Optimization of sub-arc collimator angles in volumetric modulated arc therapy: a heatmap-based blocking index approach for multiple brain metastases.

To develop and assess an automated Sub-arc Collimator Angle Optimization (SACAO) algorithm and Cumulative Blocking Index Ratio (CBIR) metrics for single-isocenter coplanar volumetric modulated arc therapy (VMAT) to treat multiple brain metastases. This study included 31 patients with multiple brain metastases, each having 2 to 8 targets. Initially, for each control point, the MLC blocking index was calculated at different collimator angles, resulting in a two-dimensional heatmap. Optimal sub-arc segmentation and collimator angle optimization were achieved using an interval dynamic programming algorithm. Subsequently, VMAT plans were designed using two approaches: SACAO and the conventional Full-Arc Fixed Collimator Angle. CBIR was calculated as the ratio of the cumulative blocking index between the two plan approaches. Finally, dosimetric and planning parameters of both plans were compared. Normal brain tissue, brainstem, and eyes received better protection in the SACAO group (P < 0.05).Query Notable reductions in the SACAO group included 11.47% in gradient index (GI), 15.03% in monitor units (MU), 15.73% in mean control point Jaw area (AJaw,mean), and 19.14% in mean control point Jaw-X width (WJaw-X,mean), all statistically significant (P < 0.001). Furthermore, CBIR showed a strong negative correlation with the degree of plan improvement. The SACAO method enhanced protection of normal organs while improving transmission efficiency and optimization performance of VMAT. In particular, the CBIR metrics show promise in quantifying the differences specifically in the 'island blocking problem' between SACAO and conventional VMAT, and in guiding the enhanced application of the SACAO algorithm.

Personalized selection of unequal sub-arc collimator angles in VMAT for multiple brain metastases.

PURPOSE: Investigating the effects of unequal sub-arc personalized collimator angle selection on the quality of Volumetric Modulated Arc Therapy (VMAT) plans for treating multiple brain metastases. METHODS: This study included 21 patients, each with 2-4 target volumes of multiple brain metastases. Two stereotactic radiotherapy (SRT) approaches were utilized: sub-arc collimator VMAT (SAC-VMAT) and fixed collimator VMAT (FC-VMAT). In the SAC-VMAT group, multi-leaf collimators (MLC) shaped the target area, dividing the full arc into four unequal sub-arcs under the beam's eye view (BEV). Each sub-arc had an appropriate collimator angle selected to mitigate 'island blocking problems'. Conversely, the FC-VMAT group used a fixed collimator angle of 15° or 345°. A comparative analysis of the dosimetric parameters of the target volumes and normal tissues, along with the monitor units (MU), was conducted between the two groups. RESULTS: The mean dose and dose-volume to normal brain tissue (2-26 Gy, with a step of 2 Gy) were significantly lower in the SAC-VMAT group (P < 0.01). There was no statistical difference between the two groups in dose to the target volumes, conformity index (CI), homogeneity index (HI), and other normal tissues (P > 0.05). Compared with the FA-VMAT group, the SAC-VMAT group significantly reduced the gradient index (GI) (4.5 ± 0.59 vs 5.2 ± 0.75, P < 0.001) and MU (1774.33 ± 181.77 vs 2001.0 ± 344.86, P < 0.001). Notably, with an increase in the number of PTV, the SAC-VMAT group demonstrated more significant improvements in the dose-volume of normal brain tissue, GI, and MU. CONCLUSIONS: In this study, personalized selection of the unequal sub-arc collimator angle ensured the prescribed dose to the PTV, CI, and HI, while significantly reducing the GI, MU, and the dose to normal brain tissue in the VMAT plan for multi-target brain metastases in the cohort of cases with 2-4 target volumes. Particularly as the number of targets increase, the advantages of this method become more pronounced.

Long-chain fatty acids facilitate acidogenic fermentation of food waste: Attention to the microbial response and the change of core metabolic pathway under saturated and unsaturated fatty acids loading.

