A Rational Design of Bio-Derived Disulfide CANs for Wearable Capacitive Pressure Sensor.

Classic approaches to integrate flexible capacitive sensor performance are to on-demand microstructuring dielectric layers and to adjust dielectric material compositions via the introduction of insoluble carbon additives (to increase sensitivity) or dynamic interactions (to achieve self-healing). However, the sensor's enhanced performances often come with increased material complexity, discouraging its circular economy. Herein, a new intrinsic self-healable, closed-loop recyclable dielectric layer material, a fully nature-derived dynamic covalent poly(disulfide) decorated with rich H bonding and metal-catechol complexations is introduced. The polymer network possesses a mechanically ductile character with an Arrhenius-type temperature-dependent viscoelasticity. The assembled capacitive pressure sensor is able to achieve a sensitivity of up to 9.26 kPa-1, fast response/recovery time of 32/24 ms, and can deliver consistent signals of continuous consecutive cycles even after being self-healed or closed-loop recycled for real-time detection of human motions. This is expected to be of high interest for current capacitive sensing research to move toward a life-like, high performance, and circular economy direction.

Mechanically interlocked [c2]daisy chain backbone enabling advanced shape-memory polymeric materials.

The incorporation of mechanically interlocked structures into polymer backbones has been shown to confer remarkable functionalities to materials. In this work, a [c2]daisy chain unit based on dibenzo-24-crown-8 is covalently embedded into the backbone of a polymer network, resulting in a synthetic material possessing remarkable shape-memory properties under thermal control. By decoupling the molecular structure into three control groups, we demonstrate the essential role of the [c2]daisy chain crosslinks in driving the shape memory function. The mechanically interlocked topology is found to be an essential element for the increase of glass transition temperature and consequent gain of shape memory function. The supramolecular host-guest interactions within the [c2]daisy chain topology not only ensure robust mechanical strength and good network stability of the polymer, but also impart the shape memory polymer with remarkable shape recovery properties and fatigue resistance ability. The incorporation of the [c2]daisy chain unit as a building block has the potential to lay the groundwork for the development of a wide range of shape-memory polymer materials.

Denticity governs the formation of ß-thioketiminato tri-copper(I) and mono-copper(I) complexes.

Two classes of ß-thioketiminate ligands, SN chelators (HL1 and HL2) and SNN chelators (HL3 and HL4), were prepared to understand their coordination behavior in copper(I) complex formation. The formation of these copper(I) complexes bearing ß-thioketiminate ligands and their corresponding adducts toward isocyanide, PPh3, and CO was investigated to address two important issues. First, whether the denticity governs the copper(I) thiolate species formation between SN chelators and SNN chelators. Second, how the length of the pendant pyridyl arm affects the coordination and reactivity behaviors of copper(I) complexes. Based on the characterization results, it was found that the denticity of SN chelators and SNN chelators led to different nuclearity of copper(I)-thiolate species. The coordination modes of the pendant pyridyl arm were confirmed by FTIR measurements, which allow us to conclude that the electron donating ability of the LCu fragment is in the order of SNN-chelator (SNN bound) > SNN-chelators (SN bound) > SN-chelator.

Molecular Physiological Evidence for the Role of Na+-Cl- Co-Transporter in Branchial Na+ Uptake in Freshwater Teleosts.

The gills are the major organ for Na+ uptake in teleosts. It was proposed that freshwater (FW) teleosts adopt Na+/H+ exchanger 3 (Nhe3) as the primary transporter for Na+ uptake and Na+-Cl- co-transporter (Ncc) as the backup transporter. However, convincing molecular physiological evidence to support the role of Ncc in branchial Na+ uptake is still lacking due to the limitations of functional assays in the gills. Thus, this study aimed to reveal the role of branchial Ncc in Na+ uptake with an in vivo detection platform (scanning ion-selective electrode technique, SIET) that has been recently established in fish gills. First, we identified that Ncc2-expressing cells in zebrafish gills are a specific subtype of ionocyte (NCC ionocytes) by using single-cell transcriptome analysis and immunofluorescence. After a long-term low-Na+ FW exposure, zebrafish increased branchial Ncc2 expression and the number of NCC ionocytes and enhanced gill Na+ uptake capacity. Pharmacological treatments further suggested that Na+ is indeed taken up by Ncc, in addition to Nhe, in the gills. These findings reveal the uptake roles of both branchial Ncc and Nhe under FW and shed light on osmoregulatory physiology in adult fish.

