

Structural basis of phosphorylation-induced activation of the response regulator VbrR.

Two-component systems typically consist of a paired histidine kinase and response regulator and couple environmental changes to adaptive responses. The response regulator VbrR from Vibrio parahaemolyticus, a member of the OmpR/PhoB family, regulates virulence and antibiotic resistance genes. The activation mechanism of VbrR remains unclear. Here, we report the crystal structures of full-length VbrR in complex with DNA in the active conformation and the N-terminal receiver domain (RD) and the C-terminal DNA-binding domain (DBD) in both active and inactive conformations. Structural and biochemical analyses suggest that unphosphorylated VbrR adopts mainly as inactive dimers through the DBD at the autoinhibitory state. The RD undergoes a monomer-to-dimer transition upon phosphorylation, which further induces the transition of DBD from an autoinhibitory dimer to an active dimer and enables its binding with target DNA. Our study suggests a new model for phosphorylation-induced activation of response regulators and sheds light on the pathogenesis of V. parahaemolyticus.

The renal pelvis urobiome in the unilateral kidney stone patients revealed by 2bRAD-M.

BACKGROUND: The pathogenesis of kidney stone disease (KSD) is not fully understood, and potential contributing factors remain to be explored. Several studies have revealed that the urinary microbiome (urobiome) of stone formers was distinct from that of healthy individuals using 16S rRNA gene sequencing, most of which only provided microbial identification at the genus level. 2bRAD sequencing for Microbiome (2bRAD-M) is a novel sequencing technique that enables accurate characterization of the low-biomass microbiome at the species resolution. We aimed to apply 2bRAD-M to profile the renal pelvis urobiome of unilateral kidney stone patients and compared the urobiome with and without stone(s). METHOD: A total of 30 patients with unilateral stones were recruited, and their renal pelvis urine from both sides was collected. A ureteroscope was inserted into the renal pelvis with stone(s) and a ureteral catheter was placed into the ureteroscope to collect renal pelvis urine. This procedure was repeated again with new devices to collect the urine of the other side. 2bRAD-M was performed to characterize the renal pelvis urobiome of unilateral stone formers to explore whether microbial differences existed between the stone side and the non-stone side. RESULTS: The microbial community composition of the stone side was similar to that of the non-stone side. Paired comparison showed that Corynebacterium was increased and Prevotella and Lactobacillus were decreased in the stone side. Four species (Prevotella bivia, Lactobacillus iners, Corynebacterium aurimucosum, and Pseudomonas sp_286) were overrepresented in the non-stone side. 24 differential taxa were also identified between two groups by linear discriminant analysis effect size (LEfSe). Extensive and close connections among genera and species were observed in the correlation analysis. Moreover, a random forest classifier was constructed using specific enriched species, which can distinguish the stone side from the non-stone side with an accuracy of 71.2%. CONCLUSION: This first 2bRAD-M microbiome survey gave an important hint towards the potential role of urinary dysbiosis in KSD and provided a better understanding of mechanism of stone formation.

Validation and derivation of short-term prognostic risk score in acute decompensated heart failure in China.

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.

ATAD2 silencing decreases VEGFA secretion through targeting has-miR-520a to inhibit angiogenesis in colorectal cancer.

ATPase family AAA domain-containing protein 2 (ATAD2) is involved in various types of cancers, including colorectal cancer. This study aimed to determine the role of ATAD2 in angiogenesis in colorectal cancer. Here, we downregulated ATAD2 expression in HCT116 and SW480 cells, and collected the conditioned medium (CM) from control and ATAD2-silenced cells. The effect of CM on human umbilical vein endothelial cells (HUVEC) was evaluated by using CCK-8, wound healing, tube formation, Western blot, and dual-luciferase reporter assays. Our results showed that the proliferation, migration, and tube formation of HUVEC were reduced in presence of ATAD2-silenced CM, and the levels of phosphorylated vascular endothelial growth factor receptor 2 (P-VEGFR2), CD31, and CD34 were downregulated. Mechanism studies showed that ATAD2 silencing regulated the expression of vascular endothelial growth factor A (VEGFA) and miR-520a. Moreover, we found that miR-520a could bind to ATAD2, and its inhibitor partly reversed the alterations in HUVEC induced by CM from ATAD2-silenced cells. In addition, we demonstrated that miR-520a directly bound to 3'-UTR of VEGFA and inhibited its expression. Collectively, our results indicate that ATAD2 inhibition suppresses VEGFA secretion by increasing miR-520a levels. Our study suggests ATAD2 as a potential therapeutic target for angiogenesis in colorectal cancer.

