Ultrasound-Based Micro-/Nanosystems for Biomedical Applications.

Due to the intrinsic non-invasive nature, cost-effectiveness, high safety, and real-time capabilities, besides diagnostic imaging, ultrasound as a typical mechanical wave has been extensively developed as a physical tool for versatile biomedical applications. Especially, the prosperity of nanotechnology and nanomedicine invigorates the landscape of ultrasound-based medicine. The unprecedented surge in research enthusiasm and dedicated efforts have led to a mass of multifunctional micro-/nanosystems being applied in ultrasound biomedicine, facilitating precise diagnosis, effective treatment, and personalized theranostics. The effective deployment of versatile ultrasound-based micro-/nanosystems in biomedical applications is rooted in a profound understanding of the relationship among composition, structure, property, bioactivity, application, and performance. In this comprehensive review, we elaborate on the general principles regarding the design, synthesis, functionalization, and optimization of ultrasound-based micro-/nanosystems for abundant biomedical applications. In particular, recent advancements in ultrasound-based micro-/nanosystems for diagnostic imaging are meticulously summarized. Furthermore, we systematically elucidate state-of-the-art studies concerning recent progress in ultrasound-based micro-/nanosystems for therapeutic applications targeting various pathological abnormalities including cancer, bacterial infection, brain diseases, cardiovascular diseases, and metabolic diseases. Finally, we conclude and provide an outlook on this research field with an in-depth discussion of the challenges faced and future developments for further extensive clinical translation and application.

Identify gestational diabetes mellitus by deep learning model from cell-free DNA at the early gestation stage.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy, which has significant adverse effects on both the mother and fetus. The incidence of GDM is increasing globally, and early diagnosis is critical for timely treatment and reducing the risk of poor pregnancy outcomes. GDM is usually diagnosed and detected after 24 weeks of gestation, while complications due to GDM can occur much earlier. Copy number variations (CNVs) can be a possible biomarker for GDM diagnosis and screening in the early gestation stage. In this study, we proposed a machine-learning method to screen GDM in the early stage of gestation using cell-free DNA (cfDNA) sequencing data from maternal plasma. Five thousand and eighty-five patients from north regions of Mainland China, including 1942 GDM, were recruited. A non-overlapping sliding window method was applied for CNV coverage screening on low-coverage (~0.2×) sequencing data. The CNV coverage was fed to a convolutional neural network with attention architecture for the binary classification. The model achieved a classification accuracy of 88.14%, precision of 84.07%, recall of 93.04%, F1-score of 88.33% and AUC of 96.49%. The model identified 2190 genes associated with GDM, including DEFA1, DEFA3 and DEFB1. The enriched gene ontology (GO) terms and KEGG pathways showed that many identified genes are associated with diabetes-related pathways. Our study demonstrates the feasibility of using cfDNA sequencing data and machine-learning methods for early diagnosis of GDM, which may aid in early intervention and prevention of adverse pregnancy outcomes.

General room-temperature Suzuki-Miyaura polymerization for organic electronics.

π-Conjugated polymers (CPs) have broad applications in high-performance optoelectronics, energy storage, sensors and biomedicine. However, developing green and efficient methods to precisely synthesize alternating CP structures on a large scale remains challenging and critical for their industrialization. Here a room-temperature, scalable and homogeneous Suzuki-Miyaura-type polymerization reaction is developed with broad generality validated for 24 CPs including donor-donor, donor-acceptor and acceptor-acceptor connectivities, yielding device-quality polymers with high molecular masses. Furthermore, the polymerization protocol significantly reduces homocoupling structural defects, yielding more structurally regular and higher-performance electronic materials and optoelectronic devices than conventional thermally activated polymerizations. Experimental and theoretical studies reveal that a borate transmetalation process plays a key role in suppressing protodeboronation, which is critical for large-scale structural regularity. Thus, these results provide a general polymerization tool for the scalable production of device-quality CPs with alternating structural regularity.

Low-Cost Nonfused-Ring Electron Acceptors Enabled by Noncovalent Conformational Locks.

