Linker Mediated Electronic-State Manipulation of Conjugated Organic Polymers Enabling Highly Efficient Oxygen Reduction.

Conjugated polymers with tailorable composition and microarchitecture are propitious for modulating catalytic properties and deciphering inherent structure-performance relationships. Herein, we report a facile linker engineering strategy to manipulate the electronic states of metallophthalocyanine conjugated polymers and uncover the vital role of organic linkers in facilitating electrocatalytic oxygen reduction reaction (ORR). Specifically, a set of cobalt phthalocyanine conjugated polymers (CoPc-CPs) wrapped onto carbon nanotubes (denoted CNTs@CoPc-CPs) are judiciously crafted via in situ assembling square-planar cobalt tetraaminophthalocyanine (CoPc(NH2)4) with different linear aromatic dialdehyde-based organic linkers in the presence of CNTs. Intriguingly, upon varying the electronic characteristic of organic linkers from terephthalaldehyde (TA) to 2,5-thiophenedicarboxaldehyde (TDA) and then to thieno/thiophene-2,5-dicarboxaldehyde (bTDA), their corresponding CNTs@CoPc-CPs exhibit gradually improved electrocatalytic ORR performance. More importantly, theoretical calculations reveal that the charge transfer from CoPc units to electron-withdrawing linkers (i.e., TDA and bTDA) drives the delocalization of Co d-orbital electrons, thereby downshifting the Co d-band energy level. Accordingly, the active Co centers with more positive valence state exhibit optimized binding energy toward ORR-relevant intermediates and thus a balanced adsorption/desorption pathway that endows significant enhancement in electrocatalytic ORR. This work demonstrates a molecular-level engineering route for rationally designing efficient polymer catalysts and gaining insightful understanding of electrocatalytic mechanisms.

CyTOF analysis revealed platelet heterogeneity in breast cancer patients received T-DM1 treatment.

T-DM1 (Trastuzumab Emtansine) belongs to class of Antibody-Drug Conjugates (ADC), where cytotoxic drugs are conjugated with the antibody Trastuzumab to specifically target HER2-positive cancer cells. Platelets, as vital components of the blood system, intricately influence the immune response to tumors through complex mechanisms. In our study, we examined platelet surface proteins in the plasma of patients before and after T-DM1 treatment, categorizing them based on treatment response. We identified a subgroup of platelets with elevated expression of CD63 and CD9 exclusively in patients with favorable treatment responses, while this subgroup was absent in patients with poor responses. Another noteworthy discovery was the elevated expression of CD36 in the platelet subgroups of patients exhibiting inadequate responses to treatment. These findings suggest that the expression of these platelet surface proteins may be correlated with the prognosis of T-DM1 treatment. These indicators offer valuable insights for predicting the therapeutic response to T-DM1 and may become important references in future clinical practice, contributing to a better understanding of the impact of ADC therapies and optimizing personalized cancer treatment strategies.

Anionic Coordination Control in Building Cu-Based Electrocatalytic Materials for CO2 Reduction Reaction.

Renewable energy-driven conversion of CO2 to value-added fuels and chemicals via electrochemical CO2 reduction reaction (CO2RR) technology is regarded as a promising strategy with substantial environmental and economic benefits to achieve carbon neutrality. Because of its sluggish kinetics and complex reaction paths, developing robust catalytic materials with exceptional selectivity to the targeted products is one of the core issues, especially for extensively concerned Cu-based materials. Manipulating Cu species by anionic coordination is identified as an effective way to improve electrocatalytic performance, in terms of modulating active sites and regulating structural reconstruction. This review elaborates on recent discoveries and progress of Cu-based CO2RR catalytic materials enhanced by anionic coordination control, regarding reaction paths, functional mechanisms, and roles of different non-metallic anions in catalysis. Finally, the review concludes with some personal insights and provides challenges and perspectives on the utilization of this strategy to build desirable electrocatalysts.

Cryogenic Thermal Shock Effects on Optical Properties of Quantum Emitters in Hexagonal Boron Nitride.