SUMO and PIAS repress NF-κB activation in a basal chordate.

Small ubiquitin-like modifier (SUMO) regulates various biological processes, including the MyD88/TICAMs-IRAKs-TRAF6-NF-κB pathway, one of the core immune pathways. However, its functions are inconsistent between invertebrates and vertebrates and have rarely been investigated in lower chordates, including amphioxus and fishes. Here, we investigated the SUMOylation gene system in the amphioxus, a living basal chordate. We found that amphioxus has a SUMOylation system that has a complete set of genes and preserves several ancestral traits. We proceeded to study their molecular functions using the mammal cell lines. Both amphioxus SUMO1 and SUMO2 were shown to be able to attach to NF-κB Rel and to inhibit NF-κB activation by 50-75% in a dose-dependent fashion. The inhibition by SUMO2 could be further enhanced by the addition of the SUMO E2 ligase UBC9. In comparison, while human SUMO2 inhibited RelA, human SUMO1 slightly activated RelA. We also showed that, similar to human PIAS1-4, amphioxus PIAS could serve as a SUMO E3 ligase and promote its self-SUMOylation. This suggests that amphioxus PIAS is functionally compatible in human cells. Moreover, we showed that amphioxus PIAS is not only able to inhibit NF-κB activation induced by MyD88, TICAM-like, TRAF6 and IRAK4 but also able to suppress NF-κB Rel completely in the presence of SUMO1/2 in a dose-insensitive manner. This suggests that PIAS could effectively block Rel by promoting Rel SUMOylation. In comparison, in humans, only PIAS3, but not PIAS1/2/4, has been reported to promote NF-κB SUMOylation. Taken together, the findings from amphioxus, together with those from mammals and other species, not only offer insights into the functional volatility of the animal SUMO system, but also shed light on its evolutionary transitions from amphioxus to fish, and ultimately to humans.

Development of Multiplex Drop-Off Digital PCR Assays for Hotspot Mutation Detection of KRAS, NRAS, BRAF, and PIK3CA in the Plasma of Colorectal Cancer Patients.

The detection of mutations in KRAS, NRAS, BRAF, and PIK3CA has become essential in managing the treatment of metastatic colorectal cancer (CRC) with the approval of new targeted therapies. We developed novel multiplex drop-off digital PCR (MDO-dPCR) assays by combining amplitude-/ratio-based multiplexing with drop-off/double drop-off strategies that allow for the detection of at least the 69 most frequent hotspot mutations in all four genes with only three reactions. The analytical performance of the assays was assessed using synthetic oligonucleotides, which were further validated on plasma cell-free DNA samples from a large cohort of CRC patients and compared with next-generation sequencing data. The MDO-dPCR assays showed a high sensitivity with a limit of detection ranging from 0.084% to 0.182% in mutant allelic frequency. The screening of plasma cell-free DNAs from 106 CRC patients identified mutations in 42.45% of them, with a sensitivity of 95.24%, a specificity of 98.53%, and an accuracy of 96.98% for mutation detection, and a strong correlation of measured mutant allelic frequencies compared with next-generation sequencing results. The high sensitivity and comprehensive mutation coverage of the MDO-dPCR assays make them suitable for rapid and cost-effective detection of KRAS, NRAS, BRAF, and PIK3CA mutations in the plasma of CRC patients, and could be useful in early response assessment and longitudinal disease monitoring.

Empirical analysis on lumbar disc herniation treated with "sinew-bone three needling technique" of Chinese medicine / 中国针灸

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.

