[Screening for Characteristic Genes of Different Traditional Chinese Medicine Syndromes of Psoriasis Vulgaris: A Study Based on Bioinformatics and Machine Learning]. / ç”Ÿç‰©ä¿¡æ¯å­¦å’Œæœºå™¨å­¦ä¹ ç­›é€‰é“¶å±‘ç— ä¸­åŒ»è¯åž‹ç‰¹å¾åŸºå› .

Objective: To screen for the key characteristic genes of the psoriasis vulgaris (PV) patients with different Traditional Chinese Medicine (TCM) syndromes, including blood-heat syndrome (BHS), blood stasis syndrome (BSS), and blood-dryness syndrome (BDS), through bioinformatics and machine learning and to provide a scientific basis for the clinical diagnosis and treatment of PV of different TCM syndrome types. Methods: The GSE192867 dataset was downloaded from Gene Expression Omnibus (GEO). The limma package was used to screen for the differentially expressed genes (DEGs) of PV, BHS, BSS, and BDS in PV patients and healthy populations. In addition, KEGG (Kyoto Encyclopedia of Genes and Genes) pathway enrichment analysis was performed. The DEGs associated with PV, BHS, BSS, and BDS were identified in the screening and were intersected separately to obtain differentially characterized genes. Out of two algorithms, the support vector machine (SVM) and random forest (RF), the one that produced the optimal performance was used to analyze the characteristic genes and the top 5 genes were identified as the key characteristic genes. The receiver operating characteristic (ROC) curves of the key characteristic genes were plotted by using the pROC package, the area under curve (AUC) was calculated, and the diagnostic performance was evaluated, accordingly. Results: The numbers of DEGs associated with PV, BHS, BSS, and BDS were 7699, 7291, 7654, and 6578, respectively. KEGG enrichment analysis was focused on Janus kinase (JAK)/signal transducer and activator of transcription (STAT), cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), apoptosis, and other pathways. A total of 13 key characteristic genes were identified in the screening by machine learning. Among the 13 key characteristic genes, malectin (MLEC), TUB like protein 3 (TULP3), SET domain containing 9 (SETD9), nuclear envelope integral membrane protein 2 (NEMP2), and BTG anti-proliferation factor 3 (BTG3) were the key characteristic genes of BHS; phosphatase 15 (DUSP15), C1q and tumor necrosis factor related protein 7 (C1QTNF7), solute carrier family 12 member 5 (SLC12A5), tripartite motif containing 63 (TRIM63), and ubiquitin associated protein 1 like (UBAP1L) were the key characteristic genes of BSS; recombinant mouse protein (RRNAD1), GTPase-activating protein ASAP3 Protein (ASAP3), and human myomesin 2 (MYOM2) were the key characteristic genes of BDS. Moreover, all of them showed high diagnostic efficacy. Conclusion: There are significant differences in the characteristic genes of different PV syndromes and they may be potential biomarkers for diagnosing TCM syndromes of PV.

Distribution and correlation of refractive parameters in children with different corneal curvatures in southeast China.

AIM: To analyze the distribution of refractive status in school-age children with different corneal curvatures (CC) and the correlation between CC and refractive status. METHODS: A total of 2214 school-aged children of grade 4 in Hangzhou who were screened for school myopia were included. Uncorrected distance visual acuity (UCDVA), non-cycloplegic refraction, axial length (AL), horizontal and vertical corneal curvature (K1, K2) were measured and spherical equivalent (SE), corneal curvature radius (CCR) and axial length/corneal radius of curvature ratio (AL/CR) were calculated. UCDVA<5.0 and SE≤-0.50 D were classified as school-screening myopia. According to the different CCRs, the patients were divided into the lower corneal curvature (LCC) group (CCR≥7.92) and the higher corneal curvature (HCC) group (CCR<7.92). Each group was further divided into the normal AL subgroup and the long AL subgroup. The refractive parameters were compared to identify any differences between the two groups. RESULTS: Both SE and AL were greater in the LCC group (P=0.013, P<0.001). The prevalence of myopia was 38% in the LCC group and 44% in the HCC group (P<0.001). The proportion of children without screening myopia was higher in the LCC group (62%) than in the HCC group (56%). Among these children without screening myopia, the proportion of long AL in the LCC group (24%) was significantly higher than that in the HCC group (0.012%; P<0.001). The change of SE in the LCC group was less affected by the increase of AL than that in the HCC group. CONCLUSION: School-aged children in the LCC group have a lower incidence of screening myopia and longer AL. Low CC can mask SE reduction and AL growth to some extent, and the change of AL growth change more in children with low CC than high CC. Before the onset of myopia, its growth rate is even faster than that after the onset of myopia.

Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

Taurocholic acid ameliorates hypertension through the activation of TGR5 in the hypothalamic paraventricular nucleus.

Diets rich in taurine can increase the production of taurine-conjugated bile acids, which are known to exert antihypertensive effects. Despite their benefits to the heart, kidney and arteries, their role in the central nervous system during the antihypertensive process remains unclear. Since hypothalamic paraventricular nucleus (PVN) plays a key role in blood pressure regulation, we aimed to investigate the function of bile acids in the PVN. The concentration of bile acids in the PVN of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKY) fed with normal chow was measured using LC-MS/MS, which identified taurocholic acid (TCA) as the most down-regulated bile acid. To fully understand the mechanism of TCA's functions in the PVN, bi-lateral PVN micro-infusion of TCA was carried out. TCA treatment in the PVN led to a significant reduction in the blood pressure of SHRs, with decreased plasma levels of norepinephrine and improved morphology of cardiomyocytes. It also decreased the number of c-fos+ neurons, reduced the inflammatory response, and suppressed oxidative stress in the PVN of the SHRs. Most importantly, the TGR5 receptors in neurons and microglia were activated. PVN infusion of SBI-115, a TGR5 specific antagonist, was able to counteract with TCA in the blood pressure regulation of SHRs. In conclusion, TCA supplementation in the PVN of SHRs can activate TGR5 in neurons and microglia, reduce the inflammatory response and oxidative stress, suppress activated neurons, and attenuate hypertension.

Loss of Slc39a12 in hippocampal neurons is responsible for anxiety-like behavior caused by temporomandibular joint osteoarthritis.

Background: An evident association between mood disorders and TMJ dysfunction has been demonstrated in previous studies. This study observed both the behavioral changes and the pathological changes in hippocampal tissue of rats in an animal model of TMJ-OA by injecting MIA into TMJ. Methods: Eighteen SD rats were randomly assigned to the NC group and the MIA groups. A TMJ-OA model was established to assess the HWT in the TMJ region, and the rats were subjected to the OFT and EPM. HE, O-fast green staining, qRT-PCR and immunofluorescence were used to detect condylar damage. Serum and hippocampal oxidative stress levels were detected. Functions of genes obtained by RNA-Seq were investigated using H2O2, ZnCl2 and transfection of siRNA on HT22 cells. Results: Injection of MIA resulted in disorganization of the chondrocyte layer on the condylar surface of rats, with reduced synthesis and increased degradation of the condylar cartilage matrix and reduced HWT. The results of the OFT and EPM showed that the rats in the MIA group developed anxiety-like behavior during the sixth week of MIA injection. Increased Nox4 expression, decreased SOD2 expression, elevated MDA level, and reduced GSH level were detected in serum and hippocampal neurons in the MIA group, with nuclear pyknosis and reduced Nissl bodies observed in neurons. The expression of Slc39a12 in hippocampal neurons of rats in the MIA group decreased. Slc39a12 knockdown in HT22 cells induced increased Nox4 expression, decreased SOD2 expression, increased MDA level, and reduced GSH and intracellular Zn2+. Oxidative stress in HT22 cells after transfection and H2O2 stimulation was reversed when ZnCl2 was added. Conclusion: Loss of Slc39a12 in hippocampal neurons results in cellular oxidative stress, further leading to neuronal damage. This may potentially explain how TMJ-OA triggers anxiety-like behavior in rats.

