SERS surgical navigation with postsurgical immunotherapy of local microtumors and distant metastases for improved anticancer outcomes.

The standard of clinical care of most malignant solid cancers is surgery, followed by postsurgical adjuvant therapy, but microtumor lesions left behind after surgery and invisible distant metastases are the major reasons for treatment failure. Here, we report an integrated strategy combining surface-enhanced Raman spectroscopy (SERS) surgical navigation with postsurgical immunotherapy elicited by near-infrared II photothermal treatment and programmed death-1 antibody. The SERS surgical navigation is principally based on the multifunctional optical probes (namely, MATRA probes) integrating with T1-weighted magnetic resonance (MR) imaging, photothermal effect and Raman spectroscopic detection. We demonstrate in a 4T1 breast tumor mouse model that the pre-surgical MR/SERS dual-modal imaging is capable of providing comprehensive tumor information, and intraoperative SERS detection allows accurately delineating the tumor margins and guiding the surgical resection in real time with the least residual microscopic foci. We verify that the postsurgical immunotherapy effectively eradicates those local microtumor lesions and invisible distant metastases, greatly inhibiting the postsurgical cancer recurrence and distant metastasis.

Prediction of non-muscle invasive bladder cancer recurrence using deep learning of pathology image.

We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

Using -NH and -OH rich organic cathodes to explore proton transport in aqueous zinc-ion batteries.

An organic cathode material for zinc-ion batteries shows a reliable proton transport mechanism. It uses a pyrazine ring as the energy storage unit and H+ as the shuttle ion, enabling high functionality utilization with rapid redox kinetics.

Biguanide-Vancomycin Conjugates are Effective Broad-Spectrum Antibiotics against Actively Growing and Biofilm-Associated Gram-Positive and Gram-Negative ESKAPE Pathogens and Mycobacteria.

Strategies to increase the efficacy and/or expand the spectrum of activity of existing antibiotics provide a potentially fast path to clinically address the growing crisis of antibiotic-resistant infections. Here, we report the synthesis, antibacterial efficacy, and mechanistic activity of an unprecedented class of biguanide-antibiotic conjugates. Our lead biguanide-vancomycin conjugate, V-C6-Bg-PhCl (5e), induces highly effective cell killing with up to a 2 orders-of-magnitude improvement over its parent compound, vancomycin (V), against vancomycin-resistant enterococcus. V-C6-Bg-PhCl (5e) also exhibits improved activity against mycobacteria and each of the ESKAPE pathogens, including the Gram-negative organisms. Furthermore, we uncover broad-spectrum killing activity against biofilm-associated Gram-positive and Gram-negative bacteria as well as mycobacteria not observed for clinically used antibiotics such as oritavancin. Mode-of-action studies reveal that vancomycin-like cell wall synthesis inhibition with improved efficacy attributed to enhanced engagement at vancomycin binding sites through biguanide association with relevant cell-surface anions for Gram-positive and Gram-negative bacteria. Due to its potency, remarkably broad activity, and lack of acute mammalian cell toxicity, V-C6-Bg-PhCl (5e) is a promising candidate for treating antibiotic-resistant infections and notoriously difficult-to-treat slowly growing and antibiotic-tolerant bacteria associated with chronic and often incurable infections. More generally, this study offers a new strategy (biguanidinylation) to enhance antibiotic activity and facilitate clinical entry.

Comprehensive review on the novel immunotherapy target: Leucine-rich repeat-containing 8A/volume-regulated anion channel.

Leucine-rich repeat-containing 8A (LRRC8A) is a key component of the volume-regulated anion channel (VRAC) that influences essential homeostatic processes in various immune cells. These processes include the regulation of cell volume and membrane potential and the facilitation of the transport of organic agents used as anticancer drugs and immune-stimulating factors. Therefore, understanding the structure-function relationship of LRRC8A, exploring its physiological role in immunity, assessing its efficacy in treating diseases, and advancing the development of compounds that regulate its activity are important research frontiers. This review emphasized the emerging field of LRRC8A, outlined its structure and function, and summarized its role in immune cell development and immune cell-mediated antiviral and antitumor effects. Additionally, it explored the potential of LRRC8A as an immunotherapeutic target, offering insights into resolving persistent challenges and future research directions.