Inhibitory effect of three strains of biocontrol microbes on pathogens causing rhizome rot of Polygonatum cyrtonema / 中国中药杂志

Rhizome rot is one of the main disease in the cultivation of Polygonatum cyrtonema, and it is also a global disease which seriously occurs on the perennial medicinal plants such as Panax notoginseng and P. ginseng. There is no effective control method at present. To identify the effects of three biocontrol microbes(Penicillium oxalicum QZ8, Trichoderma asperellum QZ2, and Brevibacillus amyloliquefaciens WK1) on the pathogens causing rhizome rot of P. cyrtonema, this study verified six suspected pathogens for their pathogenicity on P. cyrtonema. The result showed that Fusarium sp. HJ4, Colletotrichum sp. HJ4-1, and Phomopsis sp. HJ15 were the pathogens of rhizome rot of P. cyrtonema, and it was found for the first time that Phomopsis sp. could cause rhizome rot P. cyrtonema. Furthermore, the inhibitory effects of biocontrol microbes and their secondary metabolites on three pathogens were determined by confrontation culture. The results showed that the three tested biocontrol microbes significantly inhibited the growth of three pathogens. Moreover, the secondary metabolites of T. asperellum QZ2 and B. amyloliquefaciens WK1 showed significant inhibition against the three pathogens(P<0.05), and the effect of B. amyloliquefaciens WK1 sterile filtrate was significantly higher than that of high tempe-rature sterilized filtrate(P<0.05). B. amyloliquefaciens WK1 produced antibacterial metabolites to inhibit the growth of pathogens, and the growth inhibition rate of its sterile filtrate against three pathogens ranged from 87.84% to 93.14%. T. asperellum QZ2 inhibited the growth of pathogens through competition and antagonism, and P. oxalicum QZ8 exerted the inhibitory effect through competition. The research provides new ideas for the prevention and treatment of rhizome rot of P. cyrtonema and provides a basis for the di-sease control in other crops.

Multicolor emission based on a N, N'-Disubstituted dihydrodibenzo [a, c] phenazine crown ether macrocycle.

Dynamic fluorophore 9,14-diphenyl-9,14-dihydrodibenzo[a,c]phenazine (DPAC) affords a new platform to produce diverse emission outputs. In this paper, a novel DPAC-containing crown ether macrocycle D-6 is synthesized and characterized. Host-guest interactions of D-6 with different ammonium guests produced a variety of fluorescence with hypsochromic shifts up to 130 nm, which are found to be affected by choice of solvent or guest and host/guest stoichiometry. Formation of supramolecular complexes were confirmed by UV-vis titration, 1H NMR and HRMS spectroscopy.

In Vivo Functional Assay in Fish Gills: Exploring Branchial Acid-Excreting Mechanisms in Zebrafish.

Molecular and physiological analyses in ionoregulatory organs (e.g., adult gills and embryonic skin) are essential for studying fish ion regulation. Recent progress in the molecular physiology of fish ion regulation was mostly obtained in embryonic skin; however, studies of ion regulation in adult gills are still elusive and limited because there are no direct methods for in vivo functional assays in the gills. The present study applied the scanning ion-selective electrode technique (SIET) in adult gills to investigate branchial H+-excreting functions in vivo. We removed the opercula from zebrafish and then performed long-term acid acclimation experiments. The results of Western blot and immunofluorescence showed that the protein expression of H+-ATPase (HA) and the number of H+-ATPase-rich ionocytes were increased under acidic situations. The SIET results proved that the H+ excretion capacity is indeed enhanced in the gills acclimated to acidic water. In addition, both HA and Na+/H+ exchanger (Nhe) inhibitors suppressed the branchial H+ excretion capacity, suggesting that H+ is excreted in association with HA and Nhe in zebrafish gills. These results demonstrate that SIET is effective for in vivo detection in fish gills, representing a breakthrough approach for studying the molecular physiology of fish ion regulation.

Combining Pre- and Postoperative Lymphocyte-C-Reactive Protein Ratios Can Better Predict Hepatocellular Carcinoma Prognosis After Partial Hepatectomy.

