Self-powered soft robot in the Mariana Trench.

The deep sea remains the largest unknown territory on Earth because it is so difficult to explore1-4. Owing to the extremely high pressure in the deep sea, rigid vessels5-7 and pressure-compensation systems8-10 are typically required to protect mechatronic systems. However, deep-sea creatures that lack bulky or heavy pressure-tolerant systems can thrive at extreme depths11-17. Here, inspired by the structure of a deep-sea snailfish15, we develop an untethered soft robot for deep-sea exploration, with onboard power, control and actuation protected from pressure by integrating electronics in a silicone matrix. This self-powered robot eliminates the requirement for any rigid vessel. To reduce shear stress at the interfaces between electronic components, we decentralize the electronics by increasing the distance between components or separating them from the printed circuit board. Careful design of the dielectric elastomer material used for the robot's flapping fins allowed the robot to be actuated successfully in a field test in the Mariana Trench down to a depth of 10,900 metres and to swim freely in the South China Sea at a depth of 3,224 metres. We validate the pressure resilience of the electronic components and soft actuators through systematic experiments and theoretical analyses. Our work highlights the potential of designing soft, lightweight devices for use in extreme conditions.

Establishing national reference materials for genetic testing of cytochrome P450.

OBJECTIVES: Reference materials for in-vitro diagnostic reagents play a critical role in determining the quality of reagents and ensuring the accuracy of clinical test results. This study aimed to establish a national reference material (NRM) for detecting cytochrome P450 (CYP) genes related to drug metabolism by screening databases on the Chinese population to identify CYP gene polymorphism characteristics. METHODS: To prepare the NRM, we used DNA extracted from healthy human immortalized B lymphoblastoid cell lines as the raw material. Samples of these cell lines were obtained from the Chinese Population PGx Gene Polymorphism Biobank. Further, we used Sanger sequencing, next-generation sequencing, and commercial assay kits to validate the polymorphic genotypes. RESULTS: Among the CYP superfamily genes, we confirmed 24 riboswitch loci related to drug metabolism, with evidence levels of 1A, 2A, 3, and 4. We confirmed the polymorphic loci and validated their genotypes using various sequencing techniques. Our results were consistent with the polymorphism information of samples obtained from the biobank, thus demonstrating high precision and stability of the established NRM. CONCLUSION: An NRM (360 056-202 201) for CYP genetic testing covering 24 loci related to drug metabolism was established and approved to assess in-vitro diagnostic reagents containing CYP family gene polymorphisms and perform clinical inter-room quality evaluations.

Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop.

BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.

Observation of Nonlinear Exceptional Points with a Complete Basis in Dynamics.

The exotic physics associated with exceptional points (EPs) is always under the scrutiny of theoretical and experimental science. Recently, considerable effort has been invested in the combination of nonlinearity and non-Hermiticity. The concept of nonlinear EPs (NEPs) has been introduced, which can avoid the loss of completeness of the eigenbasis in dynamics while retaining the key features of linear EPs. Here, we present the first direct experimental demonstration of a NEP based on two non-Hermition coupled circuit resonators combined with a nonlinear saturable gain. At the NEP, the response of the eigenfrequency to perturbations demonstrates a third-order root law and the eigenbasis of the Hamiltonian governing the system dynamics is still complete. Our results bring this counterintuitive aspect of the NEP to light and possibly open new avenues for applications.

Exploring and clinical validation of prognostic significance and therapeutic implications of copper homeostasis-related gene dysregulation in acute myeloid leukemia.