Biomechanical Effects of Multi-segment Fixation on Lumbar Spine and Sacroiliac Joints: A Finite Element Analysis.

OBJECTIVE: Spine fixation surgery affects the biomechanical environment in the sacroiliac joint (SIJ), which may lead to the SIJ pain or degeneration after surgery. The purpose of this study is to determine the impact of the number and position of fixed segments on the SIJs and provide references for surgeons to plan fixation levels and enhance surgical outcomes. METHODS: The intact lumbar-pelvis finite element (FE) models and 11 fixation FE models with different number and position of fixed segments were developed based on CT images. A 400N follower load and 10° range of motion (ROM) of the spine were applied to the superior endplate of L1 to simulate the flexion, extension, bending and torsion motion after surgery. The peak stress on the SIJs, lumbar intervertebral discs, screws and rods were calculated to evaluate the biomechanical effects of fixation procedures. RESULTS: With the lowermost instrumented vertebra (LIV) of L5 or S1, the peak stress on SIJs increased with the number of fixed segments increasing. The flexion motion led to the greater von Mises stress on SIJ compared with other load conditions. Compared with the intact model, peak stress on all fixed intervertebral discs was reduced in the models with less than three fixed segments, and it increased in the models with more than three fixed segments. The stress on the SIJ was extremely high in the models with all segments from L1 to L5 fixed, including L1-L5, L1-S1 and L1-S2 fixation models. The stress on the segment adjacent to the fixed segments was significant higher compared to that in the intact model. The peak stress on rods and screws also increased with the number of fixed segments increasing in the flexion, extension and bending motion, and the bending and flexion motions led to the greater von Mises stress on SIJs. CONCLUSION: Short-term fixation (≤2 segments) did not increase the stress on the SIJs significantly, while long-term segment fixation (≥4 segments) led to greater stress on the SIJs especially when all the L1-L5 segments were fixed. Unfixed lumbar segments compensated the ROM loss of the fixed segments, and the preservation of lumbar spine mobility would reduce the risks of SIJ degeneration.

Comprehensive Screening and Characterization of α-glucosidase Inhibitory Components in the Edible Medicinal Plant Pholidota cantonensis Rolfe Using UPLC-Q-TOF-MS/MS Analysis and Molecular Docking.

Pholidota cantonensis Rolfe is an edible medicinal plant in the genus Pholidota of the family Orchidaceae. This plant is used to prepare medicated food in China and has been reported to possess anti-α-glucosidase activity. To date, little is known about the active substances responsible for the observed anti-α-glucosidase activity. In the present study, we aimed to screen and characterize the α-glucosidase inhibitory fraction of P. cantonensis using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) analysis and molecular docking. As a result, the 50% ethanol fraction obtained from D101 macroporous adsorption resin column chromatography (D50 fraction) had the highest total phenol content (353.83 ± 6.06 mg GAE/g) and the most prominent α-glucosidase inhibitory activity (IC50 = 30.01 ± 7.30 µg/mL). Forty-five compounds were identified from the D50 fraction by using UPLC-Q-TOF-MS/MS analysis. Molecular docking results showed that six main constituents, namely, crepidatin, 2,7-dihydroxy-4-methoxyl-9,10-dihydrophenylene, 4,4',5,6-tetrahydroxystilbene, 4,7-dihydroxy-2-methoxyl-9,10-dihydrophenylene, (-)-lariciresinol, and thunalbene, in the D50 fraction occupied the catalytic sites of α-glucosidase through strong hydrophobic interactions, hydrogen bonding, and other patterns. The binding energies were between - 29.95 and - 11.41 kJ/mol, indicating good binding between the tested compounds and α-glucosidase. The active ingredients responsible for the α-glucosidase inhibitory activity may include phenanthrenes, stilbenes, dibenzyls, and lignans. The D50 fraction has potential value for developing innovative drugs for the prevention and treatment of diabetes mellitus (DM) and is worthy of in-depth research.

Techniques for imaging the choroid and choroidal blood flow in vivo.