Effect of Anchor Length on the Pullout Strength of Palatal Mini Implants.

PURPOSE: The aim of this study was to evaluate the pullout strength of 3 different orthodontic mini implants. MATERIALS AND METHODS: Twenty-seven mini implants (diameter: 2 mm, length: 7 mm) were implanted into artificial bone (Sawbones; Pacific Research Laboratories Inc.) at depths of 3, 4, and 5 mm. The insertion torque (IT), resonance frequency (RF), pullout strength (PS), and anchor length (AL) were measured. One-way analysis of variance with Tukey honest significant difference (HSD) postcomparison were used to detect intergroup differences. The null hypothesis was that IT, RF, and PS would significantly correlate in the same brand. RESULTS: In the implantation depths (ID) (5 and 4 mm), IT of Types C (16.67 and 14.33 N·cm) and Type B (14 and 13.33 N·cm) were significantly higher than Type A (10.33 and 9.33 N·cm). Type A had a largest AL and PS at the IDs (5 and 4 mm). In the IDs (3 mm), PS was no different. Type C had no correlation among the RF, IT, and PS. Therefore, null hypothesis was rejected. CONCLUSION: AL exerted crucial effects on the PS of the mini implants.

[Effect of PEG-6000 Simulation Drought Stress on Physiological Characteristics of Guangfeng Medicinal Yam Plantlets].

Objective: In order to provide the theoretical basis for the Guangfeng medicinal yam( Dioscorea opposita) in field transplanting, the effect of PEG-6000 simulation drought stress on physiological characteristics of Guangfeng medicinal yam plantlets was studied. Methods: Using the method of spectrophotometer,the content of total chlorophyll,soluble total sugar, soluble protein and praline,as well as the activities of SOD,CAT and POD of Guangfeng medicinal yam plantlets were tested under PEG-6000 treatment. Results: Under PEG-6000 simulated drought stress, with the increasing of drought stress and the extension of stress time, the total chlorophyll content of Guangfeng medicinal yam plantlets continued to decline, the content of total soluble sugar, proline and MDA of Guangfeng medicinal yam plantlets significantly increased, the content of soluble protein and the activities of CAT,POD and SOD of Guangfeng medicinal yam plantlets increased at first and then decreased. Conclusion: This study reveals the changes of physiological indices of Guangfeng medicinal yam plantlets under PEG-6000 simulation drought stress, which indicated that Guangfeng medicinal yam plantlets have certain drought tolerance.

[Rapid Propagation in vitro of Dioscorea opposita 'Guangfeng'and Its Stomatal Observation,FCM Analysis of Chromosome Ploidy and ISSR Detection of DNA Mutation].

Objective: To study the rapid propagation in vitro of Dioscorea opposita'Guangfeng', and to observe the stomas of the transplanting plantlets and potted seedlings, to test chromosome ploidy by FCM, and to detect DNA mutation by ISSR,in order to provide the technical basis for the large-scale production of Dioscorea opposita 'Guangfeng' plantlets. Methods: The technique system of Dioscorea opposita 'Guangfeng'rapid propagation in vitro was established and optimized by plant tissue culture method. The parameters of transplanting plantlets and potted seedlings were studied as follows, the stomatal parameters were observed by transparent adhesive tape method, chromosome ploidy were analyzed by FCM, and DNA mutation were detected by ISSR molecular marker. Results: The technique system of Dioscorea opposite 'Guangfeng' rapid propagation in vitro was as follows, slightly woody stem segment with a bud were selected and inoculated onto MS + KT 1 mg / L + NAA 0. 2 mg / L solid culture medium and cultured in the photoperiod of 14 h / d( the temperature was( 25 ± 2) ℃ and light intensity was 1 500 ~ 2 000 Lx) after disinfected for 1 min in 70% alcohol prior to sterilized for 12 min with 0. 1% Hg Cl2,the materials were washed with sterile water for 3 times, respectively. The new bud was cut off when it grew to 2 ~ 3cm and inoculated into MS + KT 2 mg / L + NAA 0. 5 mg / L liquid culture medium and continued to culture in above culture conditions. The whole plant was formed after cultured for about 90 d. The sealing membrane was opened in transplanting, and the plantlets was still placed in above culture conditions and cultured for 2 ~ 3 d, and then the whole plant was taken out, and the culture medium washed off and then transferred into the vessel with shallow liquid MS basic culture medium and domesticated indoor. The acclimated plantlets were taken out and transplanted in the outdoor pots with the sandy soil when the new shoots grew out, and watered one time with tap water in the morning and evening per day, the survival rate reached 100%. The results of stomatal observation, FCM analysis and ISSR detection of transplanting plantlets and potted seedlings showed that the stomatal parameters, chromosome ploidy and DNA mutation of plantlets and potted seedlings had no variation. Conclusion: The results reveal that the establishment and optimization of the technique system of Dioscorea opposita 'Guangfeng' rapid propagation in vitro is feasible, and the regenerated plants do not have genetic variation which can ensure the stability of the genetic.