The patterns and biological functions of copper homeostasis-related genes (CHRGs) in acute myeloid leukemia (AML) remain unclear. We explored the patterns and biological functions of CHRGs in AML. Using independent cohorts, including TCGA-GTEx, GSE114868, GSE37642, and clinical samples, we identified 826 common differentially expressed genes. Specifically, 12 cuproptosis-related genes (e.g., ATP7A, ATP7B) were upregulated, while 17 cuproplasia-associated genes (e.g., ATOX1, ATP7A) were downregulated in AML. We used LASSO-Cox, Kaplan-Meier, and Nomogram analyses to establish prognostic risk models, effectively stratifying patients with AML into high- and low-risk groups. Subgroup analysis revealed that high-risk patients exhibited poorer overall survival and involvement in fatty acid metabolism, apoptosis, and glycolysis. Immune infiltration analysis indicated differences in immune cell composition, with notable increases in B cells, cytotoxic T cells, and memory T cells in the low-risk group, and increased monocytes and neutrophils in the high-risk group. Single-cell sequencing analysis corroborated the expression characteristics of critical CHRGs, such as MAPK1 and ATOX1, associated with the function of T, B, and NK cells. Drug sensitivity analysis suggested potential therapeutic agents targeting copper homeostasis, including Bicalutamide and Sorafenib. PCR validation confirmed the differential expression of 4 cuproptosis-related genes (LIPT1, SLC31A1, GCSH, and PDHA1) and 9 cuproplasia-associated genes (ATOX1, CCS, CP, MAPK1, SOD1, COA6, PDK1, DBH, and PDE3B) in AML cell line. Importantly, these genes serve as potential biomarkers for patient stratification and treatment. In conclusion, we shed light on the expression patterns and biological functions of CHRGs in AML. The developed risk models provided prognostic implications for patient survival, offering valuable information on the regulatory characteristics of CHRGs and potential avenues for personalized treatment in AML.

Processing bulk natural wood into a high-performance structural material.

Synthetic structural materials with exceptional mechanical performance suffer from either large weight and adverse environmental impact (for example, steels and alloys) or complex manufacturing processes and thus high cost (for example, polymer-based and biomimetic composites). Natural wood is a low-cost and abundant material and has been used for millennia as a structural material for building and furniture construction. However, the mechanical performance of natural wood (its strength and toughness) is unsatisfactory for many advanced engineering structures and applications. Pre-treatment with steam, heat, ammonia or cold rolling followed by densification has led to the enhanced mechanical performance of natural wood. However, the existing methods result in incomplete densification and lack dimensional stability, particularly in response to humid environments, and wood treated in these ways can expand and weaken. Here we report a simple and effective strategy to transform bulk natural wood directly into a high-performance structural material with a more than tenfold increase in strength, toughness and ballistic resistance and with greater dimensional stability. Our two-step process involves the partial removal of lignin and hemicellulose from the natural wood via a boiling process in an aqueous mixture of NaOH and Na2SO3 followed by hot-pressing, leading to the total collapse of cell walls and the complete densification of the natural wood with highly aligned cellulose nanofibres. This strategy is shown to be universally effective for various species of wood. Our processed wood has a specific strength higher than that of most structural metals and alloys, making it a low-cost, high-performance, lightweight alternative.

Radiofrequency radiation reshapes tumor immune microenvironment into antitumor phenotype in pulmonary metastatic melanoma by inducing active transformation of tumor-infiltrating CD8+ T and NK cells.

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.

A new perspective on hippocampal synaptic plasticity and post-stroke depression.

Post-stroke depression, a common complication after stroke, severely affects the recovery and quality of life of patients with stroke. Owing to its complex mechanisms, post-stroke depression treatment remains highly challenging. Hippocampal synaptic plasticity is one of the key factors leading to post-stroke depression; however, the precise molecular mechanisms remain unclear. Numerous studies have found that neurotrophic factors, protein kinases and neurotransmitters influence depressive behaviour by modulating hippocampal synaptic plasticity. This review further elaborates on the role of hippocampal synaptic plasticity in post-stroke depression by summarizing recent research and analysing possible molecular mechanisms. Evidence for the correlation between hippocampal mechanisms and post-stroke depression helps to better understand the pathological process of post-stroke depression and improve its treatment.

A new thinking: extended application of genomic selection to screen multiomics data for development of novel hypoxia-immune biomarkers and target therapy of clear cell renal cell carcinoma.