The choroid, which is a highly vascularized layer between the retina and sclera, is essential for supplying oxygen and nutrients to the outer retina. Choroidal vascular dysfunction has been implicated in numerous ocular diseases, including age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, and myopia. Traditionally, the in vivo assessment of choroidal blood flow relies on techniques such as laser Doppler flowmetry, laser speckle flowgraphy, pneumotonometry, laser interferometry, and ultrasonic color Doppler imaging. While the aforementioned methods have provided valuable insights into choroidal blood flow regulation, their clinical applications have been limited. Recent advancements in optical coherence tomography and optical coherence tomography angiography have expanded our understanding of the choroid, allowing detailed visualization of the larger choroidal vessels and choriocapillaris, respectively. This review provides an overview of the available techniques that can investigate the choroid and its blood flow in vivo. Future research should combine these techniques to comprehensively image the entire choroidal microcirculation and develop robust methods to quantify choroidal blood flow. The potential findings will provide a better picture of choroidal hemodynamics and its effect on ocular health and disease.

The Establishment of a Novel Upper Cervical Complex Fracture Classification System.

BACKGROUND CONTEXT: Upper cervical complex fractures are associated with high rates of neurological damage and mortality. The Dickman's classification is widely used in the diagnosis of upper cervical complex fractures. However, it falls short of covering the full spectrum of complex fractures. This limitation hinders effective diagnosis and treatment of these injuries. PURPOSE: To address the diagnostic gap in upper cervical complex fractures, the study introduces a novel classification system for these injuries, assessing its reliability and usability. STUDY DESIGN: Proposal of a new classification system for upper cervical complex fractures. PATIENT SAMPLE: The study comprised the clinical data of 242 patients with upper cervical complex fractures, including 32 patients treated at our hospital, along with an additional 210 cases from the literature. OUTCOME MEASURES: The inter-observer and intra-observer reliability (kappa coefficient, κ) of this classification system were investigated by 3 spine surgeons. The three researchers independently re-evaluated the upper cervical complex fracture classification system 3 months later. METHODS: The proposed classification categorizes upper cervical complex fractures into three main types: Type I combines odontoid and Hangman's fractures into two subtypes; Type II merges C1 with odontoid/Hangman's fractures into three subtypes; and Type III encompasses a combination of C1, odontoid, and Hangman's fractures, divided into two subtypes. Meanwhile, a questionnaire was administered in 15 assessors to evaluate the system's ease of use and clinical applicability. RESULTS: A total of 45 cases (18.6%) unclassifiable by Dickman's classification were successfully categorized using our system. The mean κ value of inter-observer reliability was 0.783, indicating substantial reliability. The mean κ value of intra-observer reliability was 0.862, indicating almost perfect reliability. Meanwhile, thirteen assessors (87.7%) stated that the classification system is easy to remember, easy to apply, and they expressed intentions to apply it in clinical practice in the future. CONCLUSIONS: This system not only offers high confidence and reproducibility but also serves as a precise guide for clinicians in formulating treatment plans. Future prospective applications are warranted to further evaluate this classification system.

Effectiveness, safety, and treatment pattern of sodium zirconium cyclosilicate in Chinese patients with hyperkalemia: interim analysis from a multicenter, prospective, real-world study (Actualize Study).

Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis. Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness. Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated. Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

Sequential delivery of photosensitizers and checkpoint inhibitors by engineered bacteria for enhanced cancer photodynamic immunotherapy.

Engineered bacteria-based cancer therapy has increasingly been considered to be a promising therapeutic strategy due to the development of synthetic biology. Wherein, engineering bacteria-mediated photodynamic therapy (PDT)-immunotherapy shows greater advantages and potential in treatment efficiency than monotherapy. However, the unsustainable regeneration of photosensitizers (PSs) and weak immune responses limit the therapeutic efficiency. Herein, we developed an engineered bacteria-based delivery system for sequential delivery of PSs and checkpoint inhibitors in cancer PDT-immunotherapy. The biosynthetic pathway of 5-aminolevulinic acid (5-ALA) was introduced into Escherichia coli, yielding a supernatant concentration of 172.19 mg/L after 10 h of growth. And another strain was endowed with the light-controllable releasement of anti-programmed cell death-ligand 1 nanobodies (anti-PD-L1). This system exhibited a collaborative effect, where PDT initiated tumor cell death and the released tumor cell fragments stimulated immunity, followed by the elimination of residual tumor cells. The tumor inhibition rate reached 74.97%, and the portion of activated T cells and inflammatory cytokines were reinforced. The results demonstrated that the engineered bacteria-based collaborative system could sequentially deliver therapeutic substance and checkpoint inhibitors, and achieve good therapeutic therapy. This paper will provide a new perspective for the cancer PDT-immunotherapy.

