Mismatched Supramolecular Interactions Facilitate the Reprocessing of Super-Strong and Ultratough Thermoset Elastomers.

Thermoset elastomers have been extensively applied in many fields because of their excellent mechanical strengths and durable characteristics, such as an excellent chemical resistance. However, in the context of environmental issues, the nonrecyclability of thermosets has become a major barrier to the further development of these materials. Here, a well-tailored strategy is reported to solve this problem by introducing mismatched supramolecular interactions (MMSIs) into a covalently cross-linked poly(urethane-urea) network with dynamic acylsemicarbazide moieties. The MMSIs significantly strengthen and toughen the thermoset elastomer by effectively dissipating energy and resisting external stress. In addition, the elastomer recycling efficiency is improved 2.7-fold due to the superior reversibility of the MMSIs. The optimized thermoset elastomer features outstanding characteristics, including an ultrahigh tensile strength (110.8 MPa), an unprecedented tensile toughness (1245.2 MJ m-3), as well as remarkable resistance to chemical media, creep, and damage. Most importantly, it exhibits an extraordinary multirecyclability, and the 4th recycling efficiency remains close to 100%. This scalable method promotes the development of thermosets with both high performance and excellent recyclability, thereby providing valuable guidance for addressing the issue of nonrecyclability from a molecular design standpoint.

"Seeing Is Believing": Additive Utility of 68Ga-PSMA-11 PET/CT in Prostate Cancer Diagnosis.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68Ga-PSMA-11 PET/CT.

WSSV early protein WSSV004 enhances viral replication by suppressing LDH activity.

White spot syndrome virus (WSSV) is known to upregulate glycolysis to supply biomolecules and energy for the virus's replication. At the viral genome replication stage, lactate dehydrogenase (LDH), a glycolytic enzyme, shows increased activity without any increase in expression. In the present study, yeast 2-hybrid screening was used to identify WSSV proteins that interacted with LvLDH isoform 1 and 2, and these included the WSSV early protein WSSV004. The interaction between WSSV004 and LvLDH1/2 was confirmed by co-immunoprecipitation. Immunofluorescence showed that WSSV004 co-localized with LvLDH1/2 in the cytoplasm. dsRNA silencing experiments showed that WSSV004 was crucial for WSSV replication. However, although WSSV004 silencing led to the suppression of total LvLDH gene expression during the viral late stage, there was nevertheless a significant increase in LvLDH activity at this time. We also used affinity purification-mass spectrometry to identify cellular proteins that interact with WSSV004, and found a total of 108 host proteins and 3 WSSV proteins with which it potentially interacts. Bioinformatics analysis revealed that WSSV004 and its interacting proteins might be responsible for various biological pathways during infection, including vesicular transport machinery and RNA-related functions. Collectively, our study suggests that WSSV004 serves as a multifunctional modulator to facilitate WSSV replication.

The highly selective and sensitive fluorescence probe for detection of copper (II) ions and its bioimaging in vitro and vivo.

We designed and developed the probe W-3 for detection of Cu2+. The results showed probe can selectively detect Cu2+, accompanied by noticeable color change. The probe can detect the Cu2+ in water samples and drinks based on absorption detection. In addition, the combination of portable test paper and the smartphone platform obtained great convenience for on-site and visual detection of Cu2+, with satisfactory sensitivity and reliability. More importantly, the fluorescence probe W-3 can be used for the detection of Cu2+ in cells and mice. Therefore, the W-3 provided potential chemical tools for detecting Cu2+ in vitro and vivo.

Real-world retrospective study of prostate-specific antigen and safety assessment with darolutamide plus androgen deprivation therapy for metastasis hormone-sensitive prostate cancer.