Increasing evidences show the clinical significance of the interaction between hypoxia and immune in clear cell renal cell carcinoma (ccRCC) microenvironment. However, reliable prognostic signatures based on a combination of hypoxia and immune have not been well established. Moreover, many studies have only used RNA-seq profiles to screen the prognosis feature of ccRCC. Presently, there is no comprehensive analysis of multiomics data to mine a better one. Thus, we try and get it. First, t-SNE and ssGSEA analysis were used to establish tumor subtypes related to hypoxia-immune, and we investigated the hypoxia-immune-related differences in three types of genetic or epigenetic characteristics (gene expression profiles, somatic mutation, and DNA methylation) by analyzing the multiomics data from The Cancer Genome Atlas (TCGA) portal. Additionally, a four-step strategy based on lasso regression and Cox regression was used to construct a satisfying prognostic model, with average 1-year, 3-year and 5-year areas under the curve (AUCs) equal to 0.806, 0.776 and 0.837. Comparing it with other nine known prognostic biomarkers and clinical prognostic scoring algorithms, the multiomics-based signature performs better. Then, we verified the gene expression differences in two external databases (ICGC and SYSU cohorts). Next, eight hub genes were singled out and seven hub genes were validated as prognostic genes in SYSU cohort. Furthermore, it was indicated high-risk patients have a better response for immunotherapy in immunophenoscore (IPS) analysis and TIDE algorithm. Meanwhile, estimated by GDSC and cMAP database, the high-risk patients showed sensitive responses to six chemotherapy drugs and six candidate small-molecule drugs. In summary, the signature can accurately predict the prognosis of ccRCC and may shed light on the development of novel hypoxia-immune biomarkers and target therapy of ccRCC.

Nonlinear Exceptional Points with a Complete Basis in Dynamics.

Exceptional points (EPs) are special spectral singularities at which two or more eigenvalues, and their corresponding eigenvectors, coalesce and become identical. In conventional wisdom, the coalescence of eigenvectors inevitably leads to the loss of completeness of the eigenbasis. Here, we show that this scenario breaks down in general at nonlinear EPs (NEPs). As an example, we realize a fifth-order NEP (NEP_{5}) within only three coupled resonators with both a theoretical model and simulations in circuits. One stable and another four auxiliary steady eigenstates of the nonlinear Hamiltonian coalesce at the NEP_{5}, and the response of eigenfrequency to perturbations demonstrates a fifth-order root law. Intriguingly, the biorthogonal eigenbasis of the Hamiltonian governing the system dynamics is still complete, and this fact is corroborated by a finite Petermann factor instead of a divergent one at conventional EPs. Consequently, the amplification of noise, which diverges at other EPs, converges at our NEP_{5}. Our finding transforms the understanding of EPs and shows potential for miniaturizing various key applications operating near EPs.

ASPECTS-based net water uptake outperforms target mismatch for outcome prediction in patients with acute ischemic stroke and late therapeutic window.

OBJECTIVE: To compare the prognostic value of net water uptake (NWU) and target mismatch (TM) on CT perfusion (CTP) in acute ischemic stroke (AIS) patients with late time window. METHODS: One hundred and nine consecutive AIS patients with anterior-circulation large vessel occlusion presenting within 6-24 h from onset/last seen well were enrolled. Automated Alberta Stroke Program Early CT Score-based NWU (ASPECTS-NWU) was calculated from admission CT. The correlation between ASPECTS-NWU and CTP parameters was assessed. Predictors for favorable outcome (modified Rankin Scale score ≤ 2) at 90 days were assessed using logistic regression analysis. The ability of outcome prediction between ASPECTS-NWU and TM (an ischemic core < 70 mL, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 mL) was compared using receiver operating characteristic (ROC) curve. RESULTS: A higher level of ASPECTS-NWU was associated with a larger ischemic core (r = 0.66, p < 0.001) and a larger hypoperfusion volume (r = 0.38, p < 0.001). ASPECTS-NWU performed better than TM for outcome stratification (area under the curve [AUC], 0.738 vs 0.583, p = 0.004) and was the only independent neuroimaging marker associated with favorable outcomes compared with CTP parameters (odds ratio, 0.73; 95% confidence interval [CI] 0.62-0.87, p < 0.001). An outcome prediction model including ASPECTS-NWU and clinical variables (National Institutes of Health Stroke Scale scores and age) yielded an AUC of 0.828 (95% CI 0.744-0.893; sensitivity 65.4%; specificity 87.7%). CONCLUSION: ASPECTS-NWU performed better than TM for outcome prediction in AIS patients with late time window and might be an alternative imaging biomarker to CTP for patient selection. CLINICAL RELEVANCE STATEMENT: Automated Alberta Stroke Program Early CT Score-based net water uptake outperforms target mismatch on CT perfusion for the outcome prediction in patients with acute ischemic stroke and can be an alternative imaging biomarker for patient selection in late therapeutic window. KEY POINTS: • A higher ASPECTS-based net water uptake was associated with larger ischemic cores and hypoperfusion volumes on CT perfusion. • ASPECTS-based net water uptake outperformed target mismatch for outcome prediction in acute ischemic stroke with extended therapeutic window. • ASPECTS-based net water uptake can be an alternative biomarker to target mismatch for selecting acute ischemic stroke patients with late therapeutic window.

