Preparation of BN Nanoparticle with High Sintering Activity and Its Formation Mechanism.

Hexagonal boron nitride (h-BN) nanoparticles have attracted increasing attention due to their unique structure and properties. However, it is difficult to synthesize h-BN nanoparticles with uniform spherical morphology due to their crystal characteristic. The morphology control by tuning their precursor synthesis is a promising and effective strategy to solve this problem. Especially, the treatment temperature of precursors plays an important role in the morphology and surface area of h-BN nanoparticles. Herein, h-BN nanoparticles with different morphologies were synthesized via regulating the treatment temperature of precursors. The result shows that treatment temperature will affect the microstructure and state of precursor and further influence the morphology of h-BN products. Benefiting from the unique structure, the h-BN obtained using 250 °C precursors shows higher specific surface area (61.1 m2 g-1) than that of 85 °C (36.5 m2 g-1) and 145 °C (27.9 m2 g-1). h-BN products obtained using 250 °C precursors show higher specific surface area than that of 85 °C and 145 °C. The optimal condition for obtaining high-quality spherical h-BN is the pretreatment temperature of 250 °C and sintering temperature of 1300 °C. Importantly, compared with commercial h-BN nanoparticles, the synthesized h-BN nanoparticles show more uniform structure and larger specific surface area, indicating that sintering activity will be greatly improved. Furthermore, the reaction pathway and formation mechanism of h-BN was revealed by DFT calculations. The result shows that the five stationary states and five transition states exist in the reaction pathway, and the energy barrier can be overcome at high temperatures to form a ring h-BN. In view of its simplicity and efficiency, this work is promising for designing and guiding the synthesis of h-BN nanoparticles with uniform morphology.

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.

Molecular understanding of the therapeutic potential of melanin inhibiting natural products.

With the development of society and the improvement of people's living standards, there is an increasing demand for melanin-inhibiting products that prioritize health, safety, and efficacy. Therefore, the development of natural products that can safely and efficiently inhibit melanin synthesis is of great social significance and has significant market potential. In this paper, by reviewing the literature reported in recent years, we summarized the natural products with inhibition of melanin synthesis effects that have been put into or not yet put into the market, and classified them according to the chemical groups of their compounds or the extraction methods of the natural products. Through the summary analysis, we found that these compounds mainly include terpenoids, phenylpropanoids, flavonoids and so on, while the natural product extracts mainly include methanol extracts, ethanol extracts, and aqueous extracts. Their main inhibition of melanin synthesis mechanisms include: (1) direct inhibition of tyrosinase activity; (2) down-regulation of the α-MSH-MC1R, Wnt, NO, PI3K/Akt and MAPK pathways through the expression of MITF and its downstream genes TYR, TRP-1, and TRP-2; (3) antioxidant; (4) inhibition of melanocyte growth through cytotoxicity; (5) inhibition of melanosome production and transport. This paper provides an in-depth discussion on the research progress of whitening natural products and their market value. The aim is to offer guidance for future research and development of natural skin whitening products.

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.

Semaphorin 4A Maintains Trophoblastic Function via Activating the STAT3 Pathway.

The migration, proliferation, and apoptosis of trophoblastic cells play a crucial role in ensuring the effective preservation of pregnancy at the maternal-fetal interface. Any deviations in the structure and function of these cells might potentially result in the development of numerous pregnancy-related disorders, including missed abortion (MA). This study involved the examination of semaphorin 4A (SEMA4A) expression in missed abortion (n = 18) and normal early pregnancy (n = 18) villus. The findings of this study indicate a statistically significant decrease in the expression of SEMA4A in the villi of individuals diagnosed with missed abortion, as compared to the control group. The results of our vitro study showed that SEMA4A promoted the migration and proliferation of trophoblast cells and inhibited their apoptosis. Subsequent studies have shown that SEMA4A may be involved in regulating p-STAT3/STAT3, MMP9, bcl-2, and BAX levels. In summary, the findings of this study indicate a correlation between the decreased level of SEMA4A in chorionic villi and missed abortion. These results offer novel theoretical insights into the proper implantation and development of SEMA4A embryos at the maternal-fetal interface.

Effects of metaraminol and norepinephrine on hemodynamics and kidney function in a miniature pig model of septic shock.

Objective: To compare the effects of metaraminol and norepinephrine on hemodynamics and kidney injury in the treatment of septic shock, and calculate the conversion dose ratio between the two vasopressors. Methods: This randomized controlled study was performed on 15 Guizhou miniature pigs. Septic shock was induced by fecal peritonitis in 10 animals, and 5 were used as a sham-operated group (shams). Fluid resuscitation and vasopressors were initiated 30 min after the onset of septic shock. The septic shock pigs were randomly assigned to receive one of the two drugs to restore and maintain mean arterial pressure (MAP) ≥ 65 mmHg for 3 h. Hemodynamics and heart rate were continuously monitored. Results: There was no significant difference in MAP, heart rate, cardiac output (CO) and central venous pressure (CVP) between the two groups after treatment. No arrhythmias such as atrial fibrillation and ventricular fibrillation presented during continuous monitoring. After septic shock, the animals showed obvious kidney injury. In addition, compared with norepinephrine, the creatinine at 3 h was significantly lower with metaraminol. According to propensity score matching, the ratio of 6: 1 was considered appropriate for the dose equivalence calculation of metaraminol (µg·kg-1·min-1): norepinephrine (µg·kg-1·min-1). Conclusion: Metaraminol has a similar pressor effect to norepinephrine in septic shock; it does not increase heart rate and aggravate kidney injury after shock compared with norepinephrine. And our research may provide some laboratory evidence for the clinical usage of metaraminol.

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.

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.

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.

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.

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.