Long-chain fatty acids (LCFAs) are recognized as a significant inhibitory factor in anaerobic digestion of food waste (FW), yet they are inevitably present in FW due to lipid hydrolysis. Given their distinct synthesis mechanism from traditional anaerobic digestion, little is known about the effect of LCFAs on FW acidogenic fermentation. This study reveals that total volatile fatty acids (VFAs) production increased by 9.98 % and 4.03 % under stearic acid and oleic acid loading, respectively. Acetic acid production increased by 20.66 % under stearic acid loading compared to the control group (CK). However, the LCFA stress restricted the degradation of solid organic matter, particularly under oleic acid stress. Analysis of microbial community structure and quorum sensing (QS) indicates that LCFA stress enhanced the relative abundance of Lactobacillus and Klebsiella. In QS system, the relative abundance of luxS declined from 0.157 % to 0.116 % and 0.125 % under oleic acid and stearic acid stress, respectively. LCFA stress limited the Autoinducer-2 (AI-2) biosynthesis, suggesting that microorganisms cannot use QS to resist the LCFA stress. Metagenomic sequencing showed that LCFA stress promoted acetic acid production via the conversion of pyruvate and acetyl-CoA to acetate. Direct conversion of pyruvate to acetic acid increased by 47.23 % compared to the CK group, accounting for the enhanced acetic acid production under stearic acid loading. The abundance of ß-oxidation pathway under stearic acid loading was lower than under oleic acid loading. Overall, the stimulating direct conversion of pyruvate plays a pivotal role in enhancing acetic acid biosynthesis under stearic acid loading, providing insights into the effect of LCFA on mechanism of FW acidogenic fermentation.

siRNA nanoparticle targeting Usp20 lowers lipid levels and ameliorates metabolic syndrome in mice.

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr-/- mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.

Study on the dry shrinkage characteristics and size effect of swell-shrink characteristic soil.

Swell-shrink characteristic soils exhibit a high susceptibility to cracking during the drying process, which poses a significant risk of various geological disasters. Among these, the occurrence of drying shrinkage acts as a prerequisite for the cracking phenomenon. Therefore, it is of utmost importance to comprehend the specific characteristics associated with the drying shrinkage mechanism. To investigate the drying shrinkage behavior of swell-shrink characteristic soils, a series of drying shrinkage experiments were conducted on long strip samples of red clay and expansive soil. Utilizing three-dimensional digital image correlation (DIC) technology, the surface displacement, strain, and anisotropic shrinkage rates of the soil samples during the drying process were obtained, and the size effect on the drying shrinkage of swell-shrink characteristic soil were analyzed. The research findings are as follows: The displacement development of the soil samples in the X and Y directions can be divided into two stages: a linear growth stage and a stable displacement stage. In the Z direction, the soil surface deformation can be divided into three stages: soil surface arching, vertical shrinkage, and shrinkage stabilization. The drying shrinkage of swell-shrink characteristic soil exhibits anisotropy, with the vertical shrinkage rate being the largest, followed by the longitudinal and then the transverse directions. Additionally, the soil sample shrinkage exhibits a size effect, whereby the shrinkage rates in all directions increase with increasing sample width and thickness. During the drying shrinkage process, the stress state on the soil surface evolves from initial tensile strain to subsequent compressive strain. The strain at different positions and times within the soil sample is not uniform, resulting in the non-uniformity and anisotropy of the sample shrinkage. This study provides important insights into the cracking mechanism of swell-shrink characteristic soils and serves as a valuable reference for related laboratory experiments, which will contribute to better prediction and control the geological hazards caused by the drying shrinkage of swell-shrink characteristic soils.

MB38(M=Be and Zn): A Quasi-Planar Structure Rather Than A Core-Shell Octahedral Borospherene Structure.

In a recent paper (ChemPhysChem, 2023, 24, e202200947), based on the results computed using DFT method, the perfect core-shell octahedral configuration Be@B38 and Zn@B38 was reported to be the global minima of the MB38(M=Be and Zn) clusters. However, this paper presents the lower energy structures of MB38(M=Be and Zn) clusters as a quasi-planar configuration, the Be atom is found to reside on the convex surface of the quasi-planar B38 isomer, while the Zn atom tends to be attached to the top three B atoms of the quasi-planar B38 isomer. Our results show that quasi-planar MB38(M=Be and Zn) at DFT method have lower energy than core-shell octahedral configuration M@B38(M=Be and Zn). Natural atomic charges, valence electron density, electron localization function (ELF) analyses identify the MB38(M=Be and Zn) to be charge transfer complexes (Be2+B382-and Be1+B381-) and suggest primarily the electrostatic interactions between doped atom and B38 fragment. The photoelectron spectra of the corresponding anionic structures were simulated, providing theoretical basis for future structural identification.