Correlation Between Blood Loss and Patient-Related Factors in the Bilateral Parasymphyseal Osteotomy.

The aim of this study was to determine the correlation between pre- and postsurgical loss of blood and blood components among patients undergoing treatment of facial deformities by bilateral parasymphyseal osteotomy (BPsO).The pre- and postoperative values of blood components were determined in 30 facial deformity patients who underwent orthognathic surgery by hypotensive anesthesia. Correlations among the blood loss, sex, age, operation time, and reduced values of blood components were assessed by a correlation matrix. The mean blood loss and operation time were 437.5 (± 52.5) mL and 355.8 (± 209.42) minutes, respectively. Two patients included in this study had required blood transfusion. The mean reduced red blood cell (× 10/µL), hemoglobin (g/dL), and hematocrit (%) were -1.02, -2.98, and -9.18, respectively. There was no significant correlation between blood loss and other related factors (eg, age, operation time, and reduced blood components). All patients, however, showed significantly lower values of blood components after surgery. In conclusion, no significant factor was associated with blood loss and reduced blood components among patients undergoing BPsO. Furthermore, hypotensive anesthesia is a well-accepted method to reduce blood loss during orthognathic surgery.

Effects of Ti surface treatments with silane and arginylglycylaspartic acid peptide on bone cell progenitors.

Achieving optimal aesthetic appearance is a major objective in dental implant design, and the interaction between the materials and the bone cell progenitors is an important factor in the attainment of this objective. In this study, a novel concept was evaluated by varying the surface modifications on titanium (Ti). Different levels of roughness can be attained by machine grinding (M), sand blasting, and acid etching (SLA) of the samples. The behavior of bone cell progenitors (D1) on the surfaces of Ti disks with different surface modifications was investigated. The surfaces of M or SLA disks were silanized (MS or SLAS group) through treatment with silane/Gly-Arg-Gly-Asp-Ser (GRGDS) peptide (MSP or SLASP group) and anchored particles of tetracalcium phosphate (TTCP) on the specimen surfaces (SLA-TTCP group). Physicochemical analysis was performed by metallographic microscopy, scanning electron microscopy, and contact angle analysis. The proliferation and the quantitative alkaline phosphatase (ALP) production of D1 cells on the surface of different sample groups were determined. The SLASP group had a significantly larger D1 cell proliferation than the other groups after 4 and 7 d of incubation (p < 0.05). ALP expression was a very early marker of differentiation, and was the first indication of the increasing number of cells at 7 d of culture. Among the groups in the M substrate series (i.e., M, MS, and MSP) and in the SLA series (i.e., SLA, SLAS, and SLASP), the MSP and SLASP specimens exhibited superior differentiation abilities on respective cultures until day 7 and day 10. A high number of hydrophilic surfaces dominated cell proliferation in the early stage of cell attachment. However, factors affecting the pore structure and the surface morphology can improve cell proliferation and differentiation. According to analyses of proliferation and ALP expression of bone cell progenitors D1, the original SLA implant surface can be improved with surface treatment methods, such as silanization and treatment with graft GRGDS pentapeptide. These methods can be potential candidates for the promotion of bone growth.

Analysis of maximum mouth opening and its related factors in 3- to 5-year-old Taiwanese children.

Maximum mouth opening (MMO) can reflect the function of the dentofacial musculature and joint system, and routine oral examinations should include its assessment. To diagnose abnormalities using MMO measurements, it is necessary to establish the normal range of MMO; however, few studies have investigated this subject in Taiwan. Therefore, the purposes of this study were to determine the normal MMO range in 3- to 5-year-old preschool children and to investigate the factors correlated with MMO. We examined the interincisal distance, defined as the distance between the edges of the upper and lower incisors, in 518 preschool children (age range 3-5 years; 271 boys and 247 girls) with a plastic sliding caliper. The MMO on both sides of the mouth and mouth width (MW) was measured 3 times. No differences in MMO were found between the genders. The interincisal distance was 37.47 (±4.11) mm for boys and 36.93 (±3.85) mm for girls, whereas the mean MMO was 37.21 (±3.99) mm. The MMO increased with the increasing age of the children, and the mean value of MMO in children aged 3, 4, and 5 was 35.31 (±4.03), 36.61 (±3.79), and 38.31 (±3.88) mm, respectively. Furthermore, MMO was found to correlate with weight and MW. MMO increased by 0.19 mm per increased weight and 0.37 mm per increased MW. The mean value of MMO in 3- to 5-year-old preschool children was 37.21 (±3.99) mm. MMO in 3- to 5-year-old preschool children increased with age and was correlated with weight and MW.

