Polarization and wavelength routers based on diffractive neural network.

In the field of information processing, all-optical routers are significant for achieving high-speed, high-capacity signal processing and transmission. In this study, we developed three types of structurally simple and flexible routers using the deep diffractive neural network (D2NN), capable of routing incident light based on wavelength and polarization. First, we implemented a polarization router for routing two orthogonally polarized light beams. The second type is the wavelength router that can route light with wavelengths of 1550, 1300, and 1100 nm, demonstrating outstanding performance with insertion loss as low as 0.013 dB and an extinction ratio of up to 18.96 dB, while also maintaining excellent polarization preservation. The final router is the polarization-wavelength composite router, capable of routing six types of input light formed by pairwise combinations of three wavelengths (1550, 1300, and 1100 nm) and two orthogonal linearly polarized lights, thereby enhancing the information processing capability of the device. These devices feature compact structures, maintaining high contrast while exhibiting low loss and passive characteristics, making them suitable for integration into future optical components. This study introduces new avenues and methodologies to enhance performance and broaden the applications of future optical information processing systems.

Vancomycin-Loaded Sol-Gel System for In Situ Coating of Artificial Bone to Prevent Surgical Site Infections.

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

Evaluation of the correlation between trigeminal nerve atrophy and trigeminal neuralgia using multimodal image fusion: A single-center retrospective study.

BACKGROUND: 3D-Slicer is an open-source medical image processing and visualization software. In the surgical treatment of trigeminal neuralgia, it is commonly used to predict the responsible vessels. However, there are few reports on the use of 3D-Slicer software to quantitatively measure the bilateral trigeminal nerve volume in patients with primary trigeminal neuralgia (PTN) based on the three-dimensional images. Therefore, this study aims to explore the role of three-dimensional fused images processed by 3D-Slicer in the evaluation of trigeminal nerve atrophy, providing an objective basis for the diagnosis of PTN. METHODS: 57 PTN patients who underwent microvascular decompression (MVD) or percutaneous balloon compression (PBC) surgery in Hebei general hospital between January 2020 and April 2023 were included. Additionally, 30 patients with facial spasms(HFS) were included as a control group. All patients underwent 3D-TOF-MRA and 3D-FIESTA sequence examinations. Comparisons of bilateral trigeminal nerve volumes within and between groups were conducted by performing image fusion using 3D-slicer. RESULTS: The volume of the affected trigeminal nerve in the MVD group (33.96 mm³±12.61 mm³) and PBC group (23.05 mm³±7.71 mm³) was smaller than that of the unaffected trigeminal nerve in the MVD group (39.61 mm³±12.83 mm³) and PBC group (26.14 mm³±6.42 mm³), as well as the average volume of the trigeminal nerve in the control group (40.27 mm³±10.25 mm³) (P<0.05). The differences in bilateral trigeminal ganglion volume (∆V) was significant between the MVD group (∆V=23.59 %±14.32 %) and the control group (∆V=14.64 %±10.00 %) (P<0.05). There was no statistical difference in the trigeminal nerve volume difference between the MVD group (∆V=23.59 %±14.32 %) and the PBC group (∆V=26.52 %±15.00 %) (P>0.05). CONCLUSION: Trigeminal nerve atrophy is correlated with primary trigeminal neuralgia. 3D-slicer software can quantitatively measure trigeminal nerve volume and assist in the diagnosis of primary trigeminal neuralgia based on the difference in bilateral trigeminal nerve volumes. However, trigeminal nerve atrophy is not associated with postoperative pain recurrence in patients.

A novel coupling process to replace the traditional multi-stage anammox process-sulfur autotrophic denitrification coupled anammox system.