Background: Various preoperative inflammatory indicators have been identified as potential predictors of poor prognosis in patients with hepatocellular carcinoma (HCC), but the role of postoperative inflammatory indicators remains unclear. This study aimed to explore the prognostic value of the postoperative lymphocyte-C-reactive protein ratio (PostLCR) on its own and combined with preoperative LCR (PreLCR). Methods: A total of 290 patients with primary HCC were retrospectively enrolled in the study. Univariate analysis was used to identify factors significantly associated with poor disease-free survival (DFS) and overall survival (OS), then multivariate analysis was performed to identify independent prognostic indicators of poor survival. Prognostic models based on preoperative, postoperative, and both types of indicators were then constructed, and their predictive performance were evaluated using time-dependent receiver operating characteristic curves and the concordance index (C-index). Results: PreLCR and PostLCR levels correlated with DFS and OS more strongly than other pre- and postoperative inflammatory indicators, respectively. Decreased PreLCR and PostLCR were independent prognostic factors for both DFS and OS, while HCC patients with decreased PreLCR and PostLCR had worse prognosis than patients with increased PreLCR and PostLCR. Patients into three groups based on their cut-off values of PreLCR and PostLCR, Kaplan-Meier survival analysis indicated that HCC patients with low PreLCR and PostLCR had the worst DFS and OS. The combined model showed better predictive performance at 1 and 3 years post-surgery than individual pre- and postoperative models, the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system and the Barcelona Clinic Liver Cancer system. The combine model demonstrated a markedly superior C-index compared with the other models in DFS and OS. Conclusion: Our study showed PreLCR and PostLCR are independent predictors of DFS and OS in HCC patients after partial hepatectomy. Models that include both PreLCR and PostLCR can predict prognosis better than well-established clinical staging systems.

Enhancing the nonlinearity of optomechanical system via multiple mechanical modes.

We theoretically investigate the nonlinear dynamics of an optomechanical system, where the system consists of N identical mechanical oscillators individually coupled to a common cavity field. We find that the optomechanical nonlinearity can be enhanced N times through theoretical analysis and numerical simulation in such a system. This leads to the power thresholds to observe the nonlinear behaviors (bistable, period-doubling, and chaotic dynamics) being reduced to 1/N. In addition, we find that changing the sign (positive or negative) of the coupling strength partly does not affect the threshold of driving power for generating corresponding nonlinear phenomena. Our work may provide a way to engineer optomechanical devices with a lower threshold, which has potential applications in implementing secret information processing and optical sensing.

Self-Evolution of High Mechanical Strength Dry-Network Polythiourethane Thermosets into Neat Macroscopic Hollow Structures.

Organism-inspired hollow structures are attracting increasing interest for the construction of various bionic functional hollow materials. Next-generation self-evolution hollow materials tend to combine simple synthesis, high mechanical strength, and regular shape. In this study, we designed and synthesized a novel dry-network polythiourethane thermoset with excellent mechanical performance. The polymer film could evolve into a neat and well-organized object with a macroscopic hollow interior structure after being immersed in an aqueous NaOH solution. The self-evolution hollow structure originated from a hydrogen-bonded polymer network, which was later transformed into a network bearing both hydrogen bonds and ionic bonds. The swelling and thickness growth of this material could be controlled by the NaOH concentration and the immersion time. This unique self-evolution behavior was further utilized to produce a series of macroscopic 3D hollow-containing molds, which could be potentially applied in the production of smart materials.

Estrogen-related receptor γ2 controls NaCl uptake to maintain ionic homeostasis.