Subtractionless compressed-sensing-accelerated whole-body MR angiography using two-point Dixon fat suppression with single-pass half-reduced contrast dose: feasibility study and initial experience.

PURPOSE: To investigate the feasibility and clinical utility of a compressed-sensing-accelerated subtractionless whole-body MRA (CS-WBMRA) protocol with only contrast injection for suspected arterial diseases, by comparison to conventional dual-pass subtraction-based whole-body MRA (conventional-WBMRA) and available computed tomography angiography (CTA). MATERIALS AND METHODS: This prospective study assessed 86 patients (mean age, 56 years ± 16.4 [standard deviation]; 25 women) with suspected arterial diseases from May 2021 to December 2022, who underwent CS-WBMRA (n = 48, mean age, 55.9 years ± 16.4 [standard deviation]; 25 women) and conventional-WBMRA (n = 38, mean age, 48 years ± 17.4 [standard deviation]; 20 women) on a 3.0 T MRI after random group assignment based on the chronological order of enrolment. Of all enrolled patients administered the CS-WBMRA protocol, 35% (17/48) underwent CTA as required by clinical demands. Two experienced radiologists independently scored the qualitative image quality and venous enhancement contamination. Quantitative image assessment was carried out by determining and comparing the apparent signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of four representative arterial segments. The total examination time and contrast-dose were also recorded. The independent samples t-test or the Wilcoxon rank sum test was used for statistical analysis. RESULTS: The overall scores of CS-WBMRA outperformed those of conventional-WMBRA (3.40 ± 0.60 vs 3.22 ± 0.55, P < 0.001). In total, 1776 and 1406 arterial segments in the CS-WBMRA and conventional-WBMRA group were evaluated. Qualitative image scores for 7 (of 15) vessel segments in the CS-WMBRA group had statistically significantly increased values compared to those of the conventional-WBMRA groups (P < 0.05). Scores from the other 8 segments showed similar image quality (P > 0.05) between the two protocols. In the quantitative analysis, overall apparent SNRs were significantly higher in the conventional-WBMRA group than in the CS-WBMRA group (214.98 ± 136.05 vs 164.90 ± 118.05; P < 0.001), while overall apparent CNRs were not significantly different in these two groups (CS vs conventional: 107.13 ± 72.323 vs 161.24 ± 118.64; P > 0.05). In the CS-WBMRA group, 7 of 1776 (0.4%) vessel segments were contaminated severely by venous enhancement, while in the convention-WBMRA group, 317 of 1406 (23%) were rated as severe contamination. In the CS-WBMRA group, total examination and reconstruction times were only 7 min and 10 min, respectively, vs 20 min and < 30 s for the conventional WBMRA group, respectively. The contrast agent dose used in the CS-WBMRA protocol was reduced by half compared to conventional-WBMRA protocol (18.7 ± 3.5 ml vs 37.2 ± 5.4 ml, P = 0.008). CONCLUSION: The CS-WBMRA protocol provides excellent image quality and sufficient diagnostic accuracy for whole-body arterial disease, with relatively faster workflow and half-dose reduction of contrast agent, which has greater potential in clinical practice compared with conventional-WBMRA.

Di- and Triterpenoids from the Rhizomes of Isodon amethystoides and Their Anti-inflammatory Activities.