Association between Dietary Consumption of Vitamin B1 and Advanced Age-Related Macular Degeneration: A Cross-Sectional Observational Study in NHANES 2005-2008.

INTRODUCTION: One of the most common conditions that causes permanent blindness globally is age-related macular degeneration (AMD). The purpose of the present study was to determine the association between vitamin B1 consumption and the prevalence of late AMD in a representative US sample. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008 were utilized for this cross-sectional analysis. The logistic regression model was used to evaluate the association between vitamin B1 consumption levels and late AMD. RESULTS: Our study included 5,107 people aged 40 years old and above. Vitamin B1 intake levels were inversely associated with the prevalence of late AMD, with OR being 0.40 (95% CI: 0.26-0.62), 0.53 (95% CI: 0.29-0.94), 0.55 (95% CI: 0.31-0.99) for the crude model 1, adjusted model 2, and fully adjusted model 3, respectively. CONCLUSION: Our study found that vitamin B1 intake levels were inversely associated with the prevalence of late AMD in the USA. Further randomized clinical trials among multiple centers are still warranted to investigate the longitudinal and causal relationship between vitamin B1 intake and late AMD.

All-Natural, Robust, and pH-Responsive Glycyrrhizic Acid-Based Double Network Hydrogels for Controlled Nutrient Release.

Supramolecular hydrogels self-assembled from naturally occurring small molecules (e.g., glycyrrhizic acid, GA) are promising materials for controlled bioactive delivery due to their facile fabrication processes, excellent biocompatibility, and versatile stimuli-responsive behaviors. However, most of these natural hydrogels suffer from poor mechanical strength and processability for practical applications. In this work, through adopting a multicomponent gel approach, we developed a novel mechanically robust GA-based hydrogel with an interpenetrating double network (DN) that is composed of a Ca2+-enhanced hydrogen-bond supramolecular GA nanofibril (GN) network and a Ca2+cross-linked natural polysaccharide sodium alginate (ALG) network. Compared to the single GN network (SN) hydrogel, the GN-ALG hybrid hydrogels (GN-ALG-DN) with the hierarchical double-network structure possess excellent mechanical properties and shaping adaptation, encouraging small and large amplitude oscillatory shear (SAOS and LAOS) rheological performances, better thermal stability, higher resistance to large compression deformations, and lower swelling behaviors. Furthermore, the GN-ALG-DN hydrogels exhibit a pH-responsive and sustained release behavior of nutrients (i.e., vitamin B12, VB12), showing a faster VB12 release rate with a higher swelling ratio in an alkaline condition (pH 7.5) than in an acidic condition (pH 2.5). This is ascribed to the fact that the higher dissociation degree of carboxylic groups in GA and ALG molecules in an alkaline environment induces the erosion and looseness of the self-assembled GN network and the ionic-cross-linked ALG network, which can lead to the decomposition of the hybrid hydrogels and thereby increases the release of nutrients. Cytotoxicity tests further demonstrate the excellent biocompatibility of the GN-ALG-DN hydrogels. This study highlights the design of robust shaped and structured supramolecular hydrogels from natural herb small molecules, which can serve as solid, edible, and stimuli-responsive active cargo delivery platforms for food, biomedical, and sustainable applications.

Development of antibacterial nanocomposites by combination of bacterial cellulose/chitin nanofibrils and all-natural bioactive nanoparticles.

In this study, a functional composite membrane was facilely fabricated by using a dual nanofibril system of bacterial cellulose (BC) and chitin (CH) nanofibrils as bio-based building blocks. The BC-CH membranes with enhanced antibacterial activity were constructed by incorporation of all-natural bioactive nanoparticles (GBTPs), which were formed by spontaneous molecular interactions of three naturally occurring active small molecules, i.e., glycyrrhizic acid (GA), berberine (BR), and tannic acid (TA). The microstructure, physicochemical properties, and antibacterial behaviors of the resulting BC-CH-GBTPs nanocomposites were then characterized. The obtained results showed that the GBTPs with a diameter of around 50-100 nm and membrane matrix were bound by non-covalent interactions, and the addition of GBTPs did not compromise the structural integrity and thermal stability of the composites, which retained good mechanical properties. Furthermore, the addition of GBTPs led to a rougher surface structure and increased the water contact angle of the membrane surfaces from 48.13° to 59.80°. The antimicrobial tests indicate that the BC-CH-GBTPs nanocomposites exhibited significant inhibitory effects against Escherichia coli and Staphylococcus aureus, showing a satisfactory antibacterial ability. These results suggest that the BC-CH-GBTPs nanocomposites based on all-natural, plant-based building blocks, hold promising potentials as active packaging materials for sustainable applications.