A novel coupling process to replace the traditional multi-stage anammox process-sulfur autotrophic denitrification (SAD) coupled anaerobic ammonium oxidation (anammox) system was designed, which solved problems of nitrate produced in anammox process and low nitrate conversion rate caused by nitrite accumulation in SAD process. Different filter structures (SAD filter and anammox granular sludge) were investigated to further explore the excellent performance of the novel integrated reactor. The results of sequential batch experiments indicated that nitrite accumulation occurred during SAD, which inhibited the conversion of nitrate to dinitrogen gas. When SAD filter and anammox granular sludge were added to packed bed reactor simultaneously, the nitrate removal rate increased by 37.21% and effluent nitrite concentration decreased by 100% compared to that achieved using SAD. The stratified filter structure solved groove flow. Different proportion influence of SAD filter and anammox granular sludge on the stratified filter structure was evaluated. More suitable ratio of SAD filter to anammox granular sludge was 2:1. Proteobacteria (57.26%), Bacteroidetes (20.12%) and Chloroflexi (9.95%) were the main phyla. The dominant genera of denitrification functional bacteria were Thiobacillus (39.80%), Chlorobaculum (3.99%), norank_f_PHOs-HE36 (2.90%) and Ignavibacterium (2.64%). The dominant genus of anammox bacterium was Candidatus_Kuenenia (3.05%).

Esculentoside H reduces the PANoptosis and protects the blood-brain barrier after cerebral ischemia/reperfusion through the TLE1/PI3K/AKT signaling pathway.

AIMS: Matrix metalloproteinases 9 (MMP9) plays a role in the destruction of blood-brain barrier (BBB) and cell death after cerebral ischemic/reperfusion (I/R). Esculentoside H (EH) is a saponin found in Phytolacca esculenta. It can block JNK1/2 and NF-κB signal mediated expression of MMP9. In this study, we determined whether EH can protect against cerebral I/R injury by inhibiting MMP9 and elucidated the underlying mechanism. MAIN METHODS: Male SD rats were used to construct middle cerebral artery occlusion (MCAO) models. We determined the effect of EH on MMP9 inhibition, BBB destruction, neuronal death, PANoptosis, infarct volume, and the protective factor TLE1. Adeno-associated virus (AAV) infection was used to establish TLE1 gene overexpression and knockdown rats, which were used to determine the function. LY294002 was used to determine the role of PI3K/AKT signaling in TLE1 function. KEY FINDINGS: After EH treatment, MMP9 expression, BBB destruction, neuronal death, and infarct volume decreased. We found that TLE1 expression decreased obviously after cerebral I/R. TLE1-overexpressing rats revealed distinct protective effects to cerebral I/R injury. After treatment with LY294002, the protective effect was inhibited. The curative effect of EH also decreased when TLE1 was knocked down. SIGNIFICANCE: EH alleviates PANoptosis and protects BBB after cerebral I/R via the TLE1/PI3K/AKT signaling pathway. Our findings reveal a novel strategy and new target for treating cerebral I/R injury.

Research progress on the protective effect of hormones and hormone drugs in myocardial ischemia-reperfusion injury.

Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy.

Tumor Microenvironment-Responsive Nanocapsule Delivery CRISPR/Cas9 to Reprogram the Immunosuppressive Microenvironment in Hepatoma Carcinoma.

Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients. The previous study revealed that GDF15 can promote immunosuppression in the tumor microenvironment. Therefore, knocking out GDF15 through gene editing could potentially reverse the suppressive tumor immune microenvironment permanently. To deliver the CRISPR/Cas9 system specifically to HCC, nanocapsules (SNC) coated with HCC targeting peptides (SP94) on their surface is utilized. These nanocapsules incorporate disulfide bonds (SNCSS) that release their contents in the tumor microenvironment characterized by high levels of glutathione (GSH). In vivo, the SNCSS target HCC cells, exert a marked inhibitory effect on HCC progression, and promote HCC immunotherapy. Mechanistically, CyTOF analysis showed favorable changes in the immune microenvironment of HCC, immunocytes with killer function increased and immunocytes with inhibitive function decreased. These findings highlight the potential of the CRISPR-Cas9 gene editing system in modulating the immune microenvironment and improving the effectiveness of existing immunotherapy approaches for HCC.

The application of large language models in medicine: A scoping review.

