Omni-polarized Faraday isolator based on non-Hermitian Faraday system.

Non-Hermitian systems have recently attracted significant attention in photonics due to the realization that the interplay between gain and loss can lead to entirely new and unexpected features. Here, we propose and demonstrate a non-Hermitian Faraday system capable of non-reciprocal omni-polarizer action at the exceptional point. Notably, both forward and backward propagating light with arbitrary polarization converge to the same polarization state. Leveraging the robustness and non-reciprocity of the non-Hermitian Faraday system, we realize an omni-polarized Faraday isolator that can effectively isolate any polarized light without the need for a polarizer at the incident port of backward propagation. Remarkably, under the given parameter configuration, the isolator achieves a maximum isolation ratio of approximately 100 dB and a minimum isolation ratio of around 45 dB for various polarized light, accompanied by near-zero insertion loss. Furthermore, our research reveals the remarkable tolerance of the non-Hermitian Faraday isolator to nonlinear effects. This unique characteristic allows us to harness nonlinear effects to achieve various optical functions, all while maintaining excellent isolation performance. The proposed non-Hermitian Faraday system paves the way for the realization of magnetically or optically switchable non-reciprocal devices.

Fine mapping of BnDM1-the gene regulating indeterminate inflorescence in Brassica napus.

KEY MESSAGE: A candidate gene Bndm1 related to determinate inflorescence was mapped to a 128-kb interval on C02 in Brassica napus. Brassica napus plants with determinate inflorescence exhibit improved traits in field production, such as lower plant height, improved lodging resistance, and consistent maturity. Compared to plants with indeterminate inflorescence, such features are favorable for mechanized harvesting techniques. Here, using a natural mutant 6138 with determinate inflorescence, it is demonstrated that determinate inflorescence reduces plant height significantly without affecting thousand-grain weight and yield per plant. Determinacy was regulated by a single recessive gene, Bndm1. Using a combination of SNP arrays and map-based cloning, we mapped the locus of determinacy to a 128-kb region on C02. Based on sequence comparisons and the reported functions of candidate genes in this region, we predicted BnaC02.knu (a homolog of KNU in Arabidopsis) as a possible candidate gene of Bndm1 for controlling determinate inflorescence. We found a 623-bp deletion in a region upstream of the KNU promoter in the mutant. This deletion led to the significant overexpression of BnaC02.knu in the mutant compared to that in the ZS11 line. The correlation between this deletion and determinate inflorescence was examined in natural populations. The results indicated that the deletion affected the normal transcription of BnaC02.knu in the plants with determinate inflorescence and played an important role in maintaining flower development. This study presents as a new material for optimizing plant architecture and breeding novel canola varieties suitable for mechanized production. Moreover, our findings provide a theoretical basis for analyzing the molecular mechanisms underlying the formation of determinate inflorescence in B. napus.

Molecular Networking-Guided Isolation of Cyclopentapeptides from the Hydrothermal Vent Sediment Derived Fungus Aspergillus pseudoviridinutans TW58-5 and Their Anti-inflammatory Effects.

Repetitive isolation of known compounds remains a major challenge in natural-product-based drug discovery. LC-MS/MS-based molecular networking has become a highly efficient strategy for the discovery of new natural products from complex mixtures. Herein, we report a molecular networking-guided isolation procedure, which resulted in the discovery of seven new cyclopentapeptides, namely, pseudoviridinutans A-F (1-7), from the marine-derived fungus Aspergillus pseudoviridinutans TW58-5. Compounds 1-7 feature a rare amino acid moiety, O,ß-dimethyltyrosine, observed for the first time from a marine-derived fungus. The planar structures of 1-7 were elucidated by detailed analyses of IR, UV, HR ESI-Q-TOF MS, and 1D and 2D NMR spectroscopic data. Meanwhile, their absolute configurations were determined through a combination of Marfey's method and X-ray diffraction. Subsequent bioassay revealed the anti-inflammation potential of 1-7, especially 6, which inhibited the production of nitric oxide (NO), a vital inflammatory mediator, in LPS-induced murine macrophage RAW264.7 cells by regulating the expression level of NLRP3 and iNOS.