[Study on Rapid Micropropagation in Vitro Technique of Guangfeng Medicinal Yam (Dioscorea opposita) Plantlets].

OBJECTIVE: In order to provide methodology reference for virus-free and germplasm conservation of Guangfeng medicinal yam (Dioscorea opposita) plantlets, rapid micropropagation in vitro technique of Guangfeng medicinal yam plantlets was studied. METHODS: Using the method of plant tissue culture, single factor test and flow-cytometry, the basic procedure of Guangfeng medicinal yam tissue culture was established and the DNA content of Guangfeng medicinal yam plantlets and its potted seedlings was detected. RESULTS: The best disinfection procedure of stems with a bud of Guangfeng medicinal yam was washed with sterile water for three times after sterilized with 70% alcohol for 20 - 30 s and then washed with sterile water for three times again after sterilized with 0.1% mercuric chloride for 10 - 12 min; The best explants of stems with a bud of Guangfeng medicinal yam was slightly woody and more mature stems witha bud; The best proliferation culture medium of stems with a bud of Guangfeng medicinal yam was MS + 6-BA 2.0 mg/L + NAA 0.1 mg/L; The best rooting culture medium of stems with a bud of Guangfeng medicinal yam was MS + NAA 0.5 mg/L; The best culture method of Guangfeng medicinal yam plantlets was liquid culture; The best transplanting matrix of Guangfeng medicinal yam plantlets was the mixture of paddy clay and fine sand (1: 2) or the mixture of perlite and vermiculite (1: 2); The DNA content between Guangfeng medicinal yam plantlets and its potted seedlings had no significant difference. CONCLUSION: A fast and efficient micropropagation in vitro technological system of stems with a bud of Guangfeng medicinal yam is established, and the flow cytometry detect results also show the genetic stability of Guangfeng medicinal yam plantlets, whose results provide the technical and theoretical basis for the large-scale production of Guangfeng medicinal yam plantlets.

[Preliminary study of Dioscorea bulbifera plantlet microtuber in vitro induction].

OBJECTIVE: In order to provide a theoretical basis for the microtuber factory production and its germplasm resources preservation, in vitro induction of Dioscorea bulbifera plantlet microtubers was studied. METHODS: Through plant tissue culture technique and single factor experiment method, stems with buds of Dioscorea bulbifera plantlets as explants, the effects of various factors such as sugar, inorganic salt, cultivation mode, activated carbon and physiological state of stems with buds on in vitro induction of Dioscorea bulbifera microtubers were studied. RESULTS: The optimal sugar of Dioscorea bulbifera microtuber in vitro induction was 60 g/L sucrose or 90 g/L white sugar. The best inorganic salt concentration of Dioscorea bulbifera microtuber in vitro induction was MS. The best culture method of Dioscorea bulbifera microtuber in vitro induction was solid-liquid double layer culture. Activated carbon had a significant effect on Dioscorea bulbifera microtuber in vitro induction, whose optimum concentration was 0.03%. More mature the stem with buds was, the shorter the time of microtuber formation need. CONCLUSION: This experiment establishes a rapid method of Dioscorea bulbifera microtuber in vitro induction for the first time,which provides a new way for the application of Dioscorea bulbifera microtubers in agricultural production.

Effect of recombinant Hepatitis B virus on human glomerular mesangial cell apoptosis.