Amethystoidesic acid (1), a triterpenoid with an unprecedented 5/6/6/6 tetracyclic skeleton, and six undescribed diterpenoids, amethystoidins A-F (2-7), were isolated from the rhizomes of Isodon amethystoides along with 31 known di- and triterpenoids (8-38). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Compound 1 is the first example of a triterpenoid possessing a rare ring system (5/6/6/6) derived from a contracted A-ring and the 18,19-seco-E-ring of ursolic acid. Compounds 6, 16, 21, 22, 24, and 27 significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, which could be partly mediated by the downregulation of LPS-induced inducible nitric oxide synthase (iNOS) protein expression.

High-quality Fagopyrum esculentum genome provides insights into the flavonoid accumulation among different tissues and self-incompatibility.

Common buckwheat (Fagopyrum esculentum) and Tartary buckwheat (Fagopyrum tataricum), the two most widely cultivated buckwheat species, differ greatly in flavonoid content and reproductive mode. Here, we report the first high-quality and chromosome-level genome assembly of common buckwheat with 1.2 Gb. Comparative genomic analysis revealed that common buckwheat underwent a burst of long terminal repeat retrotransposons insertion accompanied by numerous large chromosome rearrangements after divergence from Tartary buckwheat. Moreover, multiple gene families involved in stress tolerance and flavonoid biosynthesis such as multidrug and toxic compound extrusion (MATE) and chalcone synthase (CHS) underwent significant expansion in buckwheat, especially in common buckwheat. Integrated multi-omics analysis identified high expression of catechin biosynthesis-related genes in flower and seed in common buckwheat and high expression of rutin biosynthesis-related genes in seed in Tartary buckwheat as being important for the differences in flavonoid type and content between these buckwheat species. We also identified a candidate key rutin-degrading enzyme gene (Ft8.2377) that was highly expressed in Tartary buckwheat seed. In addition, we identified a haplotype-resolved candidate locus containing many genes reportedly associated with the development of flower and pollen, which was potentially related to self-incompatibility in common buckwheat. Our study provides important resources facilitating future functional genomics-related research of flavonoid biosynthesis and self-incompatibility in buckwheat.

Plasmonic Photoelectrochemical Coupling Reactions of para-Aminobenzoic Acid on Nanostructured Gold Electrodes.

Surface plasmon resonance (SPR) bridges photonics and photoelectrochemistry by providing an effective interaction between absorption and confinement of light to surface electrons of plasmonic metal nanostructures (PMNs). SPR enhances the Raman intensity enormously in surface-enhanced Raman spectroscopy (SERS) and leads to the plasmon-mediated chemical reaction on the surface of nanostructured metal electrodes. To observe variations in chemical reactivity and selectivity, we studied the SPR photoelectrochemical reactions of para-aminobenzoic acid (PABA) on nanostructured gold electrodes. The head-to-tail coupling product "4-[(4-imino-2,5-cyclohexadien-1-ylidene)amino]benzoic acid (ICBA)" and the head-to-head coupling product p,p'-azodibenzoate (ADBA) were obtained from PABA adsorbed on PMN-modified gold electrodes. In particular, under acidic and neutral conditions, ICBA was obtained as the main product, and ADBA was obtained as the minor product. At the same time, under basic conditions, ADBA was obtained as the major product, and ICBA was obtained as the minor product. We have also provided sufficient evidence for the oxidation of the tail-to-tail coupling reaction product that occurred in a nonaqueous medium rather than in an aqueous medium. The above finding was validated by the cyclic voltammetry, SERS, and theoretical calculation results of possible reaction intermediates, namely, 4-aminophenlylenediamine, 4-hydroxyphenlylenediamine, and benzidine. The theoretical adsorption model and experimental results indicated that PABA has been adsorbed as para-aminobenzoate on the gold cluster in a bidentate configuration. This work offers a new view toward the modulation of selective surface catalytic coupling reactions on PMN, which benefits the hot carrier transfer efficiency at photoelectrochemical interfaces.

m6A-immune-related lncRNA prognostic signature for predicting immune landscape and prognosis of bladder cancer.