Solid-state quantum emitters are vital building blocks for quantum information science and quantum technology. Among various types of solid-state emitters discovered to date, color centers in hexagonal boron nitride have garnered tremendous traction in recent years, thanks to their environmental robustness, high brightness, and room-temperature operation. Most recently, these quantum emitters have been employed for satellite-based quantum key distribution. One of the most important requirements to qualify these emitters for space-based applications is their optical stability against cryogenic thermal shock. Such an understanding has, however, remained elusive to date. Here, we report on the effects caused by such thermal shock that induces random, irreversible changes in the spectral characteristics of the quantum emitters. By employing a combination of structural characterizations and density functional calculations, we attribute the observed changes to lattice strain caused by cryogenic temperature shock. Our study sheds light on the stability of the quantum emitters under extreme conditions─similar to those countered in outer space.

[Comparison of in vivo pharmacokinetics of twelve constituents in Qihe Fenqing Yin in normal rats and diabetic rats].

This paper aims to study the pharmacokinetic differences of twelve effective constituents(succinic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, protocatechuic aldehyde, caffeic acid, 5-O-ferulogeninic acid, p-coumaric acid, nuciferine, quercetin, oleanolic acid, and ursolic acid) in Qihe Fenqing Yin in normal and diabetic rats. The diabetic rat model was established by a high-fat diet combined with intraperitoneal injection of streptozocin. A UHPLC-QTRAP-MS/MS method was established for the simultaneous determination of 12 constituents in the plasma of normal rats and model rats after a single intragastric administration of Qihe Fenqing Yin. The results show that the established analytical method has a good linear relationship with the 12 components, and the specificity, accuracy, precision, and stability meet the requirements. The computational pharmacokinetic parameters are fitted by DAS 3.2.8 software, and the results show that the half-life time(t_(1/2)) of the other nine components in the model group was longer than that in the normal group except for caffeic acid, 5-O-ferulogeninic acid, and oleanolic acid. The area under curve(AUC_(0-t)) of cryptochlorogenic acid, p-coumaric acid, ursolic acid, and oleanolic acid increases compared with the normal group. Meanwhile, mean residence time(MRT) delays. The "double peaks" of quercetin and nuciferine in the normal group are not observed in the model group, suggesting that the pharmacokinetic parameters of the drugs in the disease state are significantly different.

The circadian rhythm: A new target of natural products that can protect against diseases of the metabolic system, cardiovascular system, and nervous system.

BACKGROUND: The treatment of metabolic system, cardiovascular system, and nervous system diseases remains to be explored. In the internal environment of organisms, the metabolism of substances such as carbohydrates, lipids and proteins (including biohormones and enzymes) exhibit a certain circadian rhythm to maintain the energy supply and material cycle needed for the normal activities of organisms. As a key factor for the health of organisms, the circadian rhythm can be disrupted by pathological conditions, and this disruption accelerates the progression of diseases and results in a vicious cycle. The current treatments targeting the circadian rhythm for the treatment of metabolic system, cardiovascular system, and nervous system diseases have certain limitations, and the identification of safer and more effective circadian rhythm regulators is needed. AIM OF THE REVIEW: To systematically assess the possibility of using the biological clock as a natural product target for disease intervention, this work reviews a range of evidence on the potential effectiveness of natural products targeting the circadian rhythm to protect against diseases of the metabolic system, cardiovascular system, and nervous system. This manuscript focuses on how natural products restore normal function by affecting the amplitude of the expression of circadian factors, sleep/wake cycles and the structure of the gut microbiota. KEY SCIENTIFIC CONCEPTS OF THE REVIEW: This work proposes that the circadian rhythm, which is regulated by the amplitude of the expression of circadian rhythm-related factors and the sleep/wake cycle, is crucial for diseases of the metabolic system, cardiovascular system and nervous system and is a new target for slowing the progression of diseases through the use of natural products. This manuscript provides a reference for the molecular modeling of natural products that target the circadian rhythm and provides a new perspective for the time-targeted action of drugs.

Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed non-insulin-resistant rats.

Background: Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. Methods: In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Results: Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Conclusions: Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.

Advances in Drug Therapy for Metastatic Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a notably poor prognosis. A large number of patients with PDAC develop metastases before they are diagnosed with metastatic pancreatic cancer (mPDAC). For mPDAC, FOLFIRINOX or gemcitabine plus nab-paclitaxel are the current first-line treatments. It is important to note, however, that many patients will fail chemotherapy because of drug resistance. ​Heterogeneous tumors and complex tumor microenvironments are key factors. As a result, clinical researchers are exploring a variety of alternative treatment modalities. Current understanding of the molecular signature and immune landscape of PDAC has motivated the emergence of different targeted and immune-based therapeutic approaches, some of which have shown promising results. The purpose of this review is to discuss the new targets and new drugs for mPDAC in terms of specific pathogenic factors such as metabolic vulnerability, DNA damage repair system, tumor microenvironment and immune system, in order to identify potential vulnerabilities in mPDAC patients and hopefully improve the prognosis of mPDAC patients.

Peg-IFNα combined with hepatitis B vaccination contributes to HBsAg seroconversion and improved immune function.

PURPOSE: The purpose of this study was to investigate immunological variations between a group that received the hepatitis B vaccine and a non-vaccine group. We focused on a cohort that achieved HBsAg seroclearance after Peg-IFNα treatment of CHB. METHODS: We enrolled twenty-eight individuals who achieved HBsAg seroclearance after Peg-IFNα treatment. They were divided into two groups: a vaccine group (n = 14) and a non-vaccine group (n = 14). We assessed lymphocyte subpopulations, B cell- and T cell-surface costimulatory/inhibitory factors, cytokines and immunoglobulin levels were detected at different time points to explore immune-function differences between both groups. RESULTS: The seroconversion rate in the vaccine group at 24 weeks post-vaccination was 100%, which was significantly higher (p = 0.006) than that of the non-vaccine group (50%). Additionally, more individuals in the vaccine group exhibited anti-HBs levels exceeding 100 IUs/L and 300 IUs/L compared to the non-vaccine group (p < 0.05). The vaccine group demonstrated significantly increase total B cells and class-switched B cells at 24 weeks and plasma cells, CD80+B cells, Tfh cells, and ICOS+Tfh cell at 12 weeks, compared with baseline levels (p < 0.05). Conversely, Bregs (CD24+CD27+ and CD24+CD38high) decreased significantly at 24 weeks (p < 0.05). None of the above changes were statistically significance in the non-vaccine group (p > 0.05). Total IgG increased significantly in the vaccine group, and IL-2, IL-5, and IL-6 concentrations increased significantly at week 24 (p < 0.05). Differences in various types of cytokines and immunoglobulins in the plasma of the non-vaccine group were not significant (p > 0.05). Anti-HBs titers positively correlated with Th1/Th2 cells at 24 weeks (r = 0.448 and 0.458, respectively, p = 0.022 and 0.019, respectively), and negatively with CD24+CD38highBreg cells (r = -0.402, p = 0.042). CONCLUSIONS: After achieving HBsAg seroclearance through Peg-IFNα treatment for CHB, administering the hepatitis B vaccine significantly increased anti-HBs-seroconversion rates and antibody levels. We also observed significant immunological differences between the vaccine and non-vaccine groups. Specifically, the vaccine group exhibited significant increases in B cells, plasma cells, and Tfh cells, while Breg levels was significantly lower. These immunological changes are likely conducive to the production of anti-HBs antibodies. However, in the non-vaccine group, the observed changes were not significantlly significant.