Estrogen-related receptors (ERRs) are known to function in mammalian kidney as key regulators of ion transport-related genes; however, a comprehensive understanding of the physiological functions of ERRs in vertebrate body fluid ionic homeostasis is still elusive. Here, we used medaka (Oryzias melastigma), a euryhaline teleost, to investigate how ERRs are involved in ion regulation. After transferring medaka from hypertonic seawater to hypotonic freshwater (FW), the mRNA expression levels of errγ2 were highly upregulated, suggesting that Errγ2 may play a crucial role in ion uptake. In situ hybridization showed that errγ2 was specifically expressed in ionocytes, the cells responsible for Na+/Cl- transport. In normal FW, ERRγ2 morpholino knockdown caused reductions in the mRNA expression of Na+/Cl- cotransporter (Ncc), the number of Ncc ionocytes, Na+/Cl- influxes of ionocytes, and whole-body Na+/Cl- contents. In FW with low Na+ and low Cl-, the expression levels of mRNA for Na+/H+ exchanger 3 (Nhe3) and Ncc were both decreased in Errγ2 morphants. Treating embryos with DY131, an agonist of Errγ, increased the whole-body Na+/Cl- contents and ncc mRNA expression in Errγ2 morphants. As such, medaka Errγ2 may control Na+/Cl- uptake by regulating ncc and/or nhe3 mRNA expression and ionocyte number, and these regulatory actions may be subtly adjusted depending on internal and external ion concentrations. These findings not only provide new insights into the underpinning mechanism of actions of ERRs, but also enhance our understanding of their roles in body fluid ionic homeostasis for adaptation to changing environments during vertebrate evolution.

Motorized Macrocycle: A Photo-responsive Host with Switchable and Stereoselective Guest Recognition.

Designing photo-responsive host-guest systems can provide versatile supramolecular tools for constructing smart systems and materials. We designed photo-responsive macrocyclic hosts, modulated by light-driven molecular rotary motors enabling switchable chiral guest recognition. The intramolecular cyclization of the two arms of a first-generation molecular motor with flexible oligoethylene glycol chains of different lengths resulted in crown-ether-like macrocycles with intrinsic motor function. The octaethylene glycol linkage enables the successful unidirectional rotation of molecular motors, simultaneously allowing the 1:1 host-guest interaction with ammonium salt guests. The binding affinity and stereoselectivity of the motorized macrocycle can be reversibly modulated, owing to the multi-state light-driven switching of geometry and helicity of the molecular motors. This approach provides an attractive strategy to construct stimuli-responsive host-guest systems and dynamic materials.

Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay.

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPß. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

Experience in treatment of cervical spondylotic radiculopathy by relaxing the sinew of hand three / 中国针灸

The clinical experience of professor

Cyclooxygenase-2 Inhibitor Parecoxib Was Disclosed as a PPAR-γ Agonist by In Silico and In Vitro Assay

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

Arginine Vasopressin Modulates Ion and Acid/Base Balance by Regulating Cell Numbers of Sodium Chloride Cotransporter and H+-ATPase Rich Ionocytes.

Arginine vasopressin (Avp) is a conserved pleiotropic hormone that is known to regulate both water reabsorption and ion balance; however, many of the mechanisms underlying its effects remain unclear. Here, we used zebrafish embryos to investigate how Avp modulates ion and acid-base homeostasis. After incubating embryos in double-deionized water for 24 h, avp mRNA expression levels were significantly upregulated. Knockdown of Avp protein expression by an antisense morpholino oligonucleotide (MO) reduced the expression of ionocyte-related genes and downregulated whole-body Cl- content and H+ secretion, while Na+ and Ca2+ levels were not affected. Incubation of Avp antagonist SR49059 also downregulated the mRNA expression of sodium chloride cotransporter 2b (ncc2b), which is a transporter responsible for Cl- uptake. Correspondingly, avp morphants showed lower NCC and H+-ATPase rich (HR) cell numbers, but Na+/K+-ATPase rich (NaR) cell numbers remained unchanged. avp MO also downregulated the numbers of foxi3a- and p63-expressing cells. Finally, the mRNA expression levels of calcitonin gene-related peptide (cgrp) and its receptor, calcitonin receptor-like 1 (crlr1), were downregulated in avp morphants, suggesting that Avp might affect Cgrp and Crlr1 for modulating Cl- balance. Together, our results reveal a molecular/cellular pathway through which Avp regulates ion and acid-base balance, providing new insights into its function.