BACKGROUND: N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) may have prognostic value in bladder cancer for their key role in tumorigenesis and innate immunity. METHODS: Bladder cancer transcriptome data and the corresponding clinical data were acquired from the Cancer Genome Atlas (TCGA) database. The m6A-immune-related lncRNAs were identified using univariate Cox regression analysis and Pearson correlation analysis. A risk model was established using least absolute shrinkage and selection operator (LASSO) Cox regression analyses, and analyzed using nomogram, time-dependent receiver operating characteristics (ROC) and Kaplan-Meier survival analysis. The differences in infiltration scores, clinical features, and sensitivity to Talazoparib of various immune cells between low- and high-risk groups were investigated. RESULTS: Totally 618 m6A-immune-related lncRNAs and 490 immune-related lncRNAs were identified from TCGA, and 47 lncRNAs of their intersection demonstrated prognostic values. A risk model with 11 lncRNAs was established by Lasso Cox regression, and can predict the prognosis of bladder cancer patients as demonstrated by time-dependent ROC and Kaplan-Meier analysis. Significant correlations were determined between risk score and tumor malignancy or immune cell infiltration. Meanwhile, significant differences were observed in tumor mutation burden and stemness-score between the low-risk group and high-risk group. Moreover, high-risk group patients were more responsive to Talazoparib. CONCLUSIONS: An m6A-immune-related lncRNA risk model was established in this study, which can be applied to predict prognosis, immune landscape and chemotherapeutic response in bladder cancer.

100 Gb/s NRZ OOK signal regeneration using four-wave mixing in a silicon waveguide with reverse-biased p-i-n junction.

A silicon waveguide with reverse-biased p-i-n junction is used to experimentally demonstrate all-optical regeneration of non-return-to-zero (NRZ) on-off keying (OOK) signal based on four-wave mixing. The silicon waveguide allows a high conversion efficiency of -12 dB. The 0.22 dB (1.1 dB) quality (Q) factor and 0.74 dB (6.3 dB) extinction ratio (ER) improvements on average are achieved for 100 Gb/s (50 Gb/s) NRZ OOK signal regeneration at different receiving powers via the optimal match between the input signal optical power and input-output transfer curve. To the best of our knowledge, this silicon-based all-optical regenerator exhibits superior regeneration performance, including large ER and Q factor improvements, and the highest regeneration speed of NRZ OOK signal, and it has wide applications in 5 G/6 G networks.

Discovery of honokiol thioethers containing 1,3,4-oxadiazole moieties as potential α-glucosidase and SARS-CoV-2 entry inhibitors.

Honokiol, isolated from a traditional Chinese medicine (TCM) Magnolia officinalis, is a biphenolic compound with several biological activities. To improve and broaden its biological activity, herein, two series of honokiol thioethers bearing 1,3,4-oxadiazole moieties were prepared and assessed for their α-glucosidase and SARS-CoV-2 entry inhibitory activities. Among all the honokiol thioethers, compound 7l exhibited the strongest α-glucosidase inhibitory effect with an IC50 value of 18.9 ± 2.3 µM, which was superior to the reference drug acarbose (IC50 = 24.4 ± 0.3 µM). Some interesting results of structure-activity relationships (SARs) have also been discussed. Enzyme kinetic study demonstrated that 7l was a noncompetitive α-glucosidase inhibitor, which was further supported by the results of molecular docking. Moreover, honokiol thioethers 7e, 9a, 9e, and 9r exhibited potent antiviral activity against SARS-CoV-2 pseudovirus entering into HEK-293 T-ACE2h. Especially 9a displayed the strongest inhibitory activity against SARS-CoV-2 pseudovirus entry with an IC50 value of 16.96 ± 2.45 µM, which was lower than the positive control Evans blue (21.98 ± 1.98 µM). Biolayer interferometry (BLI) binding and docking studies suggested that 9a and 9r may effectively block the binding of SARS-CoV-2 to the host ACE2 receptor through dual recognition of SARS-CoV-2 spike RBD and human ACE2. Additionally, the potent honokiol thioethers 7l, 9a, and 9r displayed relatively no cytotoxicity to normal cells (LO2). These findings will provide a theoretical basis for the discovery of honokiol derivatives as potential both α-glucosidase and SARS-CoV-2 entry inhibitors.