Autoimmune enteropathy complicated with primary biliary cholangitis.

Autoimmune enteropathy is a rare intestinal disease. Here we report an elderly female with autoimmune enteropathy and primary biliary cholangitis who presented with chronic diarrhea, malnutrition and severe hypokalemia and metabolic acidosis. Enteroscopy showed atrophied small intestinal villi with scallop-like and fissure-like changes. Hormone treatment relieved diarrhea. Four months later, she developed primary biliary cholangitis, and the liver function returned to normal after treatment with ursodeoxycholic acid, corticosteroids and immunosuppressants.

Epsilon-poly-l-lysine conjugated erythromycin for enhanced antibiotic therapy.

Antibiotic resistance is a big threat to public health. How to improve the therapeutic efficacy of conventional antibiotics is an effective way to address this issue. In order to enhance the antibacterial activity of conventional antibiotic erythromycin (EM), EM is conjugated to positively charged ε-poly-l-lysine (EPL) to obtain EPL modified EM (EPL-EM). The grafting ratio of EM can be calculated from the 1H NMR spectrum. EPL-EM is stable in physiological environment, while EM can be readily released from EPL-EM upon incubating with esterase which can be secreted by most bacteria. Because of the presence of cationic EPL, EPL-EM showed much stronger antibacterial activity than free EM, with much lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Moreover, compared to free EM, the development of drug resistance can be slowed down if EPL-EM is used, which can be ascribed to the reduction of EM dosage. Meanwhile, EPL-EM cannot induce hemolysis and cytotoxicity, which indicates that EPL-EM exhibits excellent biocompatibility. The design of EPL-EM with enhanced antibacterial activity and excellent biocompatibility provides an innovative way to combat antibiotic resistance.

Multiple neuroendocrine tumors in the stomach, duodenum and pancreas of a MEN1 patient.

Gastrinoma, a common type of GEP-NENs, is often sporadic, rarely manifested as multiple endocrine neoplasia type 1 (MEN1). We described a rare case of MEN1-related gastrinomas in the stomach, duodenum and pancreas along with lymph node metastases. The female patient had a long history of recurrent abdominal pain and diarrhea. G1 neuroendocrine tumors were diagnosed by endoscopic biopsy in the pylorus, duodenal bulb and the neck of the pancreas successively. Her symptoms lessened and serum gastrin level decreased after surgery. This case will help us learn more about MEN1-associated patients who are confirmed with multiple neuroendocrine tumors.

Residue analysis and dietary risk assessment of thiamethoxam, flonicamid and their metabolites in cucumber under field conditions in China.