Effects of plant natural products on metabolic-associated fatty liver disease and the underlying mechanisms: a narrative review with a focus on the modulation of the gut microbiota.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by the excessive accumulation of fat in hepatocytes. However, due to the complex pathogenesis of MAFLD, there are no officially approved drugs for treatment. Therefore, there is an urgent need to find safe and effective anti-MAFLD drugs. Recently, the relationship between the gut microbiota and MAFLD has been widely recognized, and treating MAFLD by regulating the gut microbiota may be a new therapeutic strategy. Natural products, especially plant natural products, have attracted much attention in the treatment of MAFLD due to their multiple targets and pathways and few side effects. Moreover, the structure and function of the gut microbiota can be influenced by exposure to plant natural products. However, the effects of plant natural products on MAFLD through targeting of the gut microbiota and the underlying mechanisms are poorly understood. Based on the above information and to address the potential therapeutic role of plant natural products in MAFLD, we systematically summarize the effects and mechanisms of action of plant natural products in the prevention and treatment of MAFLD through targeting of the gut microbiota. This narrative review provides feasible ideas for further exploration of safer and more effective natural drugs for the prevention and treatment of MAFLD.

pH-Responsive, Self-Assembled Ruthenium Nanodrug: Dual Impact on Lysosomes and DNA for Synergistic Chemotherapy and Immunogenic Cell Death.

Several DNA-damaging antitumor agents, including ruthenium complexes, induce immunogenic cell death (ICD). In this study, an arginyl-glycyl-aspartic acid (RGD) peptide-modified carboline ruthenium complex (KS-Ru) is synthesized as a chemotherapeutic nanodrug and an ICD inducer. The RGD peptide, an integrin ligand, provides tumor-specific targeting and promotes self-assembly of the KS-Ru complex. The pH-responsive self-assembly is assessed through transmission and scanning electron microscopy. Additionally, in vitro cytotoxic activity and anti-metastasis ability are evaluated using MTT and Transwell assays, respectively, along with cellular immunofluorescence staining and imaging flow cytometry. The ability of the complex to inhibit primary tumor formation and lung metastasis in vivo is evaluated using Lewis lung cancer and A549 xenograft models. Furthermore, the tumor immune microenvironment is evaluated using single-cell flow mass cytometry. KS-Ru translocates to the nucleus, causing DNA damage and inducing ICD. Within the lysosomes, KS-Ru self-assembled into nanoflowers, leading to lysosomal swelling and apoptosis. Notably, the as-synthesized pH-dependent ruthenium nanomedicine achieves dual functionality-chemotherapy and immunotherapy. Moreover, the pH-responsive self-assembly of KS-Ru enables simultaneous mechanisms in the lysosome and nucleus, thereby lowering the likelihood of drug resistance. This study provides valuable insight for the design of novel ruthenium-based nanoantitumor drugs.

Symmetry Breaking Induced Amorphization of Cobalt-Based Catalyst for Boosted CO2 Photoreduction.

Photocatalytic reduction of CO2 to energy carriers is intriguing in the industry but kinetically hard to fulfil due to the lack of rationally designed catalysts. A promising way to improve the efficiency and selectivity of such reduction is to break the structural symmetry of catalysts by manipulating coordination. Here, inspired by analogous CoO6 and CoSe6 octahedral structural motifs of the Co(OH)2 and CoSe, a hetero-anionic coordination strategy is proposed to construct a symmetry-breaking photocatalyst prototype of oxygen-deficient Se-doped cobalt hydroxide upon first-principles calculations. Such involvement of large-size Se atoms in CoO6 octahedral frameworks experimentally lead to the switching of semiconductor type of cobalt hydroxide from p to n, generation of oxygen defects, and amorphization. The resultant oxygen-deficient Se,O-coordinated Co-based amorphous nanosheets exhibit impressive photocatalytic performance of CO2 to CO with a generation rate of 60.7 µmol g-1  h-1 in the absence of photosensitizer and scavenger, superior to most of the Co-based photocatalysts. This work establishes a correlation between the symmetry-breaking of catalytic sites and CO2 photoreduction performances, opening up a new paradigm in the design of amorphous photocatalysts for CO2 reduction.

Synergistic Effect of the Moisture Content and pH Value of Aqueous Solutions on Oxidation Characteristics of Coal.