Asymmetric reflection based on asymmetric coupling in single-layer extrinsic chiral metasurfaces.

We propose and experimentally demonstrate that giant asymmetric reflection of circularly polarized light based on asymmetric coupling can be achieved in single-layer extrinsic chiral metasurfaces at oblique incidence. The asymmetric coupling and asymmetric reflection in the extrinsic chiral metasurfaces are caused by extrinsic chirality, allowing them to have extremely high values. An asymmetric reflection of approximately 40% is measured. Furthermore, the asymmetric reflection of extrinsic chiral metasurfaces is demonstrated not only in intensity but also in phase retardation, which induces asymmetric polarization state conversion. An approximately 14° asymmetric reflected polarization offset from the symmetry axis is achieved. Our research provides an effective new method for constructing huge asymmetric coupled systems to manipulate electromagnetic waves.

Machine Learning-Assisted Measurement Device-Independent Quantum Key Distribution on Reference Frame Calibration.

In most of the realistic measurement device-independent quantum key distribution (MDI-QKD) systems, efficient, real-time feedback controls are required to maintain system stability when facing disturbance from either external environment or imperfect internal components. Traditionally, people either use a "scanning-and-transmitting" program or insert an extra device to make a phase reference frame calibration for a stable high-visibility interference, resulting in higher system complexity and lower transmission efficiency. In this work, we build a machine learning-assisted MDI-QKD system, where a machine learning model-the long short-term memory (LSTM) network-is for the first time to apply onto the MDI-QKD system for reference frame calibrations. In this machine learning-assisted MDI-QKD system, one can predict out the phase drift between the two users in advance, and actively perform real-time phase compensations, dramatically increasing the key transmission efficiency. Furthermore, we carry out corresponding experimental demonstration over 100 km and 250 km commercial standard single-mode fibers, verifying the effectiveness of the approach.

Weak Value Amplification-Based Biochip for Highly Sensitive Detection and Identification of Breast Cancer Exosomes.

Exosomes constitute an emerging biomarker for cancer diagnosis because they carry multiple proteins that reflect the origins of the parent cell. The highly sensitive detection of exosomes is a crucial prerequisite for the diagnosis of cancer. In this study, we report an exosome detection system based on quantum weak value amplification (WVA). The WVA detection system consists of a reflection detection light path and a Zr-ionized biochip. Zr-ionized biochips effectively capture exosomes through the specific interaction between zirconium dioxide and the phosphate groups on the lipid bilayer of exosomes. Aptamer-modified gold nanoparticles (Au NPs) are then used to specifically recognize proteins on exosomes to enhance the detection signal. The sensitivity and resolution of the detection system are 2944.07 nm/RIU and 1.22 × 10-5 RIU, respectively. The concentration of exosomes can be directly quantified by the WVA system, ranging from 105-107 particles/mL with the detection limit of 3 × 104 particles/mL. The use of Au NPs-EpCAM for the specific enhancement of breast cancer MDA-MB-231 exosomes is demonstrated. The results indicate that the WVA detection system can be a promising candidate for the detection of exosomes as tumor markers.