Thiamethoxam and flonicamid are two representative insecticides of neonicotinoids which are used to treat cucumber aphids, causing food safety and human health problems. A 60% thiamethoxam-flonicamid commercial mixture water dispersible granule (WDG) is being prepared for registering in China, so it is essential to investigate the residue levels of these neonicotinoids and their metabolites in cucumber and evaluate the dietary risks of these insecticides. We developed a modified quick, easy, cheap, effective, rugged and safe (QuEChERS) method combined with high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) for the simultaneous determination of thiamethoxam and its metabolite clothianidin, flonicamid and its metabolites 4-trifluoromethylnicotinic acid (TFNA), 4-trifluoromethilnicotinamide (TFNA-AM), 4-(trifluoromethyl) nicotinol glycine (TFNG) in cucumber. Method validation indicated good selectivity, linearity (r ≥ 0.9996), accuracy (recoveries of 80-101%), precision (relative standard deviations (RSD) ≤ 9.1%), sensitivity (limits of detection (LOD), 0.28-1.44 × 10-3 mg/L; limits of quantification (LOQ), 0.01 mg/kg) and minor matrix effect (ME) ( ≤|± 5%|). In the terminal residue trials under good agricultural practice (GAP) conditions, the residue levels of six analytes in cucumber samples were ˂0.01-0.215 mg/kg after application trice with an interval of 7 days based on pre-harvest interval (PHI) of 3 days under the high recommended dosage of 54 g active ingredient/ha (g a.i./ha). Relevant toxicological, residual chemistry parameters and dietary consumption of the residents were applied to assess the potential risk of dietary exposure. The chronic and acute dietary exposure assessment risk quotient (RQ) values were less than 1. The above results indicated that the potential dietary intake risk of this formulation was negligible to consumers.

Evaluation of Taraxacum mongolicum flavonoids in diets for Channa argus based on growth performance, immune responses, apoptosis and antioxidant defense system under lipopolysaccharide stress.

To ascertain the effects of Taraxacum mongolicum flavonoids (TMF) on the growth performance, digestive enzyme activity, immune indices, inflammatory response and antioxidant capacity of Channa argus, 400 C. argus with an average body weight of (8.08 ± 0.21) g were selected and divided randomly into four groups. They were fed with four experimental diets supplemented with TMF of 0 (control), 25, 50 and 100 mg/kg for 56 d, and then challenged with lipopolysaccharide (LPS) for 96 h, afterwards indices were detected. The results manifested that the addition of TMF above 50 mg/kg in the dietary could significantly improve the final body weight, WGR, SGR and PER of C. argus, while decreased FCR (P < 0.05). Similarly, the 50 mg/kg group had the highest activity of digestive enzymes (protease, lipase, amylase) in intestine and hepatopancreas, which were notably higher than those in the control group (P < 0.05). Nevertheless, 100 mg/kg group could effectively inhibit the liver and gut injury caused by LPS and reduce the contents of ALT and AST, LPS and LBP in serum. In the immune (LY, AKP, ACP, IgM, C3) and antioxidant (T-AOC, SOD, CAT, GSH-PX, GR, ASA, MDA) systems, 100 mg/kg groups were the optimal group, which were remarkably higher than those of the control group (P < 0.05). Additionally, the expression of genes revealed that 100 mg/kg group could noteworthy restrain the expression of pro-inflammatory factors (tnf-α, il-1ß, il-8) and pro-apoptosis (cas-3,8,9, p53, bax, bcl-2) related genes, up-regulate the expression of anti-inflammatory (il-10, tgf-ß) factors, antioxidant-related (nrf2, gpx, gst, cat) genes and heat shock proteins (hsp70, hsp90). Simultaneously, the survival rate of C. argus in the 100 mg/kg TMF-supplemented group was the highest after LPS challenge. Our results elucidate that dietary supplementation TMF protects C. argus from LPS-induced inflammatory injury, to ameliorate digestion, immune response, antioxidant status and apoptosis, implying that TMF could be regarded as an anti-inflammatory and antioxidant agent adding to aquatic animal feed.

Widely tunable O-band lithium niobite/III-V transmitter.

The ever-increasing traffic has been driving the demand for compact, high-speed, and low-power-consumption optical transmitters. Thin-film lithium niobite (TFLN) platforms have emerged as promising photonic integrated solutions for next-generation optical transmitters. In this study, we demonstrated the first widely tunable optical transmitter based on a butt-coupling a TFLN modulator with an electrically pumped tunable laser. The tunable laser exhibited a side-mode suppression ratio of > 60 dB, linewidth of 475 kHz, and wavelength-tuning range of over 40 nm. The TFLN modulator presented a voltage-length product of 2.9 V·cm and an electro-optic response of 1.5 dB roll-off at 50 GHz. The optical transmitter support data rate was as high as 160 Gb/s.