Characteristics and aging of microplastics in waste activated sludge under persulfate and hydrothermal co-treatment: Impact of solid content and temperature.

Activated persulfate and hydrothermal treatment (HTT) are often employed to treat waste activated sludge, which can improve the efficiency of subsequent sludge treatment and change the distribution of pollutants in the sludge. However, the impact of sludge solid content and temperature on the occurrence and aging of microplastics (MPs) during HTT remains poorly understood. This study investigated the effects of persulfate-HTT (SPS-HTT) co-treatment on the migration, occurrence, and aging of MPs in sludge with different solid contents (2% and 5% solid content). The results indicated that SPS-HTT co-treatment triggers both the disruption of sludge flocs and the melting deformation of MPs at high temperatures, leading to variations in the increasing trend of MP concentration in the solid-liquid phase at different solid contents. 5% solid content sludge showed a weak release of MPs from the solid phase. The proportion of fiber MPs first increased and then decreased with increasing temperature, while no significant changes were observed in the color and type of MPs. Higher temperature and solid content induced the melting deformation of MPs, exacerbated the aging of polypropylene MPs, and resulted in rough surfaces, higher carbonyl index, and variations in crystallinity. Moreover, the correlation between the carbonyl index and aging indicators increased with increasing solid content. The MP-derived dissolved organic matter under HTT primarily comprised soluble microbial by-products and humic acid-like substances. These findings underscore the significance of sludge solid content in affecting the migration and aging of MPs during HTT, and offer novel insights into the application of HTT to MP management in sludge treatment.

Systematic Mendelian Randomization Exploring Druggable Genes for Hemorrhagic Strokes.

Patients with hemorrhagic stroke have high rates of morbidity and mortality, and drugs for prevention are very limited. Mendelian randomization (MR) analysis can increase the success rate of drug development by providing genetic evidence. Previous MR analyses only analyzed the role of individual drug target genes in hemorrhagic stroke; therefore, we used MR analysis to systematically explore the druggable genes for hemorrhagic stroke. We sequentially performed summary-data-based MR analysis and two-sample MR analysis to assess the associations of all genes within the database with intracranial aneurysm, intracerebral hemorrhage, and their subtypes. Validated genes were further analyzed by colocalization. Only genes that were positive in all three analyses and were druggable were considered desirable genes. We also explored the mediators of genes affecting hemorrhagic stroke incidence. Finally, the associations of druggable genes with other cardiovascular diseases were analyzed to assess potential side effects. We identified 56 genes that significantly affected hemorrhagic stroke incidence. Moreover, TNFSF12, SLC22A4, SPARC, KL, RELT, and ADORA3 were found to be druggable. The inhibition of TNFSF12, SLC22A4, and SPARC can reduce the risk of intracranial aneurysm, subarachnoid hemorrhage, and intracerebral hemorrhage. Gene-induced hypertension may be a potential mechanism by which these genes cause hemorrhagic stroke. We also found that blocking these genes may cause side effects, such as ischemic stroke and its subtypes. Our study revealed that six druggable genes were associated with hemorrhagic stroke, and the inhibition of TNFSF12, SLC22A4, and SPARC had preventive effects against hemorrhagic strokes.

Molecular Evolution of SNAREs in Vitis vinifera and Expression Analysis under Phytohormones and Abiotic Stress.

SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) play a key role in mediating a variety of plant biological processes. Currently, the function of the SNARE gene family in phytohormonal and abiotic stress treatments in grapevine is currently unknown, making it worthwhile to characterize and analyze the function and expression of this family in grapevine. In the present study, 52 VvSNARE genes were identified and predominantly distributed on 18 chromosomes. Secondary structures showed that the VvSNARE genes family irregular random coils and α-helices. The promoter regions of the VvSNARE genes were enriched for light-, abiotic-stress-, and hormone-responsive elements. Intraspecific collinearity analysis identified 10 pairs collinear genes within the VvSNARE family and unveiled a greater number of collinear genes between grapevine and apple, as well as Arabidopsis thaliana, but less associations with Oryza sativa. Quantitative real-time PCR (qRT-PCR) analyses showed that the VvSNARE genes have response to treatments with ABA, NaCl, PEG, and 4 °C. Notably, VvSNARE2, VvSNARE14, VvSNARE15, and VvSNARE17 showed up-regulation in response to ABA treatment. VvSNARE2, VvSNARE15, VvSNARE18, VvSNARE19, VvSNARE20, VvSNARE24, VvSNARE25, and VvSNARE29 exhibited significant up-regulation when exposed to NaCl treatment. The PEG treatment led to significant down-regulation of VvSNARE1, VvSNARE8, VvSNARE23, VvSNARE25, VvSNARE26, VvSNARE31, and VvSNARE49 gene expression. The expression levels of VvSNARE37, VvSNARE44, and VvSNARE46 were significantly enhanced after exposure to 4 °C treatment. Furthermore, subcellular localization assays certified that VvSNARE37, VvSNARE44, and VvSNARE46 were specifically localized at the cell membrane. Overall, this study showed the critical role of the VvSNARE genes family in the abiotic stress response of grapevines, thereby providing novel candidate genes such as VvSNARE37, VvSNARE44, and VvSNARE46 for further exploration in grapevine stress tolerance research.