Comparison of serum inflammatory indicators and radiographic results in MAKO robotic-assisted versus conventional total knee arthroplasty for knee osteoarthritis: a retrospective study of Chinese patients.

BACKGROUND: The purpose of this study was to compare the serum inflammatory indicators and radiographic results of conventional manual total knee arthroplasty (CM-TKA) with those of MAKO-robotic assisted total knee arthroplasty (MA-TKA). METHODS: We retrospectively analysed 65 patients with knee osteoarthritis who underwent unilateral TKA from December 2020 to November 2021 in our department, which included 34 patients who underwent MA-TKA and 31 patients who underwent CM-TKA. The tourniquet time and estimated blood loss (EBL) were compared between the two groups. Knee function was evaluated using range of motion (ROM), functional score and pain score. Leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), creatine kinase (CK), and neutrophil-to-lymphocyte ratio (NLR) were recorded at 3 time points (preoperative, and on the first and third postoperative days). The hip-knee-ankle angle (HKA) and the femoral and tibial component angles in the coronal and sagittal planes were used for postoperative radiographic evaluation. RESULTS: The postoperative MA-TKA group had less EBL (496.9 ± 257.8 vs. 773.0 ± 301.3 ml, p < 0.001). There was no significant difference in knee function scores at 6 weeks postoperatively (p > 0.05). IL-6 levels were significantly lower in the MA-TKA group on the 1st postoperative day (11.4 (5.2, 21.0) vs. 24.6 (86.3, 170.8), p = 0.031). This difference in inflammatory indices became more pronounced at 72 hours after the operation because CRP, ESR, IL-6, and CK values were significantly lower in the MA-TKA group on the 3rd postoperative day (72 h) (p < 0.05). Postoperative radiographic examinations performed 2 days after the MA-TKA group suggested that only 2 cases of HKA had outlier values, which was remarkably better than the 12 cases found in the CM-TKA group (5.9% vs. 38.7%, p < 0.001). The frontal femoral component was significantly closer to the expected value of 90° in the MA-TKA group (90.9 (90.5, 92.3) vs. 92.4 (91.3, 93.7), p = 0.031). The remaining imaging evaluation parameters were not significantly different between the two groups (p > 0.05). CONCLUSIONS: In Chinese patients with OA, there was a milder systemic inflammatory response in the early postoperative period after MA-TKA compared to that of CM-TKA, as well as better radiographic outcomes. However, the tourniquet time was prolonged, and no advantages were observed in terms of functional score or pain score in the short-term follow-up.

Modifying surface charge density of thermoplastic nanofluidic biosensors by multivalent cations within the slip plane of the electric double layer.

Thermoplastic nanofluidic devices are promising platforms for sensing single biomolecules due to their mass fabrication capability. When the molecules are driven electrokinetically through nanofluidic networks, surface charges play a significant role in the molecular capture and transportation, especially when the thickness of the electrical double layer is close to the dimensions of the nanostructures in the device. Here, we used multivalent cations to alter the surface charge density of thermoplastic nanofluidic devices. The surface charge alteration was done by filling the device with a multivalent ionic solution, followed by withdrawal of the solution and replacing it with KCl for conductance measurement. A systematic study was performed using ionic solutions containing Mg2+ and Al3+ for nanochannels made of three polymers: poly(ethylene glycol) diacrylate (PEGDA), poly(methyl methacrylate) (PMMA) and cyclic olefin copolymer (COC). Overall, multivalent cations within the slip plane decreased the effective surface charge density of the device surface and the reduction rate increased with the cation valency, cation concentration and the surface charge density of thermoplastic substrates. We demonstrated that a 10-nm diameter in-plane nanopore formed in COC allowed translocation of λ-DNA molecules after Al3+ modification, which is attributed to the deceased viscous drag force in the nanopore by the decreased surface charge density. This work provides a general method to manipulate surface charge density of nanofluidic devices for biomolecule resistive pulse sensing. Additionally, the experimental results support ion-ion correlations as the origin of charge inversion over specific chemical adsorption.