Application and Analysis of Improved Fuzzy Comprehensive Evaluation Method in Goodwill Evaluation and Intangible Asset Management.

In order to improve the effect of goodwill evaluation and intangible asset management, this paper combines the improved fuzzy comprehensive evaluation method to construct an intelligent algorithm. In order to consider the many influencing factors of intangible asset prices and their own influence, this experiment adopts the ARDL model for analysis. Based on the traditional LSTM model, this paper innovatively introduces sparse principal component analysis for feature dimensionality reduction and, on the other hand, adds a convolutional neural network to the model, which is suitable for feature extraction. In addition, this paper constructs a goodwill evaluation and intangible asset management model based on the improved fuzzy comprehensive evaluation method. The research shows that the improved fuzzy comprehensive evaluation method proposed in this paper has a very good application effect in goodwill evaluation and intangible asset management.

Convergence between germline and somatic mutations in pancreatic neuroendocrine tumors.

Objectives: The pancreatic neuroendocrine tumors (PanNETs) are a group of clinically heterogeneous neoplasms. Although previous studies illustrated the somatic mutation pattern for PanNETs, the germline mutation pattern is still unclear. Here, we comprehensively screened the underlying germline mutations in a cohort of multiple endocrine neoplasia type 1 (MEN1)-related and sporadic PanNETs to reveal the characteristics of germline mutation in PanNET patients. Methods: Patients diagnosed with PanNETs by biopsy or surgical pathology were enrolled in this study. Peripheral blood samples were used for genomic DNA purification and subsequent sequencing. The following sequencing techniques were used and compared for validation: (1) targeted gene capture with a customized panel; (2) whole exome sequencing data from previous study. Results: A total of 184 PanNET patients were enrolled, including 20 MEN1-related and 164 sporadic cases. In this study, MEN1 mutation rate in MEN1-related PanNETs was 60% (12/20), of which 50% were novel mutation sites. For sporadic PanNETs, the overall germline mutation rate was very low. Besides the rare MEN1 mutation, previously unreported germline variant in DAXX was found in one non-functional PanNET. Conclusions: This study revealed distinctive germline mutation rates between MEN1-related and sporadic PanNETs. The novel MEN1 mutations contribute to revealing the spectrum of MEN1 mutations in PanNETs. The newly discovered germline variant of DAXX in sporadic PanNET implies a tendency of convergence between germline and somatic mutation genes.

Compact substrate-removed thin-film lithium niobate electro-optic modulator featuring polarization-insensitive operation.

A compact polarization-insensitive electro-optic (EO) modulator, which allows the laser and modulator to be located at different locations while using a standard single-mode fiber to interconnect them, is highly desirable for 5G or future 6G wireless networks. Herein, we propose a modulator based on substrate-removed thin-film lithium niobate. The proposed device exhibits a polarization-dependent loss of 0.35 dB and on-chip loss of approximately 2 dB. The polarization insensitivity of the proposed device was experimentally demonstrated using a four-level pulse-amplitude modulation format at 50 Gbaud (100 Gb/ s).

High-performance polarization management devices based on thin-film lithium niobate.

High-speed polarization management is highly desirable for many applications, such as remote sensing, telecommunication, and medical diagnosis. However, most of the approaches for polarization management rely on bulky optical components that are slow to respond, cumbersome to use, and sometimes with high drive voltages. Here, we overcome these limitations by harnessing photonic integrated circuits based on thin-film lithium niobate platform. We successfully realize a portfolio of thin-film lithium niobate devices for essential polarization management functionalities, including arbitrary polarization generation, fast polarization measurement, polarization scrambling, and automatic polarization control. The present devices feature ultra-fast control speeds, low drive voltages, low optical losses and compact footprints. Using these devices, we achieve high fidelity polarization generation with a polarization extinction ratio up to 41.9 dB and fast polarization scrambling with a scrambling rate up to 65 Mrad s-1, both of which are best results in integrated optics. We also demonstrate the endless polarization state tracking operation in our devices. The demonstrated devices unlock a drastically new level of performance and scales in polarization management devices, leading to a paradigm shift in polarization management.