Dynamics of antibiotic resistance genes and the association with bacterial community during pig manure composting with chitin and glucosamine addition.

In modern ecological systems, the overuse and misuse of antibiotics have escalated the prevalence of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs), positioning them as emerging environmental contaminants. Notably, composting serves as a sustainable method to recycle agricultural waste into nutrient-rich fertilizer while potentially reducing ARGs and MGEs. This study conducted a 47-day composting experiment using pig manure and corn straw, supplemented with chitin and N-Acetyl-D-glucosamine, to explore the impact of these additives on the dynamics of ARGs and MGEs, and to unravel the interplay between these genetic elements and microbial communities in pig manure composting. Results showed that adding 5% chitin into composting significantly postponed thermophilic phase, yet enhanced the removal efficiency of total ARGs and MGEs by over 20% compared to the control. Additionally, the addition of N-Acetyl-D-glucosamine significantly increased the abundance of tetracycline-resistant and sulfonamide-resistant genes, as well as MGEs. High-throughput sequencing revealed that N-Acetyl-D-glucosamine enhanced bacterial α-diversity, providing diverse hosts for ARGs and MGEs. Resistance mechanisms, predominantly efflux pumps and antibiotic deactivation, played a pivotal role in shaping the resistome of composting process. Co-occurrence network analysis identified the key bacterial phyla Proteobacteria, Firmicutes, Gemmatimonadota, and Myxococcota in ARGs and MGEs transformation and dissemination. Redundancy analysis indicated that physicochemical factors, particularly the carbon-to-nitrogen ratio emerged as critical variables influencing ARGs and MGEs. The findings lay a foundation for the developing microbial regulation method to reduce the risks of ARGs in animal manure composts.

Mechanism of Musashi2 affecting radiosensitivity of lung cancer by modulating DNA damage repair.

Identifying new targets for overcoming radioresistance is crucial for improving the efficacy of lung cancer radiotherapy, given that tumor cell resistance is a leading cause of treatment failure. Recent research has spotlighted the significance of Musashi2 (MSI2) in cancer biology. In this study, we first demonstrated that MSI2 plays a key function in regulating the radiosensitivity of lung cancer. The expression of MSI2 is negatively correlated with overall survival in cancer patients, and the knockdown of MSI2 inhibits tumorigenesis and increases radiosensitivity of lung cancer cells. Cellular radiosensitivity, which is closely linked to DNA damage, is influenced by MSI2 interaction with ataxia telangiectasia mutated and Rad3-related kinase (ATR) and checkpoint kinase 1 (CHK1) post-irradiation; moreover, knockdown of MSI2 inhibits the ATR-mediated DNA damage response pathway. RNA-binding motif protein 17 (RBM17), which is implicated in DNA damage repair, exhibits increased interaction with MSI2 post-irradiation. We found that knockdown of RBM17 disrupted the interaction between MSI2 and ATR post-irradiation and increased the radiosensitivity of lung cancer cells. Furthermore, we revealed the potential mechanism of MSI2 recruitment into the nucleus with the assistance of RBM17 to activate ATR to promote radioresistance. This study provides novel insights into the potential application of MSI2 as a new target in lung cancer radiotherapy.

Size effects and electronic properties of zinc-doped boron clusters Zn B n (n = 1-15).