Comparative Study of Preoperative Sagittal Spinal Pelvic Alignment in Patients with Cervical Spondylotic Radiculopathy, Ossification of the Posterior Longitudinal Ligament, and Cervical Spondylotic Myelopathy.

OBJECTIVES: Cervical spondylosis may lead to changes in the sagittal parameters of the neck and trigger compensatory alterations in systemic sagittal parameters. However, there is currently a dearth of comparative research on the changes and compensatory alterations to sagittal parameters resulting from different types of cervical spondylosis. This study compared the preoperative sagittal alignment sequences among patients with cervical spondylotic radiculopathy (CSR), ossification of the posterior longitudinal ligament (OPLL), and cervical spondylotic myelopathy (CSM) caused by factors resulting from non-OPLL factors. MATERIALS AND METHODS: Full length lateral X-ray of the spine and cervical computed tomography (CT) of 256 patients (134 men, 122 women; mean age, 56.9 ± 9.5 years) were analyzed retrospectively. A total of 4096 radiomics features were measured through the lateral X-ray by two spinal surgeons with extensive experience. The clinical symptoms measures were the Japanese Orthopaedic Association (JOA) score, number of hand actions in 10 s, hand-grip strength, visual analog scale (VAS) score. Normally distributed data was compared using one-way analysis of variance (ANOVA) for parametric variables and χ2 test were used to analyze the categorical data. RESULTS: In the OPLL group, the C2-C7 Cobb angle was greater than in the CSR and CSM groups (19.8 ± 10.4°, 13.3 ± 10.3°, and 13.9 ± 9.9°, respectively, p < 0.001). Additionally, the C7-S1 SVA measure was found to be situated in the anterior portion with regards to the CSM and CSR groups (19.7 ± 58.4°, -6.3 ± 34.3° and -26.3 ± 32.9°, p < 0.001). Moreover, the number of individuals with C7-S1 SVA >50 mm was significantly larger than the CSM group (26/69, 11/83, p < 0.001). In the CSR group, the TPA demonstrated smaller values compared to the OPLL group (8.8 ± 8.5°, 12.7 ± 10.2°, p < 0.001). Furthermore, the SSA was comparatively smaller as opposed to both the OPLL and CSM groups (49.6 ± 11.2°, 54.2 ± 10.8° and 54.3 ± 9.3°, p < 0.05). CONCLUSION: Patients with OPLL exhibit greater cervical lordosis than those with CSR and CSM. However, OPLL is more likely to result in spinal imbalance when compared to the CSM group. Furthermore, OPLL and CSM patients exhibit anterior trunk inclination and worse global spine sagittal parameters in comparison to CSR patients.

Evaluation of thickness of individual macular retinal layers in diabetic eyes from optical coherence tomography.

The effect of diabetes mellitus (DM) on individual retinal layers remains incompletely understood. We evaluated the intra-retinal layer thickness alterations in 71 DM eyes with no diabetic retinopathy (DR), 90 with mild DR, and 63 with moderate DR without macular edema, using spectral-domain optical coherence tomography (SD-OCT) and the Iowa Reference Algorithm for automated retinal layer segmentation. The average thickness of 10 intra-retinal layers was then corrected for ocular magnification using axial length measurements, and pairwise comparisons were made using multivariable linear regression models adjusted for gender and race. In DM no DR eyes, significant thinning was evident in the ganglion cell layer (GCL; p < 0.001), inner nuclear layer (INL; p = 0.001), and retinal pigment epithelium (RPE; p = 0.014) compared to normal eyes. Additionally, mild DR eyes exhibited a thinner inner plexiform layer (IPL; p = 0.008) than DM no DR eyes. Conversely, moderate DR eyes displayed thickening in the INL, outer nuclear layer, IPL, and retinal nerve fiber layer (all p ≤ 0.002), with notably worse vision. These findings highlight distinctive patterns: early diabetic eyes experience thinning in specific retinal layers, while moderate DR eyes exhibit thickening of certain layers and slightly compromised visual acuity, despite the absence of macular edema. Understanding these structural changes is crucial for comprehending diabetic eye complications.