Chang-Kang-Fang alleviates diarrhea predominant irritable bowel syndrome (IBS-D) through inhibiting TLR4/NF-κB/NLRP3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Chang-Kang-Fang (CKF), originated from traditional Chinese medicine (TCM) formulas, has been utilized to treat diarrhea predominant irritable bowel syndrome (IBS-D) based on clinical experience. However, the underlying mechanism of CKF for treating IBS-D remains unclear and need further clarification. AIM OF THE STUDY: The objective of this present investigation was to validate the efficacy of CKF on IBS-D model rats and to uncover its potential mechanism for the treatment of IBS-D. MATERIALS AND METHODS: We first established the IBS-D rat model through neonatal maternal separation (NMS) in combination with restraint stress (RS) and the administration of senna decoction via gavage. To confirm the therapeutic effect of CKF on treating IBS-D, abdominal withdrawal reflex (AWR) scores, the quantity of fecal pellets, and the fecal water content (FWC) were measured to evaluate the influence of CKF on visceral hypersensitivity and the severity of diarrhea symptom after the intragastric administration of CKF for 14 days. Subsequently, enzyme linked immunosorbent assay (ELISA) was applied to assess the effect of CKF on neuropeptides substance P (SP) and 5-hydroxytryptamine (5-HT), as well as inflammatory cytokines in serum and in intestinal tissues. Further, colonic pathological changes, the amount of colonic mast cells, and the expression level of occludin in rat colon tissues, were investigated by hematoxylin-eosin (HE) staining, toluidine blue staining, and immunohistochemistry, respectively. To explore the underlying mechanisms, alterations in colonic RNA transcriptomics for the normal, model, and CKF treatment groups were assessed using RNA sequencing (RNA-Seq). Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB), and immunofluorescence (IF) assays were applied to validate the effect of CKF on predicted pathways in vivo and in vitro. In addition, to elucidate the potential active compounds in CKF, 11 representative components found in CKF were selected, and their anti-inflammation potentials were evaluated using LPS-treated RAW264.7 cell models. RESULTS: CKF treatment significantly reduced the number of fecal pellets, attenuated visceral hypersensitivity, and decreased 5-HT and SP concentrations in serum and colon tissues, along with a reduction in colonic mast cell counts, correlating with improved symptoms in IBS-D rats. Meanwhile, CKF treatment reduced the colonic inflammatory cell infiltration, lowered the levels of IL-6, TNF-α, and IL-1ß in serum and colon tissues, and increased the occludin protein expression in colon tissues to improve inflammatory response and colonic barrier function. RNA-Seq, in conjugation with our previous network pharmacology analysis, indicated that CKF might mitigate the symptoms of IBS-D rats by inhibiting the Toll like receptor 4/Nuclear factor kappa-B/NLR family pyrin domain-containing protein 3 (TLR4/NF-κB/NLRP3) pathway, which was confirmed by WB, IF, and qRT-PCR experiments in vivo and in vitro. Furthermore, coptisine, berberine, hyperoside, epicatechin, and gallic acid present in CKF emerged as potential active components for treating IBS-D, as they demonstrated in vitro anti-inflammatory effects. CONCLUSION: Our findings demonstrate that CKF effectively improves the symptoms of IBS-D rats, potentially through the inhibition of the TLR4/NF-κB/NLRP3 pathway. Moreover, this study unveils the potential bioactive components in CKF that could be applied in the treatment of IBS-D.

A novel sorbicillinoid compound as a potent anti-inflammation agent through inducing NLRP3 protein degradation.

BACKGROUND AND PURPOSE: Chronic inflammation is pathogenic and contributes to human diseases, causing a significant threat to public health. The NLR family pyrin domain-containing protein 3 (NLRP3) is the best-characterized factor regulating inflammation. Therefore, targeting NLRP3 has the potential to treat inflammatory diseases and improve human health. EXPERIMENTAL APPROACH: Lipopolysaccharide was used to induce inflammation in cell cultures. Lipopolysaccharide/d-galactosamine and dextran sulfate sodium salt were used to induce acute liver inflammation and ulcerative colitis respectively in C57BL/6J mice. Western blotting, immunofluorescence, immunoprecipitation, quantitative PCR and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the activation of the inflammatory response in cell cultures and in mice. KEY RESULTS: JNUTS013, a novel sorbicillinoid compound recently synthesized by us, significantly inhibited inflammation both in cell cultures and in mouse models. Mechanistically, JNUTS013 induced proteasome-dependent degradation of NLRP3. Hence, it suppressed the formation of the NLRP3 inflammasome and the production of downstream inflammatory cytokines and chemokines. The inhibitory effect of JNUTS013 on NLRP3 protein expression was confirmed in mice. Importantly, JNUTS013 failed to ameliorate bowel inflammation in Nlrp3-/- knockout mice, supporting NLRP3 as the biological target by which JNUTS013 inhibits inflammation. Further studies revealed critical chemical moieties of JNUTS013 required for inducing NLRP3 degradation. CONCLUSION AND IMPLICATIONS: This study identifies a novel compound JNUTS013 that inhibits inflammation through inducing NLRP3 protein degradation in vitro and in vivo, which not only supports the development of JNUTS013 as an anti-inflammation agent but also creates a new way for the treatment of inflammation by chemically inducing NLRP3 degradation.

Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active components identification.

Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism. Through this comprehensive analysis, a total of 150 components were identified or tentatively characterized within the CKF formula. Notably, six N-acetyldopamine oligomers from CicadaePeriostracum and eight resin glycosides from Cuscutae Semen were characterized in this formula for the first time. Meanwhile, 149 xenobiotics (58 prototypes and 91 metabolites) were detected in plasma, urine, feces, brain, and intestinal contents, and the in vivo metabolic pathways of resin glycosides were elaborated for the first time. Furthermore, network pharmacology and molecular docking analyses revealed that alkaloids, flavonoids, chromones, monoterpenes, N-acetyldopamine dimers, p-hydroxycinnamic acid, and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS, and CASP8, MARK14, PIK3C, PIK3R1, TLR4, and TNF may be its potential targets. These discoveries offer a comprehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS, facilitating the broader application of CKF in the field of medicine.

Downregulated RBM5 Enhances CARM1 Expression and Activates the PRKACA/GSK3ß Signaling Pathway through Alternative Splicing-Coupled Nonsense-Mediated Decay.

Downregulated RNA-binding motif protein 5 (RBM5) promotes the development and progression of various tumors, including bladder cancer (BC). Alternative splicing (AS) plays a crucial role in the progression of cancer by producing protein isomers with different functions or by promoting nonsense-mediated mRNA decay (NMD). However, whether RBM5 modulates the progression of BC through AS-NMD remains unexplored. In this study, we revealed that the downregulation of RBM5 expression promoted the expression of coactivator-associated arginine methyltransferase 1 (CARM1) in BC cells and tissues. Increased expression of CARM1 facilitated the activation of the Wnt/ß-catenin axis and cell proliferation, which then contributed to the poor prognosis of patients with BC. Interestingly, RBM5 bound directly to CARM1 mRNA and participated in AS-NMD, downregulating the expression of CARM1. In addition, we revealed that protein kinase catalytic subunit alpha (PRKACA) functioned as a phosphorylated kinase of GSK3ß, was regulated by CARM1 at the transcription level, and promoted the growth and progression of BC cells. Furthermore, in this study, we demonstrated a regulatory mechanism of Wnt/ß-catenin activation through the RBM5/CARM1/PRKACA axis and identified a novel potential target for treating BC.

Deciphering in vivo metabolic profile and pharmacological mechanisms of Jitongning Tablet for the treatment of Ankylosing spondylitis.