This study systematically reviewed the application of large language models (LLMs) in medicine, analyzing 550 selected studies from a vast literature search. LLMs like ChatGPT transformed healthcare by enhancing diagnostics, medical writing, education, and project management. They assisted in drafting medical documents, creating training simulations, and streamlining research processes. Despite their growing utility in assisted diagnosis and improving doctor-patient communication, challenges persisted, including limitations in contextual understanding and the risk of over-reliance. The surge in LLM-related research indicated a focus on medical writing, diagnostics, and patient communication, but highlighted the need for careful integration, considering validation, ethical concerns, and the balance with traditional medical practice. Future research directions suggested a focus on multimodal LLMs, deeper algorithmic understanding, and ensuring responsible, effective use in healthcare.

Morphological, Molecular Structural and Physicochemical Characterization of Starch Granules Formed in Endosperm of Rice with Ectopic Overexpression of α-Amylase.

The objective of this study was to characterize the endosperm starch in rice that ectopically overexpressed the α-amylase. Transgenic rice plants, transformed with cauliflower mosaic virus 35S promoter driven AmyI-1 (35S::AmyI-1) and AmyII-4 (35S::AmyII-4), and 10 kDa prolamin promoter driven AmyI-1 (P10::AmyI-1), were cultivated under standard conditions (23 °C, 12 h in the dark/ 26 °C, 12 h in the light), and brown grains were subsequently harvested. Each grain displayed characteristic chalkiness, while electron microanalyzer (EPMA)-SEM images disclosed numerous small pits on the surface of the starch granules, attributable to α-amylase activity. Fluorescence labeling and capillary electrophoresis analysis of starch chain length distribution revealed no significant alterations in the starches of 35S::AmyI-1 and 35S::AmyII-4 transgenic rice compared to the wild-type. Conversely, the extremely short α-glucan chains (DP 2-8) exhibited a dramatic increase in the P10::AmyI-1 starch. Rapid visco-analyzer analysis also identified variations in the chain length distribution of P10::AmyI-1 starch, manifesting as changes in viscosity. Moreover, 1H-NMR analysis uncovered dynamic modifications in the molecular structure of starch in rice grain transformed with P10::AmyI-1, which was found to possess unprecedented structural characteristics.

Family Environmental Risk and Perceived Stress in Adolescent Depressive Symptoms: A Network Analysis.

This study, grounded in the Process-Person-Context-Time framework, investigates the complex interplay of family environmental factors and their influence on adolescent depressive symptoms, focusing on the role of 'perceived stress'. Using network analysis, we examined data from 735 junior high students (52.1% female adolescents) from three provinces in China (Jiangsu, Shandong, and Henan), with an average age of 13.81 ± 0.92 years, ranging from 12 to 16 years, exploring the relationships between depressive symptoms, perceived stress, and seven family risk factors. The analysis identified three distinct communities. The incorporation of perceived stress led to its integration into a community that included depressive symptoms, parental restrictive monitoring, and family economic strain. Perceived stress emerged as the strongest predictor of depressive symptoms, surpassing parental restrictive monitoring. Furthermore, it overtook depressive symptoms as the node with the strongest bridging connection within its community. These findings underscore the importance of interventions targeting both family conditions and the internal processing of these stressors by adolescents, especially in challenging family environments, to mitigate the risk of depression and promote resilience.

Islr regulates satellite cells asymmetric division through the SPARC/p-ERK1/2 signaling pathway.

Satellite cells (SCs) are adult muscle stem cells responsible for muscle regeneration after acute and chronic muscle injuries. The balance between stem cell self-renewal and differentiation determines the kinetics and efficiency of skeletal muscle regeneration. This study assessed the function of Islr in SC asymmetric division. The deletion of Islr reduced muscle regeneration in adult mice by decreasing the SC pool. Islr is pivotal for SC proliferation, and its deletion promoted the asymmetric division of SCs. A mechanistic search revealed that Islr bound to and degraded secreted protein acidic and rich in cysteine (SPARC), which activated p-ERK1/2 signaling required for asymmetric division. These findings demonstrate that Islr is a key regulator of SC division through the SPARC/p-ERK1/2 signaling pathway. These data provide a basis for treating myopathy.

A Transformable Specific-Responsive Peptide for One-Step Synergistic Therapy of Bladder Cancer.

Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple-administration plan and potential side effects limit its clinical application. A transformable specific-responsive peptide (TSRP) is utilized to one-step achieve synergistic therapy integrating anti-tumor, anti-angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed. Once its binding to FGFR-1, the TSRP could cleaved by MMP-2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR-1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX-315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8+ T cells infiltration. All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer.

Effects of levothyroxine in subclinical hypothyroidism and heart failure with reduced ejection fraction: An open-label randomized trial.

We report a randomized, multicenter, open-label trial (ClinicalTrials.gov: NCT03096613) to investigate the clinical benefits of levothyroxine (L-T4) administration in subclinical hypothyroidism (SCH) patients with heart failure with reduced ejection fraction (HFrEF). Overall, 117 patients were enrolled and received L-T4 plus standard HFrEF treatment (experimental group, N = 57) or standard HFrEF therapy alone (control group, N = 60). The change of 6-min walk test distance in the experimental group was significantly higher than that in the control group at 24 weeks (70.08 ± 85.76 m vs. 27.73 ± 82.00 m, mean difference [95% confidence interval (CI)] 46.90 [12.90, 80.90], p < 0.001). Improvements in New York Heart Association (NYHA) classification (p = 0.033) and thyroid function were significant. Adverse event incidence was similar between groups (risk ratio [95% CI]: 0.942 1.053 (0.424, 2.616); p = 0.628). L-T4 addition to HFrEF treatment improved activity tolerance, NYHA class, and thyroid function within 6 months, suggesting its potential for combined therapy in HFrEF patients with SCH. Future double-blind, placebo-controlled trials should be performed to confirm these results.

CD63+ cancer-associated fibroblasts confer CDK4/6 inhibitor resistance to breast cancer cells by exosomal miR-20.

Cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (CDK4/6i) have rapidly received Food and Drug Administration (FDA) approval as a new type of therapy for patients with advanced hormone receptor-positive breast cancer. However, with the widespread application of CDK4/6i, drug resistance has become a new challenge for clinical practice and has greatly limited the treatment effect. Here, the whole microenvironment landscape of ER+ breast cancer tumors was revealed through single-cell RNA sequencing, and a specific subset of cancer-associated fibroblasts (CD63+ CAFs) was identified as highly enriched in CDK4/6i resistant tumor tissues. Then, we found that CD63+ CAFs can distinctly promote resistance to CDK4/6i in breast cancer cells and tumor xenografts. In addition, it was discovered that miR-20 is markedly enriched in the CD63+ CAFs-derived exosomes, which are used to communicate with ER+ breast cancer cells, leading to CDK4/6i resistance. Furthermore, exosomal miR-20 could directly target the RB1 mRNA 3'UTR and negatively regulate RB1 expression to decrease CDK4/6i sensitivity in breast cancer cells. Most importantly, we designed and synthesized cRGD-miR-20 sponge nanoparticles and found that they can enhance the therapeutic effect of CDK4/6i in breast cancer. In summary, our findings reveal that CD63+ CAFs can promote CDK4/6i resistance via exosomal miR-20, which induces the downregulation of RB1 in breast cancer cells, and suggest that CD63+ CAFs may be a novel therapeutic target to enhance CDK4/6i sensitivity.

A c-di-GMP signaling module controls responses to iron in Pseudomonas aeruginosa.

Cyclic dimeric guanosine monophosphate (c-di-GMP) serves as a bacterial second messenger that modulates various processes including biofilm formation, motility, and host-microbe symbiosis. Numerous studies have conducted comprehensive analysis of c-di-GMP. However, the mechanisms by which certain environmental signals such as iron control intracellular c-di-GMP levels are unclear. Here, we show that iron regulates c-di-GMP levels in Pseudomonas aeruginosa by modulating the interaction between an iron-sensing protein, IsmP, and a diguanylate cyclase, ImcA. Binding of iron to the CHASE4 domain of IsmP inhibits the IsmP-ImcA interaction, which leads to increased c-di-GMP synthesis by ImcA, thus promoting biofilm formation and reducing bacterial motility. Structural characterization of the apo-CHASE4 domain and its binding to iron allows us to pinpoint residues defining its specificity. In addition, the cryo-electron microscopy structure of ImcA in complex with a c-di-GMP analog (GMPCPP) suggests a unique conformation in which the compound binds to the catalytic pockets and to the membrane-proximal side located at the cytoplasm. Thus, our results indicate that a CHASE4 domain directly senses iron and modulates the crosstalk between c-di-GMP metabolic enzymes.