CONTEXT: To gain a deeper understanding of zinc-doped boron clusters, theoretical calculations were performed to investigate the size effects and electronic properties of zinc-doped boron clusters. The study of the electronic properties, spectral characteristics, and geometric structures of Zn B n (n = 1-15) is of great significance in the fields of semiconductor materials science, material detection, and improving catalytic efficiency. The results indicate that Zn B n (n = 1-15) clusters predominantly exhibit planar or quasi-planar structures, with the Zn atom positioned in the outer regions of the B n framework. The second stable structure of Zn B 3 is a three-dimensional configuration, indicating that the structures of zinc-doped boron clusters begin to convert from the planar or quasi-planar structures to the 3D configurations. The second low-energy structure of Zn B 15 is a novel configuration. Relative stability analyses show that the Zn B 12 has better chemical stability than other clusters with a HOMO-LUMO gap of 2.79 eV. Electric charge analysis shows that part electrons on zinc atoms are transferred to boron atoms, and electrons prefer to cluster near the B n framework. According to the electron localization function, it gets harder to localize electrons as the equivalent face value drops, and it's challenging to see covalent bond formation between zinc and boron atoms. The spectrograms of Zn B n (n = 1-15) exhibit distinct properties and notable spectral features, which can be used as a theoretical basis for the identification and confirmation of boron clusters doped with single-atom transition metals. METHODS: The calculations were performed using the ABCluster global search technique combined with density functional theory (DFT) methods. The selected low-energy structures were subjected to geometric optimization and frequency calculations at the PBE0/6-311 + G(d) level to ensure structural stability and eliminate any imaginary frequencies. To acquire more precise relative energies, we performed single-point energies calculations for the low-lying isomers of Zn B n (n = 1-15) at the CCSD(T)/6-311 + G(d)//PBE0/6-311 + G(d) level of theory. All calculations were performed using Gaussian 09 software. To facilitate analysis, we utilized software tools such as Multiwfn, and VMD.

The contribution of microbial necromass to soil organic carbon and influencing factors along a variation of habitats in alpine ecosystems.

A growing consensus is reached that microbes contributes to regulating the formation and accumulation of soil organic carbon (SOC). Nevertheless, less is known about the role of soil microbes (necromass, biomass) in SOC accumulation in different habitat conditions in alpine ecosystems. To address this knowledge gap, the composition and distribution of amino sugars (ASs) and phospholipid fatty acids (PLFAs) as biomarkers of microbial necromass and biomass were investigated in forest, meadow and wetland soil profile (0-40 cm) of Mount Segrila, Tibet, China, as well the contribution of bacterial and fungal necromass to SOC. The results revealed that microbial necromass carbon contributed 45.15 %, 72.51 % and 78.08 % on average to SOC in 0-40 cm forest, meadow and wetland soils, respectively, and decreased with microbial biomass. Fungal necromass contributed more to SOC in these habitats than bacterial necromass. Microbial necromass increased with microbial biomass and both of them decreased with soil depth in all habitats. The necromass accumulation coefficient was significantly correlated with microbial necromass and biomass, affected by habitat and soil moisture. Structural equation model indicated that soil abiotic factors indirectly mediated the accumulation of SOC through microbial necromass and biomass. This study revealed that different habitats and soil depths control considerably soil physicochemical properties and microbial community, finally influencing SOC accumulation in alpine ecosystems, which emphasized the influence of abiotic factors on microbial necromass and biomass for SOC accumulation in alpine ecosystems.

PB12+ and P2B12+/0/-: The Novel B12 Cage Doped by Nonmetallic P Atoms.

A new kind of nonmetallic atom-doped boron cluster is described herein theoretically. When a phosphorus atom is added to the B12 motif and loses an electron, a novel B12 cage is obtained, composed of two B3 rings at both ends and one B6 ring in the middle, forming a triangular bifrustum. Interestingly, this B12 cage is formed by three B7 units joined together from three directions at an angle of 120°. When two P atoms are added to the B12 motif, this novel B12 cage is also obtained, and two P atoms are attached to the B3 rings at both ends of the triangular bifrustum, forming a triangular bipyramid (Johnson solid). Amazingly, the global minimums of neutral, monocationic, and monoanionic P2B12+/0/- have the same cage structure with a D3h symmetry; this is the smallest boron cage with the same structure. The P atom has five valence electrons, according to adaptive natural density partitioning bonding analyses of cage PB12+ and P2B12, in addition to one lone pair, the other three electrons of the P atom combine with an electron of each B atom on the B3 ring to form three 2c-2e σ bonds and form three electron sharing bonds with B atoms through covalent interactions, stabilizing the B12 cage. The calculated photoelectron spectra can be compared with future experimental values and provide a theoretical basis for the identification and confirmation of PnB12- (n = 1-2).