In order to study the synergistic effect of the moisture content and pH value of aqueous solutions on coal oxidation, coal samples with different moistures were prepared by using aqueous solutions with different pH values (3, 5, 7, and 8). The CO, C2H4 production, oxygen consumption rate, and crossing point temperature parameters in the process of low-temperature oxidation of the prepared coal and raw coal samples were studied by using a low-temperature oxidation device. Thermogravimetry-derivative thermogravimetry (TG-DTG) curves of coal samples with different moistures were obtained on the basis of thermogravimetric analysis of coal by using a synchronous thermal analyzer. According to the characteristic temperature, the process of coal spontaneous combustion (CSC) can be divided into the water evaporation and desorption stage, oxygen absorption and weight gain stage, thermal decomposition and combustion stage, and burnout stage. The Coats-Redfern integral method was used to select the appropriate reaction mechanism function to calculate the apparent activation energy at different stages of the coal reaction process. The results show that the activation energy of the oxidation reaction of the coal sample with a moisture of 15% is the smallest, and the oxidation reaction is the most easy to occur. When the coal samples with a moisture of 15% were oxidized at low temperature, the CO and C2H4 emissions and oxygen consumption rates were the highest. The pH value of the aqueous solution has dual effects on CSC. When the moisture is 15%, the higher the pH value of the aqueous solution, the weaker the promotion effect on the coal oxidation process is and the lower the pH value of the aqueous solution is, the higher the production of CO and C2H4 and the oxygen consumption rate is and the earlier the crossing point temperature is reached during low-temperature oxidation of the coal sample.

Altered spontaneous brain activity in lumbar disc herniation patients: insights from an ALE meta-analysis of neuroimaging data.

Objective: To explore the characteristics of spontaneous brain activity changes in patients with lumbar disc herniation (LDH), and help reconcile the contradictory findings in the literature and enhance the understanding of LDH-related pain. Materials and methods: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), SinoMed, and Wanfang databases were searched for literature that studies the changes of brain basal activity in patients with LDH using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation/fraction amplitude of low-frequency fluctuation (ALFF/fALFF) analysis methods. Activation likelihood estimation (ALE) was used to perform a meta-analysis of the brain regions with spontaneous brain activity changes in LDH patients compared with healthy controls (HCs). Results: A total of 11 studies were included, including 7ALFF, 2fALFF, and 2ReHo studies, with a total of 269 LDH patients and 277 HCs. Combined with the data from the ALFF/fALFF and ReHo studies, the meta-analysis results showed that compared with HCs, LDH patients had increased spontaneous brain activity in the right middle frontal gyrus (MFG), left anterior cingulate cortex (ACC) and the right anterior lobe of the cerebellum, while they had decreased spontaneous brain activity in the left superior frontal gyrus (SFG). Meta-analysis using ALFF/fALFF data alone showed that compared with HCs, LDH patients had increased spontaneous brain activity in the right MFG and left ACC, but no decrease in spontaneous brain activity was found. Conclusion: In this paper, through the ALE Meta-analysis method, based on the data of reported rs-fMRI whole brain studies, we found that LDH patients had spontaneous brain activity changes in the right middle frontal gyrus, left anterior cingulate gyrus, right anterior cerebellar lobe and left superior frontal gyrus. However, it is still difficult to assess whether these results are specific and unique to patients with LDH. Further neuroimaging studies are needed to compare the effects of LDH and other chronic pain diseases on the spontaneous brain activity of patients. Furthermore, the lateralization results presented in our study also require further LDH-related pain side-specific grouping study to clarify this causation. Systematic review registration: PROSPERO, identifier CRD42022375513.

Characteristic profiling of soluble factors in the cerebrospinal fluid of patients with neurosyphilis.