Jitongning tablet (JTNT) is a Traditional Chinese Medicine (TCM) prescription used for the treatment of Ankylosing spondylitis (AS). Currently, it is in phase II clinical trial (NCT03932019) for patients with active axial Spondyloarthritis (axSpA), showing great promise for the treatment of AS. However, the potential material basis and the underlying mechanisms for JTNT to treat AS remain elusive. Here, we performed UPLC-Q-TOF-MS to determine the in vivo metabolic profile of JTNT in rats and conducted in vivo studies including acetic acid-induced writhing, hot plate models, and collagen-induced arthritis (CIA) in rats to evaluate and validate the analgesic and anti-inflammatory effects of JTNT, two main symptoms for AS. Additionally, network pharmacology combined with molecular docking was performed to investigate the potential underlying mechanisms. As a result, a total of 116 xenobiotics were identified from the plasma, urine, and brain tissues of rats after oral administration of JTN extracts. Pharmacological evaluation revealed that fractions JTN-3 and JTN-4 exerted significant analgesic activities by reducing the number of writhes in an acetic acid-induced writhing mice model. JTN extract also exerted excellent therapeutic effects in the CIA model by ameliorating paw edema and decreasing systemic manifestation of inflammation and the level of circulating immune complex (CIC) and interferon γ (IFN-γ). Fractions of JTN extract, especially JTN-2 and JTN-4, on the other hand, ameliorated the secondary lesions caused by chicken type II collagen (CII) to a certain extent. Further, network pharmacology combined with molecular docking suggested crucial roles of inflammation and immune-related genes such as MAPK1, MAPK14, NOS3, and RELA in the treatment of AS by JTNT. In conclusion, our studies suggest that the isoquinoline and diterpenoid alkaloids from Corydalis Rhizoma and Aconiti Radix Cocta, along with coumarins from Angelicae Pubescentis Radix, may be the main bioactive components, and the AS treatment mechanism may mainly involve immune regulation of JTNT. These results help clarify the potential material basis and underlying mechanisms of JTNT for the treatment of AS, facilitating the broad application of this TCM in clinical practice.

Coin Paradox Spin-Orbit Interaction Enhances Magneto-Optical Effect and Its Application in On-Chip Integrated Optical Isolator.

We designed a simple on-chip integrated optical isolator made up of a metal-insulator-metal waveguide and a disc cavity filled with magneto-optical material to enhance the transverse magneto-optical effect through the coin paradox spin-orbit interaction (SOI). The simulation results of the non-reciprocal transmission properties of this optical structure show that a high-performance on-chip integrated optical isolator is obtained. The maximum isolation ratio is greater than 60 dB with a corresponding insertion loss of about 2 dB. The great performance of the optical isolator is attributed to the strong transverse magneto-optical effect, which is enhanced by the coin paradox SOI. Moreover, the enhancement of the transverse magneto-optical effect through the coin paradox SOI is more substantial for smaller azimuthal mode number n. Benefiting from this, the transverse magneto-optical effect remains strong in a wide wavelength range. Additionally, a smaller cavity has a stronger transverse magneto-optical effect in the same wavelength range. Our research provides a new perspective for creating highly integrated magneto-optical devices.

Epidemiological, Clinical, and Immunological Features of a Cluster of COVID-19-Contracted Hemodialysis Patients.

BACKGROUND: The outbreak of highly contagious coronavirus disease 2019 (COVID-19) has posed a serious threat to human life and health, especially for those with underlying diseases. However, the impact of COVID-19 epidemic on hemodialysis (HD) centers and HD patients has not been reported. METHODS: We reviewed the whole course of the COVID-19 in the HD center of Renmin Hospital, Wuhan University (from January 14, 2020, to March 12, 2020). We compared the clinical manifestation and immune profiles among different patient groups with healthy individuals. RESULTS: Forty-two of 230 HD patients (18.26%) and 4 of 33 medical staff (12.12%) were diagnosed with COVID-19 during the study period. Fifteen HD patients (6.52%), including 10 COVID-19 diagnosed, died. Only 2 deaths of the COVID-19 HD patients were associated with pneumonia/lung failure, others were ascribed to cardiovascular/cerebrovascular diseases or hyperkalemia. Except for 3 patients who were admitted to the intensive care unit for a severe condition (8.11%), including 2 who died, most COVID-19 diagnosed patients presented mild or nonrespiratory symptoms. The flow cytometric analysis of peripheral blood showed that multiple lymphocyte populations in HD patients were significantly decreased. HD patients with COVID-19 even displayed more remarkable reduction of serum inflammatory cytokines than other patients with COVID-19. CONCLUSIONS: Compared with the general population, HD patients and health care professionals are the highly susceptible population and HD centers are high-risk areas during the outbreak. Most HD patients with COVID-19 exhibited mild clinical symptoms and did not progress to severe pneumonia, likely due to the impaired cellular immune function and incapability of mounting cytokine storm. More attention should be paid to prevent cardiovascular events, which may be the collateral impacts of the COVID-19 epidemic on HD patients.