[Effect of Baicalin on Pyroptosis of Diffuse Large B-Cell Lymphoma Cell Lines DB and Its Mechanism].

OBJECTIVE: To investigate the effect of Baicalin on the proliferation and pyroptosis of diffuse large B-cell lymphoma cell line DB and its mechanism. METHODS: DB cells were treated with baicalin at different concentrations (0, 5, 10, 20, 40 µmol/L). Cell proliferation was detected by CCK-8 assay and half maximal inhibitory concentration (IC50) was calculated. The morphology of pyroptosis was observed under an inverted microscope, the integrity of the cell membrane was verified by LDH content release assay, and the expressions of pyroptosis-related mRNA and protein (NLRP3, GSDMD, GSDME, N-GSDMD, N-GSDME) were detected by real-time fluorescence quantitative PCR and Western blot. In order to further clarify the relationship between baicalin-induced pyroptosis and ROS production in DB cells, DB cells were divided into control group, baicalin group, NAC group and NAC combined with baicalin group. DB cells in the NAC group were pretreated with ROS inhibitor N-acetylcysteine (NAC) 2 mmol/L for 2 h. Baicalin was added to the combined treatment group after pretreatment, and the content of reactive oxygen species (ROS) in the cells was detected by DCFH-DA method after 48 hours of culture. RESULTS: Baicalin inhibited the proliferation of DB cells in a dose-dependent manner (r=-0.99), and the IC50 was 20.56 µmol/L at 48 h. The morphological changes of pyroptosis in DB cells were observed under inverted microscope. Compared with the control group, the release of LDH in the baicalin group was significantly increased (P<0.01), indicating the loss of cell membrane integrity. Baicalin dose-dependently increased the expression levels of NLRP3, N-GSDMD, and N-GSDME mRNA and protein in the pyroptosis pathway (P<0.05). Compared with the control group, the level of ROS in the baicalin group was significantly increased (P<0.05), and the content of ROS in the NAC group was significantly decreased (P<0.05). Compared with the NAC group, the content of ROS in the NAC + baicalin group was increased. Baicalin significantly attenuated the inhibitory effect of NAC on ROS production (P<0.05). Similarly, Western blot results showed that compared with the control group, the expression levels of pyroptosis-related proteins was increased in the baicalin group (P<0.05). NAC inhibited the expression of NLRP3 and reduced the cleavage of N-GSDMD and N-GSDME (P<0.05). Compared with the NAC group, the NAC + baicalin group had significantly increased expression of pyroptosis-related proteins. These results indicate that baicalin can effectively induce pyroptosis in DB cells and reverse the inhibitory effect of NAC on ROS production. CONCLUSION: Baicalin can inhibit the proliferation of DLBCL cell line DB, and its mechanism may be through regulating ROS production to affect the pyroptosis pathway.

Advances in mesenchymal stem cell-derived extracellular vesicles therapy for Sjogren's syndrome-related dry eye disease.

Sjogren's syndrome (SS) is a chronic autoimmune disorder that affects exocrine glands, particularly lacrimal glands, leading to dry eye disease (DED). DED is a common ocular surface disease that affects millions of people worldwide, causing discomfort, visual impairment, and even blindness in severe cases. However, there is no definitive cure for DED, and existing treatments primarily relieve symptoms. Consequently, there is an urgent need for innovative therapeutic strategies based on the pathophysiology of DED. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool for various autoimmune disorders, including SS-related DED (SS-DED). A particularly intriguing facet of MSCs is their ability to produce extracellular vesicles (EVs), which contain various bioactive components such as proteins, lipids, and nucleic acids. These molecules play a key role in facilitating communication between cells and modulating a wide range of biological processes. Importantly, MSC-derived EVs (MSC-EVs) have therapeutic properties similar to those of their parent cells, including immunomodulatory, anti-inflammatory, and regenerative properties. In addition, MSC-EVs offer several notable advantages over intact MSCs, including lower immunogenicity, reduced risk of tumorigenicity, and greater convenience in terms of storage and transport. In this review, we elucidate the underlying mechanisms of SS-DED and discuss the relevant mechanisms and targets of MSC-EVs in treating SS-DED. In addition, we comprehensively review the broader landscape of EV application in autoimmune and corneal diseases. This review focuses on the efficacy of MSC-EVs in treating SS-DED, a field of study that holds considerable appeal due to its multifaceted regulation of immune responses and regenerative functions.