BACKGROUND: Soluble inflammatory factors have been investigated in the cerebrospinal fluid (CSF) of neurosyphilis patients with low-throughput technology. This study aimed to illustrate the characteristics of soluble factors profiles in CSF of neurosyphilis patients. METHODS: We measured the concentrations of 45 cytokines/chemokines/growth factors in CSF from 112 untreated syphilis cases, including latent syphilis (LS), asymptomatic neurosyphilis (ANS), meningeal neurosyphilis (MNS), meningovascular neurosyphilis (MVNS), paralytic dementia (PD) and ocular syphilis (OS). RESULTS: Thirty-three differentially expressed soluble factors (DeSFs) were categorized into three clusters. DeSFs scores of cluster 1 and 2 (DeSFS1 and DeSFS2) were positively correlated with elevated neopterin and neurofilament light subunit (NF-L) concentration, respectively. DeSFs scores of cluster 3 were positively correlated with WBC, protein, NF-L and neopterin. Patients with LS, ANS, and OS exhibited an overall lower abundance of DeSFs. PD patients exhibited significantly increased levels of cluster 1 and 3, and the highest total DeSFs score, while patients with MNS and MVNS showed enhanced levels of cluster 2. ROC analysis revealed that DeSFS1 effectively discriminated PD, and DeSFS2 discriminated MNS/MVNS with high accuracy. CONCLUSIONS: Patients with neurosyphilis at different stages have distinctive patterns of soluble factors in CSF, which are correlated with immune status and neuronal damage.

Optical Nonlinearity Enabled Super-Resolved Multiplexing Microscopy.

Optical multiplexing for nanoscale object recognition is of great significance within the intricate domains of biology, medicine, anti-counterfeiting, and microscopic imaging. Traditionally, the multiplexing dimensions of nanoscopy are limited to emission intensity, color, lifetime, and polarization. Here, a novel dimension, optical nonlinearity, is proposed for super-resolved multiplexing microscopy. This optical nonlinearity is attributable to the energy transitions between multiple energy levels of the doped lanthanide ions in upconversion nanoparticles (UCNPs), resulting in unique optical fingerprints for UCNPs with different compositions. A vortex beam is applied to transport the optical nonlinearity onto the imaging point-spread function (PSF), creating a robust super-resolved multiplexing imaging strategy for differentiating UCNPs with distinctive optical nonlinearities. The composition information of the nanoparticles can be retrieved with variations of the corresponding PSF in the obtained image. Four channels multiplexing super-resolved imaging with a single scanning, applying emission color and nonlinearity of two orthogonal imaging dimensions with a spatial resolution higher than 150 nm (1/6.5λ), are demonstrated. This work provides a new and orthogonal dimension - optical nonlinearity - to existing multiplexing dimensions, which shows great potential in bioimaging, anti-counterfeiting, microarray assays, deep tissue multiplexing detection, and high-density data storage.

Nanostrategy of Targeting at Embryonic Trophoblast Cells Using CuO Nanoparticles for Female Contraception.

Effective contraceptives have been comprehensively adopted by women to prevent the negative consequences of unintended pregnancy for women, families, and societies. With great contributions of traditional hormonal drugs and intrauterine devices (IUDs) to effective female contraception by inhibiting ovulation and deactivating sperm, their long-standing side effects on hormonal homeostasis and reproductive organs for females remain concerns. Herein, we proposed a nanostrategy for female contraceptives, inducing embryonic trophoblast cell death using nanoparticles to prevent embryo implantation. Cupric oxide nanoparticles (CuO NPs) were adopted in this work to verify the feasibility of the nanostrategy and its contraceptive efficacy. We carried out the in vitro assessment on the interaction of CuO NPs with trophoblast cells using the HTR8/SVneo cell line. The results showed that the CuO NPs were able to be preferably uptaken into cells and induced cell damage via a variety of pathways including oxidative stress, mitochondrial damage, DNA damage, and cell cycle arrest to induce cell death of apoptosis, ferroptosis, and cuproptosis. Moreover, the key regulatory processes and the key genes for cell damage and cell death caused by CuO NPs were revealed by RNA-Seq. We also conducted in vivo experiments using a rat model to examine the contraceptive efficacy of both the bare CuO NPs and the CuO/thermosensitive hydrogel nanocomposite. The results demonstrated that the CuO NPs were highly effective for contraception. There was no sign of disrupting the homeostasis of copper and hormone, or causing inflammation and organ damage in vivo. In all, this nanostrategy exhibited huge potential for contraceptive development with high biosafety, efficacy, clinical translation, nonhormonal style, and on-demand for women.