PFC/M1 activation and excitability: a longitudinal cohort study on fatigue symptoms in healthcare workers post-COVID-19.

BACKGROUND: Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be placed on the correlation between fatigue and cortical neurophysiological changes, especially in healthcare workers, who are at a heightened risk of COVID-19 infection. METHODS: A prospective cohort study was conducted involving 29 COVID-19 medical workers and 24 healthy controls. The assessment included fatigue, sleep and health quality, psychological status, and physical capacity. Functional near-infrared spectroscopy (fNIRS) was employed to detect activation of brain regions. Bilateral primary motor cortex (M1) excitabilities were measured using single- and paired-pulse transcranial magnetic stimulation. Outcomes were assessed at 1, 3, and 6 months into the disease course. RESULTS: At 1-month post-COVID-19 infection, 37.9% of patients experienced severe fatigue symptoms, dropping to 10.3% at 3 months. Interestingly, the remarkable decreased activation/excitability of bilateral prefrontal lobe (PFC) and M1 were closely linked to fatigue symptoms after COVID-19. Notably, greater increase in M1 region excitability correlated with more significant fatigue improvement. Re-infected patients exhibited lower levels of brain activation and excitability compared to single-infection patients. CONCLUSIONS: Both single infection and reinfection of COVID-19 lead to decreased activation and excitability of the PFC and M1. The degree of excitability improvement in the M1 region correlates with a greater recovery in fatigue. Based on these findings, targeted interventions to enhance and regulate the excitability of M1 may represent a novel strategy for COVID-19 early rehabilitation. TRIAL REGISTRATION: The Ethics Review Committee of Xijing Hospital, No. KY20232051-F-1; www.chictr.org.cn , ChiCTR2300068444.

What drives college students to use AI for L2 learning? Modeling the roles of self-efficacy, anxiety, and attitude based on an extended technology acceptance model.

Prior research highlights the critical role of AI in enhancing second language (L2) learning. However, the factors that practically affect L2 learners to engage with AI resources are still underexplored. Given the widespread availability of digital devices among college students, they are particularly poised to benefit from AI-assisted L2 learning. As such, this study, grounded in an extended Technology Acceptance Model (TAM), investigates the predictors of college L2 learners' actual use of AI tools, focusing on AI self-efficacy, AI-related anxiety, and their overall attitude toward AI. Data was gathered from 429 L2 learners at Chinese universities via an online questionnaire, utilizing four established scales. Through structural equation modeling (SEM) via AMOS 24, the results indicate that AI self-efficacy could negatively affect AI anxiety, and positively influence both learners' attitude toward AI and their actual use of AI tools. Besides, AI anxiety negatively predicted the actual use of AI. Moreover, AI self-efficacy was a positive predictor of AI use through reducing AI anxiety, enhancing attitude toward AI, or a combination of both. This study also discusses the theoretical and pedagogical implications and suggests directions for future research.

A hybrid quantum-classical classification model based on branching multi-scale entanglement renormalization ansatz.

Tensor networks are emerging architectures for implementing quantum classification models. The branching multi-scale entanglement renormalization ansatz (BMERA) is a tensor network known for its enhanced entanglement properties. This paper introduces a hybrid quantum-classical classification model based on BMERA and explores the correlation between circuit layout, expressiveness, and classification accuracy. Additionally, we present an autodifferentiation method for computing the cost function gradient, which serves as a viable option for other hybrid quantum-classical models. Through numerical experiments, we demonstrate the accuracy and robustness of our classification model in tasks such as image recognition and cluster excitation discrimination, offering a novel approach for designing quantum classification models.

Alpha oscillation mediates the interaction between suicide risk and symptom severity in Major Depressive Disorder.