[Network Meta-analysis of Chinese medicine injections for activating blood and resolving stasis in adjuvant treatment of acute ischemic stroke].

Network Meta-analysis was employed to compare the efficacy of Chinese medicine injections for activating blood and resolving stasis combined with conventional western medicine in the treatment of acute ischemic stroke and the effects on platelet aggregation rate, fibrinogen(FIB), and hypersensitive C-reactive protein(hs-CRP), with a view to providing evidence-based medicine reference for clinical medication. CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, Cochrane Library, and EMbase were searched for randomized controlled trial(RCT) on the treatment of acute ischemic stroke with Salvia Miltiorrhiza Ligustrazine Injection, Danhong Injection, Shuxuetong Injection, Xueshuantong Injection, Shuxuening Injection, Safflower Yellow Pigment Injection, and Ginkgo Diterpene Lactone Meglumine Injection combined with conventional western medicine. The retrieval time was from database inception to March 18, 2023. The articles were extracted by two researchers and their quality was evaluated. R 4.2.2 was used for network Meta-analysis. A total of 87 RCTs involving 8 580 patients were included. Network Meta-analysis showed that, in terms of reducing National Institutes of Health stroke scale(NIHSS) scores, the surface under the cumulative ranking curve(SUCRA) showed the order of Xueshuantong Injection + conventional western medicine(88.7%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(73.7%) > Shuxuetong Injection + conventional western medicine(69.7%) > Shuxuening Injection + conventional western medicine(51.8%) > Danhong Injection + conventional western medicine(43.7%) > Safflower Yellow Pigment Injection + conventional western medicine(36.8%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(35.3%) > conventional western medicine(1.7%). In terms of improving clinical total effective rate, SUCRA showed the order of Danhong Injection + conventional western medicine(63.0%) > Shuxuening Injection + conventional western medicine(59.0%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(58.9%) > Safflower Yellow Pigment Injection + conventional western medicine(57.1%) > Xueshuantong Injection + conventional western medicine(56.8%) > Shuxuetong Injection + conventional western medicine(54.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(50.5%) > conventional western medicine(0.03%). In terms of improving Barthel index, SUCRA showed the order of Danhong Injection + conventional western medicine(84.7%) > Shuxuetong Injection + conventional western medicine(72.4%) > Safflower Yellow Pigment Injection + conventional western medicine(61.6%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(44.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(43.2%) > Shuxuening Injection + conventional western medicine(42.2%) > conventional western medicine(1.4%). In terms of reducing platelet aggregation rate, SUCRA showed the order of Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(82.4%) > Shuxuetong Injection + conventional western medicine(81.6%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(40.7%) > Danhong Injection + conventional western medicine(37.3%) > conventional western medicine(8.0%). In terms of reducing FIB, SUCRA showed the order of Danhong Injection + conventional western medicine(81.0%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(71.9%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(70.0%) > Shuxuetong Injection + conventional western medicine(46.7%) > Xueshuantong Injection + conventional western medicine(22.6%) > conventional western medicine(8.7%). In terms of reducing hs-CRP, SUCRA showed the order of Shuxuening Injection + conventional western medicine(89.9%) > Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine(78.8%) > Ginkgo Diterpene Lactone Meglumine Injection + conventional western medicine(52.4%) > Danhong Injection + conventional western medicine(47.6%) > Xueshuantong Injection + conventional western medicine(43.5%) > Shuxuetong Injection + conventional Western medicine(35.6%) > conventional western medicine(2.3%). The results indicated that Xueshuantong Injection + conventional western medicine, Danhong Injection + conventional western medicine, and Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine ranked the top three. Xueshuantong Injection + conventional western medicine had the best effect on reducing NIHSS scores. Danhong Injection + conventional western medicine showed the best performance of improving clinical total effective rate, improving Barthel index, and reducing FIB in the blood. Salvia Miltiorrhiza Ligustrazine Injection + conventional western medicine had the best effect on reducing platelet aggregation rate in the blood. Shuxuening Injection + conventional western medicine had the best effect on reducing hs-CRP. However, more high-quality RCTs are needed for verification in the future to provide more reliable evidence-based medical reference.