Relationship between individual differences in pain empathy and task- and resting-state EEG.

Pain empathy is a complex form of psychological inference that enables us to understand how others feel in the context of pain. Since pain empathy may be grounded in our own pain experiences, it exhibits huge inter-individual variability. However, the neural mechanisms behind the individual differences in pain empathy and its association with pain perception are still poorly understood. In this study, we aimed to characterize brain mechanisms associated with individual differences in pain empathy in adult participants (n = 24). The 32-channel electroencephalography (EEG) was recorded at rest and during a pain empathy task, and participants viewed static visual stimuli of the limbs submitted to painful and nonpainful stimulation to solicit empathy. The pain sensitivity of each participant was measured using a series of direct current stimulations. In our results, the N2 of Fz and the LPP of P3 and P4 were affected by painful pictures. We found that both delta and alpha bands in the frontal and parietal cortex were involved in the regulation of pain empathy. For the delta band, a close relationship was found between average power, either in the resting or task state, and individual differences in pain empathy. It suggested that the spectral power in Fz's delta band may reflect subjective pain empathy across individuals. For the alpha band, the functional connectivity between Fz and P3 under painful picture stimulation was correlated to individuals' pain sensitivity. It indicated that the alpha band may reflect individual differences in pain sensitivity and be involved in pain empathy processing. Our results suggested the distinct role of the delta and alpha bands of EEG signals in pain empathy processing and may deepen our understanding of the neural mechanisms underpinning pain empathy.

Deep learning-driven MRI trigeminal nerve segmentation with SEVB-net.

Purpose: Trigeminal neuralgia (TN) poses significant challenges in its diagnosis and treatment due to its extreme pain. Magnetic resonance imaging (MRI) plays a crucial role in diagnosing TN and understanding its pathogenesis. Manual delineation of the trigeminal nerve in volumetric images is time-consuming and subjective. This study introduces a Squeeze and Excitation with BottleNeck V-Net (SEVB-Net), a novel approach for the automatic segmentation of the trigeminal nerve in three-dimensional T2 MRI volumes. Methods: We enrolled 88 patients with trigeminal neuralgia and 99 healthy volunteers, dividing them into training and testing groups. The SEVB-Net was designed for end-to-end training, taking three-dimensional T2 images as input and producing a segmentation volume of the same size. We assessed the performance of the basic V-Net, nnUNet, and SEVB-Net models by calculating the Dice similarity coefficient (DSC), sensitivity, precision, and network complexity. Additionally, we used the Mann-Whitney U test to compare the time required for manual segmentation and automatic segmentation with manual modification. Results: In the testing group, the experimental results demonstrated that the proposed method achieved state-of-the-art performance. SEVB-Net combined with the ωDoubleLoss loss function achieved a DSC ranging from 0.6070 to 0.7923. SEVB-Net combined with the ωDoubleLoss method and nnUNet combined with the DoubleLoss method, achieved DSC, sensitivity, and precision values exceeding 0.7. However, SEVB-Net significantly reduced the number of parameters (2.20 M), memory consumption (11.41 MB), and model size (17.02 MB), resulting in improved computation and forward time compared with nnUNet. The difference in average time between manual segmentation and automatic segmentation with manual modification for both radiologists was statistically significant (p < 0.001). Conclusion: The experimental results demonstrate that the proposed method can automatically segment the root and three main branches of the trigeminal nerve in three-dimensional T2 images. SEVB-Net, compared with the basic V-Net model, showed improved segmentation performance and achieved a level similar to nnUNet. The segmentation volumes of both SEVB-Net and nnUNet aligned with expert annotations but SEVB-Net displayed a more lightweight feature.