Objective: The aim of our study was to explore the relationship between changes in neural oscillatory power in the EEG, the severity of depressive-anxiety symptoms, and the risk of suicide in MDD. Methods: 350 MDD patients' demographic and clinical data were collected, and their depressive and anxious symptoms were evaluated using HDRS-17 and HAMA-14, along with a suicide risk assessment using the Nurses' Global Assessment of Suicide Risk (NGASR). EEG data were captured, processed, and analyzed to study brain activity patterns related to MDD. The participants were divided based on suicide risk levels, and statistical analyses, including chi-square, t-tests, Pearson's correlations were used to explore the associations between brain activity, symptom severity, and suicide risk. Closely related variables were identified and ultimately the optimal model was screened using stepwise regression analysis with a forward strategy, and mediation effects were further used to determine the possible interactions between the variables in the regression model. Results: The regression model showed a significant effect of HDRS-17 and alpha power of Medial Occipital Cortex (MOC) on suicide risk, with elevated HDRS-17 increasing suicide risk and elevated alpha power decreasing suicide risk. Mediation effect analyses showed that MOC alpha power partially mediated the effect of depression level on suicide risk, and that an increase in depression severity may lead to a decrease in MOC alpha power, while a decrease in MOC alpha power may lead to an increase in suicide risk. Conclusion: The severity of depression directly increases suicide risk, whereas higher alpha power in the MOC serves as a protective factor, reducing this risk. Notably, MOC alpha power not only directly impacts suicide risk but also mediates the effects of both depression severity and anxiety levels on this risk. Limitations: The relatively small sample size of this study may limit the representativeness of the overall MDD patient population and the detailed analysis of different subgroups. This study did not delve into the relationship between the severity of cognitive symptoms in MDD patients and suicide risk.

In situ tuning of platinum 5d valence states for four-electron oxygen reduction.

The oxygen reduction reaction (ORR) catalyzed by efficient and economical catalysts is critical for sustainable energy devices. Although the newly-emerging atomically dispersed platinum catalysts are highly attractive for maximizing atomic utilization, their catalytic selectivity and durability are severely limited by the inflexible valence transformation between Pt and supports. Here, we present a structure by anchoring Pt atoms onto valence-adjustable CuOx/Cu hybrid nanoparticle supports (Pt1-CuOx/Cu), in which the high-valence Cu (+2) in CuOx combined with zero-valent Cu (0) serves as a wide-range valence electron reservoir (0‒2e) to dynamically adjust the Pt 5d valence states during the ORR. In situ spectroscopic characterizations demonstrate that the dynamic evolution of the Pt 5d valence electron configurations could optimize the adsorption strength of *OOH intermediate and further accelerate the dissociation of O = O bonds for the four-electron ORR. As a result, the Pt1-CuOx/Cu catalysts deliver superior ORR performance with a significantly enhanced four-electron selectivity of over 97% and long-term durability.

Comparative Insecticidal Activity and Mechanism of Isocycloseram versus Other GABAergic Insecticides against the Fall Armyworm.

The fall armyworm (FAW) is a serious agricultural pest and has developed resistance to multiple insecticides. It is necessary to introduce novel insecticide(s) for controlling FAW. Isocycloseram is a completely novel isoxazoline insecticide. However, its activity and mode of action against FAW have not been reported. In this study, isocycloseram exhibited a higher insecticidal activity (LC50 = 0.26 mg/kg) than fipronil (LC50 = 7.72 mg/kg) against FAW. The median inhibitory concentration (IC50) of isocycloseram (IC50 = 8.52 nM) was almost equal to that of the desmethyl-broflanilide (IC50 = 7.32 nM) to the SfrRDL1 receptor. The IC50 of isocycloseram to the SfrRDL2 receptor was 11.13 nM, which was obviously less than that of desmethyl-broflanilide, dieldrin, fipronil, fluxametamide. Compared with the SfrRDL2 receptor, the SfrRDL1 receptor exhibited higher sensitivity to GABAergic insecticides. The recombinant SfrGluCl receptor was successfully stimulated by l-glutamate; however, the currents were low and weakly inhibited by isocycloseram at 10 µM. In conclusion, our results provided the theoretical basis for usage of GABAergic insecticides for controlling FAW.