Background: ARASENS has demonstrated the efficacy and safety for darolutamide (DARO) with androgen deprivation therapy (ADT) plus docetaxel in metastasis hormone-sensitive prostate cancer (mHSPC). There is a lack of reports for DARO with ADT in mHSPC though the regimen is used in clinical from time to time. Moreover, recent studies have supported the importance of early and rapid prostate-specific antigen (PSA) reduction, which correlates with reduced disease progression and improved survival in patients with mHSPC. This study aims to evaluate PSA reduction as a primary endpoint for DARO with ADT in the treatment of mHSPC and to evaluate the real-world short-term PSA control of DARO with ADT from two leading medical centers in China. Methods: We retrospectively reviewed the clinical records of patients with mHSPC receiving ADT and DARO (600 mg, b.i.d.). The collection of data spanned from March 1, 2022, to July 31, 2023. The main observation indicators were PSA level and drug-related adverse events (AE) after medication. PSA levels were closely monitored prior to treatment initiation and at 2-week intervals, as well as at 1, 3, and 6 months after the initiation of treatment. We also conducted an analysis to determine the proportion of patients achieving a PSA reduction of 50% or more (PSA50) and 90% or more (PSA90) as well as the percentage of patients with a notable decrease in PSA level to 0.2 ng/mL and PSA nadir of ≤0.02 ng/mL. Results: Fifty-one patients were included in the study, with a median age of 73 years. At diagnosis of HSPC, the majority of patients had a Gleason score ≥8 (n=40, 78.40%) and a median baseline PSA level of 88 ng/mL. Approximately 45.1% (n=23) of patients had a Charlson Comorbidity Index over 1 and were receiving one or more nontumor-related treatments. The median follow-up time was 9.3 months (range, 1.16-15.8 months). The median reductions in PSA levels compared to baseline were 84.37%, 91.48%, 94.67% and 99.81% at 2 weeks, 1 month, 3 months and 6 months after administration of DARO with ADT, respectively. The median time to PSA50, PSA90, significant PSA reduction (PSA <0.2 ng/mL), and PSA nadir (PSA <0.02 ng/mL) was 0.97, 1.27, 1.98, and 2.08 months, respectively. AE mainly included fatigue (two patients) and arm pain (one patient), all of which were grade I or II AE. No grade III or AE were observed. Conclusions: For treating prostate cancer, DARO with ADT has good early efficacy, demonstrating prompt and substantial control of PSA levels, with a favorable safety profile.

Delivery of Stem Cells and BMP-2 With Functionalized Self-Assembling Peptide Enhances Regeneration of Infarcted Myocardium.

Stem cell transplantation is a promising therapeutic strategy for myocardial infarction (MI). However, engraftment, survival and differentiation of the transplanted stem cells in ischemic and inflammatory microenvironment are poor. We designed a novel self-assembly peptide (SAP) by modifying the peptide RADA16 with cell-adhesive motif and BMP-2 (bone morphogenetic protein-2)-binding motif. Effects of the functionalized SAP on adhesion, survival and differentiation of c-kit+ MSCs (mesenchymal stem cells) were examined. Myocardial regeneration, neovascularization and cardiac function were assessed after transplantation of the SAP loading c-kit+ MSCs and BMP-2 in rat MI models. The SAP could spontaneously assemble into well-ordered nanofibrous scaffolds. The cells adhered to the SAP scaffolds and spread well. The SAP protected the cells in the condition of hypoxia and serum deprivation. Following degradation of the SAP, BMP-2 was released sustainedly and induced c-kit+ MSCs to differentiate into cardiomyocytes. At four weeks after transplantation of the SAP loading c-kit+ MSCs and BMP-2, myocardial regeneration and angiogenesis were enhanced, and cardiac function was improved significantly. The cardiomyocytes differentiated from the engrafted c-kit+ MSCs were increased markedly. The differentiated cells connected with recipient cardiomyocytes to form gap junctions. Collagen volume was decreased dramatically. These results suggest that the functionalized SAP promotes engraftment, survival and differentiation of stem cells effectively. Local sustained release of BMP-2 with SAP is a viable strategy to enhance differentiation of the engrafted stem cells and repair of the infarcted myocardium.

Residential mobility and liver cancer risk: findings from a prospective cohort study in Chinese women.

BACKGROUND: Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. METHODS: We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. RESULTS: During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44-1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44-1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. CONCLUSIONS: The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health.

A Healable Quasi-Solid Polymer Electrolyte with Balanced Toughness and Ionic Conductivity.

Solid polymer electrolytes (SPEs) have garnered extensive attention as potential alternatives to traditional liquid electrolytes, primarily due to their prowess in curbing lithium dendrite formation and preventing electrolyte leaks. The quest for SPEs that are both mechanically robust and exhibit superior ionic conductivity has been vigorous. However, achieving a harmonious balance between these two attributes remains a significant challenge. In this study, we introduce a novel quasi-solid electrolyte, ingeniously crafted from a poly(urethane-urea) network, enriched with lithium salts and plasticizers. This innovative composition not only boasts remarkable toughness but also ensures commendable ionic conductivity. Our post-gelation method yields gel polymer electrolytes that undergo rigorous evaluation, leading to an optimized version that stands out with its exceptional room-temperature ionic conductivity (2.94×10-4 S cm-1) and outstanding toughness (11.9 MJ m-3). Moreover, it demonstrates a broad electrochemical window (4.73 V), remarkable stability across a 600-hour cycle test, a high capacity retention exceeding 80 % after 100 cycles at 0.2 C, and a noteworthy self-healing capability. This quasi-solid polymer electrolyte emerges as a promising contender to replace current liquid electrolyte solutions.

Two new quinoline alkaloid with neuroprotective activities from Xylaria longipes.

Two new quinoline alkaloids with an α, ß-unsaturated amide side chain, xylarinines A and B (1 and 2), were isolated from the ethyl acetate extracts of Xylaria longipes solid fermentation. The structures of these were primarily determined though NMR and HRESIMS data analysis. The absolute configuration of compound 1 was assigned using experimental and calculated ECD data. The neuroprotective effects of compounds 1 and 2 against glutamate-induced damage in PC12 cells were evaluated in vitro bioassay. The results demonstrated that both compounds significantly improved cell viability, inhibited apoptosis, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced intracellular reactive oxygen species (ROS) accumulation. These findings suggested that these mechanisms contribute to the neuroprotective effects of the compounds.

Design and experiment of Panax notoginseng root orientation transplanting device based on YOLOv5s.

Consistent root orientation is one of the important requirements of Panax notoginseng transplanting agronomy. In this paper, a Panax notoginseng orientation transplanting method based on machine vision technology and negative pressure adsorption principle was proposed. With the cut-main root of Panax notoginseng roots as the detection object, the YOLOv5s was used to establish a root feature detection model. A Panax notoginseng root orientation transplanting device was designed. The orientation control system identifies the root posture according to the detection results and controls the orientation actuator to adjust the root posture. The detection results show that the precision rate of the model was 94.2%, the recall rate was 92.0%, and the average detection precision was 94.9%. The Box-Behnken experiments were performed to investigate the effects of suction plate rotation speed, servo rotation speed and the angle between the camera and the orientation actuator(ACOA) on the orientation qualification rate and root drop rate. Response surface method and objective optimisation algorithm were used to analyse the experimental results. The optimal working parameters were suction plate rotation speed of 5.73 r/min, servo rotation speed of 0.86 r/s and ACOA of 35°. Under this condition, the orientation qualification rate and root drop rate of the actual experiment were 89.87% and 6.57%, respectively, which met the requirements of orientation transplanting for Panax notoginseng roots. The research method of this paper is helpful to solve the problem of orientation transplanting of other root crops.

Topotactic Conversion of Titanium-Oxo Clusters to a Stable TOC-Based Metal-Organic Framework with the Selective Adsorption of Cationic Dyes.

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti6O6(OiPr)8(TTFTC)(phen)2]2 (1, where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1, in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity (qex) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1.

Multifunctional fluorescence probe for simultaneous detection of viscosity, polarity, and ONOO- and its bioimaging in vitro and vivo.

Intracellular microenvironment (viscosity and polarity) and peroxynitrite ions (ONOO-) are involved in maintaining cell morphology, cell function, and signaling so that it is crucial to explore their level changes in vitro and vivo. In this work, we designed and synthesized a mitochondria-targeted fluorescence probe XBL for monitoring the dynamic changes of viscosity, polarity, and ONOO- based on TICT and ICT mechanism. The fluorescence spectra showed obvious changes for polarity at 500 nm as well as ONOO- and viscosity at 660 nm, respectively. The XBL can image simultaneously viscosity, polarity, and ONOO- in cells, and the results showed excess ONOO- leaded to the increase of viscosity in mitochondrial. The ferroptosis process was accompanied by increase of intracellular viscosity and ONOO- levels (or decrease of polarity), which allowed us to better understand the relevant physiological and pathological processes. The XBL can distinguish normal cells and cancerous cells by the fluorescence intensity changes in green and red channels, and image viscosity in inflamed mice. Thus, XBL can provided the chemical tool to understand the physiological and pathological mechanisms of disease by simultaneous detection of viscosity, polarity and ONOO-.

Electrochemical Synthesis of Selenosulfonates from Diselenides and Sulfonyl Hydrazides.

The electrochemical oxidative radical-radical cross-coupling of sulfonyl hydrazides with diselenides for the synthesis of selenosulfonates was successfully accomplished. The method is applicable to a wide range of aromatic/aliphatic sulfonyl hydrazides and diselenides, providing products in good to excellent yields. Notably, this protocol stands out for its green and sustainable nature, as it does not rely on transition metals and oxidizing agents, and the starting materials are cost-effective and readily available.

Insect-Scale Biped Robots Based on Asymmetrical Friction Effect Induced by Magnetic Torque.

Multimodal and controllable locomotion in complex terrain is of great importance for practical applications of insect-scale robots. Robust locomotion plays a particularly critical role. In this study, a locomotion mechanism for magnetic robots based on asymmetrical friction effect induced by magnetic torque is revealed and defined. The defined mechanism overcomes the design constraints imposed by both robot and substrate structures, enabling the realization of multimodal locomotion on complex terrains. Drawing inspiration from human walking and running locomotion, a biped robot based on the mechanism is proposed, which not only exhibits rapid locomotion across substrates with varying friction coefficients but also achieves precise locomotion along patterned trajectories through programmed controlling. Furthermore, apart from its exceptional locomotive capabilities, the biped robot demonstrates remarkable robustness in terms of load-carrying and weight-bearing performance. The presented locomotion and mechanism herein introduce a novel concept for designing magnetic robots while offering extensive possibilities for practical applications in insect-scale robotics.

Open-Access Oesophagogastroduodenoscopy as an Effective and Safe Strategy for Patients With Non-alarming Symptoms.

BACKGROUND: Open-access oesophagogastroduodenoscopy (OAO) is defined as the performance of oesophagogastroduodenoscopy (OGD) requested by referring physicians without a prior specialist consultation. With the increasing demand for specialist appointments, the use of OAO has helped to reduce healthcare utilization by decreasing prior clinic visits. This also allows endoscopies to be scheduled and performed earlier. This study aims to evaluate our experience in providing OAO services to patients with non-alarming dyspepsia symptoms under the age of 60. METHODS: The records of patients scheduled for OAO from January 2019 to December 2022 at Singapore General Hospital (SGH) Department of Gastroenterology were analyzed. RESULTS: Five hundred sixty-nine patients were scheduled for OAO, and 436 patients underwent the procedure. The mean age of patients was 45.7 (SD=10.9) years old. Thirty-six percent were males, and there were 80.8% Chinese, 5.3% Malay, 8.6% Indian, and 5.3% others. The median waiting time for endoscopy was 23 days (IQR 16-36), and no major adverse events were reported. Over half of the endoscopies were unremarkable (n=231, 53%). There were 25 (5.7%) patients with major findings; three had upper gastrointestinal adenocarcinoma (one oesophageal and two gastric), one had oesophageal varices, and 21 had peptic ulcer disease (10 gastric and 11 duodenal ulcers). A rapid urease test was conducted on 409 patients, and 55 (13.4%) were positive. CONCLUSION: OAO is a safe and effective strategy for providing timely diagnostic OGD to normal-risk patients at our center. Primary care physicians are encouraged to refer non-alarming dyspepsia symptoms patients under 60 years for OAO over the conventional route.

Androgenic steroids induce pathologic scarring in a preclinical porcine model via dysfunctional extracellular matrix deposition.

Hypertrophic scarring is a major source of morbidity. Sex hormones are not classically considered modulators of scarring. However, based on increased frequency of hypertrophic scarring in patients on testosterone, we hypothesized that androgenic steroids induce abnormal scarring and developed a preclinical porcine model to explore these effects. Mini-swine underwent castration, received no testosterone (noT) or biweekly testosterone therapy (+T), and underwent excisional wounding. To create a delayed wound healing model, a subset of wounds were re-excised at 2 weeks. Scars from postoperative day 42 (POD42) and delayed wounds (POD28) were harvested 6 weeks after initial wounding for analysis via histology, bulk RNA-seq, and mechanical testing. Histologic analysis of scars from +T animals showed increased mean fibrosis area (16 mm2noT, 28 mm2+T; p = .007) and thickness (0.246 mm2noT, 0.406 mm2+T; p < .001) compared to noT. XX+T and XY+T scars had greater tensile burst strength (p = .024 and p = .013, respectively) compared to noT swine. Color deconvolution analysis revealed greater deposition of type I and type III collagen as well as increased collagen type I:III ratio in +T scars. Dermatopathologist histology scoring showed that +T exposure was associated with worse overall scarring (p < .05). Gene ontology analysis found that testosterone exposure was associated with upregulation of cellular metabolism and immune response gene sets, while testosterone upregulated pathways related to keratinization and laminin formation on pathway analysis. In conclusion, we developed a preclinical porcine model to study the effects of the sex hormone testosterone on scarring. Testosterone induces increased scar tissue deposition and appears to increase physical strength of scars via supraphysiologic deposition of collagen and other ECM factors. The increased burst strength seen in both XX and XY animals suggests that hormone administration has a strong influence on scar mechanical properties independent of chromosomal sex. Anti-androgen topical therapies may be a promising future area of research.

Telocinobufagin, a PLK1 suppressor that inhibits tumor growth and metastasis by modulating CDC25c and CTCF in HNSCC cells.

BACKGROUND: The high metastasis and mortality rates of head and neck squamous cell carcinoma (HNSCC) urgently require new treatment targets and drugs. A steroidal component of ChanSu, telocinobufagin (TBG), was verified to have anti-cancer effects in various tumors, but its activity and mechanism in anti-HNSCC were still unknown. PURPOSE: This study tried to demonstrate the anti-tumor effect of TBG on HNSCC and verify its potential mechanism. METHODS: The effect of TBG on cell proliferation and metastasis were performed and the TBG changed genes were detected by RNA-seq analysis in HNSCC cells. The GSEA and PPI analysis were used to identify the pathways targeted for TBG-regulated genes. Meanwhile, the mechanism of TBG on anti-proliferative and anti-metastasis were investigated in vitro and in vivo. RESULTS: The in vitro and in vivo experiments confirmed that TBG has favorable anti-tumor effects by induced G2/M phase arrest and suppressed metastasis in HNSCC cells. Further RNA-seq analysis demonstrated the genes regulated by TBG were enriched at the G2/M checkpoint and PLK1 signaling pathway. Then, the bioinformatic analysis of clinical data found that high expressed PLK1 were closely associated with poor overall survival in HNSCC patients. Furthermore, PLK1 directly and indirectly modulated G2/M phase and metastasis (by regulated CTCF) in HNSCC cells, simultaneously. TBG significantly inhibited the protein levels of PLK1 in both phosphorylated and non-phosphorylated forms and then, in one way, inactivated PLK1 failed to activate G2/M phase-related proteins (including CDK1, CDC25c, and cyclin B1). In another way, be inhibited PLK1 unable promote the nuclear translocation of CTCF and thus suppressed HNSC cell metastasis. In contrast, the anti-proliferative and anti-metastasis effects of TBG on HNSCC cell were vanished when cells high-expressed PLK1. CONCLUSION: The present study verified that PLK1 mediated TBG induced anti-tumor effect by modulated G2/M phase and metastasis in HNSCC cells.

Salicylaldehyde-Cobalt(II)-Catalyzed C-H Alkoxylation of Indoles with Secondary Alcohols.

A straight and efficient protocol for the synthesis of hindered indole-ethers via C-H alkoxylation of indoles was developed by a cobalt-catalyzed cross-dehydrogenative coupling reaction with secondary alcohols. The selection of the salicylaldehyde-Co(II) catalyst enables the reaction to proceed under conditions without acid or base addition in the presence of limited alcohols. The protocol has broad substrate scope for both indole and secondary alcohols and exhibits good functional tolerance. The synthetic applications are proven by gram-scale reaction and further diversification of the product. Preliminary mechanistic investigations indicate that the activation of C-H bonds is not the rate-determining step of the reaction.