Experimental investigation on the migration of leachate under flowing conditions through laboratory ERT.

With an increase of service time of landfills, a great amount of old landfills begin to leak and the leachate impairs the surrounding environment severely. Defining the flow of leachate is significant to the monitoring and restoration of the landfill. Field tests and laboratory tests are often used to investigate the leachate flow. However, many uncontrollable factors may affect the accuracy of field tests, and the application of field test results is usually limited. At the same time, it is difficult to simulate and monitor the migration process of leachate in real time in laboratory. To address this problem, a new physical simulating device is created to simulate the leachate migration under flowing conditions, and improved ERT device is designed to monitor the migration in laboratory tests. The results show that the improved ERT could delineate the migration range well in laboratory tests, providing a new method to investigate the leachate migration in laboratory test and providing a reference to the application of ERT in field tests. The relative variation rate of resistivity could reduce the influence of background, and is very suitable for time-lapse ERT. In addition, the effect of flowing rate, leakage rate, and time on the leachate migration is also investigated. The results show that the horizontal migration rate increases with an increase of flowing rate. The leakage rate has a significant influence on the vertical migration, but has limited effect on the horizontal migration. The curvature of migration front increases with an increase of flowing rate and time.

Co-delivery of doxorubicin and pH-sensitive curcumin prodrug by transferrin-targeted nanoparticles for breast cancer treatment.

The natural product curcumin and the chemotherapeutic agent doxorubicin have been used in the treatment of many cancers, including breast cancer. However, fast clearance and unspecific distribution in the body after intravenous injection are still challenges to be overcome by an ideal nano-sized drug delivery system in cancer treatment. In this study we design transferrin (Tf) decorated nanoparticles (NPs) to co-deliver CUR and DOX for breast cancer treatment. A pH-sensitive prodrug, transferrin-poly(ethylene glycol)-curcumin (Tf-PEG-CUR), was synthesized and used for the self­assembling of NPs (Tf-PEG-CUR NPs). DOX is incorporated into the Tf-PEG-CUR NPs to obtain Tf-PEG-CUR/DOX NPs. In vitro cytotoxicity studies and in vivo antitumor activity were carried out using MCF-7 cells and mice bearing MCF-7 cells, respectively. Tf-PEG-CUR/DOX NPs has a particle size of 89 nm and a zeta potential of -15.6 mV. This system displayed remarkably higher efficiency than other systems both in vitro and in vivo. DOX and CUR were successfully loaded into nanocarriers. The in vitro cell viability assays revealed the combination of Tf-PEG-CUR and DOX NPs exhibited higher cytotoxicity in vitro in MCF-7 cells compared with Tf-PEG-CUR NPs alone. Using the breast cancer xenograft mouse model, we demonstrate that this co-encapsulation approach resulted in an efficient tumor-targeted drug delivery, decreased cytotoxic effects and exhibited stronger antitumor effect.

The complete mitochondrial genome of a chronic hepatitis associated liver cancer LEC rat strain.

We sequenced a complete mitochondrial genome sequencing of a chronic hepatitis-associated liver cancer disease LEC rat strain for the first time. The total length of the mitogenome was 16,316 bp with 13 protein-coding genes, two ribosomal RNA genes and 22 transfer RNA genes. This mitochondrial genome sequence will provide new genetic resource into liver cancer disease.