Preclinical Evaluation of Azabenzimidazole-Based PET Radioligands for γ-8 Dependent Transmembrane AMPA Receptor Regulatory Protein Imaging.

AMPA glutamate receptors (AMPARs) play a pivotal role in excitatory neurotransmission, particularly in the hippocampus where the TARP γ-8 subunit is enriched and serves as a target for emerging anti-epileptic drugs. To enable in vivo visualization of TARP γ-8 distribution and expression by positron emission tomography (PET), this study focuses on the development of novel 18 F-labeled TARP γ-8 inhibitors and their corresponding precursors, stemming from the azabenzimidazole scaffold. The resulting radioligands [18 F]TARP-2204 and [18 F]TARP-2205 were successfully synthesized with acceptable radiochemical yield, high molar activity, and excellent radiochemical purity. In vitro autoradiography demonstrates high level of specific binding of [18 F]TARP-2205 to TARP γ-8 in both rat and nonhuman primate brain tissues. However, unexpected radiodefluorination in PET imaging studies of rodents emphasizes the need for further structural refinement. This work serves as an excellent starting point for the development of future 18 F-labeled TARP γ-8 PET tracers, offering valuable insights into medicinal chemistry design, radiosynthesis and subsequent PET evaluation.

Cannabidiol Exerts Sedative and Hypnotic Effects in Normal and Insomnia Model Mice Through Activation of 5-HT1A Receptor.

Cannabis sativa has been used for improving sleep for long history. Cannabidiol (CBD) has drown much attention as a non-addictive psychoactive component in Cannabis sativa extract. However, the effects of CBD on sleep architecture and it's acting mechanism remains unclear. In the present study, we evaluated the sedative-hypnotic effect of cannabidiol (CBD), assessed the effects of CBD on sleep using a wireless physiological telemetry system. We further explored the therapeutic effects of CBD using 4-chloro-dl-phenylalanine (PCPA) induced insomnia model and changes in sleep latency, sleep duration and intestinal flora were evaluated. CBD shortened sleep latency and increases sleep duration in both normal and insomnia mice, and those effects were blocked by 5-HT1A receptor antagonist WAY100635. We determined that CBD increases 5-HT1A receptors expression and 5-HT content in the hypothalamus of PCPA-pretreated mice and affects tryptophan metabolism in the intestinal flora. These results showed that activation of 5-HT1A receptors is one of the potential mechanisms underlying the sedative-hypnotic effect of CBD. This study validated the effects of CBD on sleep and evaluated its potential therapeutic effects on insomnia.

Thermal-Driven Orderly Assembly of Ir-atomic Chains on α-MnO2 with Enhanced Performance for Acidic Oxygen Evolution.

The development of acid-stable oxygen evolution reaction electrocatalysts is essential for high-performance acidic water electrolysis. Herein, we report the results of one-dimensional (1D) nanorods (NRs) IrCeMnO@Ir containing ~20 wt . % Iridium (Ir) as an efficient anode electrocatalyst, synthesized via a one-step cation exchange strategy. Owing to the presence of 1D channels of the nanorod architecture and the unique electronic structure, the IrCeMnO@Ir exhibited 69 folds more mass activity than that of commercial IrO2 as well as over 400 h stability with only a 20 mV increase in overpotential. DFT calculations and control experiments demonstrated that CeO2 serves as an electron buffer to accelerate the kinetics of the rate-determined step for the significantly enhanced activity and suppress the over-oxidation of Ir species as well as their dissolution for impressively promoted stability under practical conditions. Our work opens up a feasible strategy to boost OER activity and stability simultaneously.