The aim of this study was to investigate the expression of recombinant Hepatitis B virus (HBV) in normal human glomerular mesangial cells (NHMC) and its effect on cell apoptosis. Cell transfection was conducted by the liposome method. The levels of HBsAg and HBeAg in the culture supernatant were detected by electrochemiluminescence. Morphological changes were observed by light and fluorescence microscopy. Cell proliferation was analysed by the methyl thiazole tetrazolium (MTT) assay and cell apoptosis, by flow cytometry. The expression level of Bax and Bcl-2 mRNA was measured by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR). Caspase-3 activity was detected by a Caspase-3 activity detection kit. The results showed high expression levels of HBsAg and HBeAg in NHMC cells transfected with recombinant full-length C genotype HBV (PHY106-CHBV). Typical apoptotic morphology was observed at 48 h after PHY106-CHBV transfection. Cell proliferation was inhibited. The percentage of apoptotic cells and the expression level of Bax mRNA were significantly higher in the PHY106-CHBV group than those in the blank control group and the PHY106 group. There was no significant difference in the expression level of Bcl-2 mRNA among the three groups. Caspase-3 was significantly activated after PHY106-CHBV transfection. The results demonstrate that recombinant HBV can be expressed in NHMC and its expression induces NHMC apoptosis.

Immune persistence after different polio sequential immunization schedules in Chinese infants.

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

Chloride channelopathies of ClC-2.

Chloride channels (ClCs) have gained worldwide interest because of their molecular diversity, widespread distribution in mammalian tissues and organs, and their link to various human diseases. Nine different ClCs have been molecularly identified and functionally characterized in mammals. ClC-2 is one of nine mammalian members of the ClC family. It possesses unique biophysical characteristics, pharmacological properties, and molecular features that distinguish it from other ClC family members. ClC-2 has wide organ/tissue distribution and is ubiquitously expressed. Published studies consistently point to a high degree of conservation of ClC-2 function and regulation across various species from nematodes to humans over vast evolutionary time spans. ClC-2 has been intensively and extensively studied over the past two decades, leading to the accumulation of a plethora of information to advance our understanding of its pathophysiological functions; however, many controversies still exist. It is necessary to analyze the research findings, and integrate different views to have a better understanding of ClC-2. This review focuses on ClC-2 only, providing an analytical overview of the available literature. Nearly every aspect of ClC-2 is discussed in the review: molecular features, biophysical characteristics, pharmacological properties, cellular function, regulation of expression and function, and channelopathies.

The Protective Role of Dietary Polyphenols in Urolithiasis: Insights into Antioxidant Effects and Mechanisms of Action.

Urolithiasis is a common urological disease with increasing prevalence and high recurrence rates around the world. Numerous studies have indicated reactive oxygen species (ROS) and oxidative stress (OS) were crucial pathogenic factors in stone formation. Dietary polyphenols are a large group of natural antioxidant compounds widely distributed in plant-based foods and beverages. Their diverse health benefits have attracted growing scientific attention in recent decades. Many literatures have reported the effectiveness of dietary polyphenols against stone formation. The antiurolithiatic mechanisms of polyphenols have been explained by their antioxidant potential to scavenge free radicals and ROS, modulate the expression and the activity of endogenous antioxidant and prooxidant enzymes, regulate signaling pathways associated with OS, and maintain cell morphology and function. In this review, we first describe OS and its pathogenic effects in urolithiasis and summarize the classification and sources of dietary polyphenols. Then, we focus on the current evidence defining their antioxidant potential against stone formation and put forward challenges and future perspectives of dietary polyphenols. To conclude, dietary polyphenols offer potential applications in the treatment and prevention of urolithiasis.

Adaptive tracking control for stochastic nonlinear systems with time-varying delays using multi-dimensional Taylor network.

For stochastic nonlinear systems (SNSs) perturbed by compound uncertainties, the conventional model-based control approaches assume that the evolution behavior of uncertain variables is known. Unfortunately, such approaches are often conservative for most practical scenarios with the slow convergence speed and unsatisfactory anti-interference performance. For this sake, an adaptive control scheme based on deep deterministic policy gradient (DDPG) and multi-dimensional Taylor network (MTN) is proposed here to address the tracking problem for a category of SNSs subject to fast time-varying uncertainties, stochastic disturbance and unknown time-varying delays. The effect of time delay is embedded in the reproducing kernel Hilbert space through the error coordinate transformation. In the framework of DDPG, the MTN-based surrogate is utilized to construct the online network and target network via the temporal-difference method, which promises more desirable real-time performance due to its concise structure than conventional NN-based surrogates. In order to enhance the robustness of the system under fast time-varying uncertainties, a novel persistent excitation (PE) mechanism is designed to ensure that the control policy is appropriately rewarded or punished. Based on the PE condition, weights of MTNs converge exponentially and animate the system to evolve towards the target persistently. The tracking error and closed-loop state signals are proved theoretically to be uniformly ultimately bounded (UUB) via Lyapunov-Krasovskii functional. A numerical simulation from the process industry verifies the effectiveness of the proposed method.