ConspectusSince the first bilayer-structured organic solar cells (OSCs) in 1986, fullerenes and their derivatives have dominated the landscape for two decades due to their unique properties. In recent years, the breakthrough in nonfullerene acceptors (NFAs) was mainly attributed to the development of fused-ring electron acceptors (FREAs), whose photovoltaic performance surpassed that of fullerene derivatives. Through the unremitting efforts of the whole community, the power conversion efficiencies (PCEs) have surpassed 19% in FREA-based OSCs. However, FREAs generally suffered from complex synthetic approaches and high product costs, which hindered large-scale production. Therefore, many researchers are seeking a new type of NFA to achieve cost-effective, highly efficient OSCs.In collaboration with Marks and Facchetti in 2012, Huang et al. (Huang, H. J. Am. Chem. Soc. 2012, 134, 10966-10973, 10.1021/ja303401s) proposed the concept of "noncovalent conformational locks" (NoCLs). In the following years, our group has been focusing on the theoretical and experimental exploration of NoCLs, revealing their fundamental nature, formulating a simple descriptor for quantifying their strength, and employing this approach to achieve high-performance organic/polymeric semiconductors for optoelectronics, such as OSCs, thin-film transistors, room-temperature phosphorescence, and photodetectors. The NoCLs strategy has been proven to be a simple and effective approach for enhancing molecular rigidity and planarity, thus improving the charge transport mobilities of organic/polymeric semiconductors, attributed to reduced reorganization energy and suppressed nonradiative decay.In 2018, Chen et al. (Li, S. Adv. Mater. 2018, 30, 1705208, 10.1002/adma.201705208) reported the first example of nonfused-ring electron acceptors (NFREAs) with intramolecular noncovalent F···H interactions. The NoCLs strategy is essential in NFREAs, as it simplifies the conjugated structures while maintaining high coplanarity comparable to that of FREAs. Due to their simple structures and concise synthesis routes, NFREAs show great potential for achieving cost-effective and highly efficient OSCs. In this Account, we provide an overview of our efforts in developing NFREAs with the NoCLs strategy. We begin with a discussion on the distinct features of NFREAs compared with FREAs, and the structural simplification from FREAs to NFREAs to completely NFREAs. Next, we examine several selected typical examples of NFREAs with remarkable photovoltaic performance, aiming to provide an in-depth exploration of the molecular design principle and structure-property-performance relationships. Then, we discuss how to achieve a balance among efficiency, stability, and cost through a two-in-one strategy of polymerized NFREAs (PNFREAs). Finally, we offer our views on the current challenges and future prospects of NFREAs. We hope this Account will trigger intensive research interest in this field, thus propelling OSCs into a new stage.

Metabolic disorder and functional disturbance in the central executive network in minimal hepatic encephalopathy.

The aim of this paper is to investigate dynamical functional disturbance in central executive network in minimal hepatic encephalopathy and determine its association with metabolic disorder and cognitive impairment. Data of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging were obtained from 27 cirrhotic patients without minimal hepatic encephalopathy, 20 minimal hepatic encephalopathy patients, and 24 healthy controls. Central executive network was identified utilizing seed-based correlation approach. Dynamic functional connectivity across central executive network was calculated using sliding-window approach. Functional states were estimated by K-means clustering. Right dorsolateral prefrontal cortex metabolite ratios (i.e. glutamate and glutamine complex/total creatine, myo-inositol / total creatine, and choline / total creatine) were determined. Neurocognitive performance was determined by psychometric hepatic encephalopathy scores. Minimal hepatic encephalopathy patients had decreased myo-inositol / total creatine and choline / total creatine and increased glutamate and glutamine complex / total creatine in right dorsolateral prefrontal cortex (all P ≤ 0.020); decreased static functional connectivity between bilateral dorsolateral prefrontal cortex and between right dorsolateral prefrontal cortex and lateral-inferior temporal cortex (P ≤ 0.001); increased frequency and mean dwell time in state-1 (P ≤ 0.001), which exhibited weakest functional connectivity. Central executive network dynamic functional indices were significantly correlated with right dorsolateral prefrontal cortex metabolic indices and psychometric hepatic encephalopathy scores. Right dorsolateral prefrontal cortex myo-inositol / total creatine and mean dwell time in state-1 yielded best potential for diagnosing minimal hepatic encephalopathy. Dynamic functional disturbance in central executive network may contribute to neurocognitive impairment and could be correlated with metabolic disorder.

Radiative Thermal Management in Face Masks with a Micro/Nanofibrous Filter.

Micro/nanofiber-based face masks are recommended as personal protective equipment (PPE) against particulate matter (PM), especially PM0.3. Ensuring thermal comfort in daily use face masks is essential in many situations. Here, radiative thermal management is introduced into face masks to elevate the user comfort. An interlayered poly(lactic acid) (PLA) micro/nanofibrous filter effectively captures PM0.3 (99.69%) with minimal pressure drop (49 Pa). Thermal regulation is accomplished by controlling the mid-infrared (MIR) emissivity of the face mask's outer surface. Cooling face masks feature cotton nonwovens with high MIR emissivity (90.7%) for heat dissipation, while warming face masks utilize perforated Al/PE films with minimal MIR emissivity (10.7%) for warmth retention. Skin temperature measurements indicate that the skin covered by the cooling face mask could be 1.1 °C lower than that covered by the 3M face mask, while the skin covered by the warming face mask could be 1.3 °C higher than that covered by the 3M face mask.

Boosting Electrocatalytic Ammonia Synthesis via Synergistic Effect of Iron-Based Single Atoms and Clusters.

Electrocatalytic reduction of nitrate to ammonia (NO3RR) is gaining attention for low carbon emissions and environmental protection. However, low ammonia production rate and poor selectivity have remained major challenges in this multi-proton coupling process. Herein, we report a facile strategy toward a novel Fe-based hybrid structure composed of Fe single atoms and Fe3C atomic clusters that demonstrates outstanding performance for synergistic electrocatalytic NO3RR. By operando synchrotron Fourier transform infrared spectroscopy and theoretical computation, we clarify that Fe single atoms serve as the active site for NO3RR, while Fe3C clusters facilitate H2O dissociation to provide protons (*H) for continued hydrogenation reactions. As a result, the Fe-based electrocatalyst exhibits ammonia Faradaic efficiency of nearly 100%, with a corresponding production rate of 24768 µg h-1 cm-2 at -0.4 V vs RHE, exceeding most reported metal-based catalysts. This research provides valuable guidance toward multi-step reactions.

Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial.

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.

Impairment of Gal-9 and Tim-3 crosstalk between Tregs and Th17 cells drives tobacco smoke-induced airway inflammation.

Overexpression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) on T cells has been observed in smokers. However, whether and how galectin-9 (Gal-9)/TIM-3 signal between T-regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke-induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal-9/TIM-3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM-3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM-3 in CD4+ T cells was explored in a HAVCR2-/- mouse model and in mice that received recombinant anti-TIM3. The crosstalk between Gal-9 and Tim-3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal-9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal-9. We observed a pro-inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM-3. The restrained phenotype of CD4+ T cells was perturbed when TIM-3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal-9. The interaction between Gal-9 and TIM-3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor-related orphan receptor gamma t. The expression of Gal-9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal-9/Tim-3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke-induced airway/lung inflammation.

Immobilizing Ordered Oxophilic Indium Sites on Platinum Enabling Efficient Hydrogen Oxidation in Alkaline Electrolyte.

Addressing the sluggish kinetics in the alkaline hydrogen oxidation reaction (HOR) is a pivotal yet challenging step toward the commercialization of anion-exchange membrane fuel cells (AEMFCs). Here, we have successfully immobilized indium (In) atoms in an orderly fashion into platinum (Pt) nanoparticles supported by reduced graphene oxide (denoted as O-Pt3In/rGO), significantly enhancing alkaline HOR kinetics. We have revealed that the ordered atomic matrix enables uniform and optimized hydrogen binding energy (HBE), hydroxyl binding energy (OHBE), and carbon monoxide binding energy (COBE) across the catalyst. With a mass activity of 2.3066 A mg-1 at an overpotential of 50 mV, over 10 times greater than that of Pt/C, the catalyst also demonstrates admirable CO resistance and stability. Importantly, the AEMFC implementing this catalyst as the anode catalyst has achieved an impressive power output compared to Pt/C. This work not only highlights the significance of constructing ordered oxophilic sites for alkaline HOR but also sheds light on the design of well-structured catalysts for energy conversion.

Organoid forming potential as complementary parameter for accurate evaluation of breast cancer neoadjuvant therapeutic efficacy.

BACKGROUND: 13-15% of breast cancer/BC patients diagnosed as pathological complete response/pCR after neoadjuvant systemic therapy/NST suffer from recurrence. This study aims to estimate the rationality of organoid forming potential/OFP for more accurate evaluation of NST efficacy. METHODS: OFPs of post-NST residual disease/RD were checked and compared with clinical approaches to estimate the recurrence risk. The phenotypes of organoids were classified via HE staining and ER, PR, HER2, Ki67 and CD133 immuno-labeling. The active growing organoids were subjected to drug sensitivity tests. RESULTS: Of 62 post-NST BC specimens, 24 were classified as OFP-I with long-term active organoid growth, 19 as OFP-II with stable organoid growth within 3 weeks, and 19 as OFP-III without organoid formation. Residual tumors were overall correlated with OFP grades (P < 0.001), while 3 of the 18 patients (16.67%) pathologically diagnosed as tumor-free (ypT0N0M0) showed tumor derived-organoid formation. The disease-free survival/DFS of OFP-I cases was worse than other two groups (Log-rank P < 0.05). Organoids of OFP-I/-II groups well maintained the biological features of their parental tumors and were resistant to the drugs used in NST. CONCLUSIONS: The OFP would be a complementary parameter to improve the evaluation accuracy of NST efficacy of breast cancers.

Extended-Gate FET Biosensor Based on GaN Micropillar Array and Polycrystalline Layer: Application to Hg2+ Detection in Human Urine.

Owing to the separation of field-effect transistor (FET) devices from sensing environments, extended-gate FET (EGFET) biosensor features high stability and low cost. Herein, a highly sensitive EGFET biosensor based on a GaN micropillar array and polycrystalline layer (GMP) was fabricated, which was prepared by using simple one-step low-temperature MOCVD growth. In order to improve the sensitivity and detection limit of EGFET biosensor, the surface area and the electrical conductivity of extended-gate electrode can be increased by the micropillar array and the polycrystalline layer, respectively. The designed GMP-EGFET biosensor was modified with l-cysteine and applied for Hg2+ detection with a low limit of detection (LOD) of 1 ng/L, a high sensitivity of -16.3 mV/lg(µg/L) and a wide linear range (1 ng/L-24.5 µg/L). In addition, the detection of Hg2+ in human urine was realized with an LOD of 10 ng/L, which was more than 30 times lower than that of reported sensors. To our knowledge, it is the first time that GMP was used as extended-gate of EGFET biosensor.

Multilocus Distance-Regulated Sensor Array for Recognition of Polyphenols via Machine Learning and Indicator Displacement Assay.

Developing new strategies to construct sensor arrays that can effectively distinguish multiple natural components with similar structures in mixtures is an exceptionally challenging task. Here, we propose a new multilocus distance-modulated indicator displacement assay (IDA) strategy for constructing a sensor array, incorporating machine learning optimization to identify polyphenols. An 8-element array, comprising two fluorophores and their six dynamic covalent complexes (C1-C6) formed by pairing two fluorophores with three distinct distance-regulated quenchers, has been constructed. Polyphenols with diverse spatial arrangements and combinatorial forms compete with the fluorophores by forming pseudocycles with quenchers within the complexes, leading to varying degrees of fluorescence recovery. The array accurately and effectively distinguished four tea polyphenols and 16 tea varieties, thereby demonstrating the broad applicability of the multilocus distance-modulated IDA array in detecting polyhydroxy foods and natural medicines.

GhVIM28, a negative regulator identified from VIM family genes, positively responds to salt stress in cotton.

The VIM (belonged to E3 ubiquitin ligase) gene family is crucial for plant growth, development, and stress responses, yet their role in salt stress remains unclear. We analyzed phylogenetic relationships, chromosomal localization, conserved motifs, gene structure, cis-acting elements, and gene expression patterns of the VIM gene family in four cotton varieties. Our findings reveal 29, 29, 17, and 14 members in Gossypium hirsutum (G.hirsutum), Gossypium barbadense (G.barbadense), Gossypium arboreum (G.arboreum), and Gossypium raimondii (G. raimondii), respectively, indicating the maturity and evolution of this gene family. motifs among GhVIMs genes were observed, along with the presence of stress-responsive, hormone-responsive, and growth-related elements in their promoter regions. Gene expression analysis showed varying patterns and tissue specificity of GhVIMs genes under abiotic stress. Silencing GhVIM28 via virus-induced gene silencing revealed its role as a salt-tolerant negative regulator. This work reveals a mechanism by which the VIM gene family in response to salt stress in cotton, identifying a potential negative regulator, GhVIM28, which could be targeted for enhancing salt tolerance in cotton. The objective of this study was to explore the evolutionary relationship of the VIM gene family and its potential function in salt stress tolerance, and provide important genetic resources for salt tolerance breeding of cotton.

US-based Sequential Algorithm Integrating an AI Model for Advanced Liver Fibrosis Screening.

Background Noninvasive tests can be used to screen patients with chronic liver disease for advanced liver fibrosis; however, the use of single tests may not be adequate. Purpose To construct sequential clinical algorithms that include a US deep learning (DL) model and compare their ability to predict advanced liver fibrosis with that of other noninvasive tests. Materials and Methods This retrospective study included adult patients with a history of chronic liver disease or unexplained abnormal liver function test results who underwent B-mode US of the liver between January 2014 and September 2022 at three health care facilities. A US-based DL network (FIB-Net) was trained on US images to predict whether the shear-wave elastography (SWE) value was 8.7 kPa or higher, indicative of advanced fibrosis. In the internal and external test sets, a two-step algorithm (Two-step#1) using the Fibrosis-4 Index (FIB-4) followed by FIB-Net and a three-step algorithm (Three-step#1) using FIB-4 followed by FIB-Net and SWE were used to simulate screening scenarios where liver stiffness measurements were not or were available, respectively. Measures of diagnostic accuracy were calculated using liver biopsy as the reference standard and compared between FIB-4, SWE, FIB-Net, and European Association for the Study of the Liver guidelines (ie, FIB-4 followed by SWE), along with sequential algorithms. Results The training, validation, and test data sets included 3067 (median age, 42 years [IQR, 33-53 years]; 2083 male), 1599 (median age, 41 years [IQR, 33-51 years]; 1124 male), and 1228 (median age, 44 years [IQR, 33-55 years]; 741 male) patients, respectively. FIB-Net obtained a noninferior specificity with a margin of 5% (P < .001) compared with SWE (80% vs 82%). The Two-step#1 algorithm showed higher specificity and positive predictive value (PPV) than FIB-4 (specificity, 79% vs 57%; PPV, 44% vs 32%) while reducing unnecessary referrals by 42%. The Three-step#1 algorithm had higher specificity and PPV compared with European Association for the Study of the Liver guidelines (specificity, 94% vs 88%; PPV, 73% vs 64%) while reducing unnecessary referrals by 35%. Conclusion A sequential algorithm combining FIB-4 and a US DL model showed higher diagnostic accuracy and improved referral management for all-cause advanced liver fibrosis compared with FIB-4 or the DL model alone. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ghosh in this issue.

Comparison of long-term radial artery occlusion via distal vs. conventional transradial access (CONDITION): a randomized controlled trial.

BACKGROUND: The distal transradial access (dTRA) has become an attractive and alternative access to the conventional transradial access (TRA) for cardiovascular interventional diagnosis and/or treatment. There was a lack of randomized clinical trials to evaluate the effect of the dTRA on the long-term radial artery occlusion (RAO). METHODS: This was a prospective, randomized controlled study. The primary endpoint was the incidence of long-term RAO at 3 months after discharge. The secondary endpoints included the successful puncture rate, puncture time, and other access-related complications. RESULTS: The incidence of long-term RAO was 0.8% (3/361) for dTRA and 3.3% (12/365) for TRA (risk ratio = 0.25, 95% confidence interval = 0.07-0.88, P = 0.02). The incidence of RAO at 24 h was significantly lower in the dTRA group than in the TRA group (2.5% vs. 6.7%, P < 0.01). The puncture success rate (96.0% vs. 98.5%, P = 0.03) and single puncture attempt (70.9% vs. 83.9%, P < 0.01) were significantly lower in the dTRA group than in the TRA group. However, the number of puncture attempts and puncture time were higher in the dTRA group. The dTRA group had a lower incidence of bleeding than the TRA group (1.5% vs. 6.0%, P < 0.01). There was no difference in the success rate of the procedure, total fluoroscopy time, or incidence of other access-related complications between the two groups. In the per-protocol analysis, the incidence of mEASY type ≥ II haematoma was significantly lower in the dTRA group, which was consistent with that in the as-treated analysis. CONCLUSIONS: The dTRA significantly reduced the incidence of long-term RAO, bleeding or haematoma. TRIAL REGISTRATION: ClinicalTrials.gov identifer: NCT05253820.

Doping-Engineered Piezoelectric Ultrathin Nanosheets for Synergistically Piezo-Chemocatalytic Antitumor and Antibacterial Therapies Against Cutaneous Melanoma.

The post-surgical melanoma recurrence and wound infections have persistently troubled clinical management. Piezocatalytic therapy features high efficiency in generating reactive oxygen species (ROS) for tumor therapy, but it faces limitations in piezoelectricity and redox-active site availability. Herein, Fe-doped ultrathin Bi4Ti3O12 nanosheets (designated as Fe-UBTO NSs) with synergistically piezo-chemocatalytic activity are engineered for antitumor and antibacterial treatment against cutaneous melanoma. The doping-engineered strategy induces oxygen vacancies and lattice distortions in Fe-UBTO NSs, which narrows bandgap to enhance piezocatalytic 1O2 and H2O2 generation by improving the electron-hole pairs separation, hindering their recombination, and increasing oxygen adsorption. Moreover, Fe doping establishes a piezo-chemocatalytic system, in which the piezocatalysis enables the self-supply of H2O2 and expedites electron transfer in Fenton reactions, inducing increased ·OH production. Besides, the atomic-level thickness and expanded surface area enhance the sensitivity to ultrasound stimuli and expose more redox-active sites, augmenting the piezo-chemocatalytic efficiency, and ultimately leading to abundant ROS generation. The Fe-UBTO-mediated piezo-chemocatalytic therapy causes intracellular oxidative stress, triggering apoptosis and excessive autophagy of tumor cells. Moreover, this strategy accelerates wound healing by facilitating sterilization, angiogenesis, and collagen deposition. This work provides distinct options to develop doping-engineered ultrathin nanosheets with augmented piezo-chemocatalytic activity for postoperative management of cutaneous melanoma.

In Situ Polymerization Bi-Functional Gel Polymer Electrolyte for High Performance Quasi-Solid-State Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries are expected to be the next-generation energy storage system due to the ultrahigh theoretical energy density and low cost. However, the notorious shuttle effect of higher-order polysulfides and the uncontrollable lithium dendrite growth are the two biggest challenges for commercially viable Li-S batteries. Herein, these two main challenges are solved by in situ polymerization of bi-functional gel polymer electrolyte (GPE). The initiator (SiCl4) not only drives the polymerization of 1,3-dioxolane (DOL) but also induces the construction of a hybrid solid electrolyte interphase (SEI) with inorganic-rich compositions on the Li anode. In addition, diatomaceous earth (DE) is added and anchored in the GPE to obtain PDOL-SiCl4-DE electrolyte through in situ polymerization. Combined with density functional theory (DFT) calculations, the hybrid SEI provides abundant adsorption sites for the deposition of Li+, inhibiting the growth of lithium dendrites. Meanwhile, the shuttle effect is greatly alleviated due to the strong adsorption capacity of DE toward lithium polysulfides. Therefore, the Li/Li symmetric cell and Li-S full cell assembled with PDOL-SiCl4-DE exhibit excellent cycling stability. This study offers a valuable reference for the development of high performance and safe Li-S batteries.

Association of triglyceride-glucose index and its combination with adiposity-related indices with the incidence of myocardial infarction: a cohort study from the UK Biobank.

BACKGROUND: The triglyceride-glucose (TyG) index performs better at reflecting insulin resistance when combined with waist circumference (WC), body mass index (BMI), and waist-to-height ratio (WHtR) than when used alone. This study aimed to prospectively examine the relationships between TyG, TyG-BMI, TyG-WC, and TyG-WHtR with the incidence of myocardial infarction (MI) and its subtypes. METHODS: This cohort study included 370,390 participants from the UK Biobank. The Cox proportional hazards model and restricted cubic spline regression model were used to assess the associations of TyG, TyG-BMI, TyG-WC, and TyG-WHtR with MI, ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI). The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were employed to examine the predictive value of four indicators. RESULTS: The hazard ratios (HRs) and 95% confidence intervals (CIs) of MI in the highest quartiles for TyG, TyG-BMI, TyG-WC, and TyG-WHtR were 1.36 (1.28-1.44), 1.47 (1.39-1.56), 1.53 (1.43-1.64), and 1.58 (1.48-1.68) in the fully-adjusted model. Comparable findings were observed when the outcomes were reclassified as STEMI or NSTEMI. However, the associations of TyG-BMI, TyG-WC, and TyG-WHtR with the risk of STEMI were weaker than MI and NSTEMI. A linear dose-response association between TyG and the risk of MI and NSTEMI were demonstrated. TyG-BMI, TyG-WC, and TyG-WHtR all showed nonlinear patterns in their associations with the risk of MI, STEMI, and NSTEMI. TyG-WC was most effective in diagnosing MI (AUC: 0.648, 95% CI: 0.644-0.653), STEMI (AUC: 0.631, 95% CI: 0.622-0.639), and NSTEMI (AUC: 0.647, 95% CI: 0.641-0.654). CONCLUSION: The TyG index was linearly associated with increased risk of MI and NSTEMI, whereas TyG-BMI, TyG-WC, and TyG-WHtR were nonlinearly associated with increased risk of MI and NSTEMI. There were distinct patterns in the relationships between these indicators with STEMI. TyG-WC provided the best diagnostic effectiveness for MI, STEMI, and NSTEMI.

Utility of Chimeric Mice with Humanized Livers for Predicting Hepatic Organic Anion - Transporting Polypeptide 1B (OATP1B) - Mediated Clinical Drug-Drug Interactions.

The influence of transporters on the pharmacokinetics of drugs is being increasingly recognized, and drug-drug interactions (DDIs) via modulation of transporters could lead to clinical adverse events. Organic anion-transporting polypeptide 1B (OATP1B) are liver specific uptake transporters in humans that can transport a broad range of substrates, including statins. It is a challenge to predict OATP1B-mediated DDIs using preclinical animal models because of species differences in substrate specificity and abundance levels of transporters. PXB-mice are chimeric mice with humanized livers that are highly repopulated with human hepatocytes and have been widely used for drug metabolism and pharmacokinetics studies in drug discovery. In the present study, we measured the exposure increases (blood AUC and Cmax) of ten OATP1B substrates in PXB-mice upon co-administration with rifampin, a potent OATP1B specific inhibitor. These data in PXB-mice were then compared with the observed DDIs between OATP1B substrates and single-dose rifampin in humans. Our findings suggest that the DDIs between OATP1B substrates and rifampin in PXB-mouse are comparable with the observed DDIs in the clinic. Since most OATP1B substrates are metabolized by CYPs and/or are substrates of P-glycoprotein (P-gp), we further validated the utility of PXB-mice to predict complex DDIs involving inhibition of OATP1B, CYPs and P-gp using CsA and gemfibrozil as perpetrators. Overall, the data support that the chimeric mice with humanized livers could be a useful tool for the prediction of hepatic OATP1B-mediated DDIs in humans. Significance Statement The ability of PXB-mouse with humanized liver to predict OATP1B-mediated drug-drug interactions (DDIs) in humans was evaluated. The plasma exposure increases of ten OATP1B substrates with rifampin, an OATP1B inhibitor, in PXB-mice have a good correlation with those observed in humans. More importantly, PXB-mice can predict complex DDIs including inhibition of OATP1B, CYPs and P-gp in humans. PXB-mice are a promising useful tool to assess OATP1B-